Classic psychedelics: past uses, present trends, future possibilities

Classic psychedelics, which act on the serotonin 2A receptor, show potential for treating depression and addictive disorders with surprising efficacy. The review covers mechanisms of action, clinical and non-clinical uses, and mediators like mystical experiences and psychological flexibility. It also discusses how these compounds challenge current understandings of brain and mind, noting a renaissance in scientific and public interest. The authors split the review between established knowledge and theoretical speculation to help readers navigate a rapidly changing field.

Study at a glance

Abstract

Here we consider psychedelics with respect to their mechanisms of action, use, and implications for our understandings of brain and mind. This review is somewhat nontraditional in its scope, with discussions of both basic facts as well as theoretical speculations. We chose this approach given the unique historical context we find ourselves in at present. While we have decades of investigations to draw upon with respect to the clinical science and neuropsychopharmacology of psychedelics, we are also witnessing a renaissance (or perhaps a revolution) in which scientific and public interest in these compounds seems to be exploding. We have decided to split this review between the fundamental and theoretical, with hopes that we can give readers familiarity with well-established knowledge, as well as questions to hold in mind in attempting to make sense of a rapidly shifting epistemic landscape. Below we focus on serotonin 2A receptor (5-HT2aR) agonists, or “classic psychedelics,” and discuss research suggesting their potential roles in clinical and non-clinical contexts. Particular emphasis is placed on studies suggesting potentially surprising degrees of efficacy for conditions such as depression and addictive disorders. We also evaluate potential mediators and moderators of therapeutic outcomes, including factors such as mystical experiences and psychological flexibility. Finally, we consider likely future directions for psychedelics in science and society.