Therapeutic infusions of ketamine: do the psychoactive effects matter?

Drug Alcohol Depend. 2014 Mar 1;136:153-7. doi: 10.1016/j.drugalcdep.2013.12.019. Epub 2014 Jan 15.


Background: Sub-anesthetic ketamine infusions may benefit a variety of psychiatric disorders, including addiction. Though ketamine engenders transient alterations in consciousness, it is not known whether these alterations influence efficacy. This analysis evaluates the mystical-type effects of ketamine, which may have therapeutic potential according to prior research, and assesses whether these effects mediate improvements in dependence-related deficits, 24h postinfusion.

Methods: Eight cocaine dependent individuals completed this double-blind, randomized, inpatient study. Three counter-balanced infusions separated by 48h were received: lorazepam (2mg) and two doses of ketamine (0.41mg/kg and 0.71mg/kg, with the former dose always preceding the latter). Infusions were followed within 15min by measures of dissociation (Clinician Administered Dissociative Symptoms Scale: CADSS) and mystical-type effects (adapted from Hood's Mysticism Scale: HMS). At baseline and 24h postinfusion, participants underwent assessments of motivation to stop cocaine (University of Rhode Island Change Assessment) and cue-induced craving (by visual analogue scale for cocaine craving during cue exposure).

Results: Ketamine led to significantly greater acute mystical-type effects (by HMS) relative to the active control lorazepam; ketamine 0.71mg/kg was associated with significantly higher HMS scores than was the 0.41mg/kg dose. HMS score, but not CADSS score, was found to mediate the effect of ketamine on motivation to quit cocaine 24h postinfusion.

Conclusions: These findings suggest that psychological mechanisms may be involved in some of the anti-addiction benefits resulting from ketamine. Future research can evaluate whether the psychoactive effects of ketamine influence improvements in larger samples.

Keywords: Cocaine; Dependence; Ketamine; Mystical experience.

Publication types

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

MeSH terms

  • Adult
  • Anesthetics, Dissociative / administration & dosage
  • Anesthetics, Dissociative / therapeutic use*
  • Cocaine-Related Disorders / drug therapy*
  • Cocaine-Related Disorders / psychology
  • Crack Cocaine
  • Cues
  • Data Interpretation, Statistical
  • Diagnostic and Statistical Manual of Mental Disorders
  • Dissociative Disorders / chemically induced
  • Dissociative Disorders / psychology
  • Dose-Response Relationship, Drug
  • Double-Blind Method
  • Female
  • Humans
  • Hypnotics and Sedatives / therapeutic use
  • Infusions, Intravenous
  • Inpatients
  • Ketamine / administration & dosage
  • Ketamine / therapeutic use*
  • Lorazepam / therapeutic use
  • Male
  • Motivation / drug effects*
  • Mysticism


  • Anesthetics, Dissociative
  • Crack Cocaine
  • Hypnotics and Sedatives
  • Ketamine
  • Lorazepam