Exploring the Potential of Cannabis in Treating Depression: A Scientific Perspective

Depressed man

This article was written by Amanda Reiman, PhD MSW, of New Frontier Data.

In recent years, there has been a growing interest in the potential therapeutic benefits of cannabis, particularly in the treatment of mental health disorders like depression. 

While cannabis remains a controversial topic, with varying opinions on its use and efficacy, scientific research has begun to shed light on the complex relationship between cannabis and depression. This article aims to explore the current state of scientific knowledge regarding the use of cannabis in treating depression.

The Endocannabinoid System and Depression

To understand the potential effects of cannabis on depression, it's essential to delve into the endocannabinoid system (ECS). The ECS is a complex cell-signaling system present in the human body that plays a crucial role in regulating various physiological processes, including mood, stress response, and sleep. The system consists of receptors, endocannabinoids (cannabinoids produced naturally by the body), and enzymes responsible for their synthesis and breakdown.

Research1 has shown that the ECS is intricately involved in the neurobiology of depression. Much like the Serotonin hypothesis of depression, it has been proposed that imbalances in the endocannabinoid system could play a role in this illness. This has led scientists to explore how phytocannabinoids, the active compounds in cannabis, might interact with the endocannabinoid system to influence mood and alleviate depressive symptoms.

Endocannabinoid system

Cannabis and Cannabinoids: A Brief Overview

Cannabis contains more than 100 different cannabinoids, with tetrahydrocannabinol (THC) and, to a lesser extent, cannabidiol (CBD) being the most well-known and extensively studied. 

While THC is responsible for the psychoactive effects commonly associated with cannabis use, it has also been studied extensively for its therapeutic properties for the past 70 years.  CBD, while non-psychoactive and, as a result, being explored for its potential therapeutic properties, has yet to be demonstrated to be effective in human beings.

Research scientist

THC and Depression

The relationship between THC and depression is complex and dose-dependent.  Low to moderate doses of THC (5-20mg) can be used to as an effective anti-depressant, particularly if administered prior to bed (and not used throughout the day).  This is interesting as it suggests that the intoxication commonly associated with mood benefit is not actually relevant, and the true benefit comes from some as-yet not understood neurochemical alteration.

As with any medications, dose matters.  High doses of THC can lead to anxiety and exacerbate depressive symptoms. Research2 suggests that THC may influence mood by interacting with the endocannabinoid receptors in the brain, affecting neurotransmitter release and neural circuitry involved in mood regulation.


CBD and Depression

Unlike THC, CBD does not produce a "high" and has been studied for its anxiolytic and antidepressant-like effects. CBD interacts with the endocannabinoid system in a more indirect manner, influencing receptor activity and modulating neurotransmitter release. Preclinical studies3 have shown promising results, indicating that CBD may have potential as an antidepressant by promoting neurogenesis, reducing inflammation, and modulating the activity of serotonin receptors.  So far, however, attempts to recreate these preclinical benefits in human beings have been unsuccessful.  


Scientific Research 

Several studies have investigated the potential use of cannabis and cannabinoids in the treatment of depression. A review4 published in the Journal of Affective Disorders in 2020 analyzed the findings of multiple studies and concluded that there is evidence supporting the antidepressant effects of cannabinoids. However, the review emphasized the need for further well-designed clinical trials to establish the safety and efficacy of cannabis-based treatments for depression.

Depression with therapist

Challenges and Considerations

While the preliminary research on cannabis and depression is promising, several challenges and considerations must be addressed. The variability in cannabis plants, concentrations of THC and CBD, and individual responses to these compounds make it challenging to establish standardized treatment protocols. Additionally, the effects of cannabis use in vulnerable populations such as adolescents, pregnant women, and individuals with a history of substance abuse, remain unclear.

Moreover, the legal and regulatory landscape surrounding cannabis use varies widely across different regions, posing obstacles to research and limiting access to potential treatments. The psychoactive effects of THC and the stigma associated with cannabis use further complicate the picture, necessitating a nuanced and evidence-based approach to its therapeutic potential.



While the relationship between cannabis and depression is still an evolving area of research, scientific evidence suggests that cannabinoids can be used, if done carefully, as a treatment for depression. The complex interactions between cannabinoids and the endocannabinoid system offer a new avenue for exploring innovative therapeutic interventions for mental health disorders.

However, it is crucial to approach this topic with caution, recognizing the need for rigorous scientific inquiry and standardized clinical trials. As our understanding of the endocannabinoid system and the effects of cannabis on mental health continues to grow, the potential for novel and effective treatments for depression may become a reality, providing hope for individuals struggling with this debilitating condition.

Amanda Reiman, PhD is the Chief Knowledge Officer for New Frontier Data. Dr. Reiman earned her PhD in Social Welfare from the University of California and conducted one of the first research studies on medical cannabis patients and the use of cannabis as a substitute for alcohol and other drugs. Having studied cannabis use and policy for over 20 years, she is an internationally recognized cannabis expert and public health researcher. Formerly the in-house cannabis expert for the Drug Policy Alliance, she has written for/been quoted in numerous national and international publications as well as peer reviewed academic journals and several textbooks.

  1. Gallego-Landin Ines, García-Baos Alba, Castro-Zavala Adriana, Valverde Olga (2021). Reviewing the Role of the Endocannabinoid System in the Pathophysiology of Depression, Frontiers in Pharmacology, 12.    https://www.frontiersin.org/articles/10.3389/fphar.2021.762738     
  2. Micale, V., Tabiova, K., Kucerova, J., Drago, F. (2015). Role of the Endocannabinoid System in Depression: from Preclinical to Clinical Evidence. In: Campolongo, P., Fattore, L. (eds) Cannabinoid Modulation of Emotion, Memory, and Motivation. Springer, New York, NY. https://doi.org/10.1007/978-1-4939-2294-9_5
  3. García-Gutiérrez MS, Navarrete F, Gasparyan A, Austrich-Olivares A, Sala F, Manzanares J. Cannabidiol: A Potential New Alternative for the Treatment of Anxiety, Depression, and Psychotic Disorders. Biomolecules. 2020; 10(11):1575. https://doi.org/10.3390/biom10111575
  4. Botsford, S.L., Yang, S. and George, T.P. (2020), Cannabis and Cannabinoids in Mood and Anxiety Disorders: Impact on Illness Onset and Course, and Assessment of Therapeutic Potential. Am J Addict, 29: 9-26. https://doi.org/10.1111/ajad.12963