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The Effects of Serotonergic Psychedelics on Neural Activity: A Meta-Analysis of Task-Based Functional Neuroimaging Studies

J. H. Shepherd, Caitlin Baten, A. C. Klassen, Gladys Zamora, Sarah Saravia, Elizabeth Pritchard, Ziad A. Ali, Saneh K. Kahlon, Kyla Whitelock, Fredy Alberto Reyes Lizcano, D. W. Hedges, J. Paul Hamilton, Matthew D. Sacchet, Chris H. Miller

European Psychiatry March 1, 2023 DOI: 10.1192/j.eurpsy.2023.1948 (opens in new tab)

Study at a glance

AI-extracted from the abstract
Characteristics Meta-analysis Peer reviewed
Interventions LSD psilocybin MDMA
Topics MDMA Psilocybin Serotonin
Keywords Functional neuroimaging Hallucinogen
Key findings Serotonergic psychedelics (LSD, psilocybin, and MDMA) produce significant effects on neural activation in the cerebral cortex and basal ganglia, with both common and drug-specific patterns.

Abstract

Introduction: Curiosity toward the effects of psychedelic drugs on neural activation has increased due to their potential therapeutic benefits, particularly serotonergic psychedelics that act as 5-HT2A receptor agonists such as LSD, psilocybin, and MDMA. However, the pattern of their effects on neural activity in various brain regions in both clinical and healthy populations is still not well understood, and primary studies addressing this issue have sometimes generated inconsistent results.

Objectives: The present meta-analysis aims to advance our understanding of the most widely used serotonergic psychedelics – LSD, psilocybin, and MDMA – by examining their effects on the functional activation throughout the whole brain among both clinical and healthy participants.

Methods: We conducted this meta-analysis by applying multilevel kernel density analysis (MKDA) with ensemble thresholding to quantitatively combine existing functional magnetic resonance imaging (fMRI) studies that examined whole-brain functional activation of clinical or healthy participants who were administered a serotonergic psychedelic.

Results: Serotonergic psychedelics, including LSD, psilocybin, and MDMA, exhibited significant effects (α=0.05) on neural activation in several regions throughout the cerebral cortex and basal ganglia, including effects that may be common across and unique within each drug.

Conclusions: These observed effects of serotonergic psychedelics on neural activity advance our understanding of the functional neuroanatomy associated with their administration and may inform future studies of both their adverse and therapeutic effects, including emerging clinical applications for the treatment of several psychiatric disorders. Disclosure of Interest None Declared

Comparable studies

Other systematic reviews and meta-analyses on serotonin, most cited first.

Study Year Design Participants
Therapeutic effects of classic serotonergic psychedelics: A systematic review of modern‐era clinical studies Patients with cancer- or illness-related anxiety and depression, major depressive... 2020 Systematic review n = 188
Efficacy, tolerability, and safety of serotonergic psychedelics for the management of mood, anxiety, and substance-use disorders: a systematic review of systematic reviews Patients with mood, anxiety, or substance-use disorders, including cancer patients and... 2018 Systematic review of systematic reviews
Adverse events in clinical treatments with serotonergic psychedelics and MDMA: A mixed-methods systematic review Patients in clinical trials with MDMA or serotonergic psychedelics 2022 Systematic review n = 598
Classic serotonergic psychedelics for mood and depressive symptoms: a meta-analysis of mood disorder patients and healthy participants Healthy volunteers and patients with mood disorders 2021 Meta-analysis n = 257
Serotonergic psychedelics and personality: A systematic review of contemporary research 2018 Systematic review

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