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Synergistic, multi-level understanding of psychedelics: three systematic reviews and meta-analyses of their pharmacology, neuroimaging and phenomenology

Summary

This comprehensive study analyzed three classic psychedelic drugs—LSD, psilocybin (from magic mushrooms), and DMT—across three levels: how people experience them, how they affect brain activity, and how they interact with brain receptors. Researchers found that LSD produces more intense visual experiences than psilocybin, and all three drugs significantly alter brain connectivity patterns. The study highlights the importance of standardizing research methods to better understand how these compounds might help treat depression and addiction.

Background

Serotonergic psychedelics including LSD, psilocybin, and DMT induce altered states of consciousness and show potential for treating neuropsychiatric disorders like depression and addiction. However, their mechanisms of action across different biological levels remain incompletely understood.

Objective

To provide a comprehensive, multi-level understanding of psychedelics by conducting systematic reviews and meta-analyses examining three hierarchical levels: subjective experience (phenomenology), neuroimaging findings, and molecular pharmacology of DMT, LSD, and psilocybin.

Results

LSD produced significantly higher visionary restructuralization and oceanic boundlessness than psilocybin at medium and high doses. Psychedelics strengthened between-network functional connectivity while diminishing within-network connectivity. LSD induced significantly more inositol phosphate formation at 5-HT2A receptors than DMT and psilocin, with no significant between-drug differences in receptor selectivity.

Conclusion

The study reveals distinct neural fingerprints for DMT, LSD, and psilocybin across phenomenological, neuroimaging, and pharmacological levels with highly non-linear relationships. High heterogeneity and bias in the literature necessitates standardization of experimental procedures and more research on emergence between different analytical levels.
  • Published in:Translational Psychiatry,
  • Study Type:Meta-analysis, Systematic Review,
  • Source: PMID: 39632810, DOI: 10.1038/s41398-024-03187-1
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