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Therapeutic infusions of ketamine: Do the psychoactive effects matter?

Elias Dakwar, C. Anerella, Carl L. Hart, Frances R. Levin, Sanjay J. Mathew, Edward V. Nunes

Drug and Alcohol Dependence January 15, 2014 DOI: 10.1016/j.drugalcdep.2013.12.019 (opens in new tab)

Study at a glance

AI-extracted from the abstract
Characteristics Double-blind, randomized, within-subjects crossover trial Peer reviewed
Sample size 8
Population Cocaine dependent individuals
Interventions Ketamine Lorazepam
Dose 0.41 mg/kg and 0.71 mg/kg ketamine; 2 mg lorazepam
Duration 48 hours between infusions, 24-hour postinfusion follow-up
Topics Esketamine Ketamine
Citations 125
Key findings Mystical-type effects from ketamine, but not dissociative effects, mediated improvements in motivation to quit cocaine 24 hours postinfusion.

Abstract

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, 24 h postinfusion.

Methods: Eight cocaine dependent individuals completed this double-blind, randomized, inpatient study. Three counter-balanced infusions separated by 48 h were received: lorazepam (2 mg) and two doses of ketamine (0.41 mg/kg and 0.71 mg/kg, with the former dose always preceding the latter). Infusions were followed within 15 min by measures of dissociation (Clinician Administered Dissociative Symptoms Scale: CADSS) and mystical-type effects (adapted from Hood's Mysticism Scale: HMS). At baseline and 24 h 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 0.71 mg/kg was associated with significantly higher HMS scores than was the 0.41 mg/kg dose. HMS score, but not CADSS score, was found to mediate the effect of ketamine on motivation to quit cocaine 24 h 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.