Lifetime use of MDMA/ecstasy and psilocybin is associated with reduced odds of major depressive episodes

J Psychopharmacol. 2022 Jan;36(1):57-65. doi: 10.1177/02698811211066714. Epub 2022 Jan 5.

Abstract

Background: Depression is a major mental health issue worldwide, with high rates of chronicity and non-recovery associated with the condition. Existing treatments such as antidepressant medication and psychological treatments have modest effectiveness, suggesting the need for alternative interventions.

Aim: The aim of this study was to examine the relationships between MDMA (3,4-methylenedioxymethamphetamine)/ecstasy and psilocybin use and major depressive episodes (MDEs).

Methods: This observational study used data from a large (N = 213,437) nationally representative sample of US adults to test the association of lifetime use of MDMA/ecstasy, psilocybin and other classic psychedelics (lysergic acid diethylamide (LSD), peyote, mescaline), other illegal substances (e.g. cocaine, phencyclidine (PCP)), and legal/medicinal substances of misuse (e.g. pain relievers, tranquilizers) with lifetime, past year, and past year severe MDEs.

Results: Results revealed that lifetime MDMA/ecstasy use was associated with significantly lowered odds of a lifetime MDE (adjusted odds ratio (aOR) = 0.84; p < 0.001), past year MDE (aOR = 0.84; p < 0.001), and past year severe MDE (aOR = 0.82; p < 0.001). Psilocybin was associated with significantly lowered odds of a past year MDE (aOR = 0.90; p < 0.05) and past year severe MDE (aOR = 0.87; p < 0.05). All other substances either shared no relationship with a MDE or conferred increased odds of an MDE.

Conclusions: These results suggest that MDMA/ecstasy and psilocybin use is associated with lower risk of depression. Experimental studies are needed to test whether there is a causal association between use of these compounds and the alleviation of depressive symptoms.

Keywords: MDMA; NSDUH; classic psychedelics; depression; psilocybin.

Publication types

  • Observational Study

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Depressive Disorder, Major / epidemiology*
  • Depressive Disorder, Major / physiopathology
  • Female
  • Hallucinogens / administration & dosage
  • Hallucinogens / pharmacology*
  • Health Surveys
  • Humans
  • Male
  • Middle Aged
  • N-Methyl-3,4-methylenedioxyamphetamine / administration & dosage
  • N-Methyl-3,4-methylenedioxyamphetamine / pharmacology*
  • Patient Acuity
  • Psilocybin / administration & dosage
  • Psilocybin / pharmacology*
  • Substance-Related Disorders / epidemiology
  • Substance-Related Disorders / psychology
  • United States
  • Young Adult

Substances

  • Hallucinogens
  • Psilocybin
  • N-Methyl-3,4-methylenedioxyamphetamine