Therapeutic infusions of ketamine: Do the psychoactive effects matter?

Summary

In a small study of eight cocaine-dependent individuals, ketamine infusions produced mystical-type experiences that helped explain increased motivation to quit cocaine a day later. Participants received two doses of ketamine (0.41 mg/kg and 0.71 mg/kg) and a control drug lorazepam (2 mg) in random order. Ketamine, especially the higher dose, caused significantly stronger mystical-type effects than lorazepam. The intensity of those mystical effects, but not dissociative symptoms, predicted greater motivation to stop using cocaine 24 hours after infusion. The findings suggest that psychological experiences during ketamine treatment may contribute to its anti-addiction benefits, though larger studies are needed.

Study at a glance

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.