Treatment-Resistant Depression (TRD)Depressive DisordersAlcohol Use Disorder (AUD)Tobacco/Nicotine Use Disorder (TUD)Set & SettingPublic Health, Prevention & Behaviour ChangeSubstance Use Disorders (SUD)LSDMDMAPsilocybin

Human behavioral pharmacology of psychedelics

This commentary (2021) provides an overview of the human behavioural pharmacology of the classic psychedelic; psilocybin, LSD and DMT. Special considerations when conducting human research with psychedelics are discussed as well as the subjective, physiological, and clinical effects of these substances.

Authors

  • Matthew Johnson

Published

Advances in Pharmacology
meta Study

Abstract

The past decade has witnessed a rapid growth of research on the basic science and clinical understanding of psychedelics. This chapter provides an overview of the human behavioural pharmacology of psychedelics focusing on three prototypic classic psychedelics-psilocybin, lysergic acid diethylamide (LSD), and dimethyltryptamine (DMT). A brief historical overview of the classic psychedelics and naming and drug classification is first specified. Next, special considerations in the conduct of human behavioural pharmacology work with psychedelics is described including the role of set and setting, mystical experience measurement, the use of effective blinding and placebos, and the abuse liability of psychedelics. Following, a description of the subjective, physiological, and clinical effects of psilocybin, LSD, and DMT is provided. This body of work clearly documents a unique and complex collection of subjective effects following psychedelic use, both during acute drug administration and as related to long-term behaviour change following use. Clinical research demonstrates potential therapeutic utility with early phase clinical trials showing positive and enduring effects in many difficult-to-treat conditions including treatment-resistant depression, alcohol use disorder, and cigarette smoking. Future work in this newly reemerged field is needed to reveal mechanisms of behaviour change in psychedelic drug action. Behavioural pharmacology is ultimately well served to provide this direction answering questions at the intersection of environment and pharmacology.

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Research Summary of 'Human behavioral pharmacology of psychedelics'

Introduction

Psychedelics are a group of psychoactive compounds that primarily act as agonists or partial agonists at the serotonin 2A receptor (5-HT2AR). Interest in their clinical potential has resurged after a long hiatus following mid-20th century research; contemporary work combines modern neuroscience and rigorous clinical methods and is focused on therapeutic applications in conditions that have been difficult to treat. Strickland and colleagues situate their chapter within this renewed effort and emphasise both the historical context and the methodological advances that distinguish modern human research from the earlier era. This paper sets out to provide an overview of the human behavioural pharmacology of three prototypic classic psychedelics—psilocybin, LSD, and DMT. The authors outline nomenclature and classification, highlight special methodological considerations for human studies (for example, set and setting, measurement of mystical experiences, blinding, and abuse liability), and then review the subjective, physiological, and emerging clinical findings for each compound. The chapter concludes by identifying outstanding questions and priorities for future research, with an emphasis on behavioural pharmacology approaches that explore interactions between pharmacology and environment.

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