Catalysts for change: the cellular neurobiology of psychedelics

Psychedelics may promote neural plasticity, which is thought to underlie their therapeutic effects in psychiatric disorders. The drugs activate signaling pathways that can produce long-term structural changes in the brain, though these mechanisms are complex and not yet fully understood. Stress and inflammation also play roles in both acute and long-term effects. Beyond altering brain structure, psychedelics challenge and expand understanding of the neural basis of psychiatric disorders, consciousness, and human behavior.

Study at a glance

Abstract

The resurgence of interest in the therapeutic potential of psychedelics for treating psychiatric disorders has rekindled efforts to elucidate their mechanism of action. In this Perspective, we focus on the ability of psychedelics to promote neural plasticity, postulated to be central to their therapeutic activity. We begin with a brief overview of the history and behavioral effects of the classical psychedelics. We then summarize our current understanding of the cellular and subcellular mechanisms underlying these drugs’ behavioral effects, their effects on neural plasticity, and the roles of stress and inflammation in the acute and long-term effects of psychedelics. The signaling pathways activated by psychedelics couple to numerous potential mechanisms for producing long-term structural changes in the brain, a complexity that has barely begun to be disentangled. This complexity is mirrored by that of the neural mechanisms underlying psychiatric disorders and the transformations of consciousness, mood, and behavior that psychedelics promote in health and disease. Thus, beyond changes in the brain, psychedelics catalyze changes in our understanding of the neural basis of psychiatric disorders, as well as consciousness and human behavior.