Will your doctor be prescribing psychedelic drugs for you?

"Initially, drugs were classified as psychedelic on the basis of similar pharmacologic properties and clinical effects (e.g., LSD, psilocybin, mescaline, and dimethyltryptamine). However, the classification has since been expanded to include psychoactive drugs that have different pharmacological targets, such as MDMA (3,4-methylenedioxymethamphetamine [“ecstasy”]) and dissociatives (phencyclidine [“angel dust”] and ketamine). Encouraging results with respect to depression, anxiety, substance use disorders, and palliative care have been reported with these drugs over the past decade. Of interest, the therapeutic effects were tied to the subjective report of the user’s mystical experience. However, these studies had methodologic limitations (the lack of comparator treatments, functional unblinding, expectancy effects, short follow-up periods, imprecise dosing, and variability in treatment settings).

A series of studies by Carhart-Harris and colleagues, culminating in the phase 2, randomized trial, published in this issue of the Journal, that compared psilocybin (25 mg at baseline and week 3 plus daily placebo) with escitalopram (20 mg plus 1 mg of psilocybin daily) over a 6-week period, provide tantalizing evidence for the efficacy of psilocybin in the treatment of major depressive disorder. However, although the psilocybin-treated patients showed a pattern of improvement, the between-group differences did not reach statistical significance with respect to the primary outcome (change in score on the 16-item Quick Inventory of Depressive Symptomatology–Self-Report), and the analyses of the numerous secondary outcomes were not adjusted for multiple comparisons. Heterogeneity among patients, who volunteered for the trial in response to advertisements, and uncertainty regarding the appropriate therapeutic dose range and frequency of administration of psilocybin may have influenced the results."