Depressive DisordersPTSDSubstance Use Disorders (SUD)

The Subjective Effects of Psychedelics May Not Be Necessary for Their Enduring Therapeutic Effects

This opinion paper (2020) argues that the neurological effects of psychedelics alone (vs subjective experience) are enough to lead to enduring therapeutic outcomes.

Authors

  • David Olson

Published

ACS Pharmacology and Translational Science
meta Study

Abstract

Psychedelics represent one of the most promising classes of experimental medicines for the treatment of neuropsychiatric disorders due to their ability to promote neural plasticity and produce both rapid and sustained therapeutic effects following a single administration. Conventional wisdom holds that peak mystical experiences induced by psychedelics are a critical component of their therapeutic mechanisms of action, though evidence supporting that claim is largely correlational. Here, I present data suggesting that the subjective effects induced by psychedelics may not be necessary to produce long-lasting changes in mood and behavior. Understanding the role of subjective effects in the therapeutic mechanisms of psychedelics will have important implications for both basic neuroscience and for increasing patient access to the next generation of medicines developed as a result of psychedelic research.

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Research Summary of 'The Subjective Effects of Psychedelics May Not Be Necessary for Their Enduring Therapeutic Effects'

Introduction

Neuropsychiatric disorders such as depression, PTSD and addiction are leading contributors to global disability, yet many patients remain treatment-resistant and current therapies have long onset times. Olson frames psychoplastogens—compounds that rapidly promote neural plasticity and structural remodelling in cortical neurons—as a promising new class of neurotherapeutics that act on circuit structure rather than solely on neurochemistry. Ketamine and serotonergic psychedelics are highlighted as exemplar psychoplastogens that can produce rapid and sustained behavioural benefits after one or a few administrations, with some clinical reports showing effects lasting beyond six months. Conventional wisdom holds that the intense subjective or “mystical” experiences induced by many psychedelics are critical to their therapeutic action. However, Olson notes that evidence for a causal role of subjective effects is largely correlational. The paper sets out to question whether acute subjective effects are necessary for enduring therapeutic outcomes, summarise converging preclinical and clinical observations that dissociate subjective phenomena from plasticity-driven benefits, and discuss the implications for mechanisms, clinical trial design and patient access to future treatments inspired by psychedelic research.

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Study Details

References (26)

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