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Neural complexity is increased after low doses of LSD, but not moderate to high doses of oral THC or methamphetamine.

Conor H. Murray, Joel Frohlich, Connor J Haggarty, Ilaria Tare, Royce Lee, Harriet de Wit

Neuropsychopharmacology June 1, 2024 DOI: 10.1038/s41386-024-01809-2 (opens in new tab)

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Study at a glance

AI-extracted from the abstract
Characteristics Within-subjects placebo-controlled study Peer reviewed
Sample size 73
Population Healthy volunteers
Interventions LSD delta-9-tetrahydrocannabinol methamphetamine
Dose 13 and 26 µg (LSD), 7.5 and 15 mg (THC), 10 and 20 mg (MA)
Duration Three laboratory visits; EEG recorded during anticipated peak drug effects
Topics Philosophy of mind Cannabis LSD
Keywords Pharmacology Psychedelics Brain research
Citations 30
Key points Low doses of LSD, but not THC or methamphetamine, dose-dependently increased neural complexity in the absence of altered states of consciousness.

Abstract

Neural complexity correlates with one's level of consciousness. During coma, anesthesia, and sleep, complexity is reduced. During altered states, including after lysergic acid diethylamide (LSD), complexity is increased. In the present analysis, we examined whether low doses of LSD (13 and 26 µg) were sufficient to increase neural complexity in the absence of altered states of consciousness. In addition, neural complexity was assessed after doses of two other drugs that significantly altered consciousness and mood: delta-9-tetrahydrocannabinol (THC; 7.5 and 15 mg) and methamphetamine (MA; 10 and 20 mg). In three separate studies (N = 73; 21, LSD; 23, THC; 29, MA), healthy volunteers received placebo or drug in a within-subjects design over three laboratory visits. During anticipated peak drug effects, resting state electroencephalography (EEG) recorded Limpel-Ziv complexity and spectral power. LSD, but not THC or MA, dose-dependently increased neural complexity. LSD also reduced delta and theta power. THC reduced, and MA increased, alpha power, primarily in frontal regions. Neural complexity was not associated with any subjective drug effect; however, LSD-induced reductions in delta and theta were associated with elation, and THC-induced reductions in alpha were associated with altered states. These data inform relationships between neural complexity, spectral power, and subjective states, demonstrating that increased neural complexity is not necessary or sufficient for altered states of consciousness. Future studies should address whether greater complexity after low doses of LSD is related to cognitive, behavioral, or therapeutic outcomes, and further examine the role of alpha desynchronization in mediating altered states of consciousness.

Comparable studies

Other randomized controlled trials on LSD, most cited first.

Study Year Design Participants
Safety and Efficacy of Lysergic Acid Diethylamide-Assisted Psychotherapy for Anxiety Associated With Life-threatening Diseases Patients with anxiety associated with life-threatening diseases 2014 Randomized controlled trial n = 12
Dose-Response Study of N,N-Dimethyltryptamine in Humans Experienced hallucinogen users 1994 Double-blind, saline placebo-controlled, randomized study n = 12
Acute Effects of Lysergic Acid Diethylamide in Healthy Subjects Healthy subjects (8 women, 8 men) 2014 Double-blind, randomized, placebo-controlled, crossover study n = 16
Changes in global and thalamic brain connectivity in LSD-induced altered states of consciousness are attributable to the 5-HT2A receptor Healthy human participants 2018 Double-blind, randomized, counterbalanced, cross-over study n = 24
LSD-induced entropic brain activity predicts subsequent personality change. Healthy adults 2016 Balanced-order, placebo-controlled study n = 19

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Philosophy of mind Cannabis LSD Addiction Altered states of consciousness Mystical experience