Alcohol Use Disorder (AUD)Tobacco/Nicotine Use Disorder (TUD)Substance Use Disorders (SUD)Neuroimaging & Brain MeasuresInterpersonal Functioning & Social ConnectednessPublic Health, Prevention & Behaviour Change

Psychedelic-Assisted Therapy for Substance Use Disorders and Potential Mechanisms of Action

This academic book chapter (2021) outlines the potential mechanisms of action of psychedelics in the treatment of substance use disorder (SUD).

Authors

  • Katrin Preller
  • Nathalie Rieser

Published

Current Topics in Behavioral Neurosciences
meta Study

Abstract

Substance use disorders (SUD) represent a significant public health issue with a high need for novel and efficacious treatment options. In light of this high unmet need, recent results reporting beneficial outcomes of psychedelic-assisted therapy in SUD are particularly relevant. However, several questions remain with regard to this treatment approach. The clinical mechanisms of action of psychedelic substances in the treatment of SUD are not well understood. Closing this knowledge gap is critical to inform and optimize the psychotherapeutic embedding of the acute substance administration. In this chapter, we discuss potential mechanisms that have implications on psychotherapeutic approaches including induced neuroplasticity, alterations in brain network connectivity, reward and emotion processing, social connectedness, insight, and mystical experiences. Furthermore, we outline considerations and approaches that leverage these mechanisms in order to optimize the therapeutic embedding by maximizing synergy between substance effects and psychotherapy. Understanding the mechanisms of action, developing psychotherapeutic approaches accordingly, and evaluating their synergistic efficacy in scientific studies will be critical to advance the framework of psychedelic-assisted therapy for addiction, create evidence-based approaches, and achieve the best treatment outcome for patients with SUD.

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Research Summary of 'Psychedelic-Assisted Therapy for Substance Use Disorders and Potential Mechanisms of Action'

Introduction

Serotonergic ‘‘classic’’ psychedelics (5-HT2A receptor agonists such as psilocybin, LSD, ayahuasca/DMT and mescaline) were investigated clinically in the 1950s–1960s for a range of psychiatric disorders, including substance use disorders (SUD). Rieser and colleagues note that early LSD trials—while methodologically limited by modern standards—yielded encouraging signals for alcohol dependence and that contemporary pharmacotherapies for alcohol use disorder remain only modestly effective (relapse rates up to 50%). Renewed clinical interest has produced a small set of modern trials and multiple ongoing studies (including registered trials for alcohol, nicotine and cocaine), and two recent small trials report beneficial effects of psilocybin on smoking cessation and alcohol use lasting up to 6 months, though both lacked rigorous controls. This chapter sets out to identify and discuss putative clinical mechanisms by which psychedelics might exert therapeutic effects in SUD, and to translate those mechanisms into implications for psychotherapeutic practice. The investigators frame two central questions: which psychedelic-induced neurobiological and psychological effects are clinically relevant in SUD, and how should psychotherapy be configured to leverage those effects? The authors limit their scope to classic psychedelics unless otherwise noted and emphasise that psychedelics are typically given within a psychotherapeutic framework (pharmacologically-assisted psychotherapy, PAT).

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