Neural complexity is increased after low doses of LSD, but not moderate to high doses of oral THC or methamphetamine
This re-analysis (n=73) investigates the effects of low doses of LSD (13-26µg; n=21), THC (7.5-15mg), and methamphetamine (MA; 10-20mg) on neural complexity in healthy volunteers without inducing altered states of consciousness. Utilizing a within-subjects design over three laboratory visits, the study records resting state EEG data to measure Lempel-Ziv complexity and spectral power. Results demonstrate that only LSD, not THC or MA, dose-dependently increases neural complexity and reduces delta and theta power, while THC and MA respectively decrease and increase alpha power, primarily in frontal regions.
Authors
- Harriet de Wit
- Richard Lee
Published
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.
Research Summary of 'Neural complexity is increased after low doses of LSD, but not moderate to high doses of oral THC or methamphetamine'
Introduction
Earlier research has linked neural complexity, often measured with EEG signal-diversity metrics, to levels of consciousness: complexity falls during sleep, anaesthesia and coma and rises during certain altered states. Psychedelics such as LSD have been reported to increase neural complexity at high doses, and the entropic brain hypothesis proposes that such increases may destabilise maladaptive patterns of thought and behaviour. At the same time, low-dose or "microdosing" practices have become popular and controlled studies have shown some acute improvements in well-being after low doses, but objective neural markers at these doses remain poorly characterised. Murray and colleagues set out to determine whether low doses of LSD (13 and 26 µg) increase neural complexity in the absence of overt psychedelic-like altered states, and to compare those effects with two other drugs that do alter consciousness and mood at the tested doses: oral THC (7.5 and 15 mg) and methamphetamine (MA; 10 and 20 mg). The investigators focused on resting-state Lempel–Ziv (Limpel-Ziv in the text) complexity as the primary neural outcome, alongside spectral power and self-reported subjective and mood measures, to clarify whether increased complexity is necessary or sufficient for altered states of consciousness.
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Study Details
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- APA Citation
Murray, C. H., Frohlich, J., Haggarty, C. J., Tare, I., Lee, R., & de Wit, H. (2024). Neural complexity is increased after low doses of LSD, but not moderate to high doses of oral THC or methamphetamine. Neuropsychopharmacology, 49(7), 1120-1128. https://doi.org/10.1038/s41386-024-01809-2
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