SPEAKERS

Introduction: Converging evidence suggests that sub-anesthetic ketamine may improve addiction-related vulnerabilities and facilitate efforts at behavioral modification. The purpose of these five studies was to test whether a single ketamine infusion improves treatment outcomes in substance dependent individuals in both laboratory and clinical settings, and to investigate mechanisms of action.

Methods: Two cross-over, controlled, inpatient laboratory studies tested ketamine on motivation to quit, craving, and cocaine self-administration more than 24 hours post-infusion; and three 5-week clinical trials investigated ketamine in cocaine, alcohol, or cannabis dependent individuals engaged in behavioral treatment. Results: In the laboratory studies, ketamine significantly improved motivation to quit cocaine, craving, behavioral reactivity, drug use in the natural ecology, and cocaine self-administration. When paired with behavioral treatment, ketamine promoted abstinence in drug or alcohol dependent individuals, and led to a significant reduction in relapse risk. Mystical-type phenomena, but not other psychoactive effects, were found to mediate the efficacy of ketamine in both laboratory and clinical settings. Conclusions: A single ketamine infusion improved a range of important treatment outcomes in dependent adults, including promoting abstinence, diminishing craving, and reducing risk of relapse. Mechanisms pertaining to perspectival shifts and existential reappraisal may be implicated. Future research is needed to expand on these results.