Mystical-type experiences occasioned by ketamine mediate its impact on at-risk drinking: Results from a randomized, controlled trial

J Psychopharmacol. 2021 Feb;35(2):150-158. doi: 10.1177/0269881120970879. Epub 2020 Dec 13.


Background: Sub-anesthetic ketamine administration may be helpful for substance use disorders. Converging evidence suggests that the efficacy of ketamine for certain conditions may implicate a subset of its psychoactive effects.

Aims: The aim of this analysis is to evaluate whether the mystical-type effects of ketamine are critical for clinical efficacy in alcohol-dependent individuals. In this secondary analysis, we determine if a subset of the psychoactive effects of ketamine, the so-called mystical-type experience, mediates the effect of ketamine, when combined with motivational enhancement therapy, on at-risk drinking behavior in alcohol-dependent individuals interested in treatment.

Methods: Forty alcohol dependent adults were randomized to either a 52-minute infusion of ketamine or midazolam, which they received on a designated quit-day during the second week of a five-week motivational enhancement therapy regimen. Psychoactive effects were assessed following the infusion, and alcohol use was monitored for the subsequent 3 weeks at each twice-weekly visit.

Results: We found that ketamine leads to significantly greater mystical-type effects (by Hood Mysticism Scale) and dissociation (by Clinician Administered Dissociative States Scale) compared to the active control. Ketamine also led to significant reduction in at-risk drinking. The Hood Mysticism Scale, but not Clinician Administered Dissociative States Scale score, was found to mediate the effect of ketamine on drinking behavior.

Conclusions: This trial adds evidence to the literature on the importance of mystical-type experiences in addiction treatment. Future research should continue to investigate the relationship between the psychoactive effects of psychedelic therapeutics and clinical outcomes for other substance use and mental health disorders.

Keywords: Ketamine; addiction treatment; alcohol use disorder; at-risk drinking; hallucinogen; motivational enhancement therapy; mystical experience; psychedelic; spirituality.

Publication types

  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alcohol Drinking / drug therapy*
  • Alcohol Drinking / psychology
  • Behavior, Addictive / drug therapy
  • Behavior, Addictive / psychology
  • Dissociative Disorders / drug therapy
  • Dissociative Disorders / psychology
  • Double-Blind Method
  • Female
  • Hallucinogens / therapeutic use
  • Humans
  • Ketamine / therapeutic use*
  • Male
  • Midazolam / therapeutic use
  • Middle Aged
  • Mysticism / psychology*
  • Substance-Related Disorders / drug therapy
  • Surveys and Questionnaires
  • Treatment Outcome


  • Hallucinogens
  • Ketamine
  • Midazolam