Editor’s note, November 2026: Loren DeVito, PhD, wrote this piece on cannabis and depression in January 2020. It appears unchanged below; an editors’ postscript at the end covers what the research has shown since.
“That’s the thing about depression: A human being can survive almost anything, as long as she sees the end in sight. But depression is so insidious, and it compounds daily, that it’s impossible to ever see the end.” ― Elizabeth Wurtzel, Prozac Nation
A heavy, indescribable feeling. An exhausted and depleted mind. This is how depression can feel. It’s not fleeting sadness or “the blues” and it’s not something you can wish away. And for the over 17 million people in the US who have experienced depression, getting effective treatment can be a matter of life and death.
Depression is difficult to diagnose. According to the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5), five or more symptoms must be present within a two-week period to be considered a Major Depression Episode. [1] These symptoms must include depressed mood or anhedonia, a lack of interest in normal activities. Additional symptoms may include changes in weight or appetite, sleep problems, fatigue, trouble concentrating, and negative thoughts, including suicidality. [1]
Psychotherapy, which can include cognitive behavioral therapy, can be very effective in managing both short- and long-term symptoms. [2] Additionally, pharmacological therapies that target neurotransmitters (chemical messengers) can also be very helpful. Selective serotonin reuptake inhibitors, or SSRIs, for example, affect the neurotransmitter serotonin by blocking its breakdown, thus leaving more of this feel-good chemical in the brain. [2] [Editors’ note: SSRIs block the reuptake of serotonin, not its breakdown.]
While these medications have been proven effective in clinical trials, many are associated with troublesome side effects, from weight gain and insomnia to more serious effects on cardiac function. [3,4] In addition to safety concerns, some people do not respond to their first (or even second or third) medication and, if they respond, it could take several weeks to feel the effects—this is less-than-ideal when immediate relief is vital to function in everyday life.
The limitations of current anti-depressant medications have caused a recent shift in the field of psychiatry. Since the so-called “monoamine hypothesis” has not proven itself in clinical practice, researchers are looking into other possible pathways involved in the disease. [5] A key network that plays a role in regulating processes relevant to depression, including pain, inflammation, and mood, is—you guessed it—the endocannabinoid system (ECS).
Several components of the ECS like cannabinoid receptor density and endocannabinoid concentrations are altered in the brains of people with depression. [5] Additionally, pre-clinical studies have suggested that increasing activity of cannabinoid receptors can promote antidepressant effects. However, these effects are not consistent—in some cases, cannabis can make depressive symptoms worse. [5]
Long-term studies have indicated that cannabis use may be associated with an increased risk in developing depression. [6] While these types of studies cannot prove direct causal relationships, it is certainly reason for pause, especially since certain cannabinoids and terpenes can induce lethargy, which is not beneficial for people who experience fatigue.
We certainly need more data on cannabis and depression, as we know that so many factors can impact the effects of cannabinoids and terpenes. Depression is complex and challenging to treat. While cannabis holds potential, we don’t have strong, current evidence to support its use as a treatment for depression. Those looking for relief should speak to their doctor and carefully consider the potential benefits and risks.
References
- Tolentino, J.C. & Schmidt, S.L. “DSM-5 Criteria and Depression Severity: Implications for Clinical Practice.” Front Psychiatry, vol.9, 2018, pp. 1-9.
- American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition. American Psychiatric Association, 2010.
- Cipriani, A, et al. “Comparative Efficacy and Acceptability of 21 Antidepressant Drugs for The Acute Treatment of Adults with Major Depressive Disorder: A Systematic Review and Network Meta-analysis.” Lancet, vol.391, no.10128, 2018, pp. 1357-1366.
- Wang, S-H, et al. “Addressing the Side Effects of Contemporary Antidepressant Drugs: A Comprehensive Review.” Chonnam Med J, vol.54, no.2, 2018, pp. 101-112.
- Micale, V., et al. “Role of the Endocannabinoid System in Depression: From Preclinical to Clinical Evidence.” Cannabinoid Modulation of Emotion, Memory, and Motivation, edited by P. Campolongo & L. Fattore, Springer, 2015.
- Stoner, S.A. “Effects of Marijuana on Mental Health: Depression.” Alcohol & Drug Abuse Institute, University of Washington, June 2017.
Cannabis and depression: what the research has shown since (November 2026)
Dr. DeVito’s caution has held. In the six years since she wrote, no controlled trial has shown cannabis or a cannabinoid to treat depression, and the few that looked found no benefit. A randomized trial in Massachusetts gave adults immediate or delayed access to a medical cannabis card; after twelve weeks the card holders used more cannabis, had more symptoms of cannabis use disorder, and their depression scores had not moved. A small placebo-controlled trial of CBD in people with bipolar depression saw both groups improve, with no difference between them. A 2021 systematic review found only eight small clinical studies of CBD or THC across mood, anxiety and trauma disorders together, and called them insufficient to recommend cannabis for any.
The observational picture has firmed up in the other direction. A 2025 meta-analysis of 22 longitudinal studies found people who use cannabis more likely to develop depression, with odds about 1.3 times higher; its authors call this an association, not a cause, and these designs cannot settle the direction, since depression also leads people to cannabis. The receptor biology Dr. DeVito points to is set out in our endocannabinoid system pillar.
What users report sits between the two. App data from medical cannabis users show a large drop in self-rated depression in the hour after use and a slow worsening of baseline depression over months; it records what people feel, not what cannabis causes.
What would settle it is a trial built for the question, and one is now registered: 120 adults with treatment-resistant depression, CBD oil or placebo added to their antidepressant for twelve weeks. For the same gap with a different molecule, see our page on psilocybin for treatment-resistant depression. Whether terpenes change mood is a separate question, covered on our cannabis and mood page.
Postscript sources
- Gilman JM et al. Effect of medical marijuana card ownership on pain, insomnia, and affective disorder symptoms in adults: a randomized clinical trial. JAMA Network Open. 2022;5(3):e222106. https://doi.org/10.1001/jamanetworkopen.2022.2106
- Pinto JV, Crippa JAS, Ceresér KM, et al. Cannabidiol as an adjunctive treatment for acute bipolar depression: a pilot study. Canadian Journal of Psychiatry. 2024. https://doi.org/10.1177/07067437231209650
- Stanciu CN, Brunette MF, Teja N, Budney AJ. Evidence for use of cannabinoids in mood disorders, anxiety disorders, and PTSD: a systematic review. Psychiatric Services. 2021;72(4):429–436. https://doi.org/10.1176/appi.ps.202000189
- Churchill V, Chubb CS, Popova L, Spears CA, Pigott T. The association between cannabis and depression: an updated systematic review and meta-analysis. Psychological Medicine. 2025;55:e44. https://doi.org/10.1017/S0033291724003143
- Cuttler C, Spradlin A, McLaughlin RJ. A naturalistic examination of the perceived effects of cannabis on negative affect. Journal of Affective Disorders. 2018;235:198–205. https://doi.org/10.1016/j.jad.2018.04.054
- Cannabidiol oil for treatment-resistant major depression (ANANDA). ClinicalTrials.gov NCT07696871; Brazilian registry RBR-6n6wzsx. https://clinicaltrials.gov/study/NCT07696871
This article is for information only and is not medical advice. If you are experiencing symptoms of depression, talk to a doctor; in the US, call or text the 988 Suicide & Crisis Lifeline.
