Therapeutic infusions of ketamine: do the psychoactive effects matter?
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.
New York State Psychiatric Institute, New York, NY, United States; Columbia College of Physicians and Surgeons, New York, NY, United States. Electronic address: dakware@nyspi.columbia.edu.
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Dakwar
New York State Psychiatric Institute, New York, NY, United States.
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Anerella
New York State Psychiatric Institute, New York, NY, United States; Columbia College of Physicians and Surgeons, New York, NY, United States; Department of Psychology, Columbia University, New York, NY, United States.
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Hart
New York State Psychiatric Institute, New York, NY, United States; Columbia College of Physicians and Surgeons, New York, NY, United States.
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Levin
Michael E. Debakey VA Medical Center, Houston, TX, United States; Menninger Department of Psychiatry & Behavioral Sciences/Baylor College of Medicine, Houston, TX, United States.
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Mathew
New York State Psychiatric Institute, New York, NY, United States; Columbia College of Physicians and Surgeons, New York, NY, United States.
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Nunes
D000328:Adult; D000778:Anesthetics, Dissociative / Q000008:administration & dosage / Q000627:therapeutic use*; D019970:Cocaine-Related Disorders / Q000188:drug therapy* / Q000523:psychology; D016578:Crack Cocaine; D003463:Cues; D003627:Data Interpretation, Statistical; D039721:Diagnostic and Statistical Manual of Mental Disorders; D004213:Dissociative Disorders / Q000139:chemically induced / Q000523:psychology; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D006993:Hypnotics and Sedatives / Q000627:therapeutic use; D007262:Infusions, Intravenous; D007297:Inpatients; D007649:Ketamine / Q000008:administration & dosage / Q000627:therapeutic use*; D008140:Lorazepam / Q000627:therapeutic use; D008297:Male; D009042:Motivation / Q000187:drug effects*; D009228:Mysticism
D000778:Anesthetics, Dissociative; D016578:Crack Cocaine; D006993:Hypnotics and Sedatives; D007649:Ketamine; D008140:Lorazepam
Cocaine; Dependence; Ketamine; Mystical experience