Depression is a complex condition of multifaceted origin often accompanying various other disorders. According to the WHO, depression is a leading cause of disability worldwide. As of their last update in 2017, they estimated that more than 264 million people of all ages suffer from depression globally.

There is a growing body of scientific evidence that homeostasis of the endocannabinoid system (ECS) is involved in the pathogenesis and possible treatment of depression, offering promising insights into potential treatments.

123 Primary Studies

17 Clinical Studies 

57 Meta-analyses/Reviews 

46 Animal studies

2 Laboratory studies

Overall Positive Results: 63%

The Endocannabinoid System and Mood Regulation:

The ECS, a complex network of receptors and signalling molecules, is distributed widely throughout various brain structures responsible for mood, emotion, and reward. Scientific evidence suggests that the ECS interacts with other neurotransmitter systems, influencing GABAergic and glutamatergic tones, as well as the release of important neurotransmitters like dopamine, serotonin, and opioids. Dysregulation of the ECS can lead to physiological and behavioural effects consistent with symptoms of depression and anxiety.

Given the limitations and adverse effects associated with conventional pharmaceutical treatments for depression, there is now a strong research focus on understanding the exact mechanism and  how to manipulate the endocannabinoid system (ECS) in order to achieve antidepressant effects.

Studies have shown that individuals with severe mood disorders, such as Major Depressive Disorder (MDD) and Bipolar Disorder (BD), exhibit decreased levels of endocannabinoids (eCBs) and disrupted cannabinoid receptor signalling. Increasing the endocannabinoid tone, through methods like preventing eCB degradation or antagonising cannabinoid receptors, has demonstrated potential benefits in alleviating depressive and anxiogenic symptoms.

Phytocannabinoids, particularly CBD, either alone or in combination with THC, can be efficacious as therapeutic drugs. CBD has shown primarily positive results in mitigating symptoms of depression, all the while presenting a very favourable safety profile.

A 2018 review of preclinical and clinical studies on CBD found that it has potential as an antidepressant and anxiolytic agent[1]. Another study found that CBD may have a rapid and sustained antidepressant effect in animal models. 

Evidence for minor cannabinoids and depression is in its infancy but theoretically possible and worthy of Investigation.

The complex nature of these disorders requires a thorough investigation into the potential benefits and risks associated with cannabinoid use. As the scientific community continues to explore the ECS and cannabinoids, we anticipate more clarity on their roles in mood regulation. Despite the compelling evidence for the ECS’s involvement in mood disorders like anxiety and depression, we still need more comprehensive randomised controlled trials to establish the efficacy of cannabinoids as treatments and produce comprehensive guidelines. 

References

• Bright, U., & Akirav, I. (2022). Modulation of Endocannabinoid System Components in Depression: Pre-Clinical and Clinical Evidence. International Journal of Molecular Sciences, 23(10), 5526. https://doi.org/10.3390/ijms23105526
• Crippa JA, Guimarães FS, Campos AC, Zuardi AW. Translational Investigation of the Therapeutic Potential of Cannabidiol (CBD): Toward a New Age. Front Immunol. 2018 Sep 21;9:2009. doi: 10.3389/fimmu.2018.02009. PMID: 30298064; PMCID: PMC6161644.
• Hasbi A, Madras BK, George SR. Endocannabinoid System and Exogenous Cannabinoids in Depression and Anxiety: A Review. Brain Sciences. 2023; 13(2):325. https://doi.org/10.3390/brainsci13020325
• Sachedina, F., Chan, C., Damji, R. S., & De Sanctis, O. J. (2022). Medical cannabis use in Canada and its impact on anxiety and depression: A retrospective study. Psychiatry Research, 313, 114573. https://doi.org/10.1016/j.psychres.2022.114573