Synergistic, Multi-level Understanding of Psychedelics: Three Systematic Reviews and Meta-analyses of Their Pharmacology, Neuroimaging and Phenomenology
OpenAlex – October 07, 2023
Source: OpenAlex
Summary
LSD induces more profound visionary experiences than psilocybin, a key finding from a meta-analysis exploring how these serotonergic hallucinogens alter consciousness. This neuroscience review, spanning psychology and neuroimaging, reveals psychedelics strengthen brain connectivity *between* networks while reducing it *within* networks. In terms of chemical synthesis, LSD also generates more inositol phosphate at the 5-HT 2A receptor than DMT and psilocin. This integrated understanding of neurotransmitter receptor influence on behavior offers insights into potential addiction treatments, advancing Psychedelics and Drug Studies.
Abstract
Abstract 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-HT 2A receptor than DMT and psilocin, yet there are no significant between-drug differences in the selectivity of psychedelics for the 5-HT 2A , 5-HT 2C , or D 2 receptors, relative to the 5-HT 1A 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.