Psychedelic agents for treatment-resistant depression

A growing body of evidence suggests that psychedelic-assisted therapy may be a safe and effective treatment for a variety of mental health conditions including depressive disorders such as treatment-resistant depression (TRD). This chapter presents an overview of treatment with classic psychedelics such as psilocybin, lysergic acid diethylamide (LSD), and N,N-dimethyltryptamine (DMT), with a special focus on implications for TRD. Topics include (1) a brief history of research with these substances; (2) chemistry and pharmacology; (3) mechanisms of action including both biological and psychological mechanisms; (4) an overview of the common features of the treatment model; (5) major clinical studies to date that have examined the effects of psychedelic-assisted therapy in depressive disorders; and (6) adverse effects and medication interactions. The chapter concludes with a discussion of future directions for research and clinical use.