Therapeutic infusions of ketamine: do the psychoactive effects matter?

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, 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.

Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Figures

Fig. 1

(A) Regression plot assessing correlation between mystical experience and change in motivation to quit and (B) β values calculated from simple regressions and mediation analyses with respect to change in dependent variables (motivation to quit and cue-induced craving) for ketamine-induced dissociation (CADSS score) or mysticism (HMS score), as well as infusion type (lorazepam vs. ketamine). The correlation between mystical experience and change in motivation to quit is represented in (A), and remained significant when controlling for infusion type (lorazepam vs. ketamine 0.41 mg/kg), β = 0.678, p = 0.005. The relationship between HMS score and motivation to quit was the only association to remain significant after mediation analyses were performed (B). This suggests that mystical-type phenomena might mediate the effect of ketamine on motivation enhancement. *p = 0.001, **p = 0.012, ***p < 0.001, ****p = 0.005.