Boosting cGMP signaling with psilocybin reduces head twitch behavior and changes synapse proteins while keeping antidepressant effects

PDE9i significantly reduced psilocybin-induced head-twitch behavior while preserving antidepressant-like effects.

• Enhancing cGMP signaling may diminish the perceptual side effects associated with psilocybin.
• The combination of PDE9i and psilocybin reduced activation of specific serotonin pathways.
• The treatment promoted signaling related to the growth of new synapses.

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