Neuroplasticity and psilocybin — separating the evidence from the hype
56 replies · Science & Research
The claim that psilocybin 'promotes neuroplasticity' gets repeated constantly now, including in mainstream coverage. I want to understand what the evidence actually shows vs. what's been extrapolated from rodent studies to humans without sufficient justification. Can someone who has read the primary literature break this down?
The primary evidence is Shao et al. (2023, Science): a single dose of psilocybin rapidly induced dendritic spine growth in mouse prefrontal cortex, with effects lasting at least 34 days. This is genuine, peer-reviewed, impressive science. The limitations: mouse not human, doses were not microdose-range, and prefrontal dendritic spine growth is not the same as 'neuroplasticity' in the general sense. The jump from 'this happened in mice' to 'psilocybin makes your brain more plastic' is an extrapolation.
BDNF (brain-derived neurotrophic factor) upregulation from psilocybin is real in rodents and plausibly in humans — it's a known downstream effect of 5-HT2A agonism. BDNF promotes synaptic plasticity. This mechanism is pharmacologically coherent. Whether it occurs at human therapeutic doses and what the downstream functional effects are in humans specifically — not yet demonstrated in controlled studies.
The honest answer: there is strong mechanistic reason to believe psilocybin promotes some forms of neural plasticity. The rodent evidence is compelling. Human evidence is indirect — changes in functional connectivity on fMRI that persist beyond acute effects, and behavioral changes consistent with increased cognitive flexibility. But the direct neuroplasticity measurement in humans hasn't been done in a definitive study yet. Watch for upcoming Hopkins and UCSF neuroimaging work.
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