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

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.

Fig. 1. Subjective drug effects across LSD, THC, and MA studies.

A Drug Effects Questionnaire measure of Feel Drug Effect over sessions. B Profile of Mood States measures of Anxiety and Elation, peak response minus baseline. C 5-Dimensions of Altered States of Consciousness rated retrospectively at session end in relation to peak drug effects. *p < 0.05, **p < 0.01, ***p < 0.001.

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.

Each dose condition shows % change relative to placebo. Red indicates increases and blue indicates decreases. Yellow rings indicate FDR-corrected significance in scalp electrodes relative to placebo conditions; seven significant electrodes in the 13 μg LSD condition did not pass FDR correction. Bar graphs show ANOVA results comparing the three doses for each study averaging all 10–20 scalp electrodes together are shown at right. ***p < 0.001.

Fig. 3. Spectral power analysis across LSD, THC, and MA studies.

Each dose condition shows % change relative to placebo. Red indicates increases and blue indicates decreases. Yellow rings map FDA-corrected significance in electrodes relative to placebo conditions. ANOVA results comparing the three doses for each study averaging all 10–20 scalp electrodes together are shown in Table S1.

Fig. 4. Pearson correlations in the high-dose condition across LSD, THC, and MA studies.

ASC: VR and ASC: DED refer to 5D-ASC Vigilance Reduction and Dread of Ego Dissolution, respectively. Yellow dots indicate significant correlation. 5D-ASC measures in the LSD study were not associated with EEG measures.