ArticleNeuropsychopharmacology : official publication of the American College of Neuropsychopharmacology2026
Enhancing cGMP signaling with psilocybin reduces head twitch and restructures the synaptic proteome while maintaining antidepressant response.
Article in Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
Psilocybin produces antidepressant effects, but perceptual effects limit tolerability. We hypothesized that enhancing cGMP signaling with a phosphodiesterase-9 inhibitor (PDE9i) would diminish a rodent behavioral readout of 5-HT₂AR activation, while preserving antidepressant-like effects. PDE9i attenuated psilocybin-induced head-twitch while maintaining the antidepressant-like response. PDE9i-psilocybin reduced 5-HT₂AR-related pathways while enhancing synaptogenesis signaling.
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