Mini-review: The neurobiology of treating substance use disorders with classical psychedelics

Since the 1960s, psychedelics have shown potential for persistently treating substance use disorders, but the biological mechanisms behind their therapeutic effects remain unclear. Serotonergic hallucinogens are known to alter gene expression and neuroplasticity, especially in prefrontal brain regions, yet how these changes specifically counteract the neuronal circuit alterations that develop during addiction is largely unknown. This narrative mini-review synthesizes established addiction research with findings and theories on the neurobiological effects of psychedelics, providing an overview of potential mechanisms underlying treatment of substance use disorders with classical hallucinogens and identifying gaps in current understanding.

Study at a glance

Abstract

The potential of psychedelics to persistently treat substance use disorders is known since the 1960s. However, the biological mechanisms responsible for their therapeutic effects have not yet been fully elucidated. While it is known that serotonergic hallucinogens induce changes in gene expression and neuroplasticity, particularly in prefrontal regions, theories on how specifically this counteracts the alterations that occur in neuronal circuitry throughout the course of addiction are largely unknown. This narrative mini-review endeavors to synthesize well-established knowledge from addiction research with findings and theories regarding the neurobiological effects of psychedelics to give an overview of the potential mechanisms that underlie the treatment of substance use disorders with classical hallucinogenic compounds and point out gaps in the current understanding.