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

Neuropsychopharmacology volume 49, pages 1120–1128 (2024)Cite this article

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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.

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Fig. 1: Subjective drug effects across LSD, THC, and MA studies.
Fig. 2: Limpel-Ziv complexity across LSD, THC, and MA studies under 10–20 electrode placements of over prefrontal (Fp), frontal (F), temporal (T), parietal (P), occipital (O), and central (C) regions.
Fig. 3: Spectral power analysis across LSD, THC, and MA studies.
Fig. 4: Pearson correlations in the high-dose condition across LSD, THC, and MA studies.

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Funding

This research was supported by the National Institutes of Health [DA02812]. CHM was supported by the National Institutes of Health [T32DA043469]. Additional support was received as a Pilot Grant from the Department of Psychiatry and Behavioral Neuroscience, University of Chicago.

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  1. Conor H. Murray

    Present address: Department of Psychiatry and Biobehavioral Sciences, University of Los Angeles, California, 760 Westwood Plaza, Los Angeles, CA, 90024, USA

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  1. Department of Psychiatry and Behavioral Neuroscience, University of Chicago, 5841 S Maryland Ave, Chicago, IL, 60637, USA

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

  2. Institute for Neuromodulation and Neurotechnology, University of Tübingen, Otfried-Müller-Straße 45, 72076, Tübingen, Germany

    Joel Frohlich

  3. Institute for Advanced Consciousness Studies, Santa Monica, California; 2811 Wilshire Blvd # 510, Santa Monica, CA, 90403, USA

    Joel Frohlich

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CHM for acquisition, analysis of data, and drafting of the manuscript. CH and IT for data acquisition. JF for the interpretation of data; critical revision of manuscript for intellectual content. RL for the interpretation of data; critical revision of manuscript for intellectual content. HdW for conception and design of the work; interpretation of data; critical revision of manuscript for intellectual content. All authors approved final manuscript for submission.

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Murray, C.H., Frohlich, J., Haggarty, C.J. et al. Neural complexity is increased after low doses of LSD, but not moderate to high doses of oral THC or methamphetamine. Neuropsychopharmacol. 49, 1120–1128 (2024). https://doi.org/10.1038/s41386-024-01809-2

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