THE LIBRARY 
 
 OF 
 
 THE UNIVERSITY 
 OF CALIFORNIA 
 
 LOS ANGELES 
 
 GIFT OF 
 DR. ROY VAN WART
 
 THE INFLUENCE OF ALCOHOL 
 AND OTHER DRUGS ON FATIGUE
 
 THE INFLUENCE OF ALCOHOL 
 AND OTHER DRUGS 
 FATIGUE 
 
 ON 
 
 THE CROONIAN LECTURES DELIVERED AT THE ROYAL 
 COLLEGE OF PHYSICIANS IN 1906 
 
 BY 
 W. H. R. RIVERS, M.D., F.R.C.P. 
 
 FELLOW OF ST. JOtiN'S COLLEGE, CAMBRIDGE 
 
 LONDON 
 
 EDWARD ARNOLD 
 1908 
 
 [All right* reserved]
 
 Bioniedical 
 Library 
 
 QV 
 
 PREFACE 
 
 THE lectures printed in this book differ from those delivered 
 at the Royal College of Physicians in some details of arrange- 
 ment, and in the addition of new matter derived from later 
 work ; but the changes have not altered the general character 
 of the lectures, nor have the additions rendered necessary any 
 essential modification of views expressed when they were 
 delivered. 
 
 I am glad here to express my thanks to the Royal 
 College of Physicians for appointing me to be Croonian 
 Lecturer, and for allowing the funds of the Croonian Trust 
 to be devoted to the expenses of the researches on which the 
 lectures are based. Many of these researches have been 
 carried out in conjunction with Mr. H. N. Webber, to whose 
 help I owe very much. Others were made in conjunction 
 with Mr. W. McDougall, and I am greatly indebted to him 
 for allowing me to take part in the early trials of his new 
 and most valuable method of studying mental fatigue. 
 
 I have also to thank Dr. W. E. Dixon for his help in 
 preparing the mixtures in which the drugs of my experi- 
 ments were taken, and Professor Langley for allowing me to 
 reproduce some of the illustrations from the Journal of 
 Physiology. 
 
 W. H. R. RIVERS. 
 ST. JOHN'S COLLEGE, 
 CAMBRIDGE, 
 
 December, 1907. 
 
 C35489
 
 CONTENTS 
 
 LECTURE I 
 
 PAGE 
 
 INTRODUCTION AND METHODS 
 
 Introduction Methods of studying muscular fatigue ; fatigue of 
 isolated muscle and general fatigue Mental fatigue ; the curve 
 of work and the curve of fatigue McDougall's method of study- 
 ing fatigue of attention Immediate and prolonged effects of 
 drugs Methods for investigation of effects of drugs ; elimination 
 of influence of interest, sensory stimulation, and suggestion by 
 means of disguise - 1 21 
 
 LECTURE II 
 
 CAFFEINE 
 
 Action of caffeine on muscular fatigue; historical; new experiments 
 with ergograph ; twofold nature of action of caffeine Action on 
 mental fatigue ; historical ; new experiments with typewriting 
 and by McDougall's method ; slightness of stimulating action 22-50 
 
 LECTURE III 
 
 ALCOHOL 
 
 Alcohol and muscular fatigue ; historical ; new experiments with ergo- 
 graph ; absence of effect with doses varying from 5 to 20 c.c. 
 of pure alcohol ; previous results due to defective control ; incon- 
 stant increase with dose of 40 c.c. - 51-88 
 
 LECTURE IV 
 
 INFLUENCE OF ALCOHOL ON MENTAL FATIGUE 
 
 Historical ; new experiments with multiplication, typewriting, and by 
 McDougall's method ; slightness of effects Mode of action of 
 alcohol in fatigue ; comparison of effects on muscular activity of 
 alcohol and mental fatigue; removal of controlling influence 89-107
 
 viii CONTENTS 
 
 LECTURE IV (continued) 
 
 ACTION OF COCAINE, STRYCHNINE, TOBACCO, ETC. 
 
 Action of cocaine, strychnine, and tobacco ; historical ; new experi- 
 ments with strychnine and tobacco The work of Rossi and Fere 
 Action of formates, orchitic extract, 'fatigue antitoxin' and 
 muscle extract Conclusions : importance of control in method ; 
 results of new experiments and suggestions for future work 
 Analysis of fatigue-process Individual differences - 108-122 
 
 APPENDIX I 
 THE FORM OF THE CURVE REPRESENTING THE COURSE OF FATIGUE 123 
 
 APPENDIX II 
 
 NEW APPARATUS FOR THE APPLICATION OF MCDOUGALL'S METHOD 
 
 OF STUDYING MENTAL FATIGUE - 125 
 
 APPENDIX III 
 GENERAL ACTION OF CAFFEINE 127 
 
 APPENDIX IV 
 
 GENERAL EFFECTS OF ALCOHOL 131 
 
 APPENDIX V 
 
 THE MULTIPLICATION METHOD . 133 
 
 INDEX - - 134
 
 THE 
 
 INFLUENCE OF ALCOHOL AND OTHER 
 DRUGS ON FATIGUE 
 
 LECTUKE I 
 INTRODUCTION AND METHODS 
 
 Introduction Methods of studying muscular fatigue; fatigue of isolated 
 muscle and general fatigue Mental fatigue ; the curve of work 
 and the curve of fatigue McDougalFs method of studying fatigue 
 of attention Immediate and prolonged effects of drugs Methods 
 for investigation of effects of drugs ; elimination of influence of 
 interest, sensory stimulation, and suggestion by means of disguise. 
 
 IN my choice of a subject for these lectures, I have been 
 guided by the desire to show that the science which I teach 
 may be of service to medicine. In accordance with this idea, 
 I shall limit myself to those aspects of the subject which seem 
 to fall within the province of the experimental psychologist. 
 Thus, I shall only deal explicitly with the methods and results 
 of the experimental observation of the living man, though in 
 any theoretical consideration of these results I may have to 
 draw attention to the phenomena of fatigue, as studied on the 
 lower animals by purely physiological methods. 
 
 In every experiment on man there come into play certain 
 psychological factors which are wholly absent in the work 
 of the physiological pharmacologist, and it will be my object 
 in these lectures to consider these factors especially, and to 
 develop the methods by means of which they may be studied ; 
 in other words, it will be my chief object to consider the 
 
 1 1
 
 2 THE INFLUENCE OF DRUGS ON FATIGUE 
 
 application of pharmacological methods to the study of the 
 living man. 
 
 It is necessary at the outset briefly to consider the defini- 
 tion of fatigue. Attempts have been made to define this 
 condition by means of its physiological causes, and even to 
 distinguish two conditions fatigue and exhaustion the 
 former depending on the accumulation of the poisonous 
 products of activity, and the latter on the exhaustion or 
 diminished supply of the substances necessary for the con- 
 tinuance of activity ; but, however satisfactory these defini- 
 tions may be ideally, their application is wholly impracticable 
 in the present state of our knowledge, even in the case of the 
 fatigue of isolated muscle, and still more so in the case of 
 general bodily fatigue or of mental fatigue. 
 
 We must be content with some less ambitious definition ; 
 and, taking fatigue as a general term applicable to both bodily 
 and mental states, it may be defined as a condition of lowered 
 capacity for work, which follows or occurs during the per- 
 formance of work of which it is the direct result. 
 
 Further, a distinction must be made between the sense of 
 fatigue the sensations which supervene during the perform- 
 ance of work and the lowered capacity for work, shown 
 objectively by diminution in the amount of work executed. 
 These conditions, which may be spoken of as subjective and 
 objective fatigue respectively, do not always run parallel 
 courses. In the performance of mental work especially, 
 decided sensations of fatigue may be experienced when the 
 objective record shows that increasing and not decreasing 
 amounts of work are being done ; and there may be complete 
 absence of any sensations of fatigue when the objective record 
 shows that the work is falling off in quantity, or in quality, 
 or in both. 
 
 This distinction is one of great importance for our present 
 purpose, for one of the problems which will have to be 
 considered is whether the apparently beneficial effects of a 
 drug on fatigue may not sometimes be due, not to any direct 
 action on the capacity for work, but to its influence on the
 
 MUSCULAR FATIGUE 3 
 
 sense of fatigue, diminishing those unpleasant sensations 
 which act as our natural warnings that we are approaching 
 the limits of most favourable activity of our organs. It is 
 obvious that a drug which acts in this way would not be 
 exerting a real beneficial action in fatigue, but would be 
 rather acting as an accelerator of exhaustion, and the problem 
 whether certain drugs act in this way will be one of the 
 questions to be considered in these lectures. 
 
 MUSCULAR FATIGUE. 
 
 In nearly all the work which has been done on the action 
 of drugs in muscular fatigue Mosso's ergograph has been used, 
 either in its original form or with various modifications. 
 Objections have been made that this method does not give a 
 true picture of the normal course of fatigue, and, so far as the 
 single ergogram is concerned, there can be no doubt that this 
 is true. It is now known that the typical Mosso's ergogram 
 is the resultant of a very special set of conditions working 
 together. It has been shown by Treves 1 that the condition 
 of complete exhaustion which occurs at the end of the ergo- 
 gram is only apparent, and that the weight has only to be 
 somewhat diminished for the finger to become again capable 
 of contractions equal in extent to those of the wholly un- 
 fatigued condition. The ergogram of Mosso only occurs with 
 a constant weight near the limit of the powers of the subject 
 of the experiment. 
 
 Treves 2 has devised a method of ergography in which the 
 weight can be easily varied, and he has called this the method 
 with variable weight, as opposed to the method with constant 
 weight of Mosso. He suggests that the true course of 
 muscular fatigue would be represented by a curve showing 
 the amounts of the successive diminutions of the weight a 
 curve which falls most rapidly at first and then more slowly, 
 
 1 Arch. ital. de BioL, 1898, t. xxix., p. 157, and t. xxx., p. 1. Also 
 Arcli.f. d. gcs. PhysioL, 1902, Bd. Ixxxviii., S. 7. 
 - 'Arch. Hal. de Biol., 1901, t. xxxvi., p. 44. 
 
 12
 
 4 THE INFLUENCE OF DRUGS ON FATIGUE 
 
 till it passes into a horizontal line corresponding to the 
 weight with which work can be continued for an indefinite 
 time. 
 
 The interest of this curve arises from the fact that it 
 corresponds closely with the fatigue curve, which is obtained 
 by another method the spring or dynamographic method. 
 In this method fatigue is produced, not by lifting a weight, 
 but by contracting a muscle or group of muscles against the 
 force of a spring. This method has in recent years had many 
 advocates, as one theoretically more satisfactory than the 
 weight method. The kind of curve produced is of the same 
 nature as that suggested by Treves as the result of the 
 ergogra.phic method with variable weight. The correspondence 
 of these two methods raises the question whether the ergogram 
 of Mosso is not an artificial product, which stands in no 
 definite relation to the true course of muscular fatigue. 
 
 The objections toMosso's method of measuring fatigue are 
 very greatly diminished if, instead of taking a single ergogram 
 as a measure of fatigue, series of such ergograms are recorded 
 at intervals insufficient to allow complete recovery from the 
 fatigue induced by the ergogram. If the amount of work 
 done in such a series of ergograms is represented in the form 
 of a curve, there is usually found to be a rapid fall at first, 
 gradually becoming less, till after a time the successive ergo- 
 grams show little variation from one another and reach a 
 constant level, the curve representing the course of a series of 
 ergograms thus showing a close correspondence with those 
 obtained by the dynamographic method and by the method 
 of Treves. In my own work I have been chiefly interested in 
 the influence of certain psychical factors which I believe to 
 have had a great effect on the results of previous workers, 
 and as nearly all these workers had used Mosso's method, I 
 had no hesitation in using it in my own work to test the 
 influence of the factors in question ; and my experience of the 
 method has shown me that, whatever may be the objections 
 to the single ergogram, the ergographic method with constant 
 weight gives a very valuable picture of the course of fatigue
 
 MUSCULAR FATIGUE 5 
 
 when series of ergograms are recorded, and is a most useful 
 method for the study of the action of drugs. 
 
 If, instead of giving the muscle its maximum task with 
 Mosso's ergograph, a weight sufficiently small is chosen, it is 
 well known that the muscle is able to continue its con- 
 tractions for an indefinite time ; if, then, the weight is slightly 
 increased, it will be found that exhaustion will only show 
 itself at the end of, say, an hour ; with a still heavier weight 
 at the end of half an hour, the curves produced being some- 
 times known as ' Maggiora's curves.' A method which has 
 been used to test the influence of a drug is to determine the 
 time required to induce fatigue with and without the drug. 
 Fatigue which comes on at the end of half an hour in the 
 normal condition may only supervene at the end of an hour, or 
 vice versa, and this method, which has been very little used, 
 may be a valuable accessory means of studying muscular 
 fatigue. 
 
 My own ergograph is the latest form of Kraepelin's 
 modification of Mosso's ergograph, in which the chief im- 
 provements are that the movement is rigorously limited to one 
 joint, and that the fingers are inserted in graduated fixtures 
 by means of which the hand can always be placed in the same 
 position. 1 One can thus be certain that the point of applica- 
 tion of the weight and its angle of application are constant. 
 A further improvement is that there is an arrangement by 
 which the weight does not fall back during the relaxation of 
 the finger, and this is combined with another feature which 
 effects a great saving of time, in that the height through 
 which the weight has been lifted can be read directly, and has 
 not to be calculated by measuring the heights of the individual 
 contractions. 
 
 In my own work I have adopted the procedure of recording 
 sets of ergograms, the interval between the successive ergo- 
 grams of a set being always two minutes, and the interval 
 
 1 For a description of the chief features of this instrument see 
 Kraepelin\s ' Psychologische Arbeiten,' 1896, Bd. i., S. 380, and 1904, 
 Bd. iv., S. 189.
 
 6 THE INFLUENCE OF DRUGS ON FATIGUE 
 
 between any two of the contractions by which the ergogram 
 is formed two seconds, the finger being contracted with one 
 and relaxed with the next beat of a metronome beating 
 seconds. Usually each set has consisted of six ergograms, 
 and the interval between successive sets has been either half 
 an hour or an hour. The weight has been hidden from 
 the view of the subject, and the kymograph on which the 
 
 FIG. 1. 
 
 ergograms are recorded has been so arranged that they also 
 have not been visible during their formation. 
 
 A record of a typical day's experiment is given in Fig. 1, 
 when three sets of ergograms were taken at intervals of half 
 an hour. For each ergogram there are recorded the total 
 amount in kilogrammetres of work executed, the number of 
 contractions, and the average height of the contractions, 
 found by dividing the total height through which the weight 
 is lifted by the number of contractions. 
 
 Investigations on muscular fatigue fall into two groups : 
 those in which there is studied the fatigue of a single muscle,
 
 MUSCULAR FATIGUE 7 
 
 or small group of muscles, so as to approach as nearly as 
 possible to the mode of investigation of isolated muscle by 
 purely physiological methods, and those in which there is 
 studied the general fatigue produced by the activity of a large 
 part of the musculature of the body. In this second line of 
 investigation, in which so far very little has been done, the 
 ergograph has been used as a test of the fatigue produced by 
 such activities as walking, raising weights by turning handles, 
 etc. These two kinds of investigation cannot be rigorously 
 separated from one another ; even in Mosso's method there 
 must always be some activity of many muscles, not only that 
 always present, but also that which is necessary to prevent 
 general movements of the body. But such movements are 
 small compared with the very heavy task given to the single 
 muscle in this method. 
 
 The influence' of drugs on general fatigue has also been 
 studied by means of observations on large masses of men 
 in campaigns, etc., but in such observations there is 
 obviously involved much more than muscular fatigue. 
 From the practical point of view the influence of drugs on 
 such general activities are of much greater interest than the 
 behaviour of an isolated muscle ; but before the complex 
 condition of general fatigue can be understood, it is necessary 
 to study in as pure a form as possible the muscular fatigue 
 and mental fatigue which form constituents of the complex 
 condition, and in my own work I have only attempted to 
 deal with these simpler problems. 
 
 MENTAL FATIGUE. 
 
 One of the advantages of Mosso's method of studying 
 muscular fatigue is that the subject is given a task which is 
 so arduous that the element of fatigue greatly predominates 
 over certain other factors which always come into play in 
 some measure in studying the capacity for work. In the 
 investigation of mental fatigue, on the other hand, the only 
 exact methods hitherto used are such that the effect of fatigue 
 is often masked by the presence of these additional features.
 
 8 THE INFLUENCE OF DRUGS ON FATIGUE 
 
 Nearly all the work on this subject comes from Kraepelin 
 and his school, and it is also to this school that we owe most 
 of our knowledge of the action of drugs on the capacity for 
 mental work. In order to measure mental work some kind of 
 unit is necessary, and to obtain such units only mental opera- 
 tions of a simple character can be employed. The units which 
 have been most frequently employed are simple arithmetical 
 operations, and the method most commonly used by Kraepelin 
 and his followers is one in which the unit of work is that in- 
 volved in the addition of two numbers. Kraepelin has drawn 
 up books containing rows of figures, and his usual procedure in 
 testing the influence of a drug on the capacity for mental 
 work has been to ascertain the number of additions which 
 can be performed in a given time, the time being divided into 
 portions, so that a curve can be constructed showing the 
 amount and rate of increase or decrease of work during the 
 whole of the experiment. 
 
 Such a curve showing the results of an hour's work is due 
 to the combined action of a number of different factors. In 
 the great majority of individuals the curve rises for some time, 
 though this rise is often broken soon after the beginning, and 
 this rise is undoubtedly in the main due to the influence of 
 practice. After a certain time the curve rises less steeply, 
 and either passes into an approximately horizontal line, or 
 may begin to fall, and this diminution of rise or actual fall 
 is due in some measure to the occurrence of fatigue, though 
 it is probable that in many experimental investigations loss of 
 interest is also largely responsible. The initial rise is due, not 
 only to practice, but also, and perhaps in large measure, to 
 the influence of another factor, for which it is difficult to 
 find a satisfactory term in English. Kraepelin has called it 
 Anregang^ and its equivalents in English are best given in 
 the phrases ' warming to work ' and ' getting into swing.' 1 It 
 is the process by which the inertia of the psycho-physical 
 machine is overcome. We all know how much this inertia 
 
 1 Mr. Wimms has recently used the term ' incitation ' as the equiva- 
 lent of Anregnng* (Brit. Journ. Psychol., 1907, vol. ii., p. 158).
 
 MENTAL FATIGUE 9 
 
 may vary, and the degree of rapidity of this process of 
 warming to work is a potent cause of irregularity in the form 
 of the curve. Perhaps a still more important source of 
 irregularity is given in the phenomenon of spurt. The work 
 used in the experimental investigation of mental fatigue is 
 always more or less monotonous, arid there are apt to occur 
 lapses of attention and application which are followed by 
 spurts, and this phenomenon of spurt is especially pronounced 
 at the beginning and end of a period of work. 
 
 The curve of mental work is, then, compounded of at least 
 five factors, three practice, warming to work, and spurt 
 tending to raise the curve, while the other two fatigue and 
 loss of interest tend to depress it. The practical determina- 
 tion of the influence of such an agent as a drug on the process 
 of fatigue is in consequence rendered a matter of the greatest 
 difficulty. Much work and thought have been expended by 
 Kraepelin and his school in the attempt to devise experi- 
 mental procedures by which the conditions may be so varied 
 as to provide data for the analysis of the curve of work into 
 its various components. 1 The matter is one of the greatest 
 difficulty, and little has yet been accomplished ; but one 
 advance has been made towards isolating the influence of 
 fatigue. If periods of rest are given between periods of work, 
 so as to allow recovery from fatigue, it is found that, other 
 conditions being the same, some people require longer periods 
 of rest than others, and the most favourable period of rest 
 may be determined for each person, and the duration of this 
 most favourable pause may be taken as a measure rough/ 
 indeed of the degree in which that person is susceptible to 
 fatigue. This test, which has so far been applied chiefly to 
 the study of individual differences, may also be used in 
 studying the action of drugs on fatigue. By pauses of 
 different lengths fatigue may be eliminated in different 
 degrees, and the influence of a drug on this factor of the 
 curve in some measure isolated. 
 
 1 See ' Die Arbeitscurve, 1 Wundt's ' Philos. Studien,' 1902, Bd. xix., 
 S. 459. In this paper Kraepelin describes an additional factor, 
 Gewohmtng, or habituation, which he distinguishes from practice.
 
 10 THE INFLUENCE OF DRUGS ON FATIGUE 
 
 Apart, however, from any exact means of analysis, we shall 
 probably not go far wrong in assuming that an earlier or 
 steeper fall of the curve is due to increase of the part played 
 by fatigue in the total effect, and, correspondingly, that a post- 
 poned or more gradual fall is due to a diminution of fatigue. 
 
 There is, however, one point of great theoretical interest to 
 which I should like to refer briefly. In the earlier work of 
 Kraepelin and his school, the problems connected with fatigue 
 were studied by means of work carried on for long periods 
 for one or even for two hours. More recently it has been 
 found that the effects of fatigue can be demonstrated even 
 with such short periods of work as ten minutes. We know 
 that if the work had been continued beyond the ten minutes, 
 its amount would have steadily increased, perhaps for another 
 half an hour or more, and the question is therefore raised 
 whether the course of mental fatigue is properly represented 
 by a curve which falls off at first slowly and then more 
 rapidly. The mental work which has to be used experi- 
 mentally is necessarily easy, and resembles the work of the 
 dynamographic rather than that of the ergographic methods 
 of measuring fatigue. We have seen that the former method 
 shows the curve of fatigue to be one which falls off most 
 rapidly at first, and then more slowly, till a constant level is 
 reached, and the question arises whether this is not also true 
 of the curve of mental fatigue. 1 
 
 I have so far referred only to the quantity of work done 
 in a given time as the measure of mental fatigue, meaning by 
 quantity of work the number of units performed in a given 
 time. It might be thought that the quality of the work 
 would be even more important as a measure of fatigue ; that 
 with the onset of fatigue there would be a decided impairment 
 of the correctness of the additions or other mental operations 
 employed. As a matter of fact, it has been found at any rate, 
 in some cases' 2 that the number of errors is so small that they 
 
 1 For further consideration of this question, see Appendix I. 
 - See Amberg, Kraepelin's ' Psychologische Arbeiten,"" 1896, Bd. i., 
 S. 336, and Rivers and Kraepelin. ibid., Bd. i., S. 656.
 
 MENTAL FATIGUE 11 
 
 are useless for the estimation of fatigue, and it is the custom to 
 neglect the quality, and rely only on the quantity of the 
 work. The possibility must not be forgotten, however, that 
 in some cases the quality of the work may suffer from 
 fatigue, and if in such a case the increase in quantity is 
 accompanied by an impairment of quality, it may become 
 extremely difficult to estimate satisfactorily the part played 
 by fatigue. 
 
 Many objections have been brought against these methods 
 of measuring mental work, both from the theoretical and 
 practical points of view, and I must confine myself to two of 
 them. All the methods employed in investigations of this 
 kind are extremely laborious, and the work itself is monotonous 
 and uninteresting, and it may be urged that we are measuring, 
 not so much fatigue comparable to that resulting from bodily 
 work, but rather the loss of interest due to the monotony of 
 the occupation. There is much force in this objection, and 
 some distinct experimental evidence might be adduced in 
 support of it. 1 Nevertheless, it is found in practice that the 
 work in question is far less monotonous than it would appear 
 to be to those who have not tried it, this being largely due to 
 the extrinsic interest given to the work by the scientific aim 
 with which it is undertaken. 
 
 The other point is that the kind of work which has been 
 chiefly used is so simple that, after a certain amount of practice 
 has been gained, the work becomes almost automatic. This 
 objection may be partly met by using mental operations 
 of somewhat greater difficulty than those employed by 
 Kraepelin ; and in my own work with arithmetical methods I 
 have used the task of multiplying four numbers mentally 
 instead of the much easier task of adding two numbers, but 
 even here, with practice, the operation tends to become very 
 automatic. 
 
 Arithmetical operations are not the only means of studying 
 
 1 Thus, Wimms has found (pp. cit.) that, if the falling off in the 
 amount of work is due to fatigue, fatigue must be greater with an easier 
 than with a more difficult task.
 
 12 THE INFLUENCE OF DRUGS ON FATIGUE 
 
 the capacity for mental work, and I have also used type- 
 writing, which has the advantage of being to most people 
 more interesting than addition or multiplication, though there 
 is the disadvantage that the task is more complex, involving 
 as it does so much muscular as well as mental activity. 
 
 When we endeavour to compare the results obtained by 
 the study of mental fatigue with those of muscular fatigue, 
 we are met by the difficulty that the two kinds of fatigue 
 have been studied by methods which have very little in 
 common. Most of the work on muscular fatigue has been 
 done by a method in which the task set is so great that 
 fatigue, apparently complete, is induced in about a minute, 
 while mental fatigue has been studied by methods in which 
 the effects of fatigue may not be obvious, even at the end of an 
 hour. This difference would probably be less striking if the 
 dynamographic instead of the ergographic method were em- 
 ployed, but even here there is a very great difference in the 
 magnitude of the task in the two cases. The methods of 
 measuring mental fatigue differ radically in another respect 
 from those used for muscular work, in that the means of 
 measurement is by time rather than by the work itself. 
 Fatigue is shown chiefly by alteration in the rapidity of 
 work, while in the study of muscular work the rapidity is 
 kept constant, and fatigue is measured by means of alterations 
 in the actual amount of work of which the worker is capable. 
 
 Mr. McDougall has recently devised 1 a method of studying 
 mental fatigue, or perhaps I should say, more precisely, fatigue 
 of attention, which is in many ways more nearly comparable 
 with the methods of measuring muscular work. An essential 
 feature of the method is that stimuli are provided which may 
 be called extrinsic. In the ordinary methods of studying 
 mental activity, the stimulus to work comes wholly from 
 within ; the subject of the experiment has to keep himself 
 working at the greatest rate possible, and it is a question 
 whether the difficulty in ascertaining the existence of fatigue 
 is not due to the occurrence of a kind of balance between 
 1 Brit. Journ. PxyclioL, 1905, vol. i., p. 435.
 
 MENTAL FATIGUE 13 
 
 effort and accomplishment, in which work goes on at a more 
 or less constant level, corresponding, perhaps, to the constant 
 level of the dynamographic method of studying muscular 
 fatigue. 
 
 In Mr. McDougall's method the subject is set the very 
 simple task of hitting a succession of dots which pass before 
 him through a slit. The rate at which the dots pass can be 
 varied, and it is found that if they are made to pass at a 
 speed which is near the maximal rate for the subject of the 
 test, the onset of fatigue is rapid and obvious. It is a 
 method in which fatigue is studied by means of the accuracy 
 of aim a method in which, in any one experiment, the rate 
 of work is kept constant, as in the methods of studying 
 muscular work, and the measure of fatigue is the quality of 
 work. 
 
 In conjunction with Mr. McDougall, I have used this 
 method to study the action of drugs ; and other experiments 
 recorded by Mr. McDougall show that the method is one well 
 adapted for the study of their influence on mental fatigue. 
 
 In the instrument described by Mr. McDougall, and used 
 by us, it was only possible to study the course of fatigue for 
 a comparatively short time ; but, with the aid of Mr. Horace 
 Darwin, I have been able to devise a modification 1 by means 
 of which the effects of fatigue can be studied for much longer 
 periods. The completion of this apparatus has been, however, 
 so long delayed that it has not yet been possible to carry out 
 fully any observations with it on the action of drugs. I 
 shall, however, be able to give the results obtained by Mr. 
 McDougall and myself with the original apparatus. 
 
 THE ACTION OF DRUGS. 
 
 Experiments on the action of drugs in fatigue may be 
 carried out by two methods. In one method a certain amount 
 of work is done every day for several periods, each of a week 
 or fortnight, or longer. During some periods the drug is taken 
 
 1 See Appendix II.
 
 14 THE INFLUENCE OF DRUGS ON FATIGUE 
 
 every day, but not at such a time of the day as to show its 
 immediate effect on the work, while during other periods 
 there is complete abstention from the drug. By this method 
 there is tested the influence on the capacity for work of 
 the general condition produced by the ingestion of the drug. 
 No such work has hitherto been done on the capacity for 
 muscular work ; but it has been employed by Kraepelin and 
 his school to test the influence on the capacity for mental 
 work of alcohol taken daily for a certain period. 
 
 The other and more usual method by which the action of 
 drugs is tested is to do a certain amount of work every day, 
 taking a dose of the drug on some days and abstaining on 
 other days. In this way, then, is tested not only the immediate 
 action of the drug on the capacity for work, but by prolong- 
 ing the work of each day the influence of the drug may be 
 followed for many hours. This method is that which has usually 
 been employed in the work I shall bring forward in these 
 lectures. 
 
 The two methods could be combined ; and this may be 
 done most easily by comparing the work of the normal or 
 control days during a drug experiment of the second class with 
 the work of a similar series consisting wholly of normal days. 
 
 I have now described the general character of the methods 
 which are employed in the study of muscular and mental 
 fatigue, and can turn to the consideration of some aspects 
 of the experimental study of fatigue which are of especial 
 importance in estimating the influence of drugs. 
 
 We shall see later that the most varied methods have been 
 used by different workers in studying the action of drugs. 
 A common method has been to work to exhaustion, and then 
 to see if the administration of a drug is able to call forth a 
 further amount of work ; others give a record of work which 
 they state is their normal amount, and then give the result 
 under the influence of a drug, but provide no indication of 
 the relation between the supposed increment or decrement 
 produced by the drug and the normal variations which occur 
 from day to day.
 
 THE ACTION OF DRUGS 15 
 
 The most satisfactory method, which was first adopted in 
 a really systematic manner by Kraepelin, is to carry out work 
 on a number of successive days (or days at regular intervals), 
 keeping all conditions exactly alike on the different days, 
 except that on some a drug is administered. The drug may 
 be given before beginning the work of each day, but there 
 are certain practical difficulties to which this procedure is 
 subject. In many cases the drug-days will give an average 
 which deviates from that of the normal days so greatly that 
 there can be no question as to the action of the drug ; but in 
 other cases the deviation may be so slight that the question 
 arises whether it may not be within the average deviation of 
 the normal days from one another. There are, of course, 
 definite methods for ascertaining the relation between a given 
 difference and the probable difference due to normal variations, 
 but their application in this branch of study is rendered very 
 difficult by the existence of practice, etc. i.e., we have to do 
 not merely with a number of days which differ from one 
 another by chance variations of daily disposition, etc., but with 
 days which differ owing to the existence of certain more or 
 less regular influences which, though they no doubt follow 
 definite laws, are not yet sufficiently understood to allow the 
 application of statistical measures. 
 
 This difficulty may, however, be overcome in large measure 
 if the drug is given at some period after the work has been 
 begun, so that the results can be expressed in relation to 
 the initial performance before the drug has been taken. This 
 latter method is that which I have usually employed. 
 
 In carrying out an experiment of this kind, extending 
 over a number of days, it is essential that all the conditions 
 of life be kept as constant as possible. The same amount of 
 sleep must be taken every night, the meals must be of the 
 same kind and at the same times every day, the same amount 
 of exercise must be taken, and the same amount of other work 
 done. To do experimental work of this kind really satisfactorily 
 means to most people that they must cut themselves off from 
 many of the ordinary pursuits of life so long as the experi-
 
 16 THE INFLUENCE OF DRUGS ON FATIGUE 
 
 ments last. In my own case the fact that my occupation 
 involves very different amounts of work on different days has 
 made it impossible, as a general rule, to carry out any experi- 
 mental work during term-time, and my own most satisfactory 
 work has been done in the country, away from all possible 
 sources of disturbance. 
 
 In the case of muscular work, the necessity for rigorous 
 equality of the conditions of life is perhaps not so great as 
 in the case of mental work ; but here the more similar the 
 conditions can be kept, the more likely is it that satisfactory 
 results will be obtained. 
 
 It must be understood that these rigorous conditions are 
 not necessary for the crude determination of the action of 
 large doses of drugs ; but it is not with such work that I am 
 now concerned. It is my object in these lectures to consider 
 the methods to be followed in the endeavour to ascertain the 
 effects of those doses of drugs which are used either for 
 dietetical or therapeutical purposes, and for such an object 
 unequivocal results can only be expected if the conditions of 
 life are kept as rigorously uniform as possible. 
 
 A difficulty which arises in drug experiments is due to 
 the practice of taking as part of the normal diet substances 
 which have an effect on the capacity for work ; and this 
 difficulty becomes especially great when it is one of these 
 drugs which is the subject of experiment. There are two 
 possible lines of action : the use of the substances may be 
 wholly discontinued before the experiment begins, or the 
 experimenter may continue to take them, but in exactly the 
 same quantity every day and at exactly the same times, 
 while he may perhaps diminish their amounts. The former 
 procedure, which has been adopted by several workers, is 
 open to a serious danger, to which my attention was called 
 by my own experience. I began my work on drugs with an 
 experiment on the effects of caffeine, and discontinued the use 
 of tea and coffee shortly before the experiment began, having 
 previously taken them in diminished quantity. The act of 
 giving up the use of these substances was followed by loss
 
 THE ACTION OF DRUGS IT 
 
 of energy, which greatly interfered with the success of the 
 experiment, and a later repetition of the experience left little 
 doubt that the condition was due, at any rate in part, to the 
 discontinuance of the use of tea and coffee. My reaction was 
 probably exceptional ; but a condition which is so pronounced 
 in one person is probably present to some extent in all> 
 though it may be masked by other variations in bodily and 
 mental health. Indeed, it seems only natural that the sudden 
 cessation of the habitual action of such a substance as caffeine 
 must have a decided effect on those vital processes on which 
 it has any influence. 
 
 If, in investigations on the effect of such a substance as 
 alcohol in one accustomed to it, the use of the active substance 
 is only given up shortly before the commencement of the 
 experiments, there is a further danger. Even in those who 
 only take such a substance in moderate amounts, its disuse is 
 probably followed in some degree by the craving which is so 
 pronounced after discontinuance of large amounts, and, slight 
 and hardly noticeable as this craving may be, it may yet be 
 sufficient to produce an obvious effect when the article of 
 which the person has been deprived is administered experi- 
 mentally. The effect of the substance given experimentally 
 may be the result, not of its normal physiological action, but 
 of the satisfaction of a craving. For these reasons it seemed 
 best to give up completely the use of all the stimulating 
 articles of diet in ordinary use for several months before 
 beginning my next research, and much of the work to be 
 described in these lectures was done more than a year after 
 the use of alcohol and caffeine-containing articles of diet had 
 been given up, except for experimental purposes or on such 
 rare occasions that there could be no question of habituation. 
 So drastic a procedure is not likely to attract workers to this 
 subject ; and though it has been followed also by Mr. Webber, 
 who has been my co-worker in many of the researches to be 
 described in these lectures, I have been content in other cases 
 to allow the continued use of tea, coffee, alcohol, or tobacco, 
 but in equal amounts and at the same times every day, and 
 
 2
 
 18 THE INFLUENCE OF DRUGS ON FATIGUE 
 
 wherever possible not till after the experimental work of the 
 day has been done. 
 
 Another difficulty arises in connexion with practice and 
 training. Some recent workers have insisted on the necessity 
 for long-continued training before beginning to use ergo- 
 graphic curves as objects for scientific study, and one, Hell- 
 sten, trained for many months before he began to study the 
 action of drugs. 
 
 By following such a rule it seems to me that a great 
 experimental opportunity is being neglected. One of the 
 features of the work of untrained muscle is the occurrence of 
 painful or unpleasant sensations ; and since one of the definite 
 problems in connexion with the effect of drugs on fatigue 
 is how far they act through their influence on the sensations 
 of fatigue, comparative work on trained and untrained muscle 
 may be of great value. In my own work, therefore, I 
 have tested the influence of drugs in various conditions of 
 training, and in every case introspective notes have been 
 recorded to show whether painful or other unpleasant 
 sensations have been experienced during the course of the 
 experiment. 
 
 I can now pass to a feature of method in which lies the 
 chief interest of the new work I hope to bring before you a 
 feature designed to eliminate the influence of certain psychical 
 factors which have undoubtedly been allowed to affect the 
 results of nearly all who have experimented on the action of 
 drugs. Many of these workers have considered the possi- 
 bility that their results may have been influenced by sugges- 
 tion, or of bias towards results which were to be expected 
 theoretically, and some have shown that effects similar to 
 those following the administration of a drug may be the con- 
 sequence of the administration of a wholly inactive sub- 
 stance which is supposed by the subject to be the drug in 
 question. Few, however, have adopted the obvious precau- 
 tions which such considerations suggest ; Schumburg 1 and 
 
 1 Arch. f. Anat. u. PhysioL, Physiol. Abth., Suppl. Bd., 1899, 
 S. 289.
 
 THE ACTION OF DRUGS 19 
 
 Sobieranski 1 are the only workers with drugs 2 who have used 
 any kind of control-substances, and even they do not make it 
 clear that the control mixtures or injections they used were 
 entirely indistinguishable from those containing the active 
 substances. 
 
 The factor which previous writers have considered 
 under the title of ' suggestion ' is far from being the only 
 source of error in work on the action of drugs. Fe're' has 
 shown that the sensory stimulation involved in the act of 
 taking a drug into the mouth and swallowing it may have a 
 very decided effect on the amount of work executed with the 
 ergograph, but even this knowledge did not lead him to adopt 
 any control in his numerous researches on drugs. 
 
 There is, however, another factor which is probably more 
 important than either sensory stimulation or suggestion viz., 
 the interest and excitement produced by taking a substance 
 when the discovery of its effect is the motive of the whole 
 experiment. The ergographic curve is an extremely delicate 
 reagent, to any form of mental excitement. Any novelty in 
 the course of an experiment may have a very decided effect 
 on the amount of work. The interest of a conversation, the 
 knowledge that the performance is being watched, the view 
 of the weight rising as one works or of the formation of the 
 ergogram on the drum, or any other variation in the routine 
 of the daily experiment, may have very obvious effects on the 
 amount of work. Similarly, the knowledge that it is the first 
 or last day of an experiment may produce a distinct increase 
 in the amount of work, so decided that I now always adopt 
 the procedure of working for one or two days before and 
 after the period which is to provide the proper data for the 
 experiment. 
 
 If such a condition of interest as that arising from its 
 
 1 Centrulbl. /. Physiol., 1896, Bd. x., S. 126. 
 
 2 Schumburg has also used dulcin as a control substance in work on 
 the action of sugar (Zeitschr.f. diatetisch. u. physical. Therapie, 1899, 
 Bd. ii., S. 185), and irreproachable work from this point of view has been 
 done by Pregl (Arch. f. d. ges. Physiol., 1896, Bd. Ixii., S. 379) on the 
 action of orchitic extract. 
 
 22
 
 20 THE INFLUENCE OF DRUGS ON FATIGUE 
 
 being the first or last day of an experiment, or that resulting 
 from the view of the weight rising as the finger contracts, can 
 have very appreciable effects on the amount of work, it is 
 clear that so interesting an occurrence as the administration 
 of a drug must have a decided influence, and the interest 
 so aroused will probably be equally great whether the nature 
 of the drug is unknown, so that there is an element of mystery 
 in the occurrence, or whether its nature is known. When in 
 the latter case the subject is himself the experimenter, keenly 
 interested in the possible results of his experiment, this factor 
 of interest must often be very strong. 
 
 In my first experiment with a drug, I soon became aware 
 x)f the existence of such interest. I noticed that the days on 
 which I took the drug interested me more than the normal 
 days on which nothing was taken. I felt at once stimulated 
 by the fact of having taken the substance, the action of which 
 I was trying to test, and it was obvious that I had no means 
 of telling whether any effect which might be produced was 
 due to this interest or to the proper physiological action of 
 the drug. In all future experiments I therefore determined 
 to endeavour to disguise the days on which the drug was 
 being taken and all the new work to be described in these 
 lectures has been carried out with the use of control mixtures 
 which have usually been wholly indistinguishable from those 
 containing the active substances. The subject of an experi- 
 ment has taken every day at some time in its course a dose 
 of a mixture, and has been wholly unaware whether he has 
 taken the substance which is the motive of the experiment or 
 some inactive imitation of it. These control mixtures have 
 in most cases been prepared for me by Dr. W. E. Dixon, to 
 whose help in this direction I am very greatly indebted. In 
 some cases in which I have myself been the subject of the 
 experiment, Dr. Dixon has given me two or more bottles, 
 and it has only been at the end of the experiment that I 
 have been made acquainted with the exact nature of their 
 contents. 
 
 My own work has been chiefly on caffeine and alcohol,
 
 THE ACTION OF DRUGS 21 
 
 and with the former of these we were rapidly successful in 
 disguising the taste. We used citrate of caffeine, and an 
 indistinguishable control mixture was made of gentian and 
 citric acid. With alcohol we had greater difficulty ; but the 
 consideration of this may be deferred till I come to deal 
 with the work on that substance. 
 
 I have not myself experimented with subcutaneous injec- 
 tions of any drug, but it is obvious that control injections are 
 in such a case just as necessary as are control mixtures when 
 the drug is given by the mouth. 
 
 Most of those who have written on the action of drugs on 
 the capacity for work have not distinguished definitely between 
 the action on the pure capacity for work in the unfatigued con- 
 dition and the action on the process of fatigue, with which we 
 have especially to do in these lectures. A complete distinc- 
 tion of this kind is, perhaps, impossible, for it is probable that 
 the fatigue process comes into play from the first moment of 
 beginning to work ; but, nevertheless, the distinction can be 
 made in practice to a great extent, and I shall endeavour to 
 make it, not only in the account of my own work, but also in 
 that of the work of others, even when it has not been made 
 by the authors themselves. 
 
 The method which I have adopted of recording sets of 
 ergograms separated by intervals of rest is particularly 
 adapted to bring out the distinction in question, and we shall 
 see that there is evidence that the effect of a drug may be 
 different at the beginning of a set of ergograms from that 
 shown as the set is continued.
 
 LECTUKE II 
 CAFFEINE 
 
 Action of caffeine on muscular fatigue ; historical ; new experiments 
 with ergograph ; twofold nature of action of caffeine Action on 
 mental fatigue ; historical ; new experiments with typewriting 
 and by McDougalPs method ; slightness of stimulating action. 
 
 I WILL begin my survey of the work which has been done on 
 the action of drugs in fatigue by taking up the group of 
 substances of which caffeine is the most important con- 
 stituent. These substances are in habitual use as stimulants 
 of work, and I may as well say at once that their universal 
 reputation is not belied by the results of experiment. 
 
 In the earliest work on muscular fatigue the dynamometer 
 was used. In 1892 De-Sarlo and Bernardini 1 found that 
 caffeine produced a slight increase in the force of the contrac- 
 tions with this instrument, and Kraepelin 2 found tea to have 
 the same effect. 
 
 Since that time most workers have used the ergograph of 
 Mosso, either in its original form or in one of its modifications. 
 In 1893 Ugolino Mosso 3 used it in his work on the action of 
 kola, which he found to have a highly stimulating effect, the 
 work done in a single ergogram being increased fourfold, this 
 action being due chiefly to the caffeine which the kola 
 contained. 
 
 In 1894 Koch 4 tested the action of a dose of caffeine taken 
 when the muscles had already been exhausted, and found that 
 
 1 Rivista sper. di Frenlatria, 1892, vol. xviii., p. 1. 
 
 2 ' Ueber die Beeinflussung einfacher psychischer Vorgange durch 
 einige ArzneimitteV Jena, 1892, S. 143. 
 
 1 Arch. ital. de BioL, 1893, t. xix., p. 241. 
 4 Inaug. Diss., Marburg, 1894. 
 
 22
 
 CAFFEINE 23 
 
 they were rendered capable of continued activity. His work 
 is notable for the demonstration that a great increase in the 
 amount of work executed with the ergograph can be produced 
 by suggestion, but Koch found that the increase produced by 
 caffeine exceeded that which could ever be produced by this 
 means. 
 
 In 1894 Rossi 1 found only a slight increase in the amount 
 of work under the influence of caffeine, the effect being due to 
 increase in the number of the contractions. 
 
 In 1896 Sobieranski 2 tested the influence of caffeine, not 
 only on the capacity for voluntary work, but also when the 
 contractions were produced by electrical stimulation of the 
 muscle, and found an increase by both methods, the effect of 
 the drug being produced more slowly with electrical stimula- , 
 tion ; and, in spite of the well-known fact that caffeine 
 stimulates muscle directly, he concluded that its effect in 
 man is chiefly through its central action. 
 
 In 1896 was published the important work of Hoch and 
 Kraepelin 3 on the action of the constituents of tea on the 
 capacity for muscular work. An improved form of Mosso's 
 ergograph was used, in which the movements were strictly 
 limited to one joint, and other disturbing features of the 
 earlier instrument were remedied. In three subjects ergo- 
 grams were taken, at intervals of ten minutes, for an hour 
 after the administration of caffeine, the essential oils of tea, 
 and mate. The caffeine was found to increase the amount of 
 work, while the oils produced a decrease ; mate" produced an 
 increase which was on the whole less pronounced than that 
 due to the caffeine. 
 
 Hoch and Kraepelin paid especial attention to the respec- 
 tive influence on the number of the contractions and on their 
 average height, and found that the action of caffeine is pre- 
 dominantly on the latter, although their figures show that there 
 is often also an obvious effect on the number. The interval 
 
 1 Riv'uita sper. di Freniatria, 1894, vol. xx., p. 458. 
 
 2 Centralbl.J. PhysioL, 1896, Bd. x., S. 126. 
 
 3 Kraepelin's ' Psychologische Arbeiten, 1 1896, Bd. i., S. 378.
 
 24 THE INFLUENCE OF DRUGS ON FATIGUE 
 
 of ten minutes allowed between successive ergograms is long 
 enough in many persons to allow a large amount of recovery 
 from the fatigue produced by an ergegram, and in a fourth 
 subject who recorded ergograms at intervals of only five 
 minutes the effect of caffeine was much less pronounced. 
 
 The interest of some work published by Tavernari 1 in 1897 
 arises from the fact that he tested the influence of coffee on 
 ergographic work, when in a state of general fatigue induced 
 by a walk of thirty kilometres, and found little influence. 
 
 In the same year Destree 2 records a stimulating action of 
 caffeine, but only in a slight degree. 
 
 The next work is by Benedicenti, 8 who worked with coffee, 
 tea, mate, and guarana, but did not use caffeine in a pure 
 form. With each substance he found an increase in the work 
 of a single ergogram, the effect of the coffee being especially 
 to prolong the ergogram, thus disagreeing with Hoch and 
 Kraepelin, who believe the effect to be chiefly on the heights 
 of the contractions. 
 
 The work by Schumburg, 4 published in the same year, 
 is more important. This worker used a control, though 
 it is not clear that his subjects were unable to distinguish 
 between the active and the control substances. On some 
 days Schumburg tested the action of kola, coffee, tea, or 
 caffeine on the work recorded in a series of ergograms ; on 
 other days the experiment was complicated by the addition 
 of work, in which general fatigue was produced by means of 
 the ergostat, an instrument in which a weight is lifted by 
 turning a handle, and Schumburg used this instrument till 
 either 18,000 or 21,600 kilogrammetres of work had been done. 
 Kola produced an increase in the ergographic work both with 
 and without general fatigue, but the caffeine only increased 
 the uncomplicated work with the ergograph, and even seems 
 to have had a depressing effect on the work done in the 
 
 1 Rivista sper. di Frematria^ 1897, vol. xxiii., p. 102. 
 - Journ. mtd. de Bnurelles^ 1897. 
 
 3 Moleschott's ' Untersuch./ 1899, Bd. xvi., S. 170. 
 
 4 Arch.f. Aiiat. u. Physlol, Physiol. Abth., Suppl. Bd., 1899, S. 289.
 
 CAFFEINE 25 
 
 presence of general fatigue, but only few experiments of this 
 kind were made. 
 
 Schumburg's work is interesting from a point of view of 
 method, in that he endeavoured to determine whether the 
 drug exerted its action chiefly on that portion of the 
 ergogram recorded without special effort, or on that portion 
 recorded only after such special effort had begun to be 
 necessary, but with no very decisive result. 
 
 In 1901 Fere 1 came to the conclusion that coffee, caffeine, 
 and theobromine acted merely as accelerators of fatigue, this 
 result being produced when the coffee was swallowed in such 
 a way as to exclude any effect due to stimulation of taste. 
 
 In the same year, Oseretzkowsky and Kraepelin 2 published 
 observations in which doses of 0*5 gramme of caffeine were 
 found to have no appreciable effect on the amount of work, 
 increasing the heights of the contractions to some extent, but 
 at the same time diminishing their number. In this case the 
 ergograms were taken at intervals of only two minutes, so 
 that the element of fatigue would have played a greater part 
 than in the work of Hoch. 
 
 The most recent papers on caffeine are those of Hellsten 3 
 and Joteyko, 4 both published in 1904. The former used a 
 new form of ergograph, in which both arms are used, so that 
 about 6,000 kilogrammetres of work are done during the per- 
 formance of one ergogram, instead of the 4 to 8 kilogrammetres 
 usual with Mosso's instrument. Tea was found to have only 
 a slight effect. 
 
 Mile. Joteyko's work is chiefly interesting as a record of 
 her attempt to draw conclusions from the mathematical 
 analysis of the ergographic curve. She believes that this 
 curve can be analysed into three component curves, one 
 rising as the square of the time which she believes to repre- 
 
 1 C. R. de la Soc. de BioL, Paris, 1901, pp. 593 and 627. See also 
 'Travail et Plaisir,' Paris, 1904, p. 311. 
 
 2 Psychologische Arbeiten,' 1901, Bd. iii., S. 617. 
 * Skcaid. Arch.f. PhysioL, 1904, Bd. xvi., S. 197. 
 
 4 'Travaux du Laboratoire de Physiologic,'' Instituts Solvay,Bruxelles, 
 1904, t. vi., p. 361.
 
 26 THE INFLUENCE OF DRUGS ON FATIGUE 
 
 sent the process going on in the central nervous system 
 during the performance of the work. The other constituent 
 curves run a descending course : one, which falls directly as 
 the time, is believed to represent the consumption of material 
 in the muscle ; while the other, which falls as the cube of the 
 time, is believed to represent the process of poisoning of the 
 muscle by the products of activity. Three-quarters of an 
 hour after taking a dose of caffeine it was found that the 
 parameters of all three curves had increased, and this is 
 ascribed to an exciting action on the central nervous system, 
 which leads to more rapid consumption of material and more 
 rapid accumulation of the poisonous products of activity. An 
 hour and a half after taking the drug, on the other hand, the 
 three parameters had diminished, and this is ascribed to a 
 depressing action on the central nervous system, with conse- 
 quent slower consumption of material and accumulation of 
 metabolites. 
 
 These conclusions of Mile. Joteyko are based on the 
 changes which take place in the form of the individual 
 ergogram. In my own work with the very much improved 
 form of Mosso's ergograph devised by Kraepelin, the form of 
 the ergogram is singularly constant, and nearly all conform to 
 the same general type, not only in the same person under 
 different conditions, but also in different persons. It becomes 
 a question how far the changes in the form of the ergogram 
 described and analysed by Mile. Joteyko are due to her 
 ergograph allowing other muscles to come into play as the 
 muscle originally used became fatigued. 
 
 This review of previous work shows a general agreement 
 as to the stimulating influence of caffeine on the capacity for 
 muscular work, though different workers are not agreed upon 
 the exact way in which the drug affects the ergogram, and 
 have found great differences in the degree of its potency. 
 Some of these differences are doubtless to be referred to 
 differences of susceptibility of the subjects of the experiments, 
 but others are probably due to differences of method, and
 
 CAFFEINE 27 
 
 others, again, to different degrees in which the factor of 
 fatigue has been of influence. 
 
 My own observations have been made on two persons 
 only, Mr. H. N. Webber and myself, who will often be 
 referred to as W. and R. respectively. Mr. Webber's ex- 
 periments have been not only more numerous, but more 
 satisfactory, than my own. This is due to several causes. 
 In the first place, he could give his whole time to the work, 
 so that he was able to keep his daily occupations almost 
 completely uniform. 
 
 In my own case, on the other hand, lectures and other 
 engagements made it impossible to keep different days on the 
 same level of general activity, and I was obliged to limit iny 
 work to vacations, and even here other work, from which I 
 could not escape, often made it impossible to keep the total 
 mental activity of a day on as uniform a level as was possible 
 in Mr. Webber's case. In the second place, I was very much 
 troubled throughout my ergographic work by muscular pain. 
 I required long-continued practice, gradually increasing the 
 amount of work done day by day, before I could carry out 
 series of ergograms of the length desired. I shall therefore 
 deal first with the work done by Mr. Webber. 
 
 EXPERIMENTS OF THE SUBJECT W. 
 
 Experiment 1. In this experiment, which lasted for eight 
 days, three sets, each of six ergograms, were recorded, be- 
 ginning on each day half an hour after a light breakfast. 
 The right and left hands were used on alternate days. The 
 weight lifted was 4 '5 kilogrammes ; the interval between the 
 successive ergograms of a set was two minutes, and that 
 between the successive lifts of each ergogram two seconds, 
 the finger being flexed with one beat and relaxed with the 
 next beat of a metronome beating seconds. Between the sets 
 there was an interval of half an hour, which was occupied in 
 attending to the apparatus while the other subject was 
 performing an experiment, so that the arms were gently
 
 28 THE INFLUENCE OF DRUGS ON FATIGUE 
 
 
 
 exercised and there was a certain amount of mental occupation 
 of an unfatiguing kind, 
 loo 
 
 FIG. 2. CAFFEINE EXPERIMENT W. i. 
 
 X, Caffeine citrate, 0*8 gramme. Y, Control mixture. Arrow shows when the 
 dose was administered. 
 
 The caffeine was taken in the form of the citrate, and the 
 control consisted of a mixture of gentian and citric acid. The 
 dose, whether of caffeine or control, was taken ten minutes
 
 CAFFEINE 29 
 
 before beginning the second set of ergograms, and in this, as 
 in all the caffeine experiments, the disguise was complete, so 
 that the taste gave no indication whether a day was one on 
 which the effect of caffeine was being tested or was one of 
 the normal days. 
 
 The general results of this experiment are shown graphic- 
 ally 1 in Fig. 2, in which the data for the ergograms of the 
 three sets are expressed as percentages of those of the first 
 ergogram of the first set. The curves in the lower part of 
 the figure represent the course of the work executed in the 
 successive ergograms, those in the middle of the table the 
 course taken by the number of contractions, and those at 
 the top of the table that of the height of the contractions, 
 found by dividing the total height through which the weight 
 was lifted by the number of contractions. The curves marked 
 X show the course of the caffeine days, and those marked Y 
 that of the days on which only the control mixture was taken. 
 
 As the dose, whether of caffeine or control mixture, was 
 not taken till the interval between the first and second sets, 
 the work of the first set was done under the same conditions 
 on the two groups of days, and the two curves should show a 
 close correspondence. 
 
 The actual correspondence is very close. In the case of 
 the curve for work, the caffeine days show at first a slight 
 falling off as compared with the normal days, followed by 
 a slight rise ; but these differences, dependent on the inevitable 
 variations from day to day, are very slight, and the closeness 
 of the correspondence may be taken as evidence that the 
 general conditions of the experiment were satisfactory. The 
 work of the second set of ergograms, begun ten minutes after 
 taking the dose, seems to show a drug-effect ; for, though the 
 caffeine curve is not much above the normal curve, it is so 
 throughout, and nowhere falls to the level of the latter. The 
 increase is most decided in the case of the first ergogram of 
 the set, where the work of the average ergogram on the 
 
 1 For the figures on which these and the succeeding curves are based, 
 see Journ. Physiol, 1907, vol. xxxvi., p. 33.
 
 30 THE LNTLUENCE OF DRUGS ON FATIGUE 
 
 caffeine days is 71 per cent, of the initial performance, while 
 that of the normal days is only 54 per cent. In the third set, 
 begun fifty-five minutes after taking the dose, the same 
 decided increase is shown in the first ergogram, the amounts 
 being 61 per cent, and 42 per cent, respectively; but the 
 increase throughout is not so constant as in the second set, 
 the third ergogram on the caffeine days falling a little below 
 that of the control days. 
 
 The effect of the caffeine comes out more obviously in the 
 figures for the total work of the sets. Since the dose was not 
 given till the end of the first set, the total work of this 
 set may be taken as a normal standard ; and if it be taken 
 as 100, the amount of work for the second and third sets 
 comes out at 74 per cent, and 55 per cent, on the caffeine 
 days, as compared with 56 per cent, and 42 per cent, on the 
 normal days. The constancy of the difference between the 
 work curves for the caffeine and control days justifies the 
 conclusion that these data show a real, though not a very 
 pronounced, effect of the drug ; for if the differences had 
 been due to chance variations, the relations between the two 
 curves would probably have been less regular. The effect, 
 however, is evidently slight, and is of an order quantitatively 
 very different from that found by some earlier workers. 
 
 The curves for height and number of contractions given in 
 Fig. 2 show that the effect on the work of the first ergogram 
 of each set is chiefly due to an increase in the number of the 
 contractions, while the effect throughout the whole course of 
 the sets shows itself chiefly in increase of their height. 
 
 It may be noted that this experiment was carried out in 
 an early condition of training, as will be very evident from 
 the sample of the ergograms of the left hand, given in Fig. 3, A. 
 The irregularity of the ergograms, especially towards the end 
 of the set, is very great, and presents a very striking contrast 
 with the ergograms (Fig. 3, B) of the same worker a few 
 months later. 
 
 Experiment 2. This experiment, carried out six months 
 later, was conducted on the same general lines as the first
 
 CAFFEINE 
 
 31 
 
 experiment, but with several important differences. In order 
 to follow the effect of the drug for a longer time, five sets of 
 ergograms were recorded. To the end of the third set the 
 intervals were half an hour, as in the earlier experiment ; but 
 the two remaining sets were taken at intervals of an hour, so 
 that the total duration of the experiment of each day was 
 four and a quarter hours, and the dose being taken, as in the 
 first experiment, ten minutes before the beginning of the 
 second set, the effect of the drug was followed for over three 
 
 FIG. 3. 
 
 and a half hours. The intervals were occupied in the same 
 way every day, In the first two intervals light work was 
 done in connexion with tracings (cutting them up, pasting 
 them in a book, etc.) ; the third interval was passed in light 
 reading and a few biscuits were eaten ; the fourth interval 
 was occupied in making calculations of percentages i.e., in 
 mental work of a tedious, but not arduous, character. A 
 second difference was that the dose was increased from 0*3 to 
 0*5 gramme. A third and very important difference was 
 connected with the condition of training. During the inter- 
 vening months a number of experiments had been carried 
 out by the subject to test the influence of alcohol in which 
 the left hand had been exclusively used. In consequence, 
 the left arm was by this time in a very completely trained
 
 32 THE INFLUENCE OF DRUGS ON FATIGUE 
 
 condition, while the right hand had had no more training than 
 in the previous experiment. 
 
 Owing to the prolonged training of the left hand, the 
 distance through which the weight of 4'5 kilogrammes was 
 lifted in the largest ergograms so nearly approached the avail- 
 able height of the scale that the weight for this hand had to 
 
 YYarK 
 
 FIG. 4. CAFFEINE EXPERIMENT W. n. 
 
 X, Caffeine citrate, 0'5 gramme. Y, Control mixture. Weight : right hand, 
 4'5 kilogrammes ; left hand, 5'0 kilogrammes. 
 
 be increased to 5 kilogrammes, but that for the right hand 
 was 4 '5 kilogrammes, as in the earlier experiment. 
 
 The results are given in Fig. 4, constructed on exactly the 
 same plan as Fig. 2. It will be seen that there is a very 
 close correspondence in the general features of the two groups 
 of curves. The curves for the first set, taken before any dose 
 had been administered, show a very satisfactory correspon-
 
 CAFFEINE 33 
 
 deuce, while in all the sets taken after the dose the caffeine 
 curves for the amount of work are above the normal curves, 
 except for one ergogram in the third set and another in the 
 last set. The first ergogram of each set on the caffeine days 
 is distinctly larger than that on the normal days, but the 
 predominance of the effect at the beginning of the sets is not 
 as pronounced as in the first experiment. The constancy of 
 the increase and the close correspondence of the curves for 
 the two experiments can leave little doubt that we have to do 
 with a real effect of the drug. 
 
 The correspondence with the results of the first experi- 
 ments comes out also very strongly on comparing the curves 
 for the number and height of the contractions. Except in 
 the second set, the increase in the number of contractions is 
 only decided in the first ergogram of each set, while the 
 effect throughout the whole course of the sets is predominantly 
 on the heights ; and this effect on the heights is very decided, 
 the irregularities of the curves for work being seen to be due 
 to fluctuations of the number of the contractions. This agree- 
 ment in the details of the results of the two experiments lends 
 further support to the conclusion that we have to do in both 
 experiments with a real effect of the drug. 
 
 In the preceding curves the results for the two hands 
 have been grouped together ; but there was some difference 
 in the amount of increase on the two sides, the effect being in 
 each case most pronounced on the right side. 
 
 EXPERIMENTS OF THE SUBJECT B. 
 
 In my own earlier experiments it was not possible to 
 record sets of six ergograms, owing to the fact that so 
 large a number produced such muscular pain as to render 
 further continuance of the experiment impossible. After 
 several fruitless attempts, an experiment of four days was 
 carried out on March 1 to 5, 1906 (omitting March 4), in which 
 three sets of ergograms were taken ; but each consisted of 
 four ergograms only, two taken with each hand. In other 
 respects the conditions of the experiment were exactly the 
 
 3
 
 34 THE INFLUENCE OF DRUGS ON FATIGUE 
 
 same as in the first experiment of W., the dose of caffeine 
 being 0'3 gramme, taken ten minutes before the beginning 
 of the second set. Even in this experiment several ergograms 
 were brought to a premature conclusion by pain, and owing to 
 this incompleteness, it is sufficient to record that, while on 
 the normal days the total work of the second and third sets, 
 as compared with the first set, decreased by 25 and 167 per 
 cent, respectively, the work of the second set on the caffeine 
 days only decreased by 3 '2 per cent , while the work of the 
 third set increased to the extent of 16*4 per cent. 
 
 Experiment 2. This experiment, with the same dose, 
 lasted for eight days (March 6 to 8 and March 12 to 16), on 
 four of which the contractions of the finger were carried out 
 in the usual manner (see Fig. 5, A), while on the other four 
 days each contraction was only allowed to reach two-thirds 
 of its usual extent (see Fig. 5, B), by means of an obstacle 
 placed in the way of the moving finger. In this experiment, 
 as in the first, only two ergograms were executed with each 
 hand in each set, and the course of the effect of caffeine could 
 be represented for so short a time that I do not give curves 
 showing the figures for each ergogram, but have grouped the 
 results of each set together in the following table : 
 
 Complete Contractions. 
 
 First Set. Second Set. Third Set. 
 
 Work fin k ff m ^ fCaffeine 6'8 (100) 7'6 (112) 8-5 (125) 
 
 ork (m Kgm.j ... . 
 
 Number of contractions f Caffeine 45 ( 10 ) 49 < 109 ) 55 
 
 18 [Control 49 (100) 49 (99) 43 (85) 
 
 Average height (in cm )/ Caffeine 3 - 4 ( 10 ) 3 ' 5 ( 101 ) 3 ' 4 ( 10 ) 
 
 im -'\Control 3.5 (100) 3-2 (91) 3-2 (91) 
 
 Incomplete Contractions. 
 
 w , /Caffeine 5'2 (100) 6*7 (130) 6'6 (126) 
 
 " \Control 5-9 (100) 5'8 (99) 5 -5 (94) 
 
 XT , f .- fCaffeine 51 (100) 65 (131) 64 (128) 
 Number of contractions | Control ^ 
 
 In the case of both complete and incomplete contractions 
 it will be seen that there was a very decided caffeine-effect 
 so decided as to be beyond all doubt. In the case of the
 
 CAFFEINE 
 
 35 
 
 complete contractions, the amount of work on the caffeine 
 days increased by 25 per cent., while on the control days 
 it fell off to the extent of 22 per cent., this increase on the 
 caffeine days being due pre-eminently to increase in the 
 number of the contractions, though there was also an effect 
 on the height, for this remained level instead of decreasing, 
 as on the control days. 
 
 In the case of the incomplete contractions, the effect of 
 the caffeine is not so pronounced, and is more decided in the 
 second than in the third set of ergograms. The figures for 
 
 FIG. 5. 
 
 the normal days show that the fatigue produced by one set 
 of ergograms was less than with complete contractions, the 
 work only falling off to the extent of 6 per cent., instead of 
 22 per cent., as with the complete contractions. 
 
 Experiment 3. Six months later a third experiment with 
 caffeine was carried out by the same subject. By this time 
 he had undergone so prolonged a training, chiefly in con- 
 nexion with work on the effect of alcohol, that he was able to 
 perform an experiment in which the work of each day con- 
 sisted of five sets, each of six ergograms, so that the work is 
 exactly comparable with that of W., except that only one 
 hand the right was used. The dose of caffeine was the 
 same as that taken by W. in his second experiment viz., 
 0'5 gramme. The experiment was designed to last for eight 
 
 32
 
 36 
 
 THE INFLUENCE OF DRUGS ON FATIGUE 
 
 days ; but at the end of six days it was found that the dose 
 of caffeine, though taken in the middle of the day, was dis- 
 turbing the sleep of the subject at night, 1 and the experiment 
 was therefore discontinued. 
 
 The results of the experiment are shown graphically in 
 Fig. 6, arranged on the same plan as in previous figures. It 
 
 FIG. 6. CAFFEINE EXPERIMENT R. in. 
 
 X, Caffeine citrate, 0*5 gramme. Y, Control mixture. 
 
 will be seen that the caffeine and normal curves of the first 
 set, recorded before the dose was taken, show a very fair 
 correspondence, and that the curves of the second set, begun 
 ten minutes after taking the dose, show no indication of a 
 caffeine-effect, the work falling somewhat below that of the 
 normal days. In the succeeding sets there is, however, a 
 very pronounced effect, of a kind very different from that of 
 the subject W. The first two ergograms of the third set 
 
 1 See Appendix III.
 
 CAFFEINE 37 
 
 show a great increase, as compared with the control days, 
 and then the remaining ergograms of the set fall decidedly 
 below those of the normal days. At the beginning of the 
 fourth set, an hour later, the stimulating effect of caffeine is 
 very pronounced ; but it disappears even earlier than in the 
 third set, and the curve falls still more below the normal 
 level. In the last set there is the same kind of effect, though 
 the initial increment and later fall are not so great. 
 
 In these observations, the course of the first set of six 
 ergograms is not so regular as in the case of W., and as it 
 seemed possible that the expedient of expressing the results 
 in percentages of the first ergogram might be unsatisfactory, 
 and give an untrue picture of the course of the fatigue and 
 of the drug-effect, the curves have been worked out in a 
 different way, the results being expressed as percentages of 
 the average ergogram of the whole of the first set i.e., as 
 percentages of the quantity obtained by dividing the total 
 work of the first set by 6 but the curves so obtained 
 agree very closely in their general features with those of 
 Fig. 6. 
 
 The curves make it very clear that in the case of this 
 subject the increase at the beginning of each set was due to 
 an effect on both number and height of the contractions, but 
 that the decrease as the sets of ergograms were continued 
 was entirely due to decrease in the number of the contrac- 
 tions, the curves for the height even remaining in some cases 
 above those of the normal days, though not to an extent 
 which would justify any decided conclusions as to the action 
 of the caffeine in this respect. 
 
 This experiment points unmistakably to the action of 
 caffeine as an accelerator of fatigue as it has been previously 
 supposed to be by Fere, a mode of action of which there is no 
 evidence in the experiments of the other subject. 
 
 There are some special features of this experiment which 
 point to the effect being of a somewhat abnormal kind. 
 Though the dose of 0*5 gramme has been taken by other 
 workers without any very pronounced effects, it was certainly
 
 38 THE INFLUENCE OF DRUGS ON FATIGUE 
 
 an excessive dose for the subject in question, for his natural 
 susceptibility to the influence of the drug had probably been 
 much enhanced by more than two years' abstinence from all 
 articles of diet containing caffeine. Further, the experiment 
 was carried out in the extremely hot weather of September, 
 1906, and at the end of a prolonged period of very hard 
 work. It is possible that the special mode of action of the 
 drug may have been due to the combination of these con- 
 ditions, and it is very unfortunate that, owing to the un- 
 avoidable limitation of the number of ergograms in each set, 
 the earlier experiments were only able to give evidence of the 
 initial increase, and we do not know whether with the smaller 
 dose and more normal conditions of these experiments the same 
 fall below the normal would have occurred. The last experi- 
 ment shows conclusively that when taken in excess caffeine 
 may act as an accelerator of fatigue, and the observations 
 recorded in Appendix III. make it not unlikely that this mode 
 of action is, at any rate in part, connected with the dulling 
 of the sensations of fatigue. The peripheral mechanism is not 
 restrained through the influence of the unpleasant sensations 
 which normally take part in the inhibition of excessive 
 activity. 
 
 The experiments of Mr. Webber and myself thus confirm, 
 in general, the conclusion reached by all previous workers 
 that caffeine stimulates the capacity for muscular work ; and it 
 is clear that this increase is not due to the various psychical 
 factors of interest, sensory stimulation, and suggestion which 
 the experiments were especially designed to exclude. The 
 greatest increase recorded in our experiments falls, however, 
 far short of that described by some previous workers, such as 
 Mosso, and it is probable that part of the effect described by 
 these workers was due to the factors in question. 
 
 The chief interest of the new experiments lies in the clear 
 demonstration of the very different way in which the same 
 doses of the drug may act on different persons. In the case 
 of one subject, the effect was so small that it is possible that 
 the increase may have been due to chance variations from day
 
 CAFFEINE 39 
 
 to day ; in the case of the other, the effect of the drug was so 
 obvious as to place it beyond all doubt. 
 
 This great difference in the action of the drug quantita- 
 tively was accompanied by a still more important qualitative 
 difference. In one subject the increase in the amount of work 
 persisted throughout each set of ergograms ; in the case of 
 the other the initial increase soon disappeared, to be replaced 
 by a decided fall below the normal level. 
 
 With this general difference in the mode of action of the 
 drug in the two subjects there was associated a difference in 
 the effect on the two chief features of the ergogram the 
 number of contractions and their height. 
 
 In one (W.) the effect is predominantly on the latter, 
 while in the other (R. ) the number is chiefly affected ; but 
 while in W. the effect throughout the sets is chiefly on the 
 height, there is a slight initial effect on the number, and 
 in the case of R. there is some indication of an increase in 
 height, which persists throughout the sets in spite of the 
 decrease in the total amount of work. The initial increase iri 
 the number of the contractions in the case of W. is sug- 
 gestive of the existence, to a slight degree, of the mode of 
 action which was so predominant in R., while the persist- 
 ence in the increase of the height of R.'s contractions may 
 be taken as evidence of the existence, in slight measure, of 
 the prolonged effect which was so pronounced in W. 
 
 There is thus decided evidence of a double action of 
 caffeine on the capacity for muscular work one effect con- 
 stant throughout a set of six ergograms, affecting chiefly the 
 height of the contractions ; the other producing an initial in- 
 crease followed by a fall, both dependent on the number of con- 
 tractions. The former effect is one which may justly be said 
 to diminish the effects of fatigue ; the latter is a transitory 
 stimulation followed by so great a reaction that we are justi- 
 fied in speaking of the effect as one of acceleration of fatigue. 
 In the subject W. there is evidence of both kinds of 
 action, but the prolonged action predominates, the transitory 
 increase being shown only in slight measure in the first ergo-
 
 40 THE INFLUENCE OF DRUGS ON FATIGUE 
 
 gram, and any reaction being altogether masked by the pro- 
 longed action. The last experiment of the subject R. seems 
 to . show that, in the conditions of that experiment, the 
 action of caffeine as an accelerator of fatigue was so great as 
 to mask almost entirely any prolonged action which may have 
 been present, but that an indication of this latter mode of 
 action is to be found in the increase of height, which persisted 
 in spite of the falling off in number. 
 
 While the experiments show the existence of this double 
 action with a high degree of probability, they tell us little 
 about the nature of each kind of action. From this point of 
 view, the most salient fact is that the prolonged action is 
 predominantly on the height of the contractions, while the 
 transitory action is chiefly on the number. Previous workers 
 who have attended to the differential action of caffeine on 
 height and number have found its action chiefly on the former, 
 though a scrutiny of their figures shows that there has also 
 been in many cases an effect on the number of contractions. 
 
 It has been supposed, especially by Kraepelin, that the 
 action of caffeine in increasing height has mainly a peripheral 
 seat, and if we adopt Kraepelin's hypothesis that peripheral 
 action shows itself chiefly by affecting the height and central 
 action by affecting the number, we shall find that the new facts 
 are, at any rate, not inconsistent with it. We should expect 
 a factor which produces an increase by central stimulation to 
 be followed by a reaction ; the effect of the central excitation 
 would be to produce greater activity, the result of which 
 would only be to exhaust the muscular mechanism more 
 rapidly. The peripheral effect, on the other hand, may be due 
 to some alteration in the supply of energy, whether the drug 
 acts as an actual source of energy, or merely as a means of 
 altering its economical use, which we might expect to show 
 itself for prolonged periods. 
 
 That caffeine has a double action is not new. Observa- 
 tions on the isolated neuro-musctilar mechanism have shown 
 that caffeine has a peripheral action, and experiments on the 
 capacity for mental work have shown that it has an effect on
 
 CAFFEINE 41 
 
 central activity. The special interest of the new experiments 
 is that the method of recording sets of ergograms separated 
 by intervals of rest has permitted the demonstration of these 
 two kinds of action in the performance of voluntary muscular 
 work, and that the two modes of action may come into play 
 so differently in different persons that an inspection of- the 
 results would make it difficult to believe that the same drug 
 had been used in the two cases. 
 
 It is doubtful whether experiments on the capacity for 
 voluntary muscular w r ork alone can go far in the elucidation 
 of this problem. Further results from this point of view 
 must be hoped for chiefly from ergographic or dynamographic 
 work in which the muscle is made to contract by electrical 
 stimuli, and this means for the analysis of the complex action 
 should go far to settle the question. 
 
 INFLUENCE OF CAFFEINE ON MENTAL ACTIVITY. 
 
 But little work has been done on the action of caffeine on 
 the capacity for mental work. Kraepelin 1 tested the effect of 
 tea on several mental operations, but his results give little 
 indication how far this substance influenced the factor of 
 fatigue. 
 
 In his later work with Hoch, 2 the influence of tea on 
 mental fatigue was especially investigated, Dr. Hoch being 
 the subject of the experiment, and the addition method being 
 employed. Here, as in the work on muscular fatigue, the action 
 of the two chief constituents of tea was tested separately. 
 Caffeine was found to exert a favourable influence on the 
 process of addition, while the influence of the essential oils of 
 tea was rather less beneficial, but in each case the favourable 
 influence was very slight. It must be remembered that in such 
 experiments the estimation of the influence of any variation of 
 conditions is rendered very difficult by the great increment in 
 the amount of work which takes place from day to day under 
 
 1 ' Ueber die Beeinflussung einfacher psychischer Vorgange durch 
 einige Arzneimittel,' 1 Jena, 1892, S. 107. 
 
 2 'Psychologische Arbeiten, 1 1896, Bd. i., S. 431.
 
 42 THE INFLUENCE OF DRUGS ON FATIGUE 
 
 the influence of practice, and, further, that the addition method 
 is one in which the mental operations involved are of an 
 extremely simple character, so that the work becomes almost 
 reflex, and the part played by fatigue is relatively very 
 slight, 
 
 The method employed by Hoch and Kraepelin gives no 
 means of isolating the special factor of fatigue, and in choosing 
 my ow r n line of work it seemed desirable to make use of 
 pauses during the work, so that the influence of the drug 
 might be tested at different levels of fatigue, or, rather, at 
 different stages of recovery from fatigue. In my first experi- 
 ment in August, 1904, I used typewriting as the method of 
 inducing fatigue. This cannot be regarded as a means of 
 testing pure mental fatigue, for many motor elements are 
 involved. The mental effort, however, in my case was con- 
 siderable, for I was only beginning to use a typewriter, and 
 I had not only to learn this new accomplishment, but at the 
 same time to write as quickly as possible. On alternate days 
 I took 0*3 gramme of citrate of caffeine ten minutes before 
 beginning to work, and on the alternate days nothing, it being 
 only during this experiment that I learnt how much one 
 might be influenced by such a method of procedure. 
 
 In this experiment I had a distinct impression that I was 
 doing better on the caffeine days, but the results showed little 
 difference either in the absolute amount of work done or in 
 the form of the curves. 
 
 The experiment, however, was rendered very unsatis- 
 factory by the disturbance of my general condition, probably 
 dependent at any rate, in part on the fact that I had 
 only just given up the use of caffeine-containing substances 
 as articles of diet. The great effects of practice, due to the 
 fact that I was only just beginning to learn typewriting, 
 also made it very difficult to estimate any effect which might 
 have been due to the drug. 
 
 My next experiment with caffeine, in March-April, 1905, 
 was one in which typewriting was done on twelve successive 
 days, and was carried out under the most satisfactory con-
 
 CAFFEINE 43 
 
 ditions away from all possible sources of disturbance. An 
 hour's work was done on both morning and evening of each 
 day, beginning at 9.45 a.m. and 5.45 p.m. On one group of 
 days the hour's work was done continuously ; on another 
 group a rest of half an hour was taken at the end of half an 
 hour's work, so that the programme was half an hour's 
 work, half an hour's rest, and then again half an hour's 
 work. On a third group of days an hour's rest was taken 
 between the two half-hour periods of work. As the experi- 
 ment lasted twelve days, four days' work was done under 
 each set of conditions. During the first six days a dose was 
 taken both morning and evening ten minutes before beginning 
 to work ; on some days the dose contained 0'3 gramme of 
 citrate of caffeine, and on other days it was a mixture of 
 gentian and citric acid. The disguise was complete, and so 
 far as the taste was concerned, I had no idea at any time 
 whether I was taking caffeine or not. 
 
 In each period of work the amount written in each five 
 minutes was measured, this amount being expressed in centi- 
 metres. The quality of the work was also investigated, and 
 the number and nature of the errors in each five minutes 
 recorded. At the time of this experiment I had abstained 
 from all articles of diet containing caffeine for six months. 
 
 At the end of the first six days it became obvious that 
 something was affecting my sleep on some nights and not on 
 others, and, as it seemed probable that this was the caffeine, 
 I discontinued taking the dose in the evening, and took it 
 only in the morning, 1 so that during the second six days the 
 caffeine or control was only taken once a day. 
 
 The influence of the caffeine may be estimated in two 
 ways by comparing the total amount of work done on the 
 normal days with that done on the days on which caffeine was 
 taken, and by comparing the course of the work of the group of 
 the caffeine days with that of the normal days. The first pro- 
 cedure is especially appropriate to bring out any effect on the 
 general capacity for work, while the second procedure will 
 1 See Appendix III.
 
 44 
 
 THE INFLUENCE OF DRUGS ON FATIGUE 
 
 show more the influence of the drug on the course of fatigue. 
 Since it is especially with fatigue that we are concerned, I 
 leave the results reached by the first procedure for another 
 occasion, and confine ray attention to the course of the work 
 as shown in the curves of Fig. 7. These curves give the 
 results for the work of the mornings only. In them the work 
 of each five minutes averaged for the twelve days, six caffeine 
 and six normal, is given as a percentage of the work of the 
 first five minutes, and it will be seen that the caffeine curve 
 rises at once above that for the normal days and remains 
 above it throughout, the rise in the second half of the whole 
 
 FIG. 7. TYPEWRITING EXPERIMENT. 
 X, Caffeine, 0'3 gramme ; Y, control. 
 
 period of work being distinctly greater than in the first half- 
 hour. It must be remembered that as the dose, whether of 
 caffeine or control, was taken ten minutes before the begin- 
 ning of the experiment of each day, the work of the first five 
 minutes would itself have been to some extent influenced by 
 the nature of the dose ; and if the dose had been taken after 
 a certain amount of work had already been executed as a 
 standard, it is probable that the effect of the caffeine would 
 have come out still more strongly. 1 On the other hand, the 
 caffeine days preceded the normal days throughout, and as 
 the effects of practice gradually grow less from day to day, 
 the caffeine curve would be raised to a greater extent by the 
 effects of practice than the normal curves. 
 
 1 This research was done before my work with the ergograph, and it 
 was only while doing the latter that I learnt how essential it is to have 
 a normal standard for each day before taking the dose.
 
 CAFFEINE 45 
 
 In order to see how far this has been of influence, I have 
 calculated the percentages, leaving out the first and last days 
 of the experiment, which would leave ten days in which the 
 normal days preceded the caffeine days. For the caffeine 
 days the percentages run : 100, 102, 101, 99, 99, 100, 104, 104, 
 102, 102. 99, 102 ; while for the normal days they are : 100, 
 100, 101, 100, 99, 101, 100, 100, 101, 96, 98, 98. Thus 
 there is little difference between the two curves in the first 
 half-hour, but the superiority of the caffeine curve is almost 
 as great in the second half-hour as when the whole twelve 
 days are taken into account. Here any advantage accruing 
 from the effects of practice would assist the normal days, and 
 yet there is a distinct superiority of the caffeine days, and, 
 though the increase is only slight, its occurrence in every five 
 minutes' period of the second half-hour is in favour of its 
 showing a real effect of the drug. 
 
 The number of mistakes of all kinds made in the type- 
 writing was determined, and here it came out quite definitely 
 that the drug was without influence. The total number of 
 errors was not very large ; for the morning work it was 459 
 on the caffeine days, and 462 on the normal days. As might 
 be expected, the number of mistakes was somewhat greater in 
 the second half-hour periods, the respective number for the 
 caffeine days being 216 and 243, and on the normal days 209 
 and 253. 
 
 It is interesting that, as has been found in the case of 
 arithmetical work, the number of errors should be relatively 
 so small, and should fail so completely to show any trace of a 
 drug-effect. 
 
 The only other research on caffeine which I have to record 
 is one carried out in conjunction with Mr. McDougall, using 
 his method of measuring fatigue of attention by estimating 
 the accuracy of aim when dots are made to pass rapidly 
 through a slit. The work with caffeine was done every 
 morning at eight o'clock. The experiment lasted for nine 
 successive days, on three of which a dose of 0'3 gramme of 
 citrate of caffeine was taken ten minutes before beginning to
 
 46 THE INFLUENCE OF DRUGS ON FATIGUE 
 
 work. On the other six mornings were taken doses of two 
 control mixtures, which to both of us were quite indistinguish- 
 able from that containing the caffeine. 
 
 On each day we began by aiming at eight rows, each of 
 120 dots ; then rested for half an hour, and repeated the 
 eight rows of dots. On some days we did the eight rows 
 continuously ; on other days we allowed an interval between 
 two rows of the same duration as that occupied in the passage 
 of a row ; and on the remaining mornings the interval between 
 two rows was twice as long. The time taken by the passage 
 of each row of dots was 26*5 seconds, so that on some morn- 
 ings work was executed for about three minutes continuously, 
 while on other mornings there was an interval of 26 - 5 seconds 
 after a period of work of the same duration, and on other 
 mornings the interval was 53 seconds. 
 
 The results may be estimated in several ways, and I give 
 here the total number of times that the dots were hit on the 
 three groups of days, those on which caffeine was taken, and 
 the two groups of days on which the two control mixtures 
 were taken. I will give Mr. McDougall's figures first. In 
 the first period he hit 1,576 dots on the three caffeine days, 
 1,606 dots on one group of control days, and 1,646 dots on 
 the three days on which the other control mixture was taken. 
 In the second period, after resting for half an hour, there 
 were 1,571 hits on the caffeine days, 1,424 and 1,486 re- 
 spectively on the two groups of control days. In the first 
 period the number of hits on the caffeine days comes out 
 midway between those for the two groups of control days, 
 while in the second period the caffeine days are decidedly 
 superior to either group of control days. This superiority 
 of the caffeine days is not due to any effect of practice, for 
 the order of the days was varied, and the experiment was only 
 begun after preliminary practice, so that the amounts do not 
 show any definite increase as the result of practice during 
 the nine days that the experiment lasted. 
 
 The experiment in my own case was carried out on the 
 same days and on exactly the same lines as that of Mr.
 
 CAFFEINE 47 
 
 McDougall, and it agrees with his in showing no indication 
 of a caffeine-effect in the first period, but a definite increase 
 in the second. In the first period there were 1,459 hits on 
 the caffeine days, and 1,511 and 1,602 on the two groups of 
 control days in the first period; and in the second period 1,460 
 on the caffeine days, and 1,339 and 1,421 on the control days. 
 As with the other subject, there was no definite increase from 
 day to day during the nine days, and the larger amount 
 on the caffeine days is certainly not due to the effects of 
 practice. 
 
 It was, of course, arranged that the days with different 
 pauses between the rows should be equally distributed over 
 the caffeine and control days : thus, one caffeine day was 
 done with no pause, another with a pause of 26 '5 seconds, 
 and the other with a pause of 53 seconds. These pauses 
 had a very decided effect on the number of hits, 1 but the 
 data are too few to allow any opinion to be formed whether 
 the effect of the caffeine was influenced by the presence or 
 absence of a period of rest between the periods of work. 
 
 There -was one feature of method in this experiment which 
 was only employed on this occasion viz., the use of two control 
 mixtures. This expedient was adopted chiefly in order to 
 assist the disguise of the caffeine (for which purpose later 
 experience has shown it to be unnecessary), but it brought 
 out very clearly the great variability of the results from day 
 to day in this method of studying mental fatigue. If we had 
 used only one control, we might have thought there was a very 
 decided caffeine effect, or a complete absence of effect, accord- 
 ing to which control had been omitted ; and the fact that the 
 difference between the results with the two inactive controls 
 was so great makes it clear that no importance whatever 
 can be attached to the differences found in the first period of 
 work, while the superiority of the caffeine days to both sets of 
 control days in the second period makes it almost certain that 
 we have to do with a real effect, though the difference between 
 the number of hits on the caffeine days and on one of the 
 1 See Brit. Jonrn. PsychoL, 1905, vol. i., p. 442.
 
 48 THE INFLUENCE OF DRUGS ON FATIGUE 
 
 control days in my own experiment is not very great. These 
 experiments are not very satisfactory, but it must be remem- 
 bered that they were the first experiments with an entirely 
 new method, and were designed chiefly as a test of the method. 
 From this point of view the results are very hopeful, and 
 there is little doubt that more prolonged experiments on the 
 same lines would demonstrate clearly the nature of the action 
 of caffeine on central activity. 1 
 
 The experiments I have recorded by two different methods 
 thus confirm the conclusion of ,Hoch and Kraepelin that caffeine 
 has a stimulating action on the capacity for mental work, 
 though the increase is not very great. There is thus clear 
 evidence of the influence on central activity which I have sup- 
 posed to take a part in the action of the drug on the capacity 
 for muscular work. The increase of mental activity which 
 followed the administration of caffeine in myself is slight 
 compared with the effect recorded in the work with the 
 ergograph, and yet the dose of the drug and general conditions 
 of the experiment were much the same in my earlier ergo- 
 graph experiments as in those on mental activity. 
 
 These observations on the capacity for muscular and 
 mental work in the same person thus show a decidedly greater 
 effect of caffeine on the former, and this may perhaps be 
 regarded as confirmatory of the view that, in the case of 
 muscular work, the central action of the drug is supplemented 
 by a peripheral action, though there are, of course, other 
 possible explanations of the difference. 
 
 In my typewriting experiments the work was carried on 
 continuously for half-hour and hour periods, and there was 
 thus abundant opportunity for the appearance of any such 
 reaction as occurred in my last experiment with the ergograph ; 
 but in this experiment the dose of the drug was considerably 
 larger, and the state of health of the subject less satisfactory, 
 so that the two experiments are not comparable. So far as it 
 goes, the typewriting experiment tends to confirm the view 
 
 1 For the results of further experiments, see W. McDougall, op. cit., 
 p. 441.
 
 CAFFEINE 49 
 
 that the special nature of the action of caffeine in my last 
 ergographic experiment was somewhat abnormal. 
 
 A point to which I may here refer shortly is concerned 
 with the rate of action of the drug. In the last recorded 
 experiment there was no evidence of the influence of the drug 
 ten minutes after its ingestion, and in my typewriting experi- 
 ment the decided rise in the curve only occurred during the 
 second period of work, which varied on different days from 
 40 to 100 minutes after the drug had been taken. There 
 is evidence in these experiments that caffeine acts very slowly, 
 but that its action persists for a considerable time. 1 
 
 With the ergograph the behaviour of the drug is different. 
 In my own last experiment there was no evidence of the action 
 of the drug from ten to twenty-five minutes after it was taken, 
 though the effect had become most pronounced after fifty-five 
 minutes. In my earlier experiments, on the other hand, and 
 in both Mr. Webber's experiments, the effect was present ten 
 minutes after its ingestion. There is no reason why the rate 
 of absorption should have differed in the different cases, and 
 the suggestion which occurs most naturally is that the central 
 effect develops slowly, while the peripheral effect is able to 
 show itself rapidly. I have pointed out reasons for believing 
 that the very pronounced effect in my third ergographic 
 experiment had a central seat, and if we accept the above 
 suggestion, the discrepancy between the results of this experi- 
 ment and both my earlier experiments and those of Mr. Webber 
 is explained : in the former the effect was almost entirely 
 central, while in the latter it was peripheral. 
 
 I acknowledge that we are here very much in the region 
 of conjecture, but it is perhaps significant that several features 
 of the action of caffeine on mental activity should thus fall into 
 line with the view that the effect of caffeine on muscular 
 activity has a twofold nature. 
 
 The general practical conclusions to be drawn from the 
 experiments which I have recorded, and from those of previous 
 
 1 For other evidence of the persistence of the central action, see 
 Appendix III. 
 
 4
 
 50 THE INFLUENCE OF DRUGS ON FATIGUE 
 
 workers, is that caffeine increases the capacity for both muscular 
 and mental work, this stimulating action persisting for a 
 considerable time after the substance has been taken without 
 there being any evidence, with moderate doses, of reaction 
 leading to a diminished capacity for work, the substance thus 
 really diminishing and not merely obscuring the effects of 
 fatigue. The results of one experiment, however, point 
 unmistakably to the conclusion that, when taken in excess, 
 the stimulating action may be so transitory, and followed by 
 so great a decrease, that it may legitimately be spoken of as 
 an accelerator of fatigue ; and it may perhaps be pointed out 
 that the general conditions of this experiment were just those 
 in which there is great danger that substances containing 
 caffeine may be taken in excess. The experiment suggests 
 strongly that caffeine is a dangerous remedy as a stimulant in 
 cases of prolonged fatigue, or of that enhanced tendency to 
 fatigue which is the characteristic feature of neurasthenia.
 
 LECTURE III 
 ALCOHOL 
 
 Alcohol and muscular fatigue ; historical ; new experiments with ergo- 
 graph ; absence of effect with doses varying from 5 to 20 c.c. 
 of pure alcohol ; previous results due to defective control ; incon- 
 stant increase with dose of 40 c.c. 
 
 THE experimental work on the action of alcohol which has 
 hitherto been recorded is far less satisfactory than that on 
 caffeine, of which I gave an account in the last lecture. 
 Though many workers have tested the effect of caffeine by 
 giving it in one of the forms tea, coffee, etc. in which it is 
 taken in everyday life, we found that we had some data 1 to 
 enable us to distinguish how far the effects of these substances 
 are due to their caffeine, and how far to other active prin- 
 ciples they may contain. Alcohol, on the other hand, has been 
 given in the most varied forms, and except for those who 
 have used pure ethyl alcohol hardly any two workers have 
 used the same means of administering the substance. Further, 
 nothing has been done towards discovering what are the 
 separate actions of the different constituents of the alcoholic 
 beverages which have been used, as has been done in the case 
 of tea and kola, and we have no evidence to tell us how 
 far the effects which have been described are due to the 
 alcohol or to other constituents. 
 
 The pungent flavour of alcohol is particularly adapted to 
 produce effects on the capacity for work by its stimulating 
 action as it is being taken into the mouth and swallowed, and 
 this stimulating action is very much enhanced when the 
 substance is taken in one of the forms in which it is habitually 
 used. Further, very much of the work on alcohol has been 
 1 Especially in the work of Hoch and Kraepelin, and of Mosso. 
 51 42
 
 52 THE INFLUENCE OF DRUGS ON FATIGUE 
 
 undertaken with an obvious bias, induced by enthusiasm 
 either for temperance or for the virtues of alcohol, and owing 
 to the very great influence of emotional factors, especially on 
 the ergographic curve, a bias may be a grave source of error, 
 even if the most earnest endeavours are made to overcome it. 
 Yet, with all these obvious dangers and sources of error, no one 
 has attempted to use in his experiments the control which 
 would have removed the most serious of these dangers. 
 
 The first worker to use the ergograph for the investigation 
 of the action of alcohol was W. P. Lombard. 1 He made only 
 a few experiments, taking small doses in the form of claret. 
 With voluntary contractions he found an increase in the 
 amount of work, the effect showing itself in a few minutes, 
 and lasting in one case for an hour and a half. With con- 
 tractions produced by electrical stimulation, on the other 
 hand, Lombard found the amount of work was diminished, and 
 he concluded that the favourable effect of the alcohol was due 
 to some central action. 
 
 Two years later Rossi 2 tested the action of alcohol in the 
 form of rum on the work executed in fifteen ergograms, taken 
 at intervals of ten minutes. With doses of 80 grammes, 
 corresponding probably to about 30 grammes of absolute 
 alcohol, he found an increase in the total amount of work ; 
 but this increase was chiefly due to the earlier ergograms, 
 the later showing a decrease as compared with the work of 
 days on which no alcohol had been taken. With smaller 
 doses of 25 grammes of rum the favourable influence was more 
 pronounced, and persisted for the whole of the two hours 
 during which the experiment lasted. 
 
 The next work on the action of alcohol excited great 
 interest, and may be regarded as the starting-point of a 
 series of investigations designed either to support or over- 
 throw it. This was the work of Frey, published in 1896, 3 
 
 1 Jmirn. PhysioL, 1892, vol. xiii., p. 49. 
 
 2 Rivlfita sper. di Frematria, 1894, vol. xx., p. 448. 
 
 3 ' Ueber den Einfluss des Alkohols auf die Muskelermudung. 
 Mitth. aus Kliniken u. med. Instituten der Schweix, 1 Reihe iv., Heft i. 
 Basel u. Leipzig, 1896.
 
 ALCOHOL 53 
 
 which had its origin in the accidental observation that a glass 
 of beer had a great effect on a patient who was being tested 
 with the ergograph to ascertain the degree of recovery of a 
 paralysed limb. 
 
 Frey found that the action of alcohol on the fatigued 
 muscle was different from that in the fresh condition. When 
 alcohol was given ten minutes before beginning to work 
 with the ergograph, the effect in most persons was to 
 diminish the amount of work, the decrease being due chiefly 
 to diminution in the height of the individual contractions. In 
 the exceptional cases in which more work was done under 
 the influence of alcohol, the effect was due to increase in the 
 number of the contractions, the height still remaining below 
 the normal. In spite of the actual decrease in the amount of 
 work, it seemed to the subject that the work was being done 
 more easily, and Frey records that this was so pronounced 
 in his own case that he thought he must be using too light a 
 weight. 
 
 If, on the other hand, the alcohol was given after a certain 
 number of ergograms had been recorded, so that some fatigue 
 had been induced, Frey found that alcohol had a beneficial 
 effect, and that the increase in the amount of work might be 
 considerable. From these observations he concluded that 
 alcohol has a double action an injurious action on the 
 nervous system, which predominates when the muscle is 
 unfatigued, and a beneficial action as a food for the muscle 
 substance. 
 
 Frey's work is open to many serious objections. He gave 
 his alcohol in all sorts of forms, and in the most varied, 
 though in all cases small doses, and though he states 
 that his conclusions are drawn from a large number of 
 observations, he gives the reader no data for the exact study 
 of the curves with and without alcohol. Further, his con- 
 clusions involve most improbable assumptions as to the value 
 of alcohol as a food for muscle. He used very small doses, 
 often not more than 5 grammes of alcohol after only three 
 or four ergograms had been recorded. If we accept his con-
 
 54 THE INFLUENCE OF DRUGS ON FATIGUE 
 
 elusions, we should have to suppose that the work of the small 
 group of muscles involved in work with the ergograph has so 
 exhausted the nutritive substances contained in the blood 
 that trifling doses of alcohol exert a decided beneficial action 
 which much more than outweighs the injurious action on 
 other parts of the neuro-muscular mechanism. Except in 
 one of his experiments with sugar, Frey made no attempt to 
 use control substances ; but he regards the play of suggestion 
 or other psychical factors as out of the question, because he 
 found exactly the same differential action of alcohol when the 
 contractions were produced by electrical stimulation of the 
 muscles. Here again Frey gives so few data that it is very 
 difficult to estimate the value of his experiments ; but it may 
 be noted that his result is directly opposed to that obtained 
 by Lombard. 
 
 Some of Frey's ergograms are so prolonged that they show 
 with certainty that accessory muscles were allowed to come 
 into play, his ergograph being of the original Mosso pattern. 
 
 The work of Frey aroused much interest and controversy, 
 and in the following year a paper was published by Destree, 1 
 in which he confirmed the conclusion of Frey that alcohol 
 stimulates the tired muscle, but differed from him in finding 
 the same effect on the work of the unfatigued muscle. In 
 both cases, however, according to Destree, the stimulating 
 action is fugitive, and is followed by a fall in the amount of 
 work below that of the normal. He also describes one case of 
 a physician who, after the administration of 10 grammes of 
 alcohol, became entirely unable to lift a weight with which 
 he had half an hour previously performed 8 kilogrammetres 
 of work. Destree used very small doses of alcohol in the 
 form of beer or brandy, corresponding probably in most cases 
 to not more than 5 grammes of absolute alcohol, and there 
 was not only no attempt to use control-substances, but usually 
 
 1 Journ. mcd. de Bruxelks^ 1897, Nos. 44 and 47. I have been 
 unable to obtain a copy of this journal, and my knowledge of Destrees 
 work is derived from a translation in the Medical Temperance Review, 
 1899, vol. ii., pp. 54 and 76.
 
 ALCOHOL 55 
 
 no real control experiments at all. He believed that the 
 stimulating effects disappeared in about fifteen minutes ; and 
 this result is so greatly in conflict with those of other workers 
 as to make it almost certain that his results were largely due 
 to accessory factors, and give no real indication of any true 
 alcohol-effect. 
 
 In the same year was published a paper by Tavernari, 1 who 
 found that 50 grammes of Marsala wine taken after a walk of 
 thirty kilometres doubled the amount of work executed with 
 the ergograph. The curves he gives leave, however, little 
 doubt that the increase was largely due to the presence of 
 accessory movements as the muscles originally in action 
 became fatigued. 
 
 I now come to observations recorded by Kraepelin, and 
 based on work by Gliick, which have not yet been published 
 in full. 2 This work differs from most of that previously 
 recorded, in that we are given definite figures, both for the 
 normal days on which no alcohol was taken and for what may 
 be called the alcohol-days. Two series of observations, each 
 of eight days, were made, the first with pauses of ten minutes, 
 and the second with pauses of three minutes, between the 
 ergograms. The drug was taken in the form of ethylic 
 alcohol in doses of 40 grammes, the amount being thus much 
 larger than in the experiments hitherto considered. In all 
 cases two ergograms were recorded before the alcohol was 
 taken, and then the work was continued for three-quarters of 
 an hour. In the first series, with pauses of ten minutes, there 
 was a marked initial increase, which disappeared to a large 
 extent in the second ergogram ; but the work remained above 
 the normal level during the whole duration of the experiment 
 until the last curve, which showed a slight sinking below the 
 level of the normal days. The whole work showed an increase 
 of 13 per cent, above that of the normal days, which was 
 entirely due to increase in the number of the contractions, the 
 alcohol having no effect on their height. 
 
 1 Rlvista aper. dl Frematria, 1897, vol. xxiii., p. 89. 
 
 2 Munch, med. IVochenschrift, 1899, Jg. xlvi., S. 1365.
 
 56 THE INFLUENCE OF DRUGS ON FATIGUE 
 
 In the second series, with pauses of only three minutes, 
 so that fatigue played a much larger part, the effect was 
 different. There was a large initial increase of 30 per cent., 
 which disappeared in the second ergogram, from which point 
 there was a diminution in the amount of work, so that at the 
 end the total work was only half that of the normal days. 
 This falling off in the latter part did little more than counter- 
 act the increase at the beginning, for the decrease in the total 
 amount of the work of the whole period was only 5 per cent. 
 This was due to a decrease in the heights of the contractions, 
 the numbers showing on the whole a slight increase. In 
 another series, in which sets of three curves were taken 
 throughout the day at intervals of one or two hours, this 
 diminution in the amount of work was found to continue for 
 ten hours, the effect depending on a diminution in the height 
 of the contractions. 
 
 In this year also Schumburg 1 published a few observations 
 on the effect of alcohol, in which exactly the same method was 
 used as in the work on caffeine considered in the last lecture. 
 He claims that in uncomplicated ergographic work alcohol 
 had a beneficial influence, but that in the presence of general 
 fatigue produced by work with the ergostat, it had no 
 influence. Only three alcohol experiments, however, were 
 made one with and the others without general fatigue, and 
 with a dose of only 10 c c. In these experiments Schumburg 
 compared the effect of alcohol with that of a mixture flavoured 
 with dulcin, but there can have been here no question of a 
 disguise. 
 
 In the same year appeared a dissertation by Heck 2 con- 
 taining some critical considerations by Professor Fick, in 
 which it is shown that the amount of alcohol taken by Frey 
 was quite insufficient to produce his results if it were acting 
 merely as a food-substance. The dissertation also contains a 
 fragmentary record of experiments with a form of spring 
 
 1 Arch.f. Anat.u.PhysioL, Physiol. Abth.,Suppl. Bd., 1899, S. 289. 
 
 2 ' Ueber den Einfluss des Alkohols auf die Muskelermiidung,' 
 Inaug. Diss., Wiirzburg, 1899.
 
 ALCOHOL 57 
 
 ergograph devised by Fick, in which no favourable effects of 
 alcohol could be detected (the dose is not recorded). 
 
 In 1900 appeared the work of Scheffer, 1 who used Mosso's 
 ergograph, but, as his tracings show, in a very different 
 manner from that ordinarily employed. He raised a weight 
 of 5 kilogrammes 150 times at a rhythm of one second, then, 
 after five minutes' rest, again made 150 contractions, and after 
 another pause of five minutes lifted a weight of 6 kilogrammes 
 the same number of times. If Scheffer could do this, he must 
 have been either a man of enormous muscular strength, far 
 beyond anything encountered by any other worker, so that 
 the weight of 5 and 6 kilogrammes was far below his maximal 
 load, or he was using many more muscles than those ordinarily 
 involved in working with Mosso's ergograph, and his results 
 cannot be immediately compared with those of other workers. 
 Ten grammes of absolute alcohol were taken immediately in 
 one series, and fifteen minutes before the beginning of the 
 work in another, and in each case the amount of work was 
 increased. In a third series, in which the same dose was 
 taken thirty minutes before beginning to work, the effect was 
 unfavourable, a smaller amount of work being done with 
 alcohol throughout. 
 
 One feature in Scheffer 's paper is of interest from the point 
 of view of individual differences. Scheffer is the only writer 
 on the effect of alcohol who has given any indication of the 
 method of action of the drug upon himself in ordinary life an 
 effect which is obviously of a depressing character. He notes 
 that the depressing features slackness, swimming in head, 
 etc. usually come on about twenty-five minutes after inges- 
 tion. Scheffer's results seem to show that in himself the 
 small dose of 10 grammes is able to produce a temporary 
 increase followed by a depression, corresponding in point of 
 time to that of his subjective experiences. It must be 
 noted, however, that he used no control, and in the absence 
 of this precaution his conclusion must be received with 
 caution. 
 
 1 Arch./, exper. Pathol. n. Pharmakol., 1900, Bd. xliv., S. 24.
 
 58 THE INFLUENCE OF DRUGS ON FATIGUE 
 
 In 1900 there also appeared work by Fen', 1 who found 
 that the act of keeping alcohol in the mouth while working 
 had a greater effect on the ergographic record than when the 
 same quantity was swallowed. Thus, it was found that if 
 20 c.c. of a mixture of equal parts of absolute alcohol and 
 water were kept in the mouth while the record was being 
 taken, the amount of work was nearly doubled, the effect 
 being due to a great increase in the number of the con- 
 tractions, which were more than trebled. Fere also tried the 
 effect of putting the same quantity of alcohol into the stomach 
 by a tube, and found a distinct decrease in the amount of 
 work, which, as he remarks, may have been due to the act of 
 passing the tube ; but it does not appear to have occurred to 
 him to try the control experiment of putting some inactive 
 substance into the stomach by means of the tube ; nor did 
 the fact that sensory stimulation has so great an influence on 
 the capacity for work lead him to adopt the measure of using 
 control-substances in his work. 
 
 In 1901 appeared an account of work by Oseretzkowsky 
 and Kraepelin' 2 which had been done in 1894. Ergograms 
 were taken at two minutes' interval, and after the seventh 
 a dose of alcohol was taken, and the work was continued 
 for an hour. The alcohol was only taken on four days, 
 15 grammes being taken t\vice, and 30 and 50 grammes on 
 the other two days. On one day the dose of 15 grammes 
 produced an increase, which continued to the end of the 
 experiment ; on the other day there was a slight falling off 
 as compared with the average of three normal days. The 
 doses of 30 and 50 grammes produced very little effect. In 
 this paper there are also recorded experiments by Moskiewicz 
 with a dose of 30 grammes taken on three days, which 
 showed a slight increase on the alcohol days, due entirely to 
 increase in the number of contractions, the height showing a 
 distinct diminution. 
 
 1 C. R. de la Soc. de Biologic, 1900, p. 825. See also 'Travail et 
 Plaisir,' Paris, 1904, p. 
 
 2 Psychologische, Arbeiten, 1 306, 1901, Bd. iii., S. 620.
 
 ALCOHOL 59 
 
 In 1903 Schnyder 1 published an interesting paper, in 
 which he gives evidence that the effect of alcohol may be 
 different according as it is taken soon after a meal or at a 
 considerable interval. He used a simple form of Mosso's 
 ergograph devised by Dubois. His first observations were 
 made four hours after a meal. 6 to 12 ergograms being recorded 
 at minute intervals. The alcohol was taken in the form of 
 claret, and in such an amount that the dose of absolute 
 alcohol would be about 15 grammes. 
 
 In one series the alcohol was taken fifteen minutes before 
 beginning to work by two subjects, and in both cases there 
 was an increase in the total amount of work, amounting to 
 10 per cent, in one case and 5 per cent, in the other i.e., 
 the increase was not very great. 
 
 In a second series the effect of alcohol was compared with 
 that of tropon, and the action of the former was found to be 
 negligible, while the tropon produced a distinct increase, 
 chiefly by affecting the number of the contractions. 
 
 In a second set of experiments Schnyder tried the effect 
 of 30-gramme doses of alcohol taken during a meal, so as to 
 show the effects of alcohol as taken in ordinary life. Here in 
 both subjects there was a decrease in the total output of 
 work, though not of any very large amount. In both subjects 
 the effect of alcohol showed itself in diminution of the number 
 of the contractions, while the height of the contractions was 
 increased. Schnyder notes that the effect was so marked as 
 to produce an obvious effect on the general form of the ergo- 
 gram, those on alcohol days being tall and slender as com- 
 pared with the normal curves. 
 
 According to this observer, then, the effect of alcohol 
 varies with its relation to a meal, increasing the amount of 
 work when taken in the fasting condition, and decreasing it 
 when taken after or during a meal. He ascribes the difference 
 to the action of alcohol as a food. He supposes that alcohol 
 has a tendency to act injuriously on the nervous system in 
 both cases, but that this injurious action is more than counter- 
 1 Arch.f. d. ge*. Phytiologie, Bd. xciii., S. 451.
 
 60 THE INFLUENCE OF DRUGS ON FATIGUE 
 
 acted if there is a deficiency of nutritive materials in the 
 blood. 
 
 In 1903, also, Frey 1 returned to the subject, with a critical 
 study of the researches of those workers who had disagreed with 
 his results. In his book he gives curves representing the results 
 of some further experiments on the action of alcohol, confirming 
 his previous conclusions so far as the action on fatigued muscle 
 was concerned, both when the fatigue was produced by sets 
 of six ergograms at intervals of a minute and when ergograms 
 were repeated at the same rate till complete exhaustion was 
 produced. Alcohol in the dose of 10 grammes was given at 
 different times in the course of the ergographic record, and 
 was found to produce a definite increase immediately after 
 its ingestion, which persisted as long as the observations were 
 continued, in one case for nearly two hours after the alcohol 
 had been taken. 
 
 Frey also records further observations in which the effects 
 of alcohol, sugar, coffee, and caffeine were compared with one 
 another. Alcohol produced the greatest increase, sugar and 
 coffee a slighter effect, and caffeine hardly any increase at 
 all, although given in a dose almost certainly larger than 
 that contained in the dose of coffee which had a much greater 
 influence ; the order of potency of action thus corresponding 
 with the order of the pleasantness and probable interest of 
 the four substances. Frey thus himself provides evidence 
 which suggests strongly that his results are due at any 
 rate, in great measure to the effects of interest and sensory 
 stimulation. 
 
 The next work on alcohol, in 1904, is that of Hellsten, 2 
 who used the ergograph already mentioned in the last lecture, 
 by means of which work is done with many more muscles 
 than with Mosso's instrument. It will be remembered that 
 one feature of the work of Hellsten is the long time devoted 
 to produce complete training before he began to use drugs, 
 and his work has therefore been done on highly trained 
 
 1 ' Alkohol u. Muskelermiidung, 1 Leipzig and Wien, 1903. 
 
 2 Skand. Arcli.f. Phys'wL, 1904, Bd. xvi., S. 160.
 
 ALCOHOL 61 
 
 muscle. He took his alcohol in the form of brandy, and in 
 his first experiments took doses which contained 25 and 
 50 grammes of absolute alcohol either five or ten minutes 
 before beginning to work, and found that the effect of the 
 alcohol was so slight that the differences on different days 
 might be due to chance variations. A much larger number 
 of observations were made with a dose of 80 grammes, which 
 Hellsten found to produce a distinctly injurious effect. In a 
 series consisting of five normal and five alcohol days, on which 
 the dose was taken thirty minutes before beginning to work, the 
 average of the total amount of work on the alcohol-days was 
 5,111 kilogrammetres, and that of the normal days 5.967 kilo- 
 grammetres ; and, further, the inferiority of the work done 
 under the influence of alcohol comes out on every one of the 
 days during which the experiment lasted. 
 
 In a further series, Hellsten tried the effect of the same 
 dose of alcohol taken at different intervals immediately, 
 thirty minutes, an hour, or two hours before beginning to 
 work. 
 
 In all cases the alcohol diminished the amount of work, 
 the diminution, when taken two hours before beginning to 
 work, amounting to 11 per cent., while it was 17 per cent, 
 when taken an hour before. These results refer to the 
 total amount of work done during twenty ergograms, but 
 when the alcohol was taken immediately or shortly before 
 beginning to work there was an initial increase, which came 
 to an end the more quickly the larger was the dose of 
 alcohol. 
 
 The work under the influence of alcohol was characterized 
 throughout by the fact that less work was done in each 
 second, even when the total amount of work was greater. 
 This means that the height of the contractions were 
 diminished, so that Hellsten agrees with those other observers 
 who have found that any favourable effect of alcohol shows 
 itself by increasing the number rather than the height of the 
 contractions. As regards the form of the curve, Hellsten 
 found that under the influence of alcohol it approached a
 
 62 THE INFLUENCE OF DRUGS ON FATIGUE 
 
 straight line, and even in one case became concave, while 
 in normal experiments the curve was, as usual, always 
 convex. 
 
 The work of Hellsten is the most extensive which has 
 hitherto been done on the action of alcohol, and at the same 
 time it is the only work which can be said clearly to prove 
 the injurious influence of alcohol on the capacity for muscular 
 work. It must be remembered that he was using the very 
 large dose of 80 grammes in the experiments which gave any 
 decisive result much larger than that used in any other work, 
 and so large that disturbances of digestion were produced 
 which made it necessary to discontinue the experiments. 
 Nevertheless, in spite of this very large dose, the diminution 
 in the amount of work was not very great, arid cannot be 
 compared with such a result as that of Destree, in which 
 a dose of 10 grammes was found in one person to abolish 
 completely the power of lifting a weight which had been lifted 
 readily in the normal condition. 
 
 The most recent work on alcohol is by Mile. Joteyko, 1 
 who has studied the action of alcohol in several ways, though 
 in each case her chief object has been to demonstrate the 
 value of her method of mathematical analysis of the ergogram. 
 She generally used small doses of 20 grammes of alcohol (it is 
 left doubtful whether absolute alcohol or brandy), and found 
 very great individual differences among the seven persons 
 who were the subjects of experiment. Three were almost 
 entirely resistant to the effect of alcohol, even when the dose 
 was increased to 50 grammes, though two then showed a 
 slight diminution in the amount of work. Two other persons 
 showed a decided increase in the amount of work after doses 
 of 20 to 30 grammes of alcohol, this increase being entirely in 
 the number of contractions. The remaining two subjects 
 showed a decided diminution in one case even with 10 grammes 
 of alcohol and this action was so pronounced in one case that 
 the weight could hardly be lifted at all after 20 grammes of 
 
 1 'Travaux du Laboratoire de Physiologic ' (Instituts Solvay), 
 Bmxelles, 1904, t. vi., p. 361.
 
 ALCOHOL 63 
 
 alcohol had been taken. No evidence could be obtained in 
 these cases of any initial phase of excitation. 
 
 On applying the method of mathematical analysis to a 
 few characteristic curves, it was found that in most cases the 
 parameter believed to indicate the activity of the central 
 process was increased. Mile. Joteyko had accepted the 
 position held by Kraepelin and others that the exciting effect 
 of alcohol is central, and therefore regarded this result as in 
 favour of the validity of her mathematical method. The 
 parameter believed to show the injurious influence of the 
 products of activity was decreased in the majority of cases, 
 the only exception being in the case of the subject on 
 whom alcohol had a very pronounced beneficial effect, and 
 Mile. Joteyko explains this by the supposed action of alcohol 
 as a food substance. 
 
 Mile. Joteyko also investigated the effects of alcohol by 
 another method, using the ergograms of Maggiora. With 
 contractions executed by herself at the rate of one every ten 
 seconds, there was no evidence of fatigue, even at the end of 
 an hour. When the rhythm was altered to a contraction 
 every eight seconds, fatigue supervened at the end of twenty- 
 five minutes ; but when this experiment was repeated after 
 taking 20 grammes of alcohol, the curve remained at a con- 
 stant level as long as the contractions were continued. With a 
 rhythm of six seconds, it was found that fatigue normally 
 showed itself in fifteen minutes, but after the same dose of 
 alcohol there was no evidence of fatigue at the end of an hour. 
 The contractions diminished slightly in extent at the end of 
 the fifteen minutes, and then continued unchanged to the end 
 of the experiment. 
 
 These ergograms with slow rate of contractions evidently 
 provide a valuable modification of the ordinary method, and 
 they seem to show that alcohol may prevent the occurrence of 
 fatigue which would otherwise show itself; but it must be 
 remembered that, in the absence of any control, the effect 
 may have been due to purely psychical causes. 
 
 The commonly accepted explanation of the fact that the
 
 64 THE INFLUENCE OF DRUGS ON FATIGUE 
 
 curve does not fall off if the rhythm is sufficiently slow is that 
 the time between two contractions is sufficiently long to 
 allow removal of the poisonous products of activity, and 
 Mile. Joteyko therefore analysed these curves to see if there 
 was any marked influence on the parameter supposed to 
 indicate the effect of these products, and she found that, 
 in accordance with her anticipation, it was enormously 
 diminished. 
 
 Work on the influence of alcohol has also been done with 
 the dynamometer. In 1892 De-Sarlo and Bernardini 1 found 
 that doses of 70 grammes of rum produced a slight increase in 
 muscular power, and in the same year Kraepelin, 2 with a dose 
 of 30 grammes in one subject, and of 20 grammes in another, 
 found a diminution. The drug was taken immediately before 
 beginning to work, there being no normal on each day to act 
 as a standard, and it is doubtful whether any great weight 
 can be attached to the comparatively small differences which 
 were found. 
 
 In 1899 De Boeck and Deladrier, 3 also using the dynamo- 
 meter, found that rum in doses corresponding to 10 grammes 
 of absolute alcohol diminished the contractions when the 
 muscles were unfatigued. In the same year De Boeck and 
 Gunzburg 4 tested the action of rum on a number of patients 
 recovering from various forms of alcoholism, and found that, 
 when the alcohol was given in the course of work with the 
 dynamometer, varying effects were produced, a transient 
 increase occurring in some persons, a decrease in others, while 
 in others, again, no action was appreciable. 
 
 In 1900 Partridge 5 published observations with Salter's 
 dynamometer, in which six sets, each of a hundred contractions, 
 were made in an hour at a rate of one every 1*6 seconds. 
 
 1 Rlv'ista sper. di Freniatria, 1892, vol. xviii., p. 16. 
 
 2 ' Ueber die Beeinfliissung einfacher psychischer Vorgiinge durch 
 einige Arzneimittel,' Jena, 1892, S. 91. 
 
 s Journ. med. de Bruxelles, 1899, No. 4 (quoted by De Boeck and 
 Gunzburg). 
 
 4 Bull, de la Soc. de Medecme Mentale, 1899, p. 307. 
 
 5 Amer. Journ. of Psychology, vol. xi., p. 371.
 
 ALCOHOL 65 
 
 In one subject it was found that a dose of 20 grammes of 
 absolute alcohol produced a decrease of power, while in another 
 doses of 15 and 30 grammes had no decided effect on the total 
 amount of work, though with the latter dose the course of 
 the work showed that was an initial increase followed by a 
 fall below the normal. 
 
 The results of this historical survey may be summed up 
 as follows : Nearly all who have used the ergograph in their 
 investigations have found that alcohol increases the capacity 
 for work, either under certain conditions, or in certain 
 persons, or for a certain time. Some, such as Fe"re, Destree, 
 and Kraepelin, believe that this increase is only temporary ; 
 others, as Joteyko, that it only occurs in some persons. Of 
 those who believe that the favourable effects of alcohol only 
 make themselves felt under certain circumstances, Schnyder 
 believes that the effect is only favourable when fasting ; 
 Schumburg, as a result of very few experiments, believes that 
 the opposite is true ; and Frey finds that alcohol only exerts 
 its beneficial effect when the muscle is already fatigued ; 
 and both Frey and Schnyder ascribe this beneficial influence 
 of alcohol to its action as a food- substance. 
 
 Very different doses have been used by different workers. 
 Some have found distinct effects produced by such small doses 
 as 10 or even 5 c.c. of pure alcohol, or of beverages containing 
 an equivalent amount. Others have obtained similar results 
 with much larger doses, and one worker failed to obtain 
 evidence of a definite effect till he had increased the dose to 
 as much as 80 c.c. of pure alcohol. 
 
 When we turn to the details of the mode of action of 
 alcohol on the ergographic curve, we find that the majority 
 of those who consider this point find that the effect of alcohol 
 is chiefly on the number of contractions ; but at least one 
 worker Schnyder finds the exact opposite, alcohol, accord- 
 ing to him, diminishing the number, while increasing the 
 height of the contractions. 
 
 Some of the results may almost certainly be put aside as 
 the result of imperfections in the ergograph employed. The
 
 66 THE INFLUENCE OF DRUGS ON FATIGUE 
 
 curves given by Tavernari and some of the earlier curves of 
 Frey show that the increase due to alcohol was exactly of 
 the kind which would be produced by accessory movements. 
 They do not do more than indicate that the curve was con- 
 tinued longer under the influence of alcohol because other 
 muscles were brought into play. A consideration of the 
 curves given by many workers shows, however, that this can 
 only be an exceptional cause of the increase in the amount 
 of work. 
 
 A more frequent, and, indeed, universal, source of error 
 is the complete absence of any adequate control. Heck 
 found that alcohol had a beneficial result when combined 
 with mental stimulation, which was absent without it ; and 
 Fere has shown that the effect of alcohol may be even more 
 stimulating when it is taken into the mouth than when it is 
 swallowed ; but neither these nor other observers have com- 
 pared the effects of two doses of similar taste and flavour, 
 one containing alcohol and the other inactive substances. It 
 seemed to me, in undertaking work with alcohol, that the first 
 step was to test whether the effects described by Frey, 
 Destree, Fere, and others would appear if the factors of 
 interest and sensory stimulation were carefully excluded. 
 
 The disguise is much more difficult than in the case of 
 caffeine. With this substance we have seen that there is 
 little difficulty in making two solutions, one containing the 
 caffeine, and the other certain inactive substances which are 
 wholly indistinguishable from one another. In my first work 
 with alcohol on mental fatigue (see p. 98), a control solution 
 was prepared for me by Dr. Dixon which contained capsicum, 
 cardamoms, and a very small amount of chloroform, which 
 was so much like a similar mixture with the addition of 
 alcohol, that it was very difficult to distinguish the two 
 from one another, when the dose of alcohol was small. 
 The suspicion that one was- alcohol was so indefinite that 
 it could have had little influence, and the factors of 
 interest and sensory stimulation were certainly present in 
 equal measure with the two mixtures. Nevertheless, it
 
 ALCOHOL 67 
 
 was probable that, with larger doses than I was using on 
 this occasion, the alcohol would be recognized, and in the 
 work with the ergograph I adopted the additional precaution 
 of comparing the effects of two different doses of alcohol with 
 the control in any one experiment. Dr. Dixon prepared 
 three mixtures, one containing the substances already men- 
 tioned, one containing in addition a certain dose of alcohol, 
 and the third containing double this dose. This use of two 
 different doses of alcohol in any one experiment not only 
 tended to enhance the disguise, but since it is to be expected 
 that up to a certain point the effect of a drug will increase 
 with the dose, the method should bring out indications 
 whether in any given case an effect is really due to the drug, 
 and the comparison between the effects of the two doses has 
 often furnished useful evidence in the estimation of the value 
 of an alteration in the amount of work. When two different 
 doses are taken in this way during the course of an experi- 
 ment, it may happen that the stronger of the two may be 
 recognized, while the weaker fails to be distinguished from 
 the control. If, then, in another experiment the former dose 
 is combined with one still stronger, the now weaker dose may 
 become wholly indistinguishable from the control, and this 
 combined investigation of two doses may thus assist the 
 disguise very materially. 
 
 EXPERIMENTS OF THE SUBJECT W. 
 
 As in the case of caffeine, Mr. Webber's experiments were 
 more numerous and more satisfactory than my own, and I 
 will begin with them. 
 
 Experiment 1. The method employed was precisely the 
 same as in the first caffeine experiment. Three sets, each of 
 six ergograms, were recorded, with intervals between the sets 
 of half an hour. The rhythm was two seconds, and the in- 
 terval between the ergograms two minutes. The weight was 
 4 - 5 kilogrammes, and the drug or control mixture was taken 
 ten minutes before the beginning of the second set of ergo- 
 
 52
 
 68 
 
 THE INFLUENCE OF DRUGS ON FATIGUE 
 
 Kork 
 
 FIG. 8. ALCOHOL EXPERIMENT W. i. 
 
 A, Control mixture. B, Alcohol 5 c.c. C, Alcohol 10 c.c. Arrow shows when the 
 dose was administered. 
 
 grams. The right and left hands were used alternately, and 
 the doses were 5 and 10 c.c. of absolute alcohol. The experi- 
 ment lasted for twelve days, so that 10 c.c. were taken on
 
 ALCOHOL 69 
 
 four days, 5 c.c. on four days, and the control mixture of 
 capsicum, etc., on the other four days, the three kinds of day 
 being arranged in an order unknown to the subject. 
 
 The result is shown in Fig. 8, 1 in which the amount of 
 work and the number and height of the contractions are 
 shown in percentages of the first ergogram. The first sets 
 were taken on all the twelve days before any dose had been 
 taken, and A, B, and C days were therefore carried out under 
 exactly the same conditions ; and the very close correspon- 
 dence of the three curves gives a most satisfactory tribute to 
 the trustworthiness of the method, and serves to justify the 
 device of expressing the results in terms of the first ergo- 
 gram, the most notable difference in the last ergograms 
 depending upon a condition which it is impossible to keep 
 constant viz., the amount of end-spurt. 
 
 The curves for the second set of ergograms, begun ten 
 minutes after taking the dose, also run together very closely, 
 showing that the alcohol had absolutely no effect either in 
 increasing or decreasing the amount of work. The curves 
 representing the heights of the contractions in this set show 
 more deviation, that for the larger dose of alcohol falling off 
 less than those for the other two days. 
 
 The third set, begun fifty-five minutes after the dose had 
 been taken, shows at first sight a drug-effect ; but it will be 
 noticed that, of the two curves which begin with an increased 
 amount of work, one represents the days on which the larger 
 dose of alcohol was taken, while the other is that of the control 
 days. It is very unlikely that a dose of 5 c.c. would produce 
 a deleterious effect an hour after it was taken, while the larger 
 dose of 10 c.c. had no effect, and the small amount of work 
 performed on the 5 c.c. days may confidently be ascribed to 
 adventitious circumstances of some kind. These curves thus 
 bring out very decidedly the advantage of the method of 
 combining two doses in one experiment. 
 
 In the curves representing height, that for the larger dose 
 
 1 For the actual figures on which these and the following curves are 
 based, see Brit. Journ. Psychol., 1908, vol. ii., p. 261.
 
 70 THE INFLUENCE OF DRUGS ON FATIGUE 
 
 of alcohol again shows less tendency to fall, and this may 
 possibly be significant, though it will be noticed that the 
 curve was showing a distinct tendency to rise in the first set, 
 which was recorded before any dose had been taken. On 
 the whole, we may regard this experiment as giving an entirely 
 negative result ; and later experiments make it highly probable 
 that such variations as occurred are due to disturbing factors 
 of some kind. In this experiment one hand was used on six 
 days and the other hand on the other six. The curves for 
 the two hands taken separately were much the same, but, 
 as might be expected, rather more irregular than those for 
 the two hands taken together ; and the study of these curves 
 tends to confirm the impression that any differences between 
 the different sets of days were due to chance variations. 
 
 Experiment 2. In this the general method and conditions 
 were as in the first experiment, except that the doses of 
 5 and 10 c.c. were taken between the first and second ergo- 
 grams of the first set, the special object being to test the 
 statement of Frey that alcohol produces a decrease in the 
 amount of work if taken before any fatigue has been induced. 
 In giving the dose after the first ergogram, there was a de- 
 parture from Frey's procedure ; but if this had not been done, 
 there would have been no normal standard for the work of 
 each day. 
 
 The intervals in this experiment were occupied with mental 
 work in the form of multiplication (see p. 93). 
 
 In this and all succeeding experiments the subject took 
 his own readings, the two minutes' interval between succes- 
 sive ergograms affording ample time for this and for any 
 necessary adjustments of the ergograph. That the subject 
 should take his own readings has some disadvantages ; but 
 it was not always possible for another person to be present 
 to record them, and unless this could be done in all cases, 
 it was thought best that it should be done in none. The 
 whole business of reading the scale and making any neces- 
 sary adjustments so soon settles down to a steady routine 
 that the subject is not led to think about the relations of the
 
 ALCOHOL 71 
 
 readings he is recording ; and it is probable that the method 
 of taking one's own readings is really less disturbing than 
 one in which the subject has two minutes of complete leisure 
 between each pair of ergograms for reflection on the nature 
 of his performance. Further, there is the great advantage 
 that the presence of another person in the experimental room, 
 with all the possible sources of disturbance involved, can be 
 dispensed with. 
 
 The special interest of the second experiment lies in the 
 failure of the control. The larger dose of 10 c.c. was definitely 
 recognized on each occasion, and the presence of alcohol was 
 suspected in the case of the smaller dose. The results repre- 
 sented graphically in Fig. 9 show a definite increase on the 
 alcohol days greater on those with the larger dose and 
 this increase was apparent immediately after the dose was 
 taken. It continued to the end of the first set, and was also 
 distinctly present in the first ergogram of the second set, this 
 curve falling slightly below that of the normal days in the 
 remaining ergograms. The curves for number and height of 
 the contractions show that the increase in the amount of 
 work on the alcohol days was chiefly due to an effect on the 
 former, though there was also a slight increase in the height 
 in the first set on the two alcohol days, the curve for 
 the smaller dose, however, here rising above that for the 
 larger. 
 
 The action of alcohol in this experiment was of the same 
 kind as that which has been described by most previous 
 workers viz., an immediate increase followed by a reaction 
 shown in a fall below the normal ; and it is suggestive that this 
 kind of action should have shown itself in an experiment in 
 which there was a failure of the control, so that the feature 
 of interest was awakened. 
 
 It must be noticed that these two experiments give results 
 exactly the opposite of those found by Frey. This worker 
 obtained no effect when the alcohol was taken before any 
 ergograms had been recorded, an increase only occurring when 
 fatigue had been induced by the performance of a certain
 
 72 THE INFLUENCE OF DRUGS ON FATIGUE 
 
 amount of work. These directly opposed results, however, 
 may safely be ascribed to different degrees in the amount of 
 
 FIG. 9. ALCOHOL EXPERIMENT W. n. 
 
 A, Control mixture. B, Alcohol 5 c.c. C, Alcohol 10 c.c. 
 
 interest in the different experiments, and they afford no 
 indication of any true physiological effects of the alcohol.
 
 ALCOHOL 73 
 
 Experiment 3. The control having failed in the second 
 experiment, it became necessary to modify the mixtures used 
 for this purpose. The mixtures had so far contained capsicum, 
 cardamoms, and chloroform only, to which Dr. Dixon now 
 added some peppermint. The new control was completely 
 successful, the disguise being so perfect that in the succeeding 
 experiments the subject was wholly unaware, so far as taste 
 was concerned, whether he had taken alcohol or the control 
 mixture. 
 
 The third experiment was begun with the idea of testing 
 the influence of doses of 10 and 20 c.c. of absolute alcohol 
 by exactly the same methods as in the second experiment, 
 except that the intervals on half the days were to be occupied 
 with multiplication, while in the other half the place of the 
 multiplication was to be taken by typewriting. At the end 
 of five days the experiment was unavoidably interrupted, by 
 which time only one day's work had been done with each 
 dose. The smaller dose of 10 c.c. had given a completely 
 negative result, while with the larger dose of 20 c.c. there had 
 been an increase only noticeable in the first ergograms of the 
 second and third sets. As there did not seem to be any 
 evidence of a definite effect, we decided not to repeat this 
 experiment, but to proceed directly to larger doses, 
 especially as the dose of 20 c.c. was to be tried in the next 
 experiment. 
 
 Experiment 4. This lasted for twenty days, on six of 
 which no dose of any kind was taken, on five the control mix- 
 ture was used, while on the other days the doses of alcohol 
 were either 20 or 40 c.c. of absolute alcohol. Each dose 
 was taken between the first and second ergograms of the 
 first set. 
 
 On each day four sets were recorded, each of six ergograms. 
 The interval between the first and second and between the 
 second and third sets was half an hour, but between the third 
 and fourth sets it was increased to one hour. The first and 
 second intervals were occupied with either multiplication or 
 typewriting, the amount done in each five minutes being
 
 74 
 
 THE INFLUENCE OF DRUGS ON FATIGUE 
 
 recorded with the help of a five-minutes clock. This work 
 was done for twenty-five minutes, leaving time at the begin- 
 ning and end for the necessary adjustments of the ergograph. 
 
 40 
 3o 
 lio 
 
 JOO , 
 qo 
 80 
 1 
 60 
 
 5o 
 40 
 30 
 20 
 
 T 
 
 Work 
 
 FIG. 10. ALCOHOL EXPERIMENT W. iv. 
 Complete contractions. A, Control mixture. B, Alcohol 20 c.c. 
 
 The third interval of an hour was passed in gentle walking 
 in the open air and in light reading, while a little food was also 
 taken. 
 
 On some of the days the contractions were of the usual
 
 ALCOHOL 75 
 
 kind ; on the other days they were only allowed to reach two- 
 thirds of their normal extent, as in my caffeine experiments 
 (see p. 34 and Fig. 5). 
 
 In this experiment it became apparent that the alcohol 
 was having a definite effect at any rate, with the larger dose 
 and that the absence of the effects previously recorded was 
 true only in the case of small doses. Since this absence of 
 effect due, I believe, to the use of proper control is the 
 subject to which I wish especially to call attention, I propose 
 to consider the effects of the two doses used in this experi- 
 ment separately, and I am the more willing to do this 
 because the effect of the larger doses has not yet been 
 established to my satisfaction, and is now the subject of 
 farther experiments by Mr. Webber. 
 
 In the following figures, therefore, are represented only the 
 results with the dose of 20 c.c. The curve for the amount of 
 work with the complete contractions" given in Fig. 10 shows 
 not the slightest trace of an immediate effect, and the two 
 curves for the first set run together as well as if no drug had 
 been taken. In the second set there is also no definite indica- 
 tion of an effect, which only appears in the third set, begun an 
 hour and a half after the alcohol had been given. The fact 
 that the alcohol curve in this set is consistently above that for 
 the normal days suggests that we may possibly have to do 
 here with a real drug-effect, though of only slight amount, 
 which has w r holly disappeared an hour later. The other 
 curves show that this increase is due to an effect on both 
 number and height of the contractions, perhaps chiefly on the 
 former. 
 
 The results with the incomplete contractions shown in 
 Fig. 1 1 seem to show an immediate depressing effect of the 
 alcohol, but not of any great amount. In the second set this 
 is replaced by an increase on the alcohol days, which becomes 
 still more definite in the third set, to disappear in the last. 
 This correspondence with the complete contractions in show- 
 ing a definite increase in the third set is almost certainly 
 significant, and seems to point to a stimulating action of the
 
 76 THE INFLUENCE OF DRUGS ON FATIGUE 
 
 alcohol asserting itself most definitely about an hour and 
 a half after its administration. The increase is, however, 
 very slight as compared with that recorded by Frey and 
 others. 
 
 This fourth experiment thus confirms the first and third 
 
 o| Contractions 
 
 Work 
 
 FIG. 11. ALCOHOL EXPERIMENT W. iv. 
 Incomplete contractions. A, Control mixture. B, Alcohol 20 c.c. 
 
 in showing no trace of an immediate stimulating action when 
 there is an adequate control, and any increase which is found 
 is considerably delayed, being most pronounced about an hour 
 and a half after the alcohol has been taken. The only definite 
 increase thus occurs at a time when the effect described 
 by most previous workers has disappeared, or a period
 
 ALCOHOL 77 
 
 beyond that to which they have followed the effects of the 
 drug. 
 
 A word must be said here on the validity of the procedure 
 of expressing the results in their relation to the first ergogram. 
 In the first alcohol experiment, and in the experiments with 
 caffeine recorded in the last lecture, the dose of drug or con- 
 trol was not taken till after the first set had been completed, 
 so that we are able to express the course of the work in terms 
 of the whole of the first set as well as in terms of the first 
 ergogram, and the correspondence of the two ways of express- 
 ing the results in those cases can leave little doubt about 
 the genuineness of the results. 
 
 In the later alcohol experiments of W. the dose was taken 
 immediately after the first ergogram, so that in this case we 
 have only one ergogram to act as a standard. As a general 
 rule, however, the course of the ergograms of the first set on 
 the normal days is so constant, and the later ergograms stand 
 in so definite a relation to the first, that one can have little 
 doubt about the validity of our procedure. Still, in such a 
 case there must always be the possibility that the first ergo- 
 gram may be exceptional in some way, and in later experi- 
 ments with other subjects the drug or control has not been 
 given till a whole set has been recorded to act as a standard. 
 
 THE EXPERIMENTS OF THE SUBJECT K. 
 
 My own experiments were much less satisfactory than 
 those of W., owing to the muscular pain produced when sets 
 of six, or even of three or four, ergograms were recorded. My 
 first experiment was planned on exactly the same lines as the 
 first experiment of W., with doses of 5 and 10 c.c. of alcohol, 
 taken ten minutes before the beginning of the second set. 
 This experiment could only be continued for five days, the 
 results of which, though irregular, gave no indication of an 
 alcohol-effect. 
 
 Experiment 2. It was not possible to do any further 
 satisfactory work till several months later, when, after pro-
 
 78 THE INFLUENCE OF DRUGS ON FATIGUE 
 
 longed training, a second experiment with incomplete contrac- 
 tions, lasting for six days, was carried out with doses of 10 
 and 20 c.c., taken one minute before beginning the second set. 
 Five sets were recorded, each of four instead of six ergograms, 
 as usual. As in our other experiments, the two earlier 
 intervals were half an hour, and those between the later sets 
 'an hour, and all were passed in some light occupation or in 
 the open air, the corresponding intervals on different days 
 being always occupied in the same manner. 
 
 The figures for the individual ergograms in this experi- 
 ment were very irregular, showing that the amount of 
 practice was still insufficient, and this was also shown by the 
 pain which the contractions still often produced. The first 
 set was done before any dose had been taken, and the total 
 amount of work done in this set was almost the same on 
 normal and alcohol days. There was also no appreciable 
 difference in the second set, begun a minute after taking the 
 dose, there being thus no trace of an immediate effect. The 
 third set showed an increase on the alcohol days, greater on 
 the days on which the larger dose was taken, and therefore 
 possibly significant of a real effect. This increase had dis- 
 appeared in the following set, recorded an hour later, but there 
 was no evidence of any reaction. The only evidence of an 
 effect was, therefore, in the third set, begun three-quarters of 
 an hour after the alcohol had been taken, but it is doubt- 
 ful whether this increase was due to anything more than 
 the irregularity caused by the imperfect condition of 
 training. 1 
 
 Experiment 3. This lasted for six days, five sets, each of 
 six ergograms, being recorded on each day with the right 
 hand and with complete contractions. The doses of alcohol 
 were 20 and 40 c.c., and they or the control were taken one 
 minute before beginning the second set of ergograms. Even 
 with the larger number of ergograms in each set, and though 
 the contractions were complete, there was less pain than in 
 
 1 For the full record of the results of this experiment, see Brit. Journ. 
 Psychol., 1908, vol. ii., p. 275.
 
 ALCOHOL 
 
 79 
 
 the second experiment, and the form of the curves showing 
 the course of the individual ergograms (see Fig. 12) is far 
 more regular than in that experiment, though still far from 
 attaining the regularity of the fully trained condition. As in 
 the case of W., the results with the larger dose will be left till 
 
 FIG. 12. ALCOHOL EXPERIMENT R. in. 
 A, Control mixture. B, Alcohol 20 c.c. 
 
 later, and the curves for the control days and those on which 
 20 c.c. were taken are given in Fig. 12. 
 
 The curves show what may be an alcohol- effect in the 
 second set begun almost directly after taking the dose, but 
 the very abnormal form of the curve for the control days 
 shows that much weight cannot be laid on the record of this
 
 80 THE INFLUENCE OF DRUGS ON FATIGUE 
 
 set. The first part of the control curve of the third set is also 
 abnormal, probably owing to the existence of some pain, and 
 it is only the first ergogram of this set in which there is any 
 decided difference between the alcohol and control days, while 
 in the fourth set the two curves run very closely together. 
 
 This experiment, then, differs from the preceding in giving 
 a possible indication of an immediate effect ; but, 011 the other 
 hand, there is no trace of the increase after an hour and a half 
 which occurred in the case of W., and the nature of the early 
 increase gives one no confidence in its dependence on the 
 action of the alcohol. 
 
 As in this experiment the dose was not taken till the first 
 set of ergograms was concluded, it is possible to use the 
 average ergogram of this set as a standard by means of which 
 to express the course of the individual ergograms. Curves 
 were, therefore, constructed resembling those of Fig. 1 2, except 
 that each ergogram was expressed, not as a percentage of 
 the first ergogram, but as a percentage of the average of the 
 whole of the first set i.e., an average obtained by dividing 
 the total work of this set by six. The curves so constructed, 
 however, were found to agree very closely in their general 
 features with those already given. 
 
 The chief result of the foregoing experiments is the failure 
 to confirm the conclusion of nearly all previous workers that 
 small doses of alcohol from 5 to 20 c.c. have an immediate 
 stimulating or depressing action on the capacity for muscular 
 work as tested by the ergograph. The experiments have 
 differed from all previously recorded in the use of control 
 substances, by means of which the days on which alcohol was 
 taken were rendered indistinguishable from the normal days, 
 and in the only case in which there was a definite immediate 
 effect there had been failure of the control. The natural 
 conclusion is that the results of previous workers have been 
 due, not to the physiological effects of the alcohol, but to the 
 presence of certain factors, and especially interest and sensory 
 stimulation, the influence of which can only be excluded by 
 the use of a control.
 
 ALCOHOL 81 
 
 Before, however, accepting this conclusion, it is necessary 
 to inquire whether there have been any other differences 
 between our experiments and those of previous workers which 
 might explain the divergent results. 
 
 One such difference is a consequence of the use of a control. 
 The mixtures in which the alcohol was taken for purposes of 
 disguise were decidedly unpleasant, and the possibility arises 
 that this may have neutralized an effect which the alcohol 
 might otherwise have produced. The control mixture con- 
 taining no alcohol, however, was equally unpleasant, and as 
 the unpleasantness was the same on both alcohol and control 
 days, any alcohol - effect which existed ought to have 
 become evident. Further, in later experiments carried out 
 by Mr. Webber, a different control, decidedly pleasant to the 
 taste, has been used, and in these experiments also there has 
 been no evidence of an alcohol-effect. 
 
 Another possibility must be borne in mind. One of the 
 most definite results of previous work on the action of alcohol 
 has been to show the presence of great individual differences 
 in the susceptibility to the action of the drug, 1 and though 
 it is possible that these differences have been largely due 
 to the part played by the psychical factors which it has 
 been the especial object of the new experiments to exclude, 
 there can be little doubt of the existence of true individual 
 differences to the physiological action of the drug. It is 
 possible that the two subjects whose work has been recorded 
 in this lecture are especially resistant to the action of alcohol. 
 The observations recorded in Appendix IV., however, show 
 that W. is certainly not an example of insusceptibility ; and 
 I have no doubt that I have rather more than the average 
 susceptibility to its general effects. 
 
 A further piece of evidence that the negative results have 
 been due to the use of an adequate control is derived from a 
 short experiment on the subject W. with doses of whisky 
 containing 10 and 20 c.c. of absolute alcohol. These observa- 
 tions were made by giving the whisky without any attempt 
 1 See p. 62. 
 
 6
 
 82 THE INFLUENCE OF DRUGS ON FATIGUE 
 
 at disguise, and it was found that both doses produced a very 
 decided increase in the amount of work as compared with a 
 normal day. The most noteworthy fact was that this increase 
 was immediate, exactly as in most previously recorded work. 
 It is, of course, open to anyone to say that the increase in 
 this case was due to some component of the whisky other 
 than ethylic alcohol, but the immediacy of its action can 
 leave little doubt that we had to do mainly with the action 
 of interest and sensory stimulation. If so, we have the 
 clearest evidence that the cause of the negative results with 
 pure alcohol in the case of the subject W. was not individual 
 insusceptibility, but the means which were taken to exclude 
 the psychical factors which have been allowed to influence all 
 previous work. 
 
 There can be little doubt that the absence or slight ness of 
 the effects with small doses of alcohol which we have found 
 are due to the use of control-substances, and that the results 
 of most of those who have found the capacity for muscular 
 work increased under the influence of such doses as 5 and 
 10 c.c. have been due, not to the physiological action of the 
 substance, but to the interest aroused by taking the alcohol 
 and the sensory stimulation involved in swallowing it, while 
 those who have found a diminution in the amount of work 
 must be open to the charge of having been influenced by 
 suggestion. 
 
 EFFECT OF LARGER DOSES. 
 
 The results so far dealt with have been derived from 
 experiments with small doses, varying from 5 to 20 c.c. of 
 pure alcohol. My special object in experimenting with these 
 small doses was to test the correctness of the previous work of 
 Frey, Destree, Schumburg, Scheifer, Schnyder, and others, who 
 had obtained what seemed to be evidence that these small doses 
 had a definite effect, and I think the results so far recorded in 
 this lecture can leave little doubt that the results hitherto 
 published have portrayed, not the true physiological effects of 
 alcohol, but merely the effects of certain accessory factors,
 
 ALCOHOL 88 
 
 which these workers allowed to complicate their experiments. 
 I have investigated with the ergograph the effects of a larger 
 dose of 40 c.c., but I propose to deal with this portion of my 
 work very briefly, partly because the results are indecisive, 
 but still more because the effects of doses larger than 20 c.c. are 
 now being submitted to further investigation by Mr. Webber 
 an investigation which, I hope, will enable us to speak as 
 decisively about the effects of these larger doses as has been 
 possible in the case of those which I have so far recorded. 
 
 The first observations with the dose of 40 c.c. were made 
 concurrently with those already recorded. In the case of the 
 subject W. there was a very pronounced increase with the com- 
 plete, and a smaller increase with the incomplete, contractions. 
 On examining the work of the individual days, however, there 
 was found to be great irregularity, the increase being very 
 decided on some days, and hardly present at all on others. 
 The interesting feature of the increase, however, was the time 
 at which it occurred. There was in each case no trace of the 
 immediate effect, which has been so pronounced a feature of 
 the results of previous workers. In the case of the complete 
 contractions, not only was there no immediate effect, but the 
 increase was hardly appreciable in the second set, begun three- 
 quarters of an hour after the alcohol had been taken, and the 
 effect was most pronounced in the third set, begun three- 
 quarters of an hour later. In the case of the incomplete con- 
 tractions, the effect was only slightly present in the second set, 
 and as in the case of the complete contractions the increase 
 was most decided in the third set, begun an hour and a half 
 after the alcohol had been taken. This experiment was 
 prolonged for over three hours, and the increase on the alcohol 
 days was distinctly present in the final set ; there was no trace 
 of any decrease following the increase which other workers 
 have found, although the experiment was continued much 
 longer than in any previous research. Certain observations 
 made by the subject of the experiments must, however, be 
 taken into account in estimating the value of the results. So 
 far as taste was concerned, the control used in this experiment 
 
 62
 
 84 THE INTLl'ENCE OF DRUGS ON FATIGUE 
 
 was almost completely successful, the nature of the different 
 doses being rarely suspected ; but the subject was soon able 
 to recognize the days on which the larger dose of alcohol 
 had been taken by means of giddiness and other symptoms. 1 
 He therefore rapidly became aware that the larger doses, 
 which were the special object of this experiment, were pro- 
 ducing an effect an observation which naturally aroused his 
 interest, especially as it came after prolonged series of experi- 
 ments in which the alcohol had usually had no definite effect. 
 Further, as soon as the increase in the amount of work was 
 decided, this was detected by the subject, and probably 
 aroused his interest still further, and this fresh interest 
 probably had some effect in accentuating the increase which 
 was already showing itself. That this awakening of interest 
 was the sole, or even the chief, cause of the increase I do not 
 believe ; but, in view of the negative results of later experiments 
 to be recorded shortly the possibility of the explanation 
 I have suggested should be borne in mind, and I have little 
 doubt that any direct effect of the alcohol was supplemented 
 by the factor of interest arising in the way I have supposed. 
 
 One interesting possibility was suggested by this experi- 
 ment viz., that the subject was, in spite of his lifelong 
 abstinence, extremely resistant to the physiological effects of 
 alcohol, and was exhibiting with this large dose of 40 c.c. the 
 same effect which had been found by other workers with 
 smaller doses. As I have already pointed out, however, 
 the subject was probably rather more susceptible to the 
 action of alcohol than the average ; and, further, the effect 
 was, of an absolutely different kind from that recorded in 
 previous researches, for, instead of being immediate, it did 
 not show itself in one case till an hour and a half after the 
 substance had been taken, a period longer than the whole 
 duration of the experiments of most other workers. Thus, in 
 the work of Kraepelin's pupils, Gliick and Oseretzkowsky, 
 with doses of 40 c.c., the ergographic work was only continued 
 on each day for about an hour after the alcohol had been 
 1 See Appendix IV.
 
 ALCOHOL 85 
 
 taken, a time at which the effects with the complete contrac- 
 tions in the case of W. had not yet shown themselves i.e., 
 the effects described by these workers had run their course 
 before those just described had even begun. 
 
 At its conclusion this experiment was taken to indicate 
 a real alcohol-effect, which at any rate, in the case of the 
 complete contractions persisted to the end of the experiment 
 i.e., for over three hours. The special object of the next 
 experiment was to ascertain whether this increase was followed 
 by any reaction in the way of a decrease, and an experiment 
 was arranged with the same doses (20 and 40 c.c.) as in the 
 last experiment, but in which, nine sets of ergograms were 
 recorded, the first two intervals being of half an hour's 
 duration, while the remaining intervals lasted for an hour, so 
 that the total duration of the experiment of each day was 
 between nine and ten hours. The experiment was continued 
 for fifteen days, and its results were almost wholly negative. 
 There was a good deal of irregularity, but the averages of the 
 different groups of days showed little to which any weight 
 could be attached. With the complete contractions the curves 
 for the control days, and for those on which 40 c.c. of alcohol 
 were taken, ran together very closely, while the days on which 
 only 20 c.c. were taken showed a diminished amount of work. 
 With the incomplete contractions, both alcohol days showed a 
 distinct falling off as compared with the control days. So far 
 as there was any difference between the alcohol and the 
 control days, it went to show an injurious effect on the 
 capacity for work, even from the beginning. 
 
 The experiment was in several respects less satisfactory 
 than the earlier experiment with the same dose. The latter 
 was carried out in May, when the subject was in good health 
 and vigour, while the later experiment was in July, during 
 the very hot weather of the summer of 1906. The subject 
 felt the heat very much, and was distinctly below his normal 
 level of health. Further, the whole experiment, continued for 
 over nine hours every day, was very arduous and wearisome, 
 and certainly could not have tended to improve the vigour
 
 86 THE INFLUENCE OF DRUGS ON FATIGUE 
 
 lowered by the external circumstances. It is probable that 
 this lowered state of health made the general condition more 
 variable from day to day, and the possibility cannot be excluded 
 that the differences between the alcohol and control days are 
 anything more than an expression of these variations. Another 
 condition of the experiment which made the records of the 
 subject more variable was the fact that the weight was not 
 maximal. Several months had elapsed since he had begun to 
 work with the ergograph, and in consequence his muscular 
 power had increased considerably so much so that, in the 
 experiment under consideration, the weight had been increased 
 to 5 kilogrammes, in order to keep within the limits of the 
 scale on the wall of the laboratory. The more gradual fall 
 of the curve for each set, however, as compared with that 
 of the early experiments, makes it obvious that even this 
 large weight gave the subject a task relatively smaller 
 than before ; the curves show that the subject was working 
 with a submaximal weight instead of with a truly maximal 
 weight, as in his earlier experiments. The results of this 
 experiment suggest that the most favourable condition for 
 bringing out a drug-effect is the use of a fully maximal 
 weight, and that even if the weight is only slightly sub- 
 maximal, the variations from day to day may be so great 
 that they may mask any slight drug-effect. 
 
 I also carried out an experiment to test the effect of a dose 
 of 40 c.c., the record forming part of the experiment already 
 described with the dose of 20 c.c. In my case the effect of the 
 larger dose was very slight, but in the direction of a decrease 
 in the amount of work under the influence of alcohol. Here 
 the dose was taken one minute before the beginning of the 
 second set of ergograms, and the work of the first set on the 
 days on which this dose was taken showed a distinct tendency 
 to fall before the drug was taken. It is thus possible that the 
 decrease on these days was nothing more than a continuation 
 of this fall, and did not indicate a true drug-effect. 
 
 It will thus be seen that the results with the dose of 
 40 c.c. are variable. The experiments were open to reproach
 
 ALCOHOL 87 
 
 from several points of view, and it will be best to suspend 
 judgment till the results of further work, now in pro- 
 gress, are available. It is possible to say, however, that 
 sometimes a dose of 40 c.c. of pure alcohol may produce 
 a decided increase in the amount of work executed with the 
 ergograph, but that at other times this increase may be 
 wholly absent, and may possibly be replaced by a decrease. 
 
 In one point the results with the larger dose of alcohol 
 agree with that of nearly all previous writers. Wherever 
 alcohol produces any effect it is on the number of the con- 
 tractions, and there is little indication that the height is 
 at all affected by the drug. Many previous workers have 
 found that the increase in the number of the contractions is 
 accompanied by a decrease in the height, but this was certainly 
 not the case in the experiments just described. 
 
 The effect of interest and mental excitement is chiefly, 
 if not entirely, on the number rather than on the height 
 of the contractions, and if the effect I have described with 
 the dose of 40 c.c. is due to the physiological effect of 
 the alcohol, this special action on number, rather than on 
 height, might perhaps be held to point to a central action of 
 the drug. 
 
 It will have been noticed that not only my own work, but 
 also all the researches of other workers, have been devoted to 
 the endeavour to ascertain the immediate effects of a dose of 
 alcohol, and that I have said nothing of its more prolonged 
 effects ; as tested by comparing periods during which alcohol 
 is taken regularly with periods of abstinence. The reason for 
 this is that these prolonged effects have not yet been investi- 
 gated by laboratory methods in the case of muscular work, 
 though, as we shall see, an attempt has been made in this 
 direction in the case of mental work. 
 
 Further, I have made little reference to the action of 
 alcohol in general fatigue. My own work has been carried 
 out in such a way as to exclude general fatigue as much as 
 possible and to study muscular fatigue in its pure state, and 
 this has also been the object of most other researches, Schum-
 
 88 THE INFLUENCE OF DRUGS ON FATIGUE 
 
 burg and Tavernari being the only workers who have attacked 
 the problem of general fatigue directly, though this must 
 have played a large part in the work of Hellsten. 
 
 The only cases in which the prolonged action of alcohol 
 in general fatigue has been tested are to be found in the 
 observations which have been made on large masses of men 
 in campaigns, etc., and here the results point strongly to the 
 conclusion that alcohol is prejudicial to the capacity for work 
 and in no way helps to diminish the effects of fatigue. 
 
 The capacity for work, which is tested in any such mass 
 observations, is of a very complicated nature. Any effect 
 which alcohol may have on the capacity to hold out during a 
 prolonged march, for example, is obviously very complex. In 
 such a feat every organ of the body is involved, and far more 
 is being tested than mere muscular fatigue, which is all that 
 has been investigated in most of the researches to which I 
 have referred in this lecture. 
 
 All that I and most others have attempted to do is to 
 study the immediate effect of alcohol on one of the con- 
 stituents of the complex viz., pure muscular fatigue and it 
 must be the task of future laboratory research to determine 
 which elements of the complex exert the injurious influence 
 which the mass observations seem to demonstrate.
 
 , LECTURE IV 
 INFLUENCE OF ALCOHOL ON MENTAL FATIGUE 
 
 Historical; new experiments with multiplication, typewriting, and by 
 McDougalTs method ; slightness of effects Mode of action of 
 alcohol in fatigue ; comparison of effects on muscular activity of 
 alcohol and mental fatigue ; removal of controlling influence. 
 
 I WILL deal with the history of work on the action of alcohol 
 on mental fatigue briefly. Nearly the whole of these 
 researches come from the school of Kraepelin, and do not 
 show the same contradictious as those with which we have 
 met in the case of the action of this substance on muscular 
 fatigue ; but they have dealt rather with the action on the 
 general capacity for work than with the factor of fatigue, 
 and most of the researches have not been devised in such a 
 way as to bring out any action on this special feature of mental 
 activity. 
 
 In his book on the action of drugs on mental processes 
 Kraepelin 1 deals with the action of alcohol on various forms 
 of mental activity, but with little reference to fatigue, and I 
 can pass on to the researches published in his ' Psych ologische 
 Arbeiten.' Of these, the one which stands in the closest 
 relation to the other researches I have been considering in 
 these lectures is that by Aschaffenburg,- on the influence of 
 alcohol on four compositors. 
 
 The special feature of this work is that the four men were 
 carrying out their usual occupation, and, as far as possible, in 
 the usual way. All were in the habit of taking alcohol one 
 
 1 ' Ueber die Beeinfliissung einfacher psychischer Vorgunge durch 
 einige Arzneimittel/ 1892, S. 41. 
 
 - ' Psychologische Arbeiten; 1896, Bd. i., S. 608. 
 
 89
 
 90 THE INFLUENCE OF DRUGS ON FATIGUE 
 
 in somewhat excessive amount and if there was any bias in 
 this experiment, it was probably in favour of alcohol. The 
 experiment lasted for four days, on two of which each man 
 took '200 grammes of a Greek wine, containing 18 per cent, of 
 absolute alcohol. The duration of the experiment of each 
 day was an hour and a quarter, which was long enough to 
 bring out a definite fatigue effect. 
 
 The results in the form in which they are given by 
 Aschaffenburg show that in two of the subjects decidedly 
 less work was done on the alcohol days, while in the other 
 two there was no great difference. There was, however, a 
 considerable increase from day to day as the result of practice, 
 and as each alcohol day followed a normal day distinctly more 
 work should have been done on the latter. The work of 
 the first quarter of an hour was done on each day before 
 the wine had been drunk, and it is therefore possible to 
 show the special action on fatigue by expressing the results 
 as percentages of that done in the first quarter of an 
 hour. 
 
 Aschaffenburg has not used this method of demonstrating 
 the effect of the alcohol, but when expressed in this way the 
 figures show in each case a steady falling off during the last 
 three-quarters of an hour (with an end-spurt in one case) on 
 the normal days, while the chief characteristic of the alcohol 
 days is their irregularity ; and it cannot be said, except, per- 
 haps, in one case, that the decrease on the alcohol days 
 becomes greater in the later periods of work. 
 
 When expressed in this way, the effect of the alcohol 
 seems to have shown itself in a diminution of the capacity for 
 work from the outset, and not to have had any special influence 
 on the latter part of the period of work. 
 
 In spite of the very definite evidence of the effect of 
 alcohol on the quantity of work, there did not seem to be any 
 change in its quality, the proportion of errors being small and 
 not different on the two sets of days. 
 
 Several researches have been recorded by Ach, 1 Maljarew- 
 1 ' Psychologische Arbeiten, 1 1901, Bd. iii., S. 203.
 
 INFLUENCE OF ALCOHOL ON MENTAL FATIGUE 91 
 
 sky, 1 and Riidin, 2 to show the effect of alcohol on the pro- 
 cesses of perception and apprehension, but they do not in 
 general give data to allow any estimation of the action of the 
 drug on fatigue. Perhaps the most important result of 
 Riidin's work is to show how great may be the degree of 
 insusceptibility to the action of alcohol in some persons. 
 He used the large dose of 100 c.c. of absolute alcohol, and 
 yet in some cases the effect was very slight in spite of the 
 fact that the subjects of his tests were abstainers. This work 
 shows that great variations in susceptibility to the action of 
 alcohol may be present in those who have always abstained 
 from the use of alcohol and need not depend on different 
 degrees of habituation to its action. 
 
 I can now turn to a group of researches which derive 
 their special interest from the fact that they deal with the 
 problem, not of the immediate effect of alcohol, but with that 
 of its influence when taken over a period of some length. We 
 have seen that this problem has not yet been taken up in 
 the case of muscular fatigue ; but several researches devoted 
 to the study of the cumulative effect on mental activity have 
 been carried out by the Kraepelin school. These researches 
 have dealt with the character of the work executed on a 
 succession of days during which the subject was taking 
 alcohol, as compared with a period during which no alcohol 
 was taken. In a preliminary experiment Fiirer 3 investigated 
 the effect of a dose of 80 grammes of alcohol taken at night 
 on the mental activity of the next day, as tested by the 
 processes of addition, learning by heart, and association. He 
 found a distinct decrease in the capacity for work, and this 
 result was confirmed later by Riidin, 4 at any rate, in some 
 persons. 
 
 The first to investigate the effect of alcohol when taken 
 
 1 See a paper by Kraepelin, ' Ueber die Merkfiihigkeit,' Monatschr. 
 /.' Psychiatric u. Neural, 1900, Bd. viii., S. 247. 
 
 2 ' Psychologische Arbeiten,' 1904, Bd. iv., S. 495. 
 
 3 See a paper by Ki'irz and Kraepelin, 'Psychologische Arbeiten, 1 1901, 
 Bd. iii.,S. 450, and Arch. f. Psychiatric, 1895, Bd. xxvii., S. 970. 
 
 4 'Psychologische Arbeiten,' 1904, Bd. iv., S. 1.
 
 92 THE INFLUENCE OF DRUGS ON FATIGUE 
 
 over a number of days was Smith, 1 who used the same mental 
 operations as Fiirer, and found a definitely injurious effect in 
 two subjects, with doses varying from 40 to 80 grammes of 
 alcohol. Only brief summaries of his work have been pub- 
 lished, and the most fully reported work of this kind is that of 
 Kiirz and Kraepelin, who investigated several forms of mental 
 activity, of which the most important from the point of view 
 with which we are now concerned were addition and learning 
 by heart. In one subject both kinds of work were carried out 
 for half an hour on each of twenty-seven successive days. 
 On six days no alcohol was taken ; then for twelve days 
 alcohol in the form of dilute spirits of wine, and in a dose 
 equivalent to 80 grammes of absolute alcohol, was taken on 
 each day, usually before going to bed ; then for five days no 
 alcohol was taken, and then again alcohol in the same manner 
 for two days, followed by two normal days. The exact 
 estimation of any effect is rendered very difficult by the 
 presence of the increase from day to day throughout the 
 experiment due to the effect of practice and by the fact that 
 sufficient time was not allowed at the end for recovery from 
 any effects which might have been produced. 
 
 The results with the addition method show, however, that 
 after alcohol had been tak-sii for about eight days there was a 
 falling off in the amount of work, although an increase might 
 have been expected, owing to the continuation of the effects of 
 practice. The work remained below the level to be expected 
 during the following five days of abstinence, but fell still further 
 on the two succeeding days on which alcohol was again taken, 
 to rise again when it was discontinued. Normal experiments 
 on another subject made it probable that the whole of the 
 latter part of the experiment, even on the normal days, was 
 under the influence of the alcohol, and it is very unfortunate 
 that the experiment could not have been continued for a 
 sufficient time after discontinuing the alcohol to see if the 
 subject of the alcohol test would have risen to a corre- 
 spondingly high level of work. 
 
 1 ' Psychologische Arbeiten, 1 1904, Bd. iii., S. 451, and Arch. f. 
 Pxyclriatrie, 1895, Bd. xxvii., S. 968.
 
 INFLUENCE OF ALCOHOL ON MENTAL FATIGUE 93 
 
 The observations with learning by heart carried out by 
 the same subject also showed an injurious influence, especially 
 on the two alcohol days in the latter part of the experi- 
 ment. 
 
 In a shorter experiment on another subject five normal 
 days were followed by six alcohol days, and these by two 
 normals ; and here the chief feature was a very decided rise 
 in the amount of work on the last two days, pointing to an 
 injurious influence of the alcohol. 
 
 These experiments almost certainly show that the dose 
 of 80 grammes of alcohol lowered the capacity for work, not 
 only during the periods when it was being taken, but also for 
 some time afterwards. It must be remembered that work 
 was only done, however, for half an hour on each day, and 
 the figures provide no data for the estimation of any special 
 action which the alcohol may have had on the factor of 
 fatigue. 
 
 Apart from the work of the Kraepelin school, the only 
 research in which the influence of alcohol on the capacity for 
 mental work has been tested is one by Partridge, 1 who in- 
 vestigated the influence of the drug on the rapidity of 
 adding, reading, and writing, and found that a dose of about 
 30 grammes had little effect. There was, perhaps, an initial 
 quickening, followed by some slowing, but the changes were 
 very slight. 
 
 I have but little new work to bring before you relating 
 to the influence of alcohol on mental activity, and even this 
 bears little on any special influence that alcohol may have on 
 fatigue., as distinguished from its general action on the 
 capacity for work. The chief point of interest about it is 
 that the effect of the alcohol was tested on the same person 
 and on the same days as those on which muscular work was 
 done. In the second of Mr. Webber's experiments with the 
 ergograph the intervals were occupied with mental work in 
 the form of multiplication, in which Kraepelin's Reclienhefte 
 were used, the subject having to multiply four numbers 
 1 Amcr. Journ. Psychology, 1900, vol. xi., p. 374.
 
 94 THE INFLUENCE OF DRUGS ON FATIGUE 
 
 mentally, and write down the final figure of the product. 1 
 This work was carried on for twenty-five minutes in each 
 interval of half an hour, time being thus allowed at the 
 beginning and end for the subject to move from and back 
 to the ergograph, and to make any necessary readings and 
 adjustments of the instrument. In the fourth experiment 
 with the ergograph the first and second intervals were 
 occupied in the same manner with mental work on some 
 days with multiplication and on others with typewriting. 
 
 In each of these experiments the dose of alcohol or 
 control was taken during the first set of ergograms, and, 
 consequently, before any mental work had been done to act 
 as a standard. It is therefore not possible to bring out any 
 effect on fatigue by expressing the results as percentages of 
 the work done before any dose has been taken, and I can 
 only give the absolute amounts of work on the different 
 days of each experiment figures from which it is not 
 possible to draw any positive conclusions owing to the com- 
 plication introduced by the effects of practice and other 
 causes of variation from day to day. I have not attempted 
 to eliminate these effects by the employment of Kraepelin's 
 methods of calculating coefficients of practice, not because 
 I believe these methods to be wrong, but because the experi- 
 ments with which I am concerned were not continued for a 
 sufficient time to allow their satisfactory application. 
 
 The number of multiplications performed in each in- 
 terval in the second experiment are given in Table I. In 
 the first interval it will be seen that there is a definite 
 increase from day to day throughout the experiment, and, 
 except on April 10, when a dose of 5 c.c. was taken, the 
 increase is fairly steady. The figures for the second interval, 
 on the other hand, show a great increase on April 11, and 
 the comparatively small increase on the following day, when 
 10 c.c. was taken, suggests an injurious effect of the alcohol ; 
 but the whole experiment was too short to allow any definite 
 conclusion to be drawn. It will be remembered that in this 
 experiment the effect of the alcohol was to increase the 
 1 See Appendix V.
 
 INFLUENCE OF ALCOHOL ON MENTAL FATIGUE 95 
 
 amount of muscular work, especially at the beginning, owing 
 probably to interest and excitement ; but the figures for the 
 mental work show little trace of this stimulating action about 
 twenty minutes after the dose had been taken. 
 
 TABLE I. 
 
 April 8. April 9. April 10. April 11. April 12. April 13. 
 
 Control. 10 c.c. 5 c.c. Control. 10 c.c. 5 c.c. 
 
 1st interval ...SIS 1 (6) 397(5) 416 (3) 484(2) 542(2) 581(7) 
 
 2nd interval ...369(5) 403(3) 394(3) 525(3) 537(8) 632(4) 
 
 In the fourth ergographic experiment multiplication by 
 the same method was done on nine days, on three of which a 
 dose of 40 c.c. of alcohol was taken, on two a dose of 20 c.c., 
 on two the control mixture, while on the remaining two no 
 dose was taken. The total amounts executed in the twenty- 
 five minutes of each interval are given in Table II., from 
 which it will be seen that the increase due to practice is 
 very much less than in the second experiment ; in fact, if the 
 first day be excluded, the effects of practice are so slight as to 
 be almost negligible. Any effect of alcohol which might be 
 present has thus a better chance of showing itself, but it is 
 very doubtful whether any such effect is present. 
 
 TABLE II. 
 
 May 18. May 20. May 22. May 24. May 26. May 28. May 30. Juncl. June 7. 
 
 Nodose. 20 c.c. Control. 40 c.c. No dose. 40~ c.c. 40 c.c. 20 c.c. Control. 
 1st interval 659* 753 673 698 751 701 736 771 792 
 2nd interval 707 735 740 755 766 774 785 780 762 
 
 Owing to the interval between the two last days of the 
 experiment, little reliance can be placed on the figures of the 
 last control day, for the effects of practice would have dis- 
 appeared to a considerable extent during the intervening 
 period. The figures for the remaining days are so irregular 
 that no definite conclusion is justifiable ; if the dose of 40 c.c. 
 had any effect at all, it was slightly injurious. 
 
 The figures for the second interval are far more regular, 
 
 1 It must be remembered that in each unit there were three 
 processes of multiplication. The figures in brackets give the number of 
 errors in each period. 
 
 - The figures give the number of multiplications performed in each 
 period of twenty-five minutes during the intervals between the records 
 of the ergographic work.
 
 96 THE INFLUENCE OF DRUGS ON FATIGUE 
 
 and here the increase due to the effects of practice, though 
 very slight, is so steady from day to day that we may with 
 some confidence exclude any definite alcohol -effect. If there 
 is any effect at all, it is in favour of the larger dose of alcohol, 
 and this comes out especially from the comparison of the 
 amounts in the two intervals, for on each of the three days 
 on which this dose was taken there is a decided increase in 
 the amount of work in the second interval as compared with 
 the first, while on several of the days on which nothing or 
 the control mixture was taken the increase in the second 
 interval is very slight, or ev 7 en absent. 
 
 We can certainly say that any action of the alcohol was 
 very slight, and perhaps the most definite indication of an 
 effect is in the direction of increase during the second hour 
 after the dose had been taken, and if so, it is noteworthy that 
 this corresponds in point of time with the increase in the 
 amount of muscular work in the same experiment. 
 
 In this experiment typewriting was done on the other 
 days, on only one of which was the dose of 40 c.c. taken, 
 while :20 c.c. were taken on two days, the control mixture on 
 three days, and no dose at all on two days. The results for 
 each interval are given in Table III., the quantity written 
 being expressed in centimetres. It will be seen that though 
 comparison of the beginning and end of the experiment 
 makes it clear that there was some increase due to the effect 
 of practice, the figures are very irregular, and little signifi- 
 cance can be attached to them. There is certainly, however, 
 no indication of any favourable action of the alcohol, and the 
 one day on which 40 c.c. were taken shows a decided falling 
 off in the second interval. 
 
 TABLE III. 
 
 May 17. May 19. May 21. May 23. May 25. May 27. May 29. May 31. 
 
 Nodose. Control. 40 c.c. 20 c.c. Nodose. 20 cr. Control. Control. 
 
 1st interval : 
 
 Quantity of work 832 824 841 884 883 847 871 902 
 
 Corrected errors 47 56 86 80 89 74 86 94 
 
 Uncorrected errors 26 30 38 26 39 27 21 31 
 
 2nd interval : 
 
 Quantity of work 797 842 805 884 956 897 885 904 
 
 Corrected errors 86 71 80 92 140 99 107 127 
 
 Uncorrected errors 45 46 31 26 42 36 44 If)
 
 INFLUENCE OF ALCOHOL ON MENTAL FATIGUE 97 
 
 I have so far dealt only with the quantity of work done in 
 each of the periods of twenty-five minutes in the intervals 
 between the sets of ergograms. The quality of the work 
 should give another means of estimating the influence of the 
 alcohol on fatigue. The result of previous researches has been 
 to show that the number of errors is generally so small with the 
 method of addition that it furnishes little indication of the 
 presence of fatigue. 1 The process of multiplication, as carried 
 out in our experiments, is so .much more arduous than 
 Kraepelin's addition method that it seemed possible that the 
 quality of the work might here be of value. The errors in 
 the earlier multiplication experiment were therefore counted, 
 and the number of each in each twenty-five minutes has been 
 added in parentheses in Table I. It will be seen that the errors 
 are so few in number that little importance can be attached 
 to the small variations they show. The chief interest is that 
 the small number of errors points to the process of multiplica- 
 tion having become very automatic. The subject noted during 
 the experiment that, in spite of the complexity of the task as 
 compared with the simple addition method, the whole process 
 nevertheless seemed to become quite automatic, and could be 
 carried on with little sense of mental effort, and the very 
 small number of errors affords a definite indication that this 
 introspective observation was correct. 
 
 The errors were also counted in the typewriting done in 
 the intervals of the fourth ergographic experiment. Errors 
 occur so easily in this operation that it seemed probable they 
 would furnish some indication of an alcohol-effect if one were 
 present. 
 
 The errors in typewriting fall into two classes those 
 which escape notice and those which are noticed and 
 corrected and the numbers of each are given in Table III. 
 It will be seen that the latter are not very numerous, and so 
 constant in number that they give not the slightest indication 
 of an alcohol-effect. The uncorrected errors occur more fre- 
 
 1 See especially Amberg, ' Psychologische Arbeiten,' 1896, Bd. i., 
 S. 336, and Rivers and Kraepelin, ibid., S. 656. 
 
 7
 
 98 THE INFLUENCE OF DRUGS ON FATIGUE 
 
 quently, and show an unmistakable tendency 1 to increase with 
 the rapidity of the work, being most numerous in the second 
 interval of the fifth day, when the amount of work reached 
 its maximum. When this increase with rapidity of work is 
 taken into account, there is no definite indication of any 
 alcohol-effect. 
 
 These few experiments, designed to study the influence of 
 alcohol on mental fatigue, give very inconclusive results ; but 
 I do not wish to lay any great stress on them, for I am far 
 from being satisfied with the method according to which they 
 were devised. I followed the customary method of Kraepelin, 
 arranging that the work should be done after the drug had 
 been taken, and trusted to the application of coefficients of 
 practice to make the different days of an experiment com- 
 parable with one another. A study of the results has shown 
 that the application of this method of correction would be 
 very arbitrary and unsatisfactory, and I now believe that the 
 only satisfactory procedure is that adopted in the ergographic 
 observations of executing work on each day of the experiment 
 before any drug has been taken, the amount of such work 
 forming a norm with which to compare the work executed after 
 the administration of the drug. In further work now in 
 progress this is being done, and in the meantime all that can 
 be said is that with the faulty method thus far employed 
 there is no definite evidence that doses varying from 5 to 
 40 c.c. of pure alcohol have any decided effect in the one 
 subject tested. 
 
 The only other research on the effect of alcohol that I 
 have to record is one carried out in conjunction with 
 Mr. McDougall, in which we used the latter 's method of 
 studying fatigue of attention, the general plan of the research 
 being exactly the same as in the corresponding work on 
 caffeine (see p. 45). The experiment lasted for nine days. 
 Alcohol, in a dose of 15 c.c., was taken on three days, and one 
 or other of two control mixtures on the remaining days. 
 
 1 The same tendency has been found in arithmetical methods. See 
 Rivers and Kraepelin, op. cit., S. 658.
 
 INFLUENCE OF ALCOHOL ON MENTAL FATIGUE 99 
 
 In Mr. McDougall's case there was no evidence of any 
 alcohol-effect. In the first period of work there were 1,826 
 hits, while on one group of control days there were 1,822 hits, 
 and on the other 1,883. In the second period of work the 
 total number of hits on the alcohol days was 1,854, while on 
 the two groups of control days the numbers were 1,740 and 
 1,824 respectively. In the latter case both sets of control 
 days had a smaller performance than the alcohol days, but 
 the difference between the alcohol days and one of the control 
 days was very small. If the figures have any significance, 
 they point to a slight stimulating effect of alcohol about 
 three-quarters of an hour after it is taken. 
 
 In the experiment in which I was myself the subject 
 there was more evidence of an effect. In the first period the 
 total number of hits on the alcohol days was 1,523, while on 
 the groups of control days the numbers were 1,582 and 1,769 
 respectively. In the second period the number on the alcohol 
 days was still smaller, being only 1,414, as against 1,562 and 
 1,590 on the two groups of control days. 
 
 Any differences found on the different sets of days are 
 certainly not due to the effects of practice, for the experiment 
 was not begun till after much practice had been acquired, 
 and the figures throughout the experiment show no evidence 
 whatever of improvement during the nine days. If there 
 were any improvement, it is wholly masked by the great 
 variations from day to day. 
 
 In both cases there was nothing decisive in the form of 
 the curves showing the number of hits in the successive rows ; 
 but, unfortunately, the dose was taken before beginning to 
 work, and therefore we have no normal standard with which 
 to compare the work of each day. 
 
 It must be pointed out that, though Mr. McDougall 
 obtained only negative results in this experiment with a dose 
 of 15 c.c. of pure alcohol, he found later 1 that 3 ounces of 
 whisky produced a very decided increase in the number of 
 failures to strike the dots ; a smaller dose of 1 ounce also 
 1 Brit. Journ. Psychol., 1905, vol. i., p. 441. 
 
 72
 
 100 THE INFLUENCE OF DRUGS ON FATIGUE 
 
 diminishing the accuracy of aim, especially three-quarters of 
 an hour after it was taken. These were, however, only single 
 observations, and the earlier experiments show that the varia- 
 tions from day to day with this method are very great. 
 
 I may now sum up the general results which have so far 
 been reached. In the case of muscular work, we have seen 
 that there is definite evidence that small doses, varying from 
 5 to 20 c.c. of absolute alcohol, have no effect on the 
 amount or nature of the work performed with the ergograph, 
 either immediately or within several hours of their administra- 
 tion, the results previously obtained by other workers being 
 almost certainly due to defects of experimental method. With 
 a larger dose of 40 c.c., there was evidence in one case, at 
 least of an increase in the amount of work under the in- 
 fluence of the substance ; but the increase was uncertain and 
 inconstant, and the possibility cannot be excluded that it was 
 due to disturbing factors. With larger doses than 40 c.c., 
 we have the work of Hellsten, showing a decided falling off 
 in the amount of work with a dose of 80 grammes. 
 
 In the case of mental work, the available evidence points 
 to a decrease in the amount of work under the influence of 
 alcohol when there is an effect at all ; but there are very 
 great individual differences, even the large dose of 100 c.c. 
 failing to show any effect in some persons. 
 
 All investigations on the action of alcohol on the capacity 
 for muscular work, and most of that on its action on the 
 capacity for mental work, have been directed to test the 
 effect of the drug over the period immediately following 
 its administration. As I have already pointed out, little 
 has hitherto been done in the investigation of its prolonged 
 action by comparing periods during which alcohol is taken 
 with periods of abstinence. From the practical point of 
 view, and especially from the point of view of the value of 
 the habitual use of alcohol as an article of diet, this latter line 
 of work is of far greater interest arid importance than 
 the former, but its experimental investigation is much more 
 difficult.
 
 INFLUENCE OF ALCOHOL ON MENTAL FATIGUE 101 
 
 The work which I have described in this and the last 
 lecture has been so much devoted to the study of method, and 
 the results have been so largely negative, that there is little 
 need for theoretical consideration. The most salient fact 
 which seems to require explanation is the combination of a 
 stimulating action of alcohol on muscular work with a 
 depressing action on mental work. It is true that these two 
 effects have not yet been demonstrated on the same person and 
 under the same conditions, and that even the separate actions 
 cannot yet be said to be placed beyond all dispute ; but some 
 observations may be cited which, while supporting the view 
 that increased amounts of muscular work may be done under 
 the influence of alcohol, at the same time help to explain its 
 nature. 
 
 The different mode of action on muscular and mental 
 activity suggests a double action of alcohol, such as I have 
 supposed to exist in the case of caffeine, and the first point to 
 be considered is whether we have any evidence of an action on 
 the isolated neuro-muscular mechanism, such as is well 
 established for caffeine. There is some evidence pointing to 
 there being such an action, and, further, that this is of a stimu- 
 lating kind. 
 
 Scheffer 1 has found that in the frog doses of alcohol amount- 
 ing to one- thousandth of the body -weight produce a very great 
 increase in the amount of work executed by the gastrocnemius 
 of that side of the body to which the alcohol is allowed access, 
 an action which continues for four hours, after which time there 
 ensues a diminution in the amount of work as compared with 
 the uninfluenced side of the body. As the result of experiments 
 with curare, Scheffer came to the conclusion that the action 
 was due to stimulation of the neural rather than of the 
 muscular part of the neuro-muscular mechanism, and he 
 suggests that this may be due to changes in the excitability 
 of the nerve fibres of the kind suggested by the experiments 
 of Waller. 
 
 A similar stimulating action of alcohol on the muscular 
 1 Arck.J. exp. Pathol. u. PharmahoL, 1900, Bd. xliv., S. 37.
 
 102 THE INFLUENCE OF DRUGS ON FATIGUE 
 
 activity of the frog has been found by Lee and Harrold. 1 
 Doses of 1 to 4 minims of a 10 per cent, alcohol per gramme 
 of the frog increased the amount of work in some cases by 
 more than 100 per cent. 
 
 The question whether this direct action which has been 
 shown to exist in the frog will also account for the increase 
 which has been found in man should be elucidated by the 
 results of electrical stimulation with the ergograph ; but, un- 
 fortunately, the work on this point is not only very scanty, 
 but contradictory, Lombard finding a decrease in the amount 
 of work, while Frey records an increase, and in the face of this 
 divergence we can only await the results of further inquiry. 
 
 In the only experiment in which I have found an increase 
 in the amount of work under the influence of alcohol this 
 increase occurred, not immediately after the administration of 
 the drug, but at an interval of more than an hour, and it 
 persisted for more than three hours after the alcohol had been 
 taken. This late and prolonged action is very suggestive of 
 the same kind of effect as that described by Scheffer, which, 
 it may be noted, lasted for four hours, and it seems possible 
 that a purely peripheral action, resembling that on the isolated 
 muscle-nerve preparation, may, at any rate, have contributed 
 to the increase. 
 
 It is probable, however, that this peripheral action is 
 complicated by a central action, and assuming for the moment 
 that alcohol at any rate, in some persons and with certain 
 doses does produce an increased output of work, the nature 
 of this central action may be briefly considered. 
 
 Kraepelin, 2 who believes that the effect of alcohol is 
 entirely central, ascribes the increase in the output of work 
 under its influence to the increased ease with which motor 
 impulses are set up under the influence of alcohol. He 
 apparently regards the increased work recorded in an ergo- 
 graphic curve as having the same cause as the increased talka- 
 tiveness and tendency to act on impulse which is characteristic 
 
 1 Arch. ital. de Biol, 1901, t. xxxvi., p. 101. 
 
 2 Psychologische Arbeiten, 1 1901, Bd. iii., S. 636.
 
 INFLUENCE OF ALCOHOL ON MENTAL FATIGUE 103 
 
 of alcoholic intoxication. The increased output of work 
 would, according to this view, be due to the removal of some 
 controlling influence, and we should expect in this case 
 that the contractions of an ergogram under the stimulating 
 influence of alcohol would be performed less regularly than 
 in the normal condition. 
 
 The only worker who has noted irregularities in the con- 
 tractions under the influence of alcohol is Hellsten, 1 but he 
 notes their presence only after the administration of very 
 large doses of alcohol large enough to produce a distinct 
 decrease in the amount of work. The observations on the 
 general condition of the subject W., described in Appendix IV., 
 show that in his case the regularity and delicacy of movement 
 were affected, though there is no evidence that the ergograms 
 themselves, or the contractions of which they are composed, 
 were less regular than usual. It may be noted, however, that 
 this general disturbance of movement was most pronounced 
 in the prolonged experiment of July, 1906, when the alcohol 
 did not produce any increase in the output of work. 
 
 That alcohol acts by removing some controlling influence 
 is suggested by the effect of mental fatigue on the capacity 
 for muscular effort. In the early work of Mosso with the 
 ergograph it was found that in some persons mental fatigue 
 could be associated with a decided increase in the output 
 of work. In the case of one of his assistants, Professor 
 Aducco, it was found 2 that the fatiguing, though at the same 
 time exciting, task of giving an inaugural lecture increased 
 the capacity for muscular work as tested by the ergograph, 
 and I have found that I am an example of this mode of 
 reaction in a condition of mental fatigue. 
 
 Repeated observations have shown that, when in a state 
 of mental fatigue, I can execute ergograms distinctly above 
 my average amount. In most, if not all, of the cases in which 
 this increase has occurred, the mental fatigue has been induced 
 by work which was decidedly interesting, and it is probable 
 
 1 Skand. Arch.f. Physiol., 1904, Bd. xvi., S. 184. 
 
 2 Mosso, Fatigue,' London, 1904, p. 244.
 
 104 THE INFLUENCE OF DRUGS ON FATIGUE 
 
 that the increased capacity for muscular work found by 
 Aducco and myself is usually due to the prolongation of the 
 effect of this interest. 
 
 In at least one case, however, in which this kind of 
 reaction occurred all trace of interest had so completely 
 disappeared that it would seem very unlikely that the effect 
 could have been due to this latter cause. At this time I was 
 recording an ergogram every night before going to bed, and a 
 good example of the average ergogram at this period of the 
 day is that marked A in Fig. 13. The curve marked B was 
 
 FIG. 13. 
 A, Normal; B, Mental fatigue ; C, Alcohol. 
 
 A. B. C. 
 
 Work (kilogrammetres) 4-8(100) (r7 (139) 8-3(172) 
 
 Number of contractions 38 (100) 46 (121) 49 (129) 
 
 Average height (centimetres) ... 3'2 (100) 3-6(113) 4-2(131) 
 
 taken one night after a very fatiguing day, when I had read 
 a paper in the evening and had reached my rooms at night so 
 tired that it was only by a great effort that I brought myself 
 to carry out my usual task of recording an ergogram. I 
 seated myself, however, at the ergograph, and, to my great 
 surprise, produced the curve B, very much larger than usual. 
 I have added in the figure a third ergogram, C, taken after a 
 dinner-party, at which I had had two glasses of champagne. 
 This ergogram, the largest I have ever recorded, probably 
 owes quite as much to the social intercourse and excitement 
 of taking an ergogram under these circumstances as to any 
 physiological action of the champagne, but this latter factor
 
 INFLUENCE OF ALCOHOL ON MENTAL FATIGUE 105 
 
 was probably in operation to some extent. Thus we see that 
 two very different conditions, enormously different subjectively, 
 can produce very similar effects on the capacity for muscular 
 work, as tested by the ergograph. 
 
 I bring forward this isolated, and it may be thought 
 trivial, observation, because it seems to me that this similarity 
 of action of alcohol and mental fatigue may give the clue to 
 the explanation of the effect of the former. 
 
 The observation seems to show that a state of pronounced 
 fatigue can have just the same effect on the capacity for 
 muscular work as is produced by alcohol. In my condition 
 of mental fatigue there can be no doubt that my capacity for 
 the performance of mental work was lowered, and we have, 
 therefore, in this observation an example of the same associa- 
 tion of increased muscular activity with lower mental activity 
 which there is reason to suspect is characteristic of the effect 
 of alcohol. The observation strongly suggests that at least 
 one action of alcohol may be to depress the activity of some 
 higher nervous mechanism which serves to control and keep 
 in check muscular activity, and that when this control is 
 weakened, increased amounts of work can be executed. 
 
 I may, perhaps, consider for a moment the possible nature 
 of this process of removal or weakening of a normal control. 
 The idea which occurs most readily is that the weakening of 
 control is due to the dulling of the sensations of fatigue, and 
 that the action of alcohol is of this kind is rendered probable 
 by the existence of the feeling of ease which has been 
 recorded by many of those who have worked with the ergo- 
 graph under the influence of alcohol. Such dulling might 
 occur in two ways it might be due to the direct influence of 
 alcohol on the sensory centres, or it might be due to its in- 
 direct effect in promoting general excitement, during which 
 the sensations aroused by the fatiguing work would remain 
 below the threshold of consciousness. 
 
 There is another possible factor in the production of the 
 stimulating effects of alcohol, which may be briefly considered. 
 We have seen that emotional conditions have a very pro-
 
 106 THE INFLUENCE OF DRUGS ON FATIGUE 
 
 nounced influence on the ergographic curve, and it is almost 
 certainly through its emotional aspect that interest acts. It 
 is also probable that pleasurable emotions have a greater 
 effect on the capacity for work than unpleasant emotions. It 
 is an undoubted fact that alcohol in most people produces a 
 pleasurable emotional condition, and it is the production of 
 this condition which has been the chief motive in making the 
 use of this substance so widely prevalent among mankind. 
 It is possible that there is some kind of relation between the 
 occurrence of pleasurable emotion and the increase of the 
 capacity for muscular work. The exact mechanism by which 
 the emotional condition acts is doubtful, but here again there 
 is the possibility that it may be through dulling, absolutely 
 or relatively, of the sensations of fatigue. 
 
 One provisional conclusion may be stated. We have seen 
 that the condition of muscular activity may be affected in 
 an apparently identical fashion by alcohol and by pronounced 
 mental fatigue. This similarity of action should make one 
 very chary in concluding that any stimulating effect of alcohol 
 on muscular activity is an indication of a physiological action 
 which is beneficial to the organism as a whole. But here I 
 should like to say one word to those who are interested in the 
 action of alcohol from the practical point of view. It is 
 obvious that the problem of the nature of the action of alcohol 
 on muscular activity is one of very great complexity, for the 
 elucidation of which much more work is necessary ; and until 
 this has been done, those interested either in the therapeutical 
 or in the dietetical value of alcohol should hesitate before 
 drawing any practical conclusions. 
 
 Before I leave the subject of alcohol, I must consider 
 briefly a problem stated at the beginning of this lecture. Most 
 of the previous work on alcohol has been done by using this 
 drug in one of the forms in which it is employed in everyday 
 life, and it is open to anyone to say that the stimulating 
 effects of small doses which have been recorded by other 
 workers are due, not, as I believe, to the neglect of the factors
 
 INFLUENCE OF ALCOHOL ON MENTAL FATIGUE 107 
 
 of interest, etc., but to the action of other constituents of the 
 alcoholic beverages which have been used. 
 
 We have already seen (p. 81) that in one subject a dose 
 of whisky may produce an effect which is wholly absent with 
 an equivalent dose of absolute alcohol, and though I believe 
 that the difference was due to the presence of interest with 
 the whisky, and its absence with the pure alcohol, this has 
 not yet been demonstrated. A positive opinion on this point 
 cannot be expressed till further experiments on this problem, 
 now being carried out by Mr. Webber, have been concluded.
 
 LECTURE IV (continued] 
 ACTION OF COCAINE, STRYCHNINE, TOBACCO, ETC. 
 
 Action of cocaine, strychnine, and tobacco ; historical ; new experiments 
 with strychnine and tobacco The work of Rossi and Fere 
 Action of formates, orchitic extract, 'fatigue antitoxin' and muscle 
 extract Conclusions ; importance of control in method ; results 
 of new experiments and suggestions for future work Analysis of 
 fatigue-process Individual differences. 
 
 I CAN now turn to* the scanty record of work on the action of 
 other drugs in fatigue. 
 
 COCAINE. 
 
 Of all the drugs which are supposed to influence the con- 
 dition of fatigue, none has a greater reputation than cocaine. 
 It is stated that the natives of South America are enabled to 
 perform great feats of endurance under its influence, and to 
 withstand severe hunger and thirst owing to its effect. This 
 popular reputation is not belied by the results of experiment. 
 The fullest work on the drug was published by Ugolino 
 Mosso 1 in 1890, in which ergographic observations on himself 
 formed only part of a systematic investigation into the physio- 
 logical action of the drug. Experiments on dogs showed that 
 in doses of 0*0005 gramme per kilogramme of body- weight of 
 the animal no effect was produced on muscular activity ; that 
 O'OOl gramme per kilogramme had a stimulating effect; and 
 that doses of 0*003 gramme per kilogramme diminished the 
 amount of work performed by the muscle, or produced complete 
 paralysis, the paralytic effect being very sudden when the dose 
 was strong. Before this time Aschenbrandt 2 had found that 
 
 1 Archivf. d. ges. Physlol, 1890, Bd. xlvii., S. 553. 
 - Deutsclie med. IVochenschr., 1883, S. 730. 
 108
 
 ACTION OF COCAINE 109 
 
 doses of O'l gramme cocaine increased the resistance of soldiers to 
 fatigue, and Freud 1 had shown that doses of O'l to O'l 5 gramme 
 increased the strength of contractions with the dynamometer. 
 Mosso found that a dose of O'l gramme taken by the stomach 
 had a decided effect on the amount of work produced by 
 means of electrical stimulation of the muscle, the increase reach- 
 ing 23 per cent. Further observations showed that the stimu- 
 lating effect became more decided if the muscle were fatigued. 
 After work had been done to exhaustion by means of electrical 
 stimuli, a dose of 0'05 gramme had a very decided effect on 
 the contractions produced by electrical stimulation, and a still 
 more marked effect on voluntary contractions. Mosso also 
 compared the effect of the drug in the fasting condition and 
 after violent and prolonged exercise. In each state the drug 
 had a most pronounced beneficial effect, both on the general 
 condition, and on muscular activity as shown by the ergo- 
 graph, the amount of work being doubled both with electrical 
 and voluntary contractions. He concluded that the beneficial 
 effect is at any rate, in part due to the direct action of the 
 cocaine on the muscle, and that the drug is able to abolish the 
 effects of fatigue directly, though he does not suggest any 
 exact mechanism by which this can have been brought about. 
 He combats the idea which had been previously suggested 
 that the stimulating effect of cocaine is due to its action on the 
 sensory side of the nervous mechanism involved, leading to a 
 dulling of the sensations of fatigue ; but it must be noted that 
 one of the most striking features of his own paper is the very 
 graphic account of the disappearance of extremely severe sensa- 
 tions of fatigue under the influence of the drug. The next work, 
 by Sobieranski, 2 on the action of cocaine I know only through 
 an abstract, the original having been published in Russian. 
 This paper is noteworthy for the fact that control injections 
 were given to eliminate the effect of suggestion, which might 
 be produced by the injections of cocaine. Sobieranski differed 
 totally from Mosso in finding that the drug had no effect on 
 
 1 Wiener med. Wochenschr., 1885, S. 129. 
 
 2 CentraKl.f. Physiol., 1896, Bd. x., S. 126.
 
 110 THE INFLUENCE OF DRUGS ON FATIGUE 
 
 the work performed by means of electrical stimuli, while having 
 a distinct effect on the work performed by voluntary contrac- 
 tions ; and he concludes that the drug acts solely through 
 the central nervous system. No indication is given in the 
 abstract of the doses employed, and in the absence of know- 
 ledge about this and other experimental conditions, critical 
 comparison is impossible. Another work on cocaine is that 
 of Benedicenti, 1 who chewed the leaves of coca, and found 
 that in consequence the amount of work with the ergograph 
 was not only doubled, but that the effect lasted longer than 
 that of other substances (tea, coffee, mate", and guarana) which 
 had been tested under similar conditions. 
 
 It is probable that part of the increase which has been 
 described as the effect of cocaine has been due to interest, 
 etc., which Sobieranski alone attempted to exclude ; but there 
 can be no doubt that, in addition, there is a physiological 
 effect on muscular activity, and it would seem that this stimu- 
 lating action is most pronounced in the presence of fatigue, 
 and especially of general fatigue. Its mode of action remains 
 doubtful, and, in view of the conflict of evidence shown by 
 the work of Mosso and Sobieranski, it must be left an open 
 question how far its effect is due to a direct action on muscle, 
 and how far to some action on the central nervous system. 
 It will be noted that we met with a similar conflict of 
 evidence in dealing with the effect of alcohol on the muscular 
 contractions produced by electrical stimulation, and it is 
 evident that this method of investigation is greatly in need of 
 further study. 
 
 STRYCHNINE. 
 
 The action of this drug has been tested with the ergograph 
 by Rossi 2 and Fere". The former found decided increase in 
 the amount of work, the effect being exclusively on the number 
 of the contractions. His method was the same as that used 
 
 1 Moleschotfs 'Untersuch., 1 1899, Bd. xvi., S. 170. 
 
 2 Rivista sper. di Freniatria, 1894, vol. xx., p. 464, and Arch. ital. 
 de BioL, 1895, t. xxiii., p. 56.
 
 ACTION OF STRYCHNINE 111 
 
 in his alcohol work. Ergograms were recorded for an hour, 
 and he found no reaction at the end of this time. 
 
 Fere 1 tried the effect of a dose of 1 milligramme injected 
 subcutaneously, and found a decided increase, followed by a 
 fall below the normal, such as he finds with nearly all other 
 drugs. When the strychnine was injected immediately before 
 the ergographic record was taken, there was an initial de- 
 crease ; but this was due, doubtless, to the act of injection, 
 and not to the effect of the drug. 
 
 Mr. P. C. V. Jones 2 has carried out an experiment with 
 strychnine on the same general lines as the other work 
 recorded in these lectures. Six sets, each of six ergograms, 
 were recorded the first two at intervals of half an hour, and 
 the remainder with hourly intervals, so that the effect of the 
 drug was followed for about five and a half hours. The 
 whole experiment lasted for fifteen days, on four of which 
 7 minims of Liq. Strychninae (4*2 milligrammes of hydrochloride 
 of strychnine) were taken by the mouth, on four days the dose 
 was 3 minims (1'8 milligrammes), and on the remaining days 
 there was taken either a mixture containing gentian, which 
 was quite indistinguishable in taste from the strychnine, or no 
 dose at all. The experiment was complicated by the occurrence 
 of a great diminution in the amount of work after it had 
 been continued for some days, the diminution being especially 
 great in the first ergograms of each day. This diminution 
 did not take place gradually, but came on fairly rapidly after 
 only three doses of strychnine had been taken, this making it 
 necessary to consider separately the earlier and later portions 
 of the experiment. 
 
 In each portion the drug produced an obvious effect. In 
 the first, there was a rapid rise in the amount of work on 
 the days on which the larger dose was taken, from which 
 point there was a gradual fall ; but the curve did not pass 
 below the normal till the fifth, to fall still furth'er in the 
 sixth. The curve for the smaller dose rose less rapidly, and 
 
 1 ' Travail et Plaisir, 1 p. 297. 
 
 2 Journ. Phy*ioL, 1908, vol. xxxvi., p. 435.
 
 112 THE INFLUENCE OF DRUGS ON FATIGUE 
 
 only fell below the normal during the last set. The form of 
 the curve in each case was determined chiefly by the number 
 of contractions. 
 
 In the second portion of the experiment there was a very 
 great increase in the amount of work in the second set on 
 the days on which the larger dose was taken, the amount 
 being more than double that of the normal days ; but here 
 again the strychnine curve falls below the normal in the 
 last two sets. The dose of 3 minims produced a smaller 
 increase, followed by a fall below the normal, but here the 
 difference was not very great. The action in the second 
 portion of the experiment is more on the height than on 
 the number of the contractions, this effect being doubtless 
 associated with the diminution in the height of the early 
 contractions, which seems to have been due to the cumulative 
 action of the drug. 
 
 The effect of the strychnine is thus to produce a decided 
 increase, followed by a reaction. 
 
 TOBACCO. 
 
 The only other drug on which much work has been done from 
 the point of view of fatigue is tobacco. The influence of this 
 drug has only been tried when administered in the customary 
 way by smoking, and I need hardly point out how in such a 
 case the factors of interest and sensory stimulation must have 
 full play. Both these factors always, so far as we know, 
 produce an increase in the amount of work, and, therefore, it 
 is significant that the evidence for the deleterious influence 
 of this drug on the capacity for muscular work is perhaps 
 more definite than in the case of any other. 
 
 The first worker with tobacco was Lombard, 1 who found 
 that smoking had a very decided effect on the strength of 
 voluntary muscular contractions. He found that one cigar of 
 moderate strength could diminish the amount of work from 
 10 '4 to only 2'1 kilogrammetres, the depressing effect passing 
 
 1 Jcnirn. Physiol., 1892, vol. xiii., p. 44.
 
 ACTION OF TOBACCO 113 
 
 off soon after he ceased to smoke, though full power was not 
 regained till more than an hour after the cigar had been laid 
 aside. It is noteworthy that this result was wholly unex- 
 pected by Lombard, who had previously thought, as the 
 result of general observation, that tobacco stimulated muscular 
 activity. Lombard also tested the influence of smoking on 
 the strength of the contractions produced by electrical stimu- 
 lation, and found that tobacco in this case had no effect, so 
 that he concluded that the depressing effect of the tobacco 
 was on some part of the central mechanism. 
 
 The next research on the effect of tobacco is by Vaughan 
 Harley. 1 This worker found that on himself the effect of 
 tobacco was much less pronounced than had been stated by 
 Lombard, but that on the whole its action was detrimental, 
 though the effect was often within the variations which are 
 found at different periods of the day. In 1901 the influence 
 of tobacco was tested by Hough 2 on the work executed by 
 means of the spring ergograph or dynamograph. He found 
 no change in the constant fatigue level, but the fall to this 
 constant level took place more slowly than on the normal 
 days. This is the only experiment with drugs by this method 
 which has been recorded, and we have no means of telling 
 whether the opposite results of Hough and Lombard are due 
 to the difference of method, or whether they depend on 
 difference of individual susceptibility or other variation of the 
 conditions of the experiment. The effect of smoking cigarettes 
 has been investigated by Fere, 3 who found an initial increase, 
 followed by a fall below the normal, when the subject began 
 to smoke five minutes before the experiment began ; but 
 when the record was taken fifteen minutes after beginning to 
 smoke, the action was purely depressing. In this case a second 
 cigarette produced a very decided though transient increase 
 after an interval. 
 
 I am able to give the result of brief experiments on two 
 
 1 Journ. Physiol.) 1894, vol. xvi., p. 118. 
 
 2 Arner. Journ. PhysioL, 1901, vol. v., p. 240. 
 
 3 'Travail et Plaisir,' p. 316.
 
 114 THE INFLUENCE OF DRUGS ON FATIGUE 
 
 subjects to test the effect of smoking a cigar after dinner. 
 In one subject the work of two days with smoking was 
 compared with that of three normal days, and in the second 
 subject there were two days with smoking and two without. 
 Ten ergograms were recorded at intervals of five minutes in 
 one case and twelve in the other without any pause, and the 
 smoking began after the first ergogram. Any kind of disguise 
 was of course impossible. 
 
 The smoking was distinctly pleasant, and there was 
 naturally strong sensory stimulation. All that we know of 
 the effects of these two conditions would lead us to expect a 
 very decided and immediate increase in the amount of work, 
 altogether apart from any physiological effect, and it cannot, 
 therefore, be regarded as without significance that any such 
 increase was completely absent. There was no trace of any 
 immediate increase, and on the whole a smaller amount of 
 work was done on the days on which the cigars were smoked 
 than on the intervening normal days. The decrease was not 
 great, and probably not beyond the limits of normal varia- 
 tion, and the point I wish to emphasize is that there seemed 
 to have been an inhibition of the effects normally produced 
 by such a pleasurable and stimulating activity as that of 
 smoking. 
 
 We thus see that tobacco comes out from the ergographic 
 test less creditably than the other drugs we have been 
 considering, though here, as in other cases, much more work 
 is necessary before we can expect to understand the mode of 
 its action. It is, however, noteworthy that the prohibition 
 of this substance during training for feats involving muscular 
 activity seems to show that this depressing action on the 
 strength of muscular contractions has been recognized by 
 general experience.
 
 ACTION OF OTHER DRUGS 115 
 
 OTHER DRUGS. 
 
 I have now considered the action of five drugs caffeine, 
 alcohol, cocaine, strychnine, and tobacco. Very little work 
 has been done on any others, and most of this is due to two 
 investigators, Eossi 1 and Fere'. 2 
 
 The Italian worker found that some of the substances he 
 tested increased the amount of work, while others had a 
 depressing effect. The former class, which he calls hyper- 
 kinetic, included caffeine, cocaine, alcohol, and strychnine, 
 and also absinthe, camphor, and ether. The other class, 
 called hypokinetic, included bromide of potassium, chloral 
 hydrate, duboisine, hyoscyamine, opium, and morphine. 
 
 It will be noticed that this division into hyperkinetic and 
 hypokinetic substances corresponds with the customary division 
 into stimulants and sedatives. It would appear that there is 
 a correlation between the action on muscular activity and the 
 action on other vital processes. Among the hyperkinetic 
 substances of Rossi, we have considered the action of three 
 fully, and have seen that behind their apparent similarity of 
 action there are very decided differences, and fuller investi- 
 gation of the other drugs investigated by Eossi will probably 
 render further subdivisions of his classes necessary. 
 
 The worker who has experimented most widely with drugs 
 is Fere, but his work is unfortunately not of a kind to inspire 
 much confidence. Nearly every drug is found to produce 
 the same kind of effect an initial increase followed by a fall 
 below, the normal, opium being, perhaps, the only substance 
 among the many tested which differed greatly from the rest 
 in showing a more pronounced depressing effect. Eecently 
 Fere 3 has published a paper, in which he shows that just 
 the same kind of effect as that produced by taking these 
 
 1 Rivista sper. di Freniatrla, 1894, vol. xx., p. 442. A resume is 
 given in Arch. ital. de BioL, 1895, t. xxiii., p. 49. 
 
 2 Most of Fere's work has been brought together in his book, 
 1 Travail et Plaisir, 1 Paris, 1904. 
 
 1 Revue de Medecine, 1906, t. xxvi., p. 1. 
 
 8 9.
 
 116 THE INFLUENCE OF DRUGS ON FATIGUE 
 
 drugs is also found after both tasting and swallowing 20 c.c. 
 of a 20 per cent, solution of sugar ; and Fdre even believes 
 that this substance is an accelerator of fatigue, as we have 
 seen he supposes to be the case with caffeine and alcohol. It 
 is very difficult to believe that the effects described by Fere" 
 can be due to the physiological effects of the substances he 
 has used, and it is probable that in, at any rate, most cases 
 his results give no indication of the true physiological action 
 of the drugs he has used, but are entirely or predominantly 
 due to the influence of interest on his muscular activity. 
 
 A few other researches on the action of drugs or other 
 substances may be briefly mentioned. Clement 1 has found a 
 decided increase in the amount of work with the ergograph 
 after taking for three days formic acid neutralized with 
 bicarbonate of soda ; but there is no evidence that he did 
 anything to eliminate the influence of interest. 
 
 The effect of orchitic extract on muscular activity has 
 been tested with the ergograph by several workers, 2 most of 
 whom have not employed any adequate control ; but a very 
 decided exception is to be found in the work of Pregl, 3 who 
 gave the extract subcutaneously, and used control injections 
 of glycerin and normal saline solution. Pregl desired to test, 
 not the immediate effect of the extract, but its action over a 
 prolonged period, and two subjects were used, one of whom 
 was given the extract and the other the control injection, both 
 being entirely ignorant of the aim and method of the experi- 
 ment. It was found that the subject into whom the orchitic 
 extract was injected executed a distinctly larger amount of 
 work than in a previous normal period, while the subject who 
 received only the glycerin did rather less. At the close of 
 the series orchitic extract w r as injected for a period into the 
 subject who had previously received the control injection, 
 the extract producing a most decided eftect on the amount of 
 work. 
 
 1 La Semaine MecL, 1904, p. 100. 
 
 2 See Zoth, Arch. f. d. i*e*. PhysioL* 1896, Bd. Ixii., S. 335, etc. 
 
 3 Arch. /. d. ges. Physiol, 1896, Bd. Ixii., S. 379.
 
 ACTION OF OTHER DRUGS 117 
 
 Another research is one on the body isolated by Weichardt, 1 
 which he believes to be the antitoxin of fatigue. Weichardt 
 only tested the effect of this substance on one person a girl 
 and found an increase after its administration. He states 
 that the influence of suggestion was excluded by giving the 
 supposed antitoxin in a pastille, the nature of which was 
 unknown both to the patient and her doctor, and he evidently 
 believed that by this device he had excluded any possible 
 disturbing factor of a psychical nature. 
 
 The last research to be mentioned is one by Slade 2 on the 
 action of Liebig's extract of muscle, which was tested by the 
 same general method as that used in other work recorded in 
 these lectures, three sets of ergograms being recorded at half- 
 hour intervals. A complete disguise was here impracticable, but 
 interest and sensory stimulation were made as equal as possible 
 by taking the extract on some days, white of egg in hot water 
 on other days, and hot normal saline solution on others. The 
 days on which the Liebig's extract was taken in doses of 
 15 grammes gave amounts of work which followed almost 
 exactly the same course in relation to the initial ergogram 
 as on the other days on which albumin or the saline solution 
 were taken. The experiment gave a very striking demon- 
 stration of the closeness of correspondence which may be 
 obtained between the curves representing the course of work 
 of three groups of days when the general conditions are kept 
 constant. The negative result of this experiment affords a 
 valuable guarantee of the value of the ergographic method, 
 and of the reality of the positive effects which have been 
 obtained with more active substances. 
 
 CONCLUSIONS. 
 
 The chief interest of the work which has been recorded in 
 these lectures lies in its bearing on method. It has been my 
 chief object to illustrate the principles which should be followed 
 
 1 Munch, rned. Wochenschr., 1904, Jg. li., S. 2125. 
 
 2 Journ. PhysioL, 1907, vol. xxxv., p. 163.
 
 118 THE INFLUENCE OF DRUGS ON FATIGUE 
 
 in the study of pharmacology when the subject is the living 
 man. One point of method has, I hope, been clearly estab- 
 lished viz., the absolute necessity that experiments with 
 drugs on man should be carried out with adequate con- 
 trol, designed to exclude the influence of interest, sensory 
 stimulation, and suggestion. Further, I have been able to 
 show that this control is possible even in the case which 
 seemed to me at first most hopeless that of the administra- 
 tion of alcohol by the mouth. It is possible so completely to 
 disguise the characteristic flavour that the subject of the 
 experiment may be quite unaware whether he is taking alcohol 
 or some inactive substance. 
 
 Although I wish to lay stress chiefly on the importance 
 of my results in connexion with method, I do not wish to 
 neglect the actual contributions to the knowledge of the 
 action of drugs, which are provided by the experiments I 
 have described in these lectures. In the case of alcohol the 
 chief result has been negative, having shown that the effects 
 previously recorded as those of small doses of alcohol are not 
 true physiological effects, but merely the consequences of 
 faulty methods of investigation. With larger doses of this 
 substance no conclusive results have so far been reached, but 
 enough has been done to point the way for further work, 
 which is now being carried on by Mr. Webber. 
 
 The chief result of the work with caffeine is the strong 
 suggestion it affords that this drug has a double action on 
 the mechanism concerned in muscular work, while the work 
 of Mr. Jones with strychnine provides a very striking demon- 
 stration of the stimulating action of a drug. 
 
 The negative results with small doses of alcohol and the 
 inconstant results with larger doses might possibly be held 
 to suggest that the ergographic method is ill suited for the 
 study of the action of drugs on fatigue, and the great value 
 of the experiment with strychnine and of my own final 
 experiment with caffeine is that they enable us to reject 
 such a suggestion decisively. These results show that the 
 ergographic method is capable of bringing out drug-effects in
 
 CONCLUSIONS 119 
 
 the most decided manner, and a study of all the work recorded 
 in these lectures can leave little doubt that the negative 
 effect with small doses of alcohol is due to the absence or to 
 the very small amount of any influence on the process of 
 muscular fatigue. 
 
 I should like here to repeat and emphasize the statement 
 that the work described in the lectures has dealt almost 
 entirely with one department of the subject viz., the in- 
 vestigation of the immediate action of drugs on the physio- 
 logical mechanism taken as a whole. I have hardly touched 
 on the question of the effects of these drugs when taken 
 over prolonged periods, nor have I dealt at any length with 
 the methods by which we may hope to effect an analysis 
 of the general action into the constituent actions on different 
 parts of the organism. I have brought forward evidence in 
 favour of complexity of action in the cases of both alcohol 
 and caffeine, but have not attempted to apply these methods 
 of analysis viz., the investigation of the action of the drugs 
 on the fatigue induced by electrical stimulation of nerves 
 in man, and the study of the action of drugs on animals 
 or on the different parts of the isolated neuro-muscular 
 mechanism. 
 
 One interest of the use of drugs from this point of view 
 arises out of the expectation that it may throw light on the 
 analysis of the fatigue-process itself. It was from interest in 
 this latter problem that I first undertook experiments with 
 drugs. It seemed to me that in the use of drugs lay the 
 chief hope for the discovery of the seat of muscular fatigue. 
 If we could find a drug which could be shown to be without 
 action on the isolated peripheral mechanism, but which 
 influenced the ergogram recorded by the living man, we 
 should have a definite instrument for the detection of the 
 part taken in the formation of the ergogram by central 
 factors. On beginning work I soon obtained evidence of the 
 unsatisfactory nature of previous researches on the capacity 
 for muscular work in man, and I have so far been occupied in 
 repeating these researches with methods designed to exclude
 
 120 THE INFLUENCE OF DRUGS ON FATIGUE 
 
 what I believe to be disturbing factors. The result has made 
 it clear that neither in alcohol nor in caffeine have we a drug 
 with a simple action, and they are, therefore, ill suited for the 
 purpose of the proposed analysis. 
 
 Such a substance is probably to be found in strychnine, 
 but at present we have too little work with this substance to 
 enable us to define its mode of action on the work executed 
 with the ergograph, the experiment described in this lecture 
 showing an action on the number of contractions at one time 
 and on the height at another. 
 
 It is in this differential action on number and height of 
 the muscular contractions that the means of analysis have so 
 far been sought. Kraepelin believes that action on the 
 nervous system shows itself predominantly by an effect on 
 the number, while action on the muscular system affects 
 chiefly the height of the contractions. Some of the facts 
 recorded in these lectures seem to be in agreement with this 
 view. In my last caffeine experiment there can be little 
 doubt that the effect was due to the central action of the 
 drug, and in this experiment the increase was almost entirely 
 on the number of contractions ; and in the earlier and less 
 complicated part of Mr. Jones's experiment with strychnine, 
 which almost certainly has a purely central action, it was also 
 the number of contractions which was increased. 
 
 It would be very dangerous, however, to conclude that 
 because in some cases a drug, acting through the nervous 
 system, increases the number of contractions, therefore such 
 an effect on number demonstrates a central action. It is 
 very doubtful whether the kind of evidence brought forward 
 in these lectures can ever furnish satisfactory data for the 
 analysis of the physiological processes concerned in muscular 
 fatigue, which must rather be sought in the comparison of 
 the work performed volitionally with that executed when the 
 muscles are made to contract by electrical stimuli applied to 
 the peripheral nervous mechanism, when any effect on central 
 activity can be excluded with certainty. But few observations 
 of this kind have hitherto been made, and those few are very
 
 CONCLUSIONS 121 
 
 unsatisfactory, the whole technique of this mode of attacking 
 the problem requiring to be reconsidered. 1 
 
 In conclusion, I should like to refer to one aspect of the 
 subject, an aspect which is of especial interest to myself. 
 The branch of psychology in which I am chiefly engaged is 
 that to which the name of individual psychology is usually 
 given. It is that branch of psychology which deals with the 
 differences in the mental constitution of different people, and 
 by an extension of the term to the differences which charac- 
 terize the members of different races. The physician is 
 interested in this subject, owing to its bearing on those 
 differences of temperament or constitution which influence 
 the incidence of disease and the reaction to therapeutical 
 measures, and I had this point among others in my mind 
 when I stated at the beginning of these lectures that I hoped 
 to show how the science of experimental psychology might be 
 of service to medicine. Of the various means by which we 
 may study these individual differences none is more hopeful 
 than that which may be called the pharmacological method. 
 
 It is a matter of general experience that different persons 
 are susceptible in very different degrees to the influence of 
 drugs. The material I have brought forward in these lectures 
 will have been sufficient to show how careful we should be in 
 ascribing such differences to definite variations of physiological 
 constitution. There can be little doubt that many of the 
 differences which have been found by previous workers are due 
 to variations in the part played by the psychical factors which 
 have been allowed to complicate most work on this subject. 
 In the experiments recorded in these lectures, however, 
 these disturbing factors have been excluded, and yet there 
 have been found at any rate, in the case of caffeine very 
 striking divergencies in action in the two persons tested, and 
 there can be little doubt that these are due to a definite 
 difference in the incidence of the action of the drug. These 
 
 1 In the older observations with the earlier forms of Mosso's ergo- 
 graph it is very improbable that the same muscles were in action 
 throughout the two kinds of experiment.
 
 122 THE INFLUENCE OF DRUGS ON FATIGUE 
 
 experiments leave little doubt that variations in the action 
 of drugs on different persons may have their basis in deeply- 
 seated physiological variations, and I believe that the study 
 of these variations of susceptibility may do more than perhaps 
 any other line of work to enable us to understand the nature 
 of temperament and the relation between the mental and 
 physical characters which form its two aspects.
 
 APPENDIX I 
 FORM OF THE CURVE REPRESENTING THE COURSE OF FATIGUE 
 
 IT is usually supposed that the course taken by the process of fatigue 
 may be represented by a curve which remains approximately level for a 
 time and then falls more or less rapidly, corresponding to a diminution 
 in the amount of work, this idea as to the form of the curve being 
 probably based on the nature of the ergogram of Mosso, which has 
 usually been supposed to represent the course of the normal process of 
 fatigue. 
 
 It has been seen (p. 4) that three different methods of studying 
 the process of muscular fatigue agree in showing a diminution of 
 capacity coming on soon after beginning to work, so that the curve falls, 
 at first rapidly and then more slowly, till it passes into a horizontal line 
 representing a condition in which the amount of work which can be 
 performed remains constant for a considerable time. Such a curve, with 
 its concavity upwards instead of downwards, which is obtained with the 
 dynamograph, agrees in its general features with that found by Treves 
 by means of his ergograph with variable weight ; and, as I have pointed 
 out, the ergograph with constant weight gives the same result if 
 attention be paid to the course of the work of a series of ergograms 
 and not to that of a single ergogram. To show to how constant 
 a level a series of ergograms may attain, I give figures for two sets of 
 observations in which ergograms were performed at intervals of two 
 minutes without the breaks which I have usually adopted to demonstrate 
 the action of drugs. In an experiment in which Mr. Webber recorded 
 ergograms at intervals of two minutes for about three hours, the figures 
 for the average ergograms of three normal days expressed in kilogram- 
 metres ran as follows : 3'4, 2'9, 2'7, 2'3, 2'3, 2'2, 2'2, 2-1, 1'8, 2'0, 2'0, 
 2-0, 1-7, 1-6, 1-6, 1-8, 1-5, 1 -9, 2'0, 2'1, 2'0, 1-9, 2'0, 2'0, and so on. In 
 a similar series by myself the work of the ergograms ran as follows : 3*3, 
 4-1, 4-6, 5-0, 5-3, 3-2, 4'5, 3'2, 4'3, 3'4, 4'0, 3*2, 3-1, 3-1, 3-1, 3-1, 3'2, 
 3-2, 3-0, 3-0, 3-0, 3-0, 3-1, 3-1. This series thus showed at first the 
 irregularities which characterize my work with the ergograph, but finally 
 settled down to a constant level. 
 
 123
 
 124 THE INFLUENCE OF DRUGS ON FATIGUE 
 
 Three different methods thus agreeing in the demonstration of the 
 course of normal muscular fatigue, the question arises whether mental 
 fatigue does not follow the same course, and there is much reason to 
 believe that it does. One of the most constant features of the curve of 
 work obtained by any of the Kraepelin methods is a fall in the second 
 five minutes, often continuing into the third period of five minutes. 
 This fall has usually been ascribed to the effect of spurt, which un- 
 doubtedly contributes to the formation of this early portion of the curve 
 of work. Recent research has shown that, when work by KraepelirTs 
 methods is carried out for short periods of ten minutes, 1 there is evidence 
 of a diminution of capacity which would seem to be due to fatigue ; and, 
 if so, part at least of the early fall of the curve must be due to the 
 presence of this factor, the rise of the curve, due to practice, only showing 
 itself after the fatigue process has reached what would, in the absence 
 of practice, have been its constant level. 
 
 The new method of McDougall would seem to afford a means of 
 putting this to the test. Introspection, when using this method, gives 
 one the impression that there is an early diminution in the power of 
 keeping up the attention to the high level demanded by this method, 
 and it would seem that this early fall is followed by a period in which 
 there is a more or less constant level of accomplishment. We have not 
 yet sufficient data to enable us to tell whether the objective record 
 corresponds with the subjective experience, but experiments now in 
 progress with new apparatus (see Appendix II.) may be expected to show 
 the nature of the curve representing the course of mental fatigue. 
 
 1 Speclit, Arch. f. d. ges. Psychologic, 1904, lid. iii., S. 24o ; and Wimms, Brit. 
 Journ. PsyckoL, 1!)07., vol. ii. 3 p. 15;3 ; Hylan and Kraepelin, ' Psychologische 
 Arbeiten/ 1904, Bd. iv., S. 454.
 
 APPENDIX II 
 
 NEW APPARATUS FOR THE APPLICATION OF MCDOUGALL'S 
 METHOD OF STUDYING MENTAL FATIGUE 
 
 THE apparatus used by Mr. McDougall 1 consisted of a large rotating 
 cylinder, round which was placed a sheet of paper covered with eight 
 rows of dots, which, when the cylinder rotated, passed in rapid succession 
 behind an aperture in a screen placed before the cylinder. This method 
 only allowed work to be continued for a limited time, amounting in the 
 experiments recorded in these lectures to about three minutes. Further, 
 the act of moving from one row to the next formed a disturbing factor, 
 which might either distract the worker or act as an incentive to 
 spurt. The chief feature of the new apparatus 2 is the use of 
 a continuous Morse tape on which dots are printed as on Mr. 
 McDougalFs sheets. This tape passes over rollers put into motion 
 by clockwork driven by a falling weight, and the time during which 
 continuous work can be done is only limited by the distance through 
 which the weight can fall. In my machine this time is ten minutes, 
 but with the short intervals necessary for winding up the weight, work 
 could, of course, be continued for a period of any length. The rate at 
 which the dots pass behind a slit placed in front of the tape can be 
 varied within wide limits by means of an arrangement which need not 
 here be described in detail. 
 
 One advantage which this machine possesses over all other means for 
 measuring the amount and nature of mental work is that the indication 
 of the amount of work done in successive intervals of time involves no 
 activity on the part of the subject of the test, but can be measured after- 
 wards in terms of length of tape, provided that the rate of movement of 
 the tape is constant. In all the ordinary methods of studying fatigue, 
 the subject has himself to mark off the limits of the intervals of time 
 into which the whole period of work is divided. One result of this in 
 some subjects certainly it is so in myself is that there is a spurt at 
 
 1 Brit. Journ. Psycho/., 1905, vol. i., p. 435. 
 
 2 This apparatus lias been made by the Cambridge Scientific Instrument 
 Company. 
 
 125
 
 126 THE INFLUENCE OF DRUGS ON FATIGUE 
 
 the beginning of each interval, and this makes it impossible to study 
 the natural time relations of the spurts, which, as introspection shows, 
 occur not only at the beginning and end of the total period of work, 
 but throughout its whole course. The new method allows an exact 
 study of the variations of volition upon which the spurts depend. 
 
 Owing to much delay in the completion of the instrument and of the 
 machinery for printing the dots on the tape, little work has so far been 
 carried out with the machine, but enough has been done to show without 
 doubt that by means of it very decided effects can be produced which 
 are undoubtedly due to mental fatigue. As I have stated in the first 
 lecture, there is some doubt how far the methods used by the Kraepelin 
 school really measure fatigue, and certainly, as means of showing 
 the influence of mental fatigue on various kinds of activity, they are 
 singularly ineffective. With this new method, on the other hand, there 
 can be not the slightest doubt as to the reality of the fatigue which is 
 induced, and ten minutes' 1 work with this instrument is capable of pro- 
 ducing an effect on the capacity for muscular work, as shown by the 
 ergograph. which far exceeds anything produced by the ordinary methods 
 of inducing mental fatigue experimentally.
 
 APPENDIX III 
 
 GENERAL ACTION OF CAFFEINE 
 
 THE experiments to test the influence of caffeine on muscular activity, 
 described in the second lecture, showed a very striking difference between 
 the two persons who were the subjects of the tests, and I propose to 
 give here some further observations which show equally decided differences 
 in the general action of the drug. Throughout the whole of the experi- 
 ments notes were taken of any conditions which might influence the 
 results, including observations of an introspective nature, and in his 
 work with the ergograph Mr. Webber noticed nothing which he could 
 ascribe to the general action of the drug, this absence of general effect 
 being associated, as we have seen, with only a slight action on muscular 
 activity. In my own case, on the other hand, there were in some 
 experiments such definite general effects as to leave no doubt that they 
 were due to the action of the drug. 
 
 It is often difficult to distinguish between the direct physiological 
 effects of a drug and those due to the knowledge that it has been 
 administered, and the special point of importance in the observations I 
 am about to describe is that they were made in the absence of knowledge 
 which was rendered possible by the use of a control. In my first 
 experiment to test the influence of caffeine on typewriting 1 seemed to 
 be generally stimulated on the caffeine days ; but as no control was used 
 in this experiment, the feeling of stimulation might have been due to 
 knowledge and consequent interest. In my second typewriting experi- 
 ment I did not experience this sense of general stimulation during the 
 actual observations, but noticed that I walked more vigorously, especially 
 uphill, after the morning work on certain days, these days being found 
 afterwards to have been those on which caffeine had been taken. The 
 most decided effect, however, was on the amount and nature of the sleep 
 at night. During the first half of the experiment I took on certain 
 days a dose of 0'3 gramme of caffeine at about 5.30 p.m., the same dose 
 having been taken in the morning. It soon became so obvious that my 
 sleep was being affected that I discontinued the evening dose of the drug 
 during the second half of the experiment. The effect of the caffeine 
 
 127
 
 128 THE INFLUENCE OF DRUGS ON FATIGUE 
 
 was to make me sleep very lightly, with many dreams and frequent 
 waking, my sleep being as a rule sound and dreamless. 
 
 In my earlier experiments with the ergograph, in which a dose of 
 0'3 gramme was taken in the middle of the day, no general effects were 
 noticed, with the exception of some sense of stimulation, and no effect 
 on the capacity for sleep was detected. In my last experiment with 
 caffeine, in which the dose was 0'5 gramme, the general effects of the 
 caffeine were, however, very decided, and to illustrate their nature I give 
 a brief abstract of my notes. 
 
 On the evenings from August 30 to September 3, the final day of an 
 alcohol experiment and normal days, I was very sleepy in the evenings 
 and slept soundly at night. September 3 was the first day of the 
 caffeine experiment, and I was wholly unable to detect the nature of the 
 dose, which was from the control mixture. On September 4 the dose 
 was of caffeine, but I was not able to recognize that it was in any way 
 different from that of the day before. Two hours later I noted a feeling 
 of malaise, 1 which became very pronounced half an hour later, but had 
 disappeared three and a half hours after taking the dose, to be replaced 
 by a slight headache. I did not seem to be especially stimulated at the 
 time or afterwards. That evening I was neither tired nor sleepy ; I 
 slept much less soundly than previously, and did not feel so refreshed in 
 the morning. On September 5, the dose being from the control mixture, 
 I noted that there was no malaise, as on the preceding afternoon, and 
 that evening I was very tired and sleepy, and slept soundly. 
 
 On September 6 the dose was of caffeine, and half an hour after 
 taking it I experienced a sense of stimulation. This was still present 
 three-quarters of an hour later, though at the same time there was a 
 feeling of malaise like that of two days earlier ; at the end of the 
 experiment there was a slight headache, though I still seemed to be 
 stimulated. The following day was a control day : no note was made 
 of any abnormal sensations, and after a very sleepy evening I had a 
 thoroughly good night. 
 
 On September 8, twenty minutes after taking the dose, again of 
 caffeine, I noted great mental activity, ideas about the experiments 
 following one another in rapid succession a state of mind which was 
 very pleasurable, though recogni/ed to be quite out of place in the 
 middle of an experiment. The accompanying ergograms were larger than 
 normal, though not to any very great extent. At the end of this set, 
 half an hour after taking the dose, I was feeling very energetic, and this 
 feeling continued, although accompanied by a definite headache. That 
 
 1 This feeling was probably of the kind which is so often described by patients as 
 one of ' sinking.'
 
 APPENDIX III. GENERAL ACTION OF CAFFEINE 129 
 
 evening I was not at all sleepy, and I had a wakeful night, with the sleep 
 much disturbed by dreams. It seemed so unsatisfactory to make the 
 following day part of the experiment that I did a day's work of the 
 usual kind, but without any dose, and slept very well at night. After 
 the work of the following day a control day I slept fairly, but I 
 was so out of sorts on the next morning that I decided to stop the 
 experiment. 
 
 It is of course possible that my disturbed sleep had no connexion 
 with the caffeine, and I have given the record in some detail in order 
 that my readers may form an estimate for themselves as to the relation 
 between the administration of the caffeine and the sleeplessness. Of one 
 thing I can be certain viz., that the effect was not due to knowledge 
 of the fact that I had taken caffeine. It was, of course, natural that the 
 sense of stimulation on the caffeine days should have made me suspect 
 that I had taken caffeine, but it never occurred to me for a moment that 
 a dose of caffeine taken in the middle of the day would influence my 
 sleep nine or ten hours later, and I need hardly say that the arrange- 
 ment of the experiment would have been very different if I had suspected 
 such a possibility. 
 
 There can be no doubt that this influence of caffeine on the capacity 
 for sleep was due to a central action, and we may regard these general 
 effects as additional evidence that the great increase of muscular activity 
 shown by the ergograph had also a central seat. 
 
 My work with caffeine also illustrated the effect of giving up the 
 habitual use of this substance, and the pronounced nature of these effects 
 affords additional evidence that I am unusually susceptible to the 
 influence of caffeine. When planning my first research with this sub- 
 stance, I gave up the use of tea and coffee about a week before the 
 lieginning of the experiment. This was followed by a condition of 
 lowered physical and mental energy, which seemed to me to have much 
 the same general character as that which is known to follow breaking 
 the habit of taking more powerful drugs, and the neurasthenic condition 
 produced was probably one of the reasons for the unsatisfactory nature 
 of the experiment which followed. The experiment was carried out 
 during a period of very hot weather, and I was inclined at the time 
 to put down my condition of lowered energy to this cause. At the 
 end of the experiment I again began to take tea and coffee, but on 
 giving up their use a second time before a projected experiment a 
 similar neurasthenic condition recurred. It seemed probable that this 
 was due to the sudden breaking of what must probably be called a drug 
 habit, and I therefore decided not to undertake a second experiment till 
 the use of tea and coffee had been given up for a time long enough to 
 
 9
 
 130 THE INFLUENCE OF DRUGS ON FATIGUE 
 
 make it certain that the breaking of the habit could have no possible 
 influence on the general state of health, and during the following two 
 years, while experiments were in progress, I abstained completely from the 
 use of tea, coffee, and cocoa. 
 
 I do not regard it as certain that these phenomena, which followed 
 the act of giving up the use of substances containing caffeine, were its 
 direct consequence. The association was only observed twice, and the 
 abnormal condition in each case may possibly have had some other 
 cause. My object is only to draw attention to the possibility that 
 the cessation of the use of even such familiar substances as tea and 
 coffee may have results the same in kind, if not in amount, as those 
 following the cessation of the use of more potent drugs.
 
 APPENDIX IV 
 GENERAL EFFECTS OF ALCOHOL 
 
 CONTRARY to what was found in the case of caffeine, the general effects 
 of alcohol were decidedly more pronounced in Mr. Webber than in 
 myself. This was probably due to the fact that the former had always 
 been an abstainer, so that, not only were the effects of the drug probably 
 more pronounced, but, as they were also quite new to him, they 
 attracted more attention. 
 
 Even with the dose of 40 c.c. I noticed very little to differentiate the 
 alcohol days from those on which only the control was taken. There 
 was on some days, within an hour after taking the dose, a feeling of 
 fullness in the head, which I know to be one of the results of taking 
 wine, but this was not sufficiently constant or pronounced to enable 
 me to recognize with certainty the days on which alcohol had been 
 administered. 
 
 In Mr. Webber's case, on the other hand, the introspective observa- 
 tions were much more definite. Very soon after taking the dose of 
 40 c.c. of alcohol, it was often noted that there was some salivation, 
 sweating, and irritation of the skin. Of these, the salivation was the 
 most definite and constant. There was often salivation on the control 
 days, but it was more obvious and lasted longer on the alcohol days. 
 
 As regards the sweating, it must be remembered that the prolonged 
 experiment with the larger dose (see p. 85) was carried out in very hot 
 weather, when a dose of any kind increased the natural tendency to 
 sweat ; but the sweating was noticed to be greater on the days which 
 turned out afterwards to have been those on which the larger dose of 
 alcohol had been taken. 
 
 Several times tingling of the skin, especially of the scalp, was noted, 
 often accompanied by flushing. These symptoms occurred immediately 
 after taking the dose, and were soon followed by a sensation of giddiness, 
 which lasted for some time, often for as long as three hours. 
 
 Not long after taking the alcohol, probably within half an hour, 
 there came on certain other symptoms, of which the most obvious 
 subjectively were lassitude and disinclination to use either mind or body. 
 
 131 92
 
 132 THE INFLUENCE OF DRUGS ON FATIGUE 
 
 Every care was taken by the subject, however, to keep the experiment 
 running smoothly, for it was known that, if anything went wrong, there 
 would arise the necessity for action which the subject was anxious to 
 avoid. 
 
 It was almost certain that the movements were slower than usual. 
 In the normal condition the two minutes between successive ergograms 
 were ample for the customary readings and adjustments of the ergograph, 
 but on the 40 c.c. days the period of two minutes was hardly long 
 enough to do what was necessary, although the time seemed no longer 
 than usual. This was so striking that the subject was at first inclined to 
 believe that the watch was in error, for it seemed to him that he had 
 been carrying out his usual task at the normal speed. 
 
 The control of movement did not seem to be as good as normal. 
 Several small accidents happened on days on which the dose of alcohol 
 was 40 c.c., and these were probably the result of awkwardness in 
 adjusting the apparatus. Some of the intervals were occupied in 
 drawing lines for tabular purposes or in pasting ergograms in a book, 
 and these operations were found afterwards to have been done roughly 
 or irregularly on the days on which the larger dose of alcohol had been 
 taken. 
 
 During the state of lassitude there was decided irritability; and a 
 fellow-worker during the long experiment of July, 1906, states that he 
 was able to recognize clearly the days on which the larger dose had been 
 taken by the general demeanour of the subject partly by means of the 
 lassitude, partly by the very obvious irritability. 
 
 It is doubtful how far the state of lassitude was preceded by one of 
 exhilaration, but, if it occurred, it was certainly of very brief duration. 
 
 It is especially noted that these effects of alcohol at first tended to 
 arouse interest, but after a day or two this ceased, and the only desire of 
 the subject was to carry out the appointed work of the day without 
 disturbance, with no feeling of interest in its result. 
 
 These pronounced general symptoms only occurred on the days on 
 which the dose of alcohol was 40 c.c., and they were much more notice- 
 able in the second experiment with this dose. With the dose of 20 c.c. 
 giddiness was occasionally noticed, and the other early symptoms may 
 possibly have been present to some degree, but they were not sufficient 
 to enable these days to be distinguished. With the smaller doses used 
 in the earlier experiments any general effects of the kind just described 
 were completely absent.
 
 APPENDIX V 
 THE MULTIPLICATION METHOD 
 
 Ix order to make mental work more arduous than that usually employed 
 to induce fatigue, a method was employed to test the action of alcohol 
 in which the operation of adding two numbers was replaced by the 
 multiplication of four numbers, a method which has also been adopted 
 and described by Mr. Wimms. 1 
 
 In order to make Kraepelin's Rechenhefte suitable for this modified 
 arithmetical method, it was found necessary to make several changes. 
 The rows of figures in these books consist of all numbers from 1 to 9, 
 and the first step was to get rid of the figures 1 and 5, replacing them 
 by other numbers. The necessity of doing without the figure 1 in a 
 multiplication method is obvious ; and even if 5 had not been an 
 especially easy figure to multiply, it would have been necessary to get 
 rid of it, owing to its becoming when multiplied by an even number. 
 After working for a time, it was found that 6 was also an unsatisfactory 
 number. It was noticed that any even number multiplied by it 
 remained the same, and this rendered multiplication by this figure so 
 simple an operation in many cases that it was not comparable with 
 others. 
 
 At first the figures to replace 1, 5, and 6 were chosen on account of 
 similarity of form to those erased, 1 being changed to 7 or 4, and 
 8 or 3 being substituted for 5. Later, care has been taken to make such 
 substitutions as will avoid products ending in 1, and a preference has 
 also been given to odd numbers, owing to the great preponderance of 
 even products which result if even and odd numbers occur with equal 
 frequency. 
 
 1 Hrit. Journ. Psychol., 1907, vol. ii., p. 153. 
 
 133
 
 INDEX 
 
 ABSINTHE, 115 
 
 Ach, Narziss, 90 
 
 Addition, 8, 41, 91 
 errors of, 10 
 
 Aducco, 103 
 
 Alcohol, 51 et seq. 
 and food, 59 
 
 as a food, 53, 56, 59, 63, 65 
 control mixture for, 56, 66, 73, 84 
 general effects of, 57, 62, 84, 131 
 immediate effects of, 65, 80, 87, 100, 
 
 118 
 
 onset of fatigue and, 5, 63 
 prolonged effects of, 13, 87, 91, 100 
 theory of action, 102 ct seq. 
 
 Amberg, Emil, 10, 97 
 
 Anregung, 8 
 
 Aschaffenburg, Gustav, 89 
 
 Aschenbrandt, Theodor, 108 
 
 Association, 91 
 
 Attention, fatigue of, 12, 45, 98, 125 
 
 Beer, 53, 54 
 Benedicenti, A., 24, 110 
 Bernardini, C., 22, 64 
 De Boeck, 64. 
 Brandy, 54, 61, 62 
 Bromide of potassium, 115 
 
 Caffeine, 22 et seq., 60, 101, 118, 120 
 
 control mixture for, 28 
 
 general action of, 38, 127 
 
 theory of action, 40 
 Camphor, 115 
 Champagne, 104] 
 Chloral hydrate, 115 
 Claret, 52, 59 
 Clement, E., 116 
 Cocaine, 108 
 
 Coffee, 24, 25, 60, 129 
 Compositors, effect of alcohol on, 89 
 Conditions, experimental, 15, 70 
 Contractions, effect of drugs on, 39, 65, 
 87, 112, 120 
 
 irregularity of, 103 
 
 method of incomplete, 34, 75, 83 
 Control injection, 21, 109, 116 
 Control mixture, 19-21, 24, 46, 75, 81, 
 118, 127 
 
 absence of, 19, 52, 66 
 
 failure of, 71, 80 
 
 for alcohol, 56, 66, 73, 84 
 
 for caffeine, 28 
 
 for muscle extract, 117 
 
 for strychnine, 111 
 
 Deladrier, 64 
 Destree, E., 24, 54,62, 65 
 Dixon, Dr. W. E., 20, 66, 73 
 Drug-craving, 17, 42, 129 
 Drugs, action of, 13 et seq., 119 
 Dubois, 59 
 Duboisine, 115 
 Dulcin, 19, 56 
 Dynamograph, 4, 113, 123 
 
 of Fick, 56 
 Dynamometer, 22, 64, 109 
 
 Salter's, 64 
 
 Ergogram, form of, 26, 123 
 
 influence of interest on, 19 
 mathematical analysis of, 25, 63 
 Ergograms of Maggiora, 5, 63 
 Ergograph, imperfections of, 65, 121 
 of Dubois, 59 
 of HeUsten, 25, 60 
 of Kraepelin, 5 
 of Mosso, 3, 5, 22, 54,, 57, 121 
 134
 
 INDEX 
 
 135 
 
 Ergograph of Treves, 3, 123 
 Ergographic method, value of, 3 et seq., 
 
 118 
 
 Ergostat, 24, 56 
 Ether, 115 
 
 Fatigue, accelerator of, 25, 37, 40, 50, 116 
 
 antitoxin of, 117 
 
 definition of, 2 
 
 experimental methods compared, 12 
 
 general, 7, 24, 56, 87, 110 
 
 McDougalTs method, 12, 45, 98, 125 
 
 mental, 7 et seq., 104, 126 
 curve of, 10, 124 
 
 muscular, 3 et seq., 24, 53, 54, 103 
 curve of, 3, 8, 61, 123 
 
 products, influence of, 26, 64 
 
 sensations of, 2, 18, 38, 105, 106, 109 
 Fatigue-process, analysis of, 119 
 Fere, Charles, 19, 25, 37, 58, 65, 111, 113, 
 
 115 
 
 Fick, 56 
 
 Formic acid, 116 
 Freud, Sigm., 109 
 
 Frey, Hermann, 52-54, 56, 60, 70, 102 
 Fiirer, 91 
 
 Giddiness, 84, 131 
 Gluck, 55, 84 
 Guarana, 24, 110 
 Gunzburg, Is., 64 
 
 Habituation, 9 
 
 Harley, Vaughan, 113 
 
 Harrold, C. C., 102 
 
 Heck, Karl, 56 
 
 Hellsten, A. F., 18, 25, 60, 88, 100, 103 
 
 Hoch, August, 23, 25, 41, 48 
 
 Hough, Theodore, 113 
 
 Hylan, John P., 124 
 
 Hyoscyamine, 115 
 
 Incitation, 8 
 
 Interest, 8, 11, 19, 60, 66, 71, 82, 84, 87, 
 95, 103, 110 
 
 Jones, P. C. Varrier, 111 
 Joteyko, Mile. J., 25, 62, 65 
 
 Koch, Wilhelm, 22 
 Kola, 22, 24 
 
 Kraepelin, Emil, 5, 8, 14, 22. 40, 41, 64, 
 
 89, 91, 102, 120 
 Kiirz, Ernst, 92 
 
 Learning by heart, 91, 92, 93 
 
 Lee, Frederic S., 102 
 
 Lombard, Warren P., 52, 54, 102, 112 
 
 Maggiora, curves of, 5, 63 
 
 Maljarewsky, 90 
 
 Mate, 24, 110 
 
 McDougall, Mr. W., 12, 45, 98, 125 
 
 Morphine, 115 
 
 Moskiewicz, 58 
 
 Mosso, Angelo, 3, 103 
 
 Ugolino, 22, 109 
 Multiplication, 11, 70, 73, 93 et seq., 133 
 
 errors of, 97 
 Muscle, alcohol and fatigued, 53, 54, 60 
 
 alcohol and frog's, 101 
 
 electrical stimulation of, 23, 52, 54, 
 102, 109, 110, 113, 119, 120 
 
 extract of, 117 
 
 Opium, 115 
 
 Orchitic extract, 19, 116 
 
 Oseretzkowsky, Alexis, 25, 58, 84 
 
 Pain, muscular, 18, 27, 33, 77 
 
 Partridge, George E., 64, 93 
 
 Practice, 4, 27, 42, 44, 46, 78, 90, 92, 99, 
 
 124 
 
 coefficients of, 94, 98 
 Pregl, Fritz, 19, 116 
 Psychology hi relation to pharmacology, 
 1, 117 et seq. 
 
 Quality of mental work, 10, 45, 97 
 
 Reading, 93 
 
 Rechenliefte, 8, 93, 133 
 
 Rhythm, effect of, 63 
 
 Rossi, Cesare, 23, 52, 110, 115 
 
 Rudin, Ernst, 91 
 
 Rum, 52, 64 
 
 De-Sarlo, F., 22, 64 
 Scheffer, J. C. Th., 57, 101 
 Schnyder, L., 59, 65 
 Schumburg, 18, 24, 56, 65, 87
 
 136 
 
 INDEX 
 
 Blade, J. G., 117 
 
 Sleep, effect of caffeine on, 36, 43, 127 
 
 Smith, 92 
 
 Smoking, 112 
 
 Sobieranski, W., 19, 23, 109 
 
 Specht, Wilhelm, 124 
 
 Spurt, 9, 124, 125 
 
 end-, 69, 90 
 Standard, normal daily, 37, 77, 80, 90, 94 
 
 importance of, 15, 98 
 Stimulation, sensory, 19, 38, 51, 58, 60, 
 
 66, 82, 112, 114, 117 
 Stomach-tube, 58 
 Strychnine, 110, 118, 120 
 Sugar, 19, 54, 60, 116 
 Suggestion, 18, 23, 38, 52, 54, 82, 109, 
 
 117 
 Susceptibility, 26, 38, 121 
 
 individual differences of, 38, 57, 62, 
 81, 84, 91, 127 
 
 Tavernari, L., 24, 55, 88 
 Tea, 22, 24, 25, 41, 129 
 
 essential oils of, 23, 41. See Drug- 
 craving 
 
 Theobromine, 25 
 Tobacco, 112 
 
 Training, 18, 30, 31, 35, 60 
 Treves, Zacharias, 3 
 Tropon, 59 
 Typewriting, 12, 42, 73, 94, 96 
 
 errors of, 45, 97 
 
 Waller, A. D., 101 
 Weichardt, Wolfgang, 117 
 Webber, Mr. H. N., 17, 27, 67 
 Whisky, 81, 99, 107 
 Wimms, J. H., 8, 11, 124, 133 
 Writing, 93 
 
 Zoth, Oskar, 116 
 
 THE END 
 
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