key: cord-0309002-ko0656ba
authors: Kim, C.; Chum, A.; Nielsen, A.; Allin, S.; Penney, T.; Rittenbach, K.; MacMaster, F.; O'Campo, P.
title: Associations between recreational cannabis legalization and cannabis-related emergency department visits by age, gender, and geographic status in Ontario, Canada: an interrupted time series study
date: 2022-05-16
journal: nan
DOI: 10.1101/2022.05.11.22274943
sha: 0c5628db3a8df42c872daaa4efdf1172fec3760a
doc_id: 309002
cord_uid: ko0656ba

Legalization of recreational cannabis in Ontario included the legalization of flower and herbs (Phase 1, October 2018), and was followed by the deregulation of cannabis retailers and sales of edibles (Phase 2, February 2020). Research on the impact of cannabis legalization on acute care utilization is nascet; no research has investigated potential age, gender, and geographically vulnerable subgroup effects. Residents living in Northern Ontario not only have higher levels of substance use problems, but also have inadequate access to primary healthcare. Our study investigated the impact of Ontarios recreational cannabis policy (including Phase 1 and 2) on cannabis-attributable emergency department (ED) visits, and estimated the impact separately for different age and gender groups, with additional analyses focused on Northern Ontarians. We created a cohort of adults (18 and over) eligible for provincial universal health insurance with continuous coverage from 2015-2021 (n=14,900,820). An interrupted time-series was used to examine the immediate impact and month-to-month changes in cannabis-related ED visits associated with Phase 1 & 2 for each subgroup. While Northern Ontario has higher rates of cannabis-related ED visits, both Northern and Southern Ontario show similar patterns of changes. Phase 1 was associated with significant increases in adults 25-64, with the strongest increases seen in women 45-64. Month-to-month trends were flattened in most groups compared to pre-legalisation. Phase 2 was associated with significant immediate increases for adults aged 18-44 in both genders, but the increases were larger in women than men. No significant month-to-month changes were detected in this period. While current preventive efforts are largely focused on reducing cannabis-related harms in youths and younger adults, our results show that adults 25-64, particularly women, have been significantly impacted by cannabis policies. Further research on gender-specific cannabis dosage and targeted interventions for adult women should be investigated. Legalization did not appear to have a differential impact on Northern versus Southern Ontario, but higher rates of ED visits in the North should be addressed.

Although prior research has shown that cannabis may be associated with fewer acute harm events compared to tobacco, alcohol, and opiates(3), problematic use can lead to anxiety, paranoia, suicidal ideation, cognitive impairment, induce temporary tachycardia and cannabinoid hyperemesis syndrome (4) , or lead to cyclical emesis with chronic use (5) . While emerging evidence suggests that legalization has led to modest increases in cannabisattributable emergency department (ED) visits (6) (7) (8) (9) , these studies have a number of limitations. First, these studies focus only on the general population or the pediatric population, which ignores the differential impact of legalization across gender and lifecourse (10) . This information is necessary for the development of age-and gender-specific interventions. Second, there has been no research that looks at the impacts of legalization on cannabis-related ED visits in Northern Ontario. Northern Canada experiences low physician . CC-BY 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.

The copyright holder for this preprint this version posted May 16, 2022. ;  https://doi.org/10.1101/2022.05.11.22274943 doi: medRxiv preprint retention (11) , a lack of comprehensive service availability, and a historical vulnerability to substance use problems (12) . In Ontario, Northern residents have double the rate of substancerelated healthcare encounters compared to the rest of the province (911.6 per 100,000 vs. 457.2 per 100,000) (13) , which underscores the importance of research on the impact of cannabis legalization on this underserved population. Our study will address these distinct gaps in the literature using disaggregated analyses of population-level health administrative data in Ontario.

We aim to investigate the impact of recreational cannabis policy (including Phase 1 and 2) on cannabis-attributable ED visits, and estimate the impact separately for different age and gender groups, with additional analyses focused on Northern Ontarians.

The study cohort (n=14,900,820) was created using health-administrative data held at To be included in the cohort, individuals must have continuous OHIP coverage and residency in Ontario for the entire study period. Age groups for our study were based on each person's age on the day of Canada's cannabis legalization. Northern Ontario, based on Statistics Canada's health regions (14) , was defined as the area of the province that is north of the French River and Algonquin Park. The Registered Person Database provides gender identity (15) ; however, gender may be mismatched if not officially changed.

This study complied with privacy regulations of the Institute for Clinical and Evaluative Science (ICES). To protect privacy, all cell sizes fewer than six individuals were . CC-BY 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review)

The copyright holder for this preprint this version posted May 16, 2022. ; https://doi.org/10.1101/2022.05.11.22274943 doi: medRxiv preprint suppressed and reported as n < 6. Consent was not obtained for participants for the use of their data in this study. ICES is an independent, non-profit research institute whose legal status under Ontario's health information privacy law allows it to collect and analyze health care and demographic data used for the study, without consent, for health system evaluation and improvement. All patient information was anonymized and de-identified prior to analysis. Ethics approval for this study was obtained through Brock University (REB# 20-134-CHUM).

The outcomes of interest were monthly cannabis-attributable ED visits from October 2015 to May 2021 in Ontario (i.e. the frequency of the event within age, gender, and regionspecific subgroups for each month of the study period). Using the National Ambulatory Care

Reporting System, Discharge Abstract Database, and Ontario Mental Health Reporting System, records were included with at least one of the following ICD-10 codes for either the primary or supplemental diagnosis: F12 (cannabis-related disorders) and T40.7 (cannabis poisoning), following the conventions from prior studies (6, 7, 16) .

Our study considers three distinct time periods related to cannabis policy in Ontario, saw the removal of the retail cap and increased edible cannabis availability. These cutoff dates were used in a prior study estimating the impact of legalization and commercialization on cannabis-related ED visits in the Ontario population(9). Following recommendations from the prior study, healthcare visits in March and April 2020 were censored to account for large . CC-BY 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review)

The copyright holder for this preprint this version posted May 16, 2022. ; https://doi.org/10.1101/2022.05.11.22274943 doi: medRxiv preprint decreases in health-seeking behaviors (including ED visits) associated with the early stages of COVID-19 pandemic.

We used an interrupted time-series with single-group, multiple-interventions design to examine the immediate and month-to-month changes associated with cannabis-related policies on cannabis-related ED visits for each age and gender group in Ontario (both North and South), Southern, and Northern Ontario. We conducted segmented regressions using the negative binomial function to estimate the incidence rate ratio while adjusting for overdispersion (i.e. extra-Poisson variation). We estimated models for each age group (18 to 24, 25 to 44, 45 to 64, and 65+) and gender separately, given prior research finding age and gender differences in the patterns of cannabis use (17) . We adjusted for the length of the month and for any seasonal effect (18) . We conducted two sensitivity analyses. First, to examine whether the results were robust regardless of the functional form and address possible residual autocorrelation in a time-series dataset, the Prais-Winsten regressions following a first-order autoregressive process were performed (19) . Second, we included the months March and April 2020 in an alternative specification of the models, and used an indicator variable for both months as an adjustment to confirm whether the estimates were robust. Table 1 shows the number of individuals with 1 or more cannabis-related ED visits in the entire study period (October 18, 2015-June 17, 2021) across age, gender, and for Northern, Southern, and the entirety of Ontario. In general, men, those in the 18-24 age group, and those living in Northern Ontario are at a higher risk of cannabis-related ED visits. Table 2 shows the gender-and age-specific average monthly rates (per 100,000 people) of cannabis-related ED visits in the pre-legalization period, Phase 1, and Phase 2. Rates for . CC-BY 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.

The copyright holder for this preprint this version posted May 16, 2022 In Southern Ontario (Table 3) , there was an increasing trend in cannabis-related ED visits across all gender and age groups during the pre-legalization period: at the lowest end, an increase of 1.6% ED visits per month among women aged 18-24 (IRR = 1.016, 95% CI 1.013-1.020), and at the highest end, an increase of 7.3% ED visits per month among boys aged 0-17 (IRR = 1.073, 95% CI 1.064-1.082). Legalization (Phase 1) was associated with an immediate (level) increase overall, and they were statistically significant in 3 groups: 1) a 20% increase in ED visits among men aged 45-64 (IRR = 1.207, 95% CI 1.015-1.436), 2) a 13% increase among women aged 25-44 (IRR = 1.134, 95% CI 1.000-1.286), and 3) a 29% increase among women aged 45-64 (IRR = 1.289, 95% CI 1.020-1.628). In Phase 1, there were no significant month-to-month (trend) increases in ED visits across all gender and age groups.

[ of the entire province's population. Figure 1 visualizes the change in monthly cannabisrelated ED visits by each subgroup.

[ Table 4 ]

[ Table 5 ]

[ Figure 1 ]

Cannabis legalization was associated with immediate increases in ED visits of adults in Ontario. Phase 1 was associated with significant immediate increases in adults 25-64, and Phase 2 was associated with immediate increases in those 18-44, with greater increases observed in women for both phases. Among these groups, the pattern is characterized by rapid immediate increase, but no significant subsequent trend (month-to-month) change is observed. Also, while Northern Ontario has higher rates of cannabis-related ED visits, both Northern and Southern Ontario show relatively similar patterns of changes with regards to Phase 1 and 2 of legalization.

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The copyright holder for this preprint this version posted May 16, 2022. ; https://doi.org/10.1101/2022.05.11.22274943 doi: medRxiv preprint

Our results are largely consistent with findings from prior research that found cannabis legalization (Phase 1) (6) and cannabis edibles legalization and commercialization (Phase 2) were associated with increases in cannabis-related ED visits in Canadian provinces (8, 9) . For example, a study reported that cannabis legalization (Phase 1) led to a small immediate increase in urban-Alberta cannabis-related ED visits; however, this study included a relatively short period (less than 1 year) and did not adjust for temporal autocorrelation and seasonality (6) . Our results also support the findings of an Ontario study which suggest that the immediate effects of cannabis legalization (Phase 1) were largely driven by adults over the age of 24 (9) . Additionally, similar to other studies that examined the Phase 2 effect (i.e. edibles and commercialization), we found evidence of an immediate increase in cannabisrelated ED visits; however, no studies including ours have been able to isolate the Phase 2 effect from the COVID-19 effects that coincided with Phase 2. Only one study from Hamilton, Ontario contradicted our results: they found that there was no change in the rate of cannabis-related ED visits following legalization (20) , but the authors only examined a single hospital, and did not measure level and trend changes.

Our study is the first to conduct age-and gender-specific analyses on legalization and cannabis-related ED visits in Canada. Since prior studies did not include age and gender stratifications, they were unable to identify whether the effects were consistent across age and gender groups, and whether the apparent effects may be driven by a specific subgroup. Our study also makes unique contributions to the study of Northern Ontario. While our study finds consistently higher rates of cannabis-related ED visits in Northern Ontario compared to the rest of the province (consistent with studies of substance-related healthcare visits in the North prior to cannabis legalization(13)), we note that ED visits in the North and South were similarly affected by Phase 1 and Phase 2.

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The copyright holder for this preprint this version posted May 16, 2022. ; https://doi.org/10.1101/2022.05.11.22274943 doi: medRxiv preprint Limitations of this study include: 1) the use of single-group interrupted time series is vulnerable to concurrent interventions, policies or events that may confound the relationship between cannabis legalization and cannabis-related ED visits. While we have adjusted for the early COVID-19 effects on ED visits, there may be other unforeseen events that impact people's willingness to visit the ED. 2) Phase 2 of the study overlapped with the COVID-19 pandemic, so we cannot confidently estimate the independent effects associated with commercialization and edibles. 3) Our study relies on administrative health records to indicate whether individuals have continuous OHIP coverage and residency in Ontario, but some individuals may not be in Ontario for the full study period (e.g. traveling while still maintaining OHIP coverage). 4) The reporting of cannabis-related ED visits may have changed over time, especially given that patients may feel less stigmatized reporting cannabis use at the ED after legalization, which may bias our results towards a significant finding for Phase 1 effects; however, prior literature on cannabis-related ED visits uses the same methods for identifying outcomes (21) .

Future studies could take a different approach to isolate the edibles/commercialization effects on cannabis-related ED visits. Such a study can include a control region that is contextually similar (e.g., comparison with a US state that was similarly impacted by COVID-19, but did not implement cannabis legalization) so that we can isolate the Phase 2 effects. Further research should be conducted on the impact of cannabis legalization on the cannabis-related ED visits and hospitalizations in specific patient and at-risk groups (e.g., people with depression, anxiety, or schizophrenia).

Our study provides evidence that the rate of increase in cannabis-related ED visits in Ontario has flattened even in the face of cannabis legalization and deregulation of retailers/edibles. Furthermore, the association between cannabis legalization and cannabis-. CC-BY 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.

The copyright holder for this preprint this version posted May 16, 2022. ; https://doi.org/10.1101/2022.05.11.22274943 doi: medRxiv preprint related ED visits varies across age, gender, and geography (i.e., Northern vs Southern Ontario). Of note, cannabis-related ED visits in adults aged 18-44 in both genders in the South and women aged 25-44 in the North were significantly increased during Phase 2; however, it is unknown how much COVID-19 contributed to these changes. While legalization (Phase 1 and 2) did not differentially impact the North (vs the South), cannabisrelated ED visits remain high and should be addressed in this region. While current preventive efforts are largely focused on reducing cannabis-related harms in youths and in school settings (22) , our results show that adults 25-64, particularly women, have been significantly impacted by cannabis policies. Further research on gender-specific cannabis dosage and targeted interventions for adults should be investigated. Legalization did not appear to have a differential impact on Northern versus Southern Ontario, but higher rates of ED visits in the North should be addressed.

This study contracted ICES Data & Analytic Services (DAS) and used de-identified data from the ICES Data Repository, which is managed by ICES with support from its funders and partners: Canada's Strategy for Patient-Oriented Research (SPOR), the Ontario SPOR Support Unit, the Canadian Institutes of Health Research and the Government of Ontario. The opinions, results and conclusions reported are those of the authors. No endorsement by ICES or any of its funders or partners is intended or should be inferred.

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The copyright holder for this preprint this version posted May 16, 2022. ; https://doi.org/10.1101/2022.05.11.22274943 doi: medRxiv preprint Parts of this material are based on data and information compiled and provided by CIHI. However, the analyses, conclusions,opinions, and statements expressed herein are those of the author, and not necessarily those of CIHI.

The dataset from this study is held securely in coded form at the Institute for Clinical Evaluative Sciences (ICES). While data sharing agreements prohibit ICES from making the dataset publicly available, access may be granted to those who meet pre-specified criteria for confidential access, available at www.ices.on.ca/DAS. The full dataset creation plan and underlying analytics code are available from the authors upon request, understanding that the computer programs may rely upon coding templates or macros that are unique to ICES and are therefore either inaccessible or may require modification.

Chungah Kim and Antony Chum co-wrote the first draft of the study. Chungah Kim analyzed the data. Chungah Kim, Antony Chum, and Sara Allin contributed to the interpretation of the data. Antony Chum, Chungah Kim, and Andrew Nielsen co-wrote the dataset creation plan. Antony Chum conceived of the initial project and provided funding and oversight of the study. All of the authors revised it critically for important intellectual content, gave final approval of the version to be published and agreed to be accountable for all aspects of the work.

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The copyright holder for this preprint this version posted May 16, 2022 Figure 1 : Change in monthly cannabis-related emergency department visits by gender, age, and geography (i.e. Northern Ontario vs Southern Ontario).

[ Figure 1 ]

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The copyright holder for this preprint this version posted May 16, 2022. ; https://doi.org/10.1101/2022.05.11.22274943 doi: medRxiv preprint

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