Synergistic, Multi-level Understanding of Psychedelics: Three Systematic Reviews and Meta-analyses of Their Pharmacology, Neuroimaging and Phenomenology
bioRxiv (Cold Spring Harbor Laboratory) October 7, 2023 Kenneth Shinozuka, Katarina Jerotic, Pedro A. M. Mediano et al. 2 citations preprint
Serotonergic psychedelics such as LSD, psilocybin, and DMT alter consciousness and show therapeutic potential for depression and addiction, but their mechanisms remain unclear. A systematic review and meta-analysis across three levels—phenomenology, neuroimaging, and pharmacology—reveals that medium and high doses of LSD produce significantly stronger visionary restructuring than psilocybin. Neuroimaging shows psychedelics generally strengthen connectivity between brain networks while weakening connectivity within networks. Pharmacologically, LSD triggers more inositol phosphate formation at the 5-HT2A receptor than DMT or psilocin, but no significant differences emerged in receptor selectivity among the drugs. The findings highlight high heterogeneity and risk of bias, underscoring the need for standardized methods.