Licit use of illicit drugs for treating depression: the pill and the process.

Psilocybin, MDMA, and ketamine show promise for rapidly treating mood and related psychiatric disorders. Clinical data for psilocybin and MDMA, with positive outcomes for depression, anxiety, PTSD, and substance use disorders, have always involved clinician-assisted intervention. Even ketamine's first successful psychiatric use for depression combined it with psychotherapy, and emerging evidence indicates that the subjective experience during ketamine treatment predicts clinical outcome. This review examines how the context and process of drug administration have been integral to published work, stresses the need for trials comparing drug alone versus drug with psychological support, and suggests future animal models that consider context, experience, and expectancy in drug effects.

Study at a glance

Abstract

Psilocybin, MDMA, and ketamine have emerged as potentially effective treatments for rapid amelioration of the symptoms of mood and related psychiatric disorders. All clinical data collected so far with regard to psilocybin or MDMA, which have reported positive outcomes for treating depression, anxiety, posttraumatic stress disorder, and drug or alcohol use disorders, have involved clinician-assisted intervention. While the case for ketamine is assumed to be different, the first report of the successful use of ketamine in psychiatry for treating depression was in combination with psychotherapy, and an emerging literature suggests that the subjective state of individual experiences with ketamine predicts clinical outcome. This Review will focus on (a) a brief review of the literature, showing that the context or the process of drug administration has been an integrative component of published work; (b) the importance of clinical trials to compare the efficacy of the drug ("pill") as a stand-alone treatment versus drug in combination with clinician-assisted psychological support ("process"); and (c) suggestions for future approaches in animal models that take into account the role of systems and behavioral neuroscience in explaining a potential role for context, experience, and expectancy in drug effect.