There is considerable evidence to suggest that the endocannabinoid system (ECS) is involved in the pathophysiology of depression. 

Endocannabinoids and CB1 receptors are widely distributed in the brain areas that are often related to mood disorders and their expression is regulated by antidepressants. Enhancement of endocannabinoid activity at various receptor sites appears to exert antidepressant-like effects. The 5-HT1A receptor is a serotonin receptor that is located in presynaptic and postsynaptic regions. Activating these receptors have been involved in the mechanism of action of anti-anxiety, antidepressant, and antipsychotic medications. 

Research has just begun to take place to understand if the ability of cannabis to regulate these receptors, support that cannabinoids, such as cannabidiol (CBD) can have anti-anxiety, antidepressant, and antipsychotic effects.

Notable quality of life improvements with CBD

Data indicate that repeated administration of CBD may produce an effect that is consistent with results from studies testing traditional anti-anxiety and antidepressant medications. These are known to be clinically relevant findings as CBD is known to benefit while exhibiting few side effects, supporting the initiation of clinical trials testing the efficacy of CBD-based compounds for the treatment of mood disorders. 

The serotonergic mechanism of CBD is distinct from commonly used antidepressant medications in that it does not appear to produce symptoms of withdrawal. CBD has also been shown to synergize with other serotonergic medications. Data suggests that CBD could facilitate the antidepressant effect induced by these antidepressant drugs, therefore allowing the SSRIs to be administered at lower doses, resulting in fewer side effects. 

In a recently published observational study, it was found that medicinal cannabis use was associated with lower self-reported depression. Initiation of medicinal cannabis during the follow-up period was associated with significantly decreased anxiety and depressive symptoms, an effect that was not observed in Controls who had not initiated cannabis use. 

A qualitative analysis published in 2022 paid close attention to the notable quality of life improvements attributed to medicinal cannabis use. The two overarching categories were “enhanced well-being” and “improved daily functioning”. Enhanced well-being includes feelings such as regaining a sense of hope, enjoying family life, and laughing more often. A woman from the study with Lyme Disease was quoted saying, “People such as myself are able to become productive and valued members of society again when we can have the quality of life improved so simply.” 

Benefits reported through RoC research

The goal of the third published paper by Realm of Caring (RoC) was to provide insight into the effects of medicinal cannabis use for symptoms of anxiety and depression.

​​The participants involved were those who were at least 18 years old and reported having anxiety and/or depression without a specific endorsement, as well as specific endorsements, including: major depressive disorder, postpartum depression, dysthymia, premenstrual dysphoric disorder, seasonal affective disorder, generalized anxiety disorder, panic disorder, social anxiety disorder, and agoraphobia. 

Of the 538 participants, 368 reported current use of medicinal cannabis products at the baseline. The other 170 participants, who were considering use but had not yet initiated, served as controls. Of the participants who completed the baseline survey, 211 completed at least one follow-up assessment (145 Cannabis Users and 66 Controls). 

Cannabis Users reported lower baseline depression, significantly better past-month sleep quality, a higher overall quality of life, and lower past-month average pain compared to Controls.

Cannabis Users did not report lower baseline anxiety, however baseline Controls who had initiated cannabis use reported a significant reduction in both mean anxiety and depression scores from baseline to follow-up surveys [evaluated using the Hospital Anxiety and Depression Scale (HADS)]. This observation was not realized among non-initiators throughout the study. A similar effect was observed among participants who sustained medicinal cannabis use throughout the study, suggesting an improvement in symptoms of anxiety and depression with both the onset of cannabis use and with extended use.

Limiting stress to limit depression

Depression itself is considered a chronic stressor, as too much stress may lead to major depression. CBD has shown to reduce the cardiovascular response to models of stress. Stress can spike blood pressure, heart rate, and stroke volume. In studies done with healthy volunteers exposed to stress; it has been found that CBD may maintain cardiac output by lowering blood pressure, increasing heart rate, and decreasing stroke volume – which are inversely related actions to balance that cardiac output.

Call for future research and finding support

Though antidepressant effects of CBD are consistently reported in preclinical observations, further studies are necessary to confirm best dosing practices to achieve antidepressant effects.

Getting started with cannabinoid therapy can be overwhelming. If you are seeking data-driven answers to your questions about cannabinoid therapy and depression, the RoC Care Team is here to assist. They care a lot about helping you to find success. Reach them by calling (719) 347-5400, emailing info@realmofcaring.org, or by scheduling an appointment.