This systematic review (2024) and meta-analysis (s=44) finds that medium/high doses of LSD yield higher ratings of visionary restructuralisation than psilocybin. It also reports that psychedelics strengthen between-network functional connectivity and diminish within-network connectivity, and that LSD induces more inositol phosphate formation at the 5-HT2A receptor than DMT or psilocin, while receptor selectivity differences remain negligible.
Abstract of Synergistic, multi-level understanding of psychedelics
“Serotonergic psychedelics induce altered states of consciousness and have shown potential for treating a variety of neuropsychiatric disorders, including depression and addiction. Yet their modes of action are not fully understood. Here, we provide a novel, synergistic understanding of psychedelics arising from systematic reviews and meta-analyses of three hierarchical levels of analysis: (1) subjective experience (phenomenology), (2) neuroimaging and (3) molecular pharmacology. Phenomenologically, medium and high doses of LSD yield significantly higher ratings of visionary restructuralisation than psilocybin on the 5-dimensional Altered States of Consciousness Scale. Our neuroimaging results reveal that, in general, psychedelics significantly strengthen between-network functional connectivity (FC) while significantly diminishing within-network FC. Pharmacologically, LSD induces significantly more inositol phosphate formation at the 5-HT2A receptor than DMT and psilocin, yet there are no significant between-drug differences in the selectivity of psychedelics for the 5-HT2A, 5-HT2C, or D2 receptors, relative to the 5-HT1A receptor. Our meta-analyses link DMT, LSD, and psilocybin to specific neural fingerprints at each level of analysis. The results show a highly non-linear relationship between these fingerprints. Overall, our analysis highlighted the high heterogeneity and risk of bias in the literature. This suggests an urgent need for standardising experimental procedures and analysis techniques, as well as for more research on the emergence between different levels of psychedelic effects.”
Authors: Kenneth Shinozuka, Katarina Jerotic, Pedro Mediano, Alex T. Zhao, Katrin H. Preller, Robin Carhart-Harris & Morten L. Kringelbach
Summary of Synergistic, multi-level understanding of psychedelics
Psychedelics, originating from the Greek terms for “mind” and “manifesting,” are hallucinogenic substances known to alter consciousness profoundly. Classic psychedelics include LSD, psilocybin, and DMT, which primarily act on serotonin receptors. These substances have been employed for millennia in cultural and spiritual contexts and are now being explored for treating neuropsychiatric conditions like depression and addiction. Despite their therapeutic promise, the precise mechanisms through which they exert their effects remain elusive. This study aims to provide a comprehensive understanding of psychedelics by synthesising findings across three hierarchical domains: subjective experience (phenomenology), brain activity (neuroimaging), and receptor interactions (pharmacology).
This approach integrates data from three systematic reviews and meta-analyses, offering insights into the intricate interplay of pharmacological, neurological, and phenomenological phenomena. By comparing data across multiple studies, the authors sought to uncover commonalities and distinct features of DMT, LSD, and psilocybin, illuminating their unique effects.
Phenomenology
Altered States of Consciousness (ASC) Scale
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https://doi.org/10.1038/s41398-024-03187-1
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Cite this paper (APA)
Shinozuka, K., Jerotic, K., Mediano, P., Zhao, A. T., Preller, K. H., Carhart-Harris, R., & Kringelbach, M. L. (2024). Synergistic, multi-level understanding of psychedelics: three systematic reviews and meta-analyses of their pharmacology, neuroimaging and phenomenology. Translational Psychiatry, 14(1), 1-16.
Study details
Compounds studied
DMT
LSD
Psilocybin
Topics studied
Neuroscience
Study characteristics
Meta-Analysis
Literature Review