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Neural effects of psychedelics: Complexity the key word

Neuropsychopharmacology (2024)Cite this article

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It is impossible to ignore the rapidly growing interest in the therapeutic use of psychedelics. Once marginalized as elements of counterculture, substances such as lysergic acid diethylamide (LSD) have catapulted into the limelight. Traditionally, psychedelic therapy has involved administering “macro” doses, leading to potent psychoactive effects (the psychedelic “trip”). Although these effects are assumed to have therapeutic merits some argue that they may limit the broader application of these emerging interventions [1]. “Microdosing”, an alternative approach that involves taking sub-hallucinogenic doses of psychedelics for mental health benefit, is being evaluated in clinical populations. At the same time, mechanisms of effects of psychedelics (both macro and microdosed) are being evaluated.

In this context, the recent report by Murray et al. published in Neuropsychopharmacology is a relevant contribution to the field [2]. Pooling data from three previous studies, the authors evaluated the relationship between electroencephalography (EEG) measures of neural complexity across drug classes and doses in healthy participants. Neural complexity refers to the diversity and richness of brain activity patterns. It is hypothesized that serotonin 2A receptor (5-HT2A) receptor agonism induces changes in neural complexity during the subjective psychedelic experience, serving as a key mechanism for therapeutic effects [2]. Murray et al. conducted a secondary analysis involving 73 healthy adults that compared microdoses of either LSD (13 and 26 µg), tetrahydrocannabinol (THC) (7.5 and 15 mg), or methamphetamine (10 and 20 mg) against placebo. Each participant underwent three sessions during which they received either a placebo or one of two doses of the respective drugs. They assessed clinical measures including the 5 Dimensions of Altered State of Consciousness (5D-ASC), a self-reported measure of the subjective psychedelic experience, and EEG measures of neural complexity (Limpel-Ziv Complexity).

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References

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Funding

BDMJ reports grants from the PSI Foundation, the University of Toronto and CIHR. MIH receives research support from the Brain and Behavior Research Foundation, Canadian Institutes of Health Research (CIHR), CAMH Foundation, Grand Challenges Canada, the PSI Foundation, and the University of Toronto. He has provided consultancy to Mindset Pharma, PsychEd Therapeutics, and Wake Network.

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Authors and Affiliations

  1. Department of Psychiatry, Temerty Faculty of Medicine, University of Toronto, Toronto, ON, Canada

    Brett D. M. Jones & M. Ishrat Husain

  2. Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health (CAMH), Toronto, ON, Canada

    Brett D. M. Jones & M. Ishrat Husain

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  1. Brett D. M. Jones
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  2. M. Ishrat Husain
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Both BDMJ and MIH drafted the manuscript.

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Correspondence to M. Ishrat Husain.

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Jones, B.D.M., Husain, M.I. Neural effects of psychedelics: Complexity the key word. Neuropsychopharmacol. (2024). https://doi.org/10.1038/s41386-024-01856-9

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