Neuroimaging & Brain MeasuresLSD

Increased global functional connectivity correlates with LSD-induced ego dissolution

This seminal fMRI, double-blind, placebo-controlled study (n=15) found that LSD (75µg) increased global connectivity in the brain, which correlated with 'ego dissolution' and which overlapped significantly with where serotonin (5-HT2a) receptors are found.

Authors

  • Suresh Muthukumaraswamy
  • Enzo Tagliazucchi
  • Robin Carhart-Harris

Published

Current Biology
individual Study

Abstract

Lysergic acid diethylamide (LSD) is a non-selective serotonin-receptor agonist that was first synthesized in 1938 and identified as (potently) psychoactive in 1943. Psychedelics have been used by indigenous cultures for millennia; however, because of LSD’s unique potency and the timing of its discovery (coinciding with a period of major discovery in psychopharmacology), it is generally regarded as the quintessential contemporary psychedelic. LSD has profound modulatory effects on consciousness and was used extensively in psychological research and psychiatric practice in the 1950s and 1960s. In spite of this, however, there have been no modern human imaging studies of its acute effects on the brain. Here we studied the effects of LSD on intrinsic functional connectivity within the human brain using fMRI. High-level association cortices (partially overlapping with the default-mode, salience, and frontoparietal attention networks) and the thalamus showed increased global connectivity under the drug. The cortical areas showing increased global connectivity overlapped significantly with a map of serotonin 2A (5-HT2A) receptor densities (the key site of action of psychedelic drugs). LSD also increased global integration by inflating the level of communication between normally distinct brain networks. The increase in global connectivity observed under LSD correlated with subjective reports of “ego dissolution.” The present results provide the first evidence that LSD selectively expands global connectivity in the brain, compromising the brain’s modular and “rich-club” organization and, simultaneously, the perceptual boundaries between the self and the environment.

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Research Summary of 'Increased global functional connectivity correlates with LSD-induced ego dissolution'

Introduction

Tagliazucchi and colleagues situate their work within a long history of psychedelic research and note that, despite LSD's central place in that literature, there were no modern human neuroimaging studies of its acute effects. Earlier studies and theoretical work implicate serotonergic mechanisms—particularly the serotonin 2A (5-HT2A) receptor—in psychedelic effects, and prior imaging with related compounds (for example psilocybin) suggested altered functional connectivity of high-level association networks such as the default-mode, salience, and frontoparietal networks. The authors therefore identified a gap: the need for whole-brain, contemporary fMRI data on how LSD affects intrinsic functional organisation and how those changes relate to subjective experiences such as "ego dissolution." This study set out to characterise LSD-induced changes in global and local functional connectivity and to test whether changes in connectivity of high-level cortical areas correlate with participants' reports of ego dissolution. Using both exploratory whole-brain measures and hypothesis-driven analyses, the investigators aimed to map regions showing increased global coupling, assess how LSD affects modular organisation and hub connectivity, and relate these neurophysiological changes to receptor distributions (5-HT2A) and to subjective ratings obtained under LSD versus placebo. The work is presented as a first modern fMRI investigation of acute LSD effects in humans and as a test of hypotheses derived from prior psychedelic imaging and receptor biology.

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Study Details

References (10)

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Increased nature relatedness and decreased authoritarian political views after psilocybin for treatment-resistant depression

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Quality of acute psychedelic experience predicts therapeutic efficacy of psilocybin for treatment-resistant depression

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Altered network hub connectivity after acute LSD administration

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142 cited
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The Mechanisms of Psychedelic Visionary Experiences: Hypotheses from Evolutionary Psychology

Winkelman, M. J. · Frontiers in Neuroscience (2017)

Increased thalamic resting state connectivity as a core driver of LSD-induced hallucinations

Lenz, C., Dolder, P. C., Lang, U. E. et al. · Acta Psychiatrica Scandinavica (2017)

Serotonin and brain function: a tale of two receptors

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Psychedelics and connectedness

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Psychedelic drug use in healthy individuals: A review of benefits, costs, and implications for drug policy

Elsey, J. W. B. · Drug Science Policy and Law (2017)

Self unbound: ego dissolution in psychedelic experience

Letheby, C., Gerrans, P. · Neuroscience of Consciousness (2017)

A Single Dose of LSD Does Not Alter Gene Expression of the Serotonin 2A Receptor Gene (HTR2A) or Early Growth Response Genes (EGR1-3) in Healthy Subjects

Liechti, M. E., Dolder, P. C., Grünblatt, E. et al. · Frontiers in Pharmacology (2017)

11 cited
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Lifetime experience with (classic) psychedelics predicts pro-environmental behavior through an increase in nature relatedness

Forstmann, M., Sagioglou, C. · Journal of Psychopharmacology (2017)

134 cited
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Looking for the Self: Phenomenology, Neurophysiology and Philosophical Significance of Drug-induced Ego Dissolution

Millière, R. · Frontiers in Human Neuroscience (2017)

Modern clinical research on LSD

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164 cited
The psychological and human brain effects of music in combination with psychedelic drugs

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Pharmacokinetics and pharmacodynamics of lysergic acid diethylamide in healthy subjects

Dolder, P. C., Schmid, Y., Steuer, A. E. et al. · Clinical Pharmacokinetics (2017)

5-HT2A Agonists: A Novel Therapy for Functional Neurological Disorders?

Bryson, A., Carter, O., Norman, T. et al. · International Journal of Neuropsychopharmacology (2017)

18 cited
Phenomenology, Structure, and Dynamic of Psychedelic States

Preller, K. H., Vollenweider, F. X. · Behavioral Neurobiology of Psychedelic Drugs (2016)

Classical hallucinogens and neuroimaging: A systematic review of human studies: hallucinogens and neuroimaging

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The Challenging Experience Questionnaire: Characterization of challenging experiences with psilocybin mushrooms

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Alterations of consciousness and mystical-type experiences after acute LSD in humans

Liechti, M. E., Dolder, P. C., Schmid, Y. · Psychopharmacology (2016)

190 cited
Ego-dissolution and psychedelics: validation of the ego-dissolution inventory (EDI)

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LSD-induced entropic brain activity predicts subsequent personality change

Lebedev, A. V., Kaelen, M., L€ Ovd En, M. et al. · Human Brain Mapping (2016)

292 cited
New World Tryptamine Hallucinogens and the Neuroscience of Ayahuasca

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Serotonergic Hallucinogen-Induced Visual Perceptual Alterations

Kometer, M., Vollenweider, F. X. · Behavioral Neurobiology of Psychedelic Drugs (2016)

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