Anxiety DisordersDepressive DisordersNeuroimaging & Brain MeasuresSchizophreniaSubstance Use Disorders (SUD)Healthy VolunteersPersonality DisordersLSD

Acute effects of lysergic acid diethylamide (LSD) on resting brain function

This review of recent fMRI studies finds that acute LSD produces widespread alterations in functional brain connectivity — predominantly increases and most consistently heightened thalamocortical coupling — supporting models of reduced cerebral filtering of external and internal information, though results are tempered by neuroimaging limitations and potential biases.

Authors

  • Felix, M.
  • Stefan, B.

Published

Swiss Medical Weekly
meta Study

Abstract

Lysergic acid diethylamide (LSD) is a potent hallucinogenic substance that was extensively investigated by psychiatrists during the 1950s and 1960s. Researchers were interested in the unique effects induced by this substance, some of which resemble symptoms seen in schizophrenia. Moreover, during that period LSD was studied and used for the treatment of several mental disorders such as depression, anxiety, addiction and personality disorders. Despite this long history of research, how LSD induces its specific effects on a neuronal level has been relatively unclear. In recent years there has been a revival of research in hallucinogenic drugs and their possible clinical applications. These contemporary studies in the UK and Switzerland include neuroimaging studies using functional magnetic resonance imaging (fMRI). In this review, we collect and interpret these recent neuroimaging findings. Overall, previous results across studies indicate that LSD administration is associated with extensive alterations in functional brain connectivity, measuring the correlated activities between different brain regions. The studies mostly reported increases in connectivity between regions and, more specifically, consistently found increased connectivity within the thalamocortical system. These latter observations are in agreement with models proposing that hallucinogenic drugs exert their effects by inhibiting cerebral filtering of external and internal data. However, studies also face several limitations, including potential biases of neuroimaging measurements.

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Research Summary of 'Acute effects of lysergic acid diethylamide (LSD) on resting brain function'

Introduction

Lysergic acid diethylamide (LSD) is a potent hallucinogen that produces profound alterations in perception, emotion and cognition even at moderate doses. Historical psychiatric research in the 1950s and 1960s explored LSD both as a treatment adjunct in psychotherapy and as a pharmacological model for psychosis; research largely halted after prohibition but has seen a modern revival. A key unresolved question motivating renewed work is how LSD’s characteristic subjective effects map onto neuronal activity, particularly patterns of functional connectivity measured with functional magnetic resonance imaging (fMRI). Felix and colleagues frame the present paper as a focused review of recent fMRI studies in healthy volunteers that examined resting-state functional connectivity following moderate LSD dosing (oral 100 µg or intravenous 75 µg). The authors restrict their scope to resting-state analyses (no task fMRI) and concentrate on measures of functional connectivity—that is, correlations of activity between brain regions—reporting and interpreting findings from three clinical trials (sample sizes reported in the extracted text ranged from 15 to 24 subjects).

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