de Vos · Frontiers in psychiatry 2021 · systematic review of preclinical and clinical studies · n=20 studies

Psychedelics and Neuroplasticity: A Systematic Review Unraveling the Biological Underpinnings of Psychedelics.

Cited 267 times in the scientific literature.

Level 5 - mechanism / opinion, no new human data

Systematic review composed predominantly of preclinical bench and animal research (16 of 20 included studies).

PubMed 34566723 · doi:10.3389/fpsyt.2021.724606 · record verified 2026-08-28

What was done

The authors conducted a systematic review evaluating the molecular and cellular neuroplasticity mechanisms induced by single and repeated administration of psychedelics (including ayahuasca, DMT, psilocybin, and LSD). A database search identified 344 records, resulting in the inclusion of 20 studies (16 preclinical and 4 clinical) to assess biological pathways and associated behavioral or clinical outcomes.

What was found

The abstract reports qualitative findings without numerical effect sizes or statistical values. Single administrations of psychedelics induced rapid molecular, neuronal, synaptic, and dendritic changes, including altered expression of plasticity-related genes and Brain-Derived Neurotrophic Factor (BDNF) protein, accompanied by increased dendritic complexity outlasting acute drug effects. Repeated administration directly stimulated neurogenesis and elevated BDNF mRNA levels up to one month post-treatment.

Why it matters

This review synthesizes biological evidence suggesting that cellular and structural neuroplasticity may be a core mechanism underlying the therapeutic, antidepressant, and anxiolytic effects observed with psychedelic compounds.

Limits

The evidence base is heavily skewed toward preclinical models (16 out of 20 studies), limiting direct generalizability to human clinical outcomes. The abstract omits quantitative effect sizes, specific dosing parameters, human participant numbers, and formal risk-of-bias evaluations.

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