The effects of MDMA-assisted therapy on alcohol and substance use in a phase 3 trial for treatment of severe PTSD

Drug Alcohol Depend. 2022 Apr 1:233:109356. doi: 10.1016/j.drugalcdep.2022.109356. Epub 2022 Feb 11.

Abstract

Background: Post-traumatic stress disorder (PTSD) is commonly associated with alcohol and substance use disorders (ASUD). A randomized, placebo-controlled, phase 3 trial demonstrated the safety and efficacy of MDMA-assisted therapy (MDMA-AT) for the treatment of severe PTSD. This analysis explores patterns of alcohol and substance use in patients receiving MDMA-AT compared to placebo plus therapy (Placebo+Therapy).

Methods: Adult participants with severe PTSD (n = 90) were randomized to three blinded trauma-focused therapy sessions with either MDMA-AT or Placebo+Therapy. Eligible participants met DSM-5 criteria for severe PTSD and could meet criteria for mild (current) or moderate (early remission) alcohol or cannabis use disorder; other SUDs were excluded. The current analyses examined outcomes on standardized measures of hazardous alcohol (i.e., Alcohol Use Disorder Identification Test; AUDIT) and drug (i.e., Drug Use Disorder Identification Test; DUDIT) use at baseline prior to randomization and at study termination.

Results: There were no treatment group differences in AUDIT or DUDIT scores at baseline. Compared to Placebo+therapy, MDMA-AT was associated with a significantly greater reduction in mean (SD) AUDIT change scores (Δ = -1.02 (3.52) as compared to placebo (Δ = 0.40 (2.70), F (80, 1) = 4.20, p = 0.0436; Hedge's g= .45). Changes in DUDIT scores were not significantly different between treatment groups.

Conclusions: MDMA-AT for severe PTSD may also lead to subclinical improvements in alcohol use. MDMA-AT does not appear to increase risk of illicit drug use. These data provide preliminary evidence to support the development of MDMA-AT as an integrated treatment for co-occurring PTSD and ASUD.

Keywords: Alcohol use; MDMA; Post-traumatic stress disorder; Substance use.

Publication types

  • Clinical Trial, Phase III
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Alcoholism* / complications
  • Alcoholism* / drug therapy
  • Combined Modality Therapy
  • Ethanol
  • Humans
  • N-Methyl-3,4-methylenedioxyamphetamine* / adverse effects
  • Stress Disorders, Post-Traumatic* / complications
  • Stress Disorders, Post-Traumatic* / drug therapy
  • Substance-Related Disorders* / complications
  • Treatment Outcome

Substances

  • Ethanol
  • N-Methyl-3,4-methylenedioxyamphetamine