Published: 26/04/2023

Cross-National Reflections on Medical Cannabis and Depression

To date, medical cannabis has been legalised in many countries, including the UK, with some jurisdictions also having approved medical cannabis registries. Such registries in countries including the UK, Canada, Israel, Canada, and the US have collected data to further assess the outcomes of people prescribed medical cannabis for pain, depression, anxiety and insomnia, in addition to their general safety and tolerability.

A recently published letter reflected on the current findings of some of these medical cannabis patient registries, including the UK Medical Cannabis Registry (UKMCR). The authors note that a growing number of patients with major depressive disorder (MDD) are turning to medical cannabis. As such, the outcomes of various studies from a cross-national sample were reviewed to reflect on this.

Observational Outcomes

The first study was an analysis of data from the UK Medical Cannabis Registry. The UKMCR was launched by Sapphire Medical Clinics in 2019 to further develop real-world evidence of the potential of medical cannabis for various indications. As noted, a total of 129 patients were included in this review. Participants completed patient-reported outcome measures (PROMs) for this study at baseline, and 1, 3, and 6 months after the initiation of medical cannabis for depression. 

Patients completed the Patient Health Questionnaire-9 (PHQ-9) – a nine-question validated tool that screens for the presence and severity of depressive symptoms. The data indicated changes in depression severity at 1, 3, and 6 months. It was also noted that these changes in PHQ-9 were greater in patients with anxiety, prior cannabis users, and patients with severe depression. Adverse effects were reported by 14% of individuals. 

A Canadian study by Round et al. similarly assessed PHQ-9 results in Canadian patients who used medical cannabis for any indication, including depression. Overall, the patient sample was found to have mild depression. Over the course of the study period, only 3.4% of patients reported improvement while 1.5% reported worsening of their anxiety, suggesting a lack of efficacy. 

Finally, an Australian observational study assessed the use of oral medical cannabis in a cohort of 3,961 cannabis naïve patients with a range of symptoms (e.g., pain, depression, anxiety). The patients in this study demonstrated changes in pain, depression, anxiety, and insomnia. These results were similar to those presented in the UK study.

A response to the authors

In response to the findings highlighted in V. Modesto-Lowe et al.’s letter, the authors of ‘Assessment of clinical outcomes of medicinal cannabis therapy for depression: analysis from the UK Medical Cannabis Registry’ – reiterated the importance of pre-clinical and observational studies in helping to determine the safety and efficacy of medical cannabis when prescribed in individuals with depression. 

“Observational evidence is of the utmost importance as a pharmacovigilance measure for patients prescribed medical cannabis, monitoring the long-term safety of these medications.”

They note that the observational evidence outlined in ‘Cross-national reflections on medicinal cannabis and depression’ builds upon pre-clinical research which suggests that cannabinoids cause direct and indirect activation of type 1 cannabinoid receptors. Furthermore, this research also supports real-world evidence from common psychiatric comorbidities with overlapping symptoms and pathophysiology with depression, such as anxiety and post-traumatic stress disorder. 

However, there remains a paucity of randomised controlled trials on the effects of medical cannabis on depression due to various challenges, including the complex biological makeup of the plant, which contains a broad spectrum of over 500 active pharmaceutical ingredients. As a result, prescribing in this setting likewise remains limited. The psychoactive and vasoactive properties of some of these ingredients (e.g., THC) can also make it difficult to create a placebo to effectively “blind” participants to the treatment they receive. Finally, some findings suggest that patients may have positive perceptions of the effects of medical cannabis – so much so that participants receiving a placebo in trials where medical cannabis is a treatment arm have better out-comes compared to those enrolled in studies with other active comparators.

With all these barriers continuing to limit the number of randomised controlled trials, the advances in real-world evidence provide insights to help improve the likelihood of their success. The authors conclude that “using these [observational studies] to inform randomised controlled trials over the next 5–10 years will provide immeasurable benefits for advancement of this nascent field.”

Share this article