Cannabis and Depression

Adv Exp Med Biol. 2021:1264:67-80. doi: 10.1007/978-3-030-57369-0_5.


There is a growing body of evidence pointing to the co-occurrence of cannabis use and depression. There is also some evidence that the use of cannabis may lead to the onset of depression; however, strong evidence points to the inverse association; i.e. that depression may lead to the onset or increase in cannabis use frequency. Observational and epidemiological studies have not indicated a positive long-term effect of cannabis use on the course and outcome of depression. The association between cannabis use and depression may be stronger among men during adolescence and emerging adulthood and stronger in women during midlife. There is an indication for potential genetic correlation contributing to the comorbidity of cannabis dependence and major depression, namely that serotonin (5-HT) may mediate such association and there is also evidence for specific risk alleles for cannabis addiction. There is preclinical evidence that alteration in the endocannabinoid system could potentially benefit patients suffering from depression. However, the issue of using cannabis as an anti-depressant is at an early stage of examination and there is little evidence to support it. Finally, there has been little support to the notion that selective serotonin reuptake inhibitors (SSRIs) may be effective in decreasing depressive symptoms or rates of substance use in adolescents treated for depression and a co-occurring substance use disorder. In conclusion, despite methodological limitations, research in the past decades has broadened our knowledge on the association between cannabis use and depression from epidemiological, neurological, genetic, and pharmacological perspectives.

Keywords: Anxiety Disorders; Bipolar Disorder; Cannabis; Major Depressive Disorder; Mental illness; Mood disorders.

Publication types

  • Review

MeSH terms

  • Cannabis / adverse effects*
  • Comorbidity
  • Depression / chemically induced*
  • Depression / drug therapy*
  • Depression / epidemiology
  • Depression / genetics
  • Depressive Disorder, Major / chemically induced*
  • Depressive Disorder, Major / drug therapy*
  • Depressive Disorder, Major / epidemiology
  • Depressive Disorder, Major / genetics
  • Humans
  • Marijuana Abuse / epidemiology