This population-based study of patients in Ontario and Alberta authorized for medical cannabis showed some clinical impact on depression symptoms as measured by the PHQ-9, in particular, 20.7% (1056) of patients - whose PHQ-9 score was re-assessed 3 to 6-months following authorization – reported a significant change in scores. However, at the population level, the overall majority of patients experienced minimal detriments to their mental health, which is reassuring for clinicians and patients using medical cannabis. Moreover, there is a subset of patients that improved over time, although it is uncertain how clinically important this improvement is as overall effects were relatively small. Many of the patients were using antidepressants while also using medical cannabis, however SSRIs were the only class of antidepressant statistically associated with a change in PHQ-9 scores, however the clinical importance of this interaction remains unknown. Given wide variability of the type of cannabis products or cannabis cultivars used, we would expect that any PHQ-9 differences would be hard to identify, however based on this study we found that the method of cannabis use does not significantly predict a change in PHQ-9 score. Despite this variability, subgroups of individuals were identified for scores that showed both improvement and worsening of symptoms.

Current recommendations from Canadian clinicians [14] and The National Academies of Science, Engineering, and Medicine [15] concur that there is very limited to insufficient evidence for medical cannabis’ efficacy in improving depression-related outcomes. From the literature, previous studies [16–19, 29] specifically utilizing the PHQ-9 tool to measure depression levels in association with (medicinal or recreational) cannabis use have shown inconsistent results. Turna et al. (2019) was the sole study from Canada (British Columbia) and found that 64.9% of patients reported a rating of 4 out of 5 (very effective) in alleviating their depression symptoms [16]. Despite this, the study also stated that this improvement was not clinically important and may have been confounded by those experiencing cannabis-withdrawal associated symptoms. Sexton et al. (2016) also reported a 86% reduction in depression-related symptoms as a result of cannabis use [4]. Conversely, Bahorik et al. (2017) reported that cannabis use worsened depression and the majority of patients had less improvements in depression symptoms [19]. Likewise, the two studies by Feingold et al. (2017) [17] and (2018) [18] reported that depression levels were markedly higher in medical cannabis users– but this study only compared the results to opioid users, and not the general population. The majority of the remaining clinical studies [10, 13, 21, 25] utilized other validation tools to measure depression outcomes and grouped depression under a general category of other mental health outcomes. Despite the mixed results, there was common observation amongst the studies that any initial increases in depression levels may not necessarily have been as a direct result of medical cannabis use [23].

The present study provides an important bridge for some of these knowledge gaps regarding cannabis and mental health outcomes. Indeed, depression is a major reason cited [16] for seeking medical cannabis authorization, hence the study provides important insight to potential safety and benefits regarding current and prospective users of medical cannabis. With the recent legalization of nonmedical cannabis in Canada, it is reassuring to observe that the majority of patients in this study did not experience a worsening of depression symptoms. These findings help contribute to the knowledge base on current and potential population health impacts of cannabis use, while at the same time, providing future direction to the field of mental health around cannabis research.

This analysis is currently the largest Canadian population-based study of medical cannabis use that we are aware of, but it is not without limitations. First, it is an observational study and thus, potential spectrum bias has to be considered as our cohort of patients are those who individually sought medical cannabis for treatment. Second, even though depression screening via the PHQ-9 is considered best practice for all clinicians, follow-up scores were not available for a large proportion of our cohort. Third, likewise to most pharmacoepidemiological studies, there is no absolute method for determining whether the medical cannabis authorized was consumed as prescribed, and if patients elected to use alternative treatments for depression. Fourth, comparative analysis with the outcomes from other studies remain challenging as previous studies predominantly do not utilize the PHQ-9 questionnaire to measure depression-related outcomes. Finally, our study is limited by the lack of clinical details: frequency, strain, quantity, and onset/age of depression symptoms.