October 2017
Psilocybin and other 5-hydroxytryptamine2A agonist classic psychedelics have been used for centuries as sacraments within indigenous cultures. In the mid-twentieth century they were a focus within psychiatry as both probes of brain function and experimental therapeutics. By the late 1960s and early 1970s these scientific inquires fell out of favor because classic psychedelics were being used outside of medical research and in association with the emerging counter culture. However, in the twenty-first century, scientific interest in classic psychedelics has returned and grown as a result of several promising studies, validating earlier research. Here, we review therapeutic research on psilocybin, the classic psychedelic that has been the focus of most recent research. For mood and anxiety disorders, three controlled trials have suggested that psilocybin may decrease symptoms of depression and anxiety in the context of cancer-related psychiatric distress for at least 6 months following a single acute administration. A small, open-label study in patients with treatment-resistant depression showed reductions in depression and anxiety symptoms 3 months after two acute doses. For addiction, small, open-label pilot studies have shown promising success rates for both tobacco and alcohol addiction. Safety data from these various trials, which involve careful screening, preparation, monitoring, and follow-up, indicate the absence of severe drug-related adverse reactions. Modest drug-related adverse effects at the time of medication administration are readily managed. US federal funding has yet to support therapeutic psilocybin research, although such support will be important to thoroughly investigate efficacy, safety, and therapeutic mechanisms.