Enhancing cGMP signaling with psilocybin reduces head twitch and restructures the synaptic proteome while maintaining antidepressant response

Paper. Floris G, Jefferson SJ, Rondeau J et al.. Neuropsychopharmacology, 12 Oct 2026.

Tags: Psilocybin.

Weekly Science Digest, 10 Oct 2026 to 16 Oct 2026, finding 1: Plasticity and the head twitch come apart

Two mouse studies dissociated psilocybin's synaptic remodeling from its hallucination proxy.

In Nature Neuroscience, 5-HT2A signaling in layer 5 cortical pyramidal neurons was necessary and sufficient for psilocybin's synapse formation and pruning, yet dispensable for the head-twitch response. Separately, a PDE9 inhibitor blunted psilocybin's head twitch while the antidepressant-like effect and synaptogenesis signaling survived.

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