Psychedelic experiences elicited by serotonergic psychedelics: Molecular mechanisms and functional connectivity changes in the brain.
Level 5 - mechanism / opinion, no new human data
Systematic review synthesizing experimental, preclinical, and mechanistic neuroimaging studies rather than clinical trial efficacy.
PubMed 41412413 · doi:10.1016/j.neubiorev.2025.106529
What was done
The authors conducted a systematic review of experimental, preclinical, and clinical literature from 1990 onward examining the neurobiological effects of classical serotonergic psychedelics (such as LSD, DMT, and psilocybin). The synthesis evaluated short-term receptor pharmacology, intracellular signaling pathways, and network-level changes in functional brain connectivity during the acute psychedelic state.
What was found
The abstract reports no quantitative metrics, effect sizes, or study counts. Qualitatively, classical psychedelics act primarily as serotonin 5-HT2A receptor agonists, initiating intracellular signaling cascades that influence glutamate release, cortical excitability, and neuroplasticity. At the network level, they disrupt resting-state functional connectivity within localized networks—particularly the default mode network—while increasing global functional integration across normally segregated brain regions, correlating with subjective experiences such as ego dissolution.
Why it matters
Connecting cellular receptor pharmacology to large-scale functional brain network alterations provides a unified mechanistic framework for how psychedelics induce altered states of consciousness. This understanding is key for identifying biological markers and optimizing targeted clinical applications in psychiatric disorders.
Limits
The abstract omits the number of studies reviewed, search criteria, and quantitative summary data. The review combines heterogeneous evidence sources ranging from cellular and animal models to human neuroimaging, which differ widely in methodology and translational applicability.