Synergistic Behavioral and Neuroplastic Effects of Psilocybin-NMDAR Modulator Administration
bioRxiv (Cold Spring Harbor Laboratory) November 28, 2024 T. Ben Tal, Ilana Pogodin, Alexaner Botvinnik et al. preprint
Combining psilocybin with NMDAR modulators D-serine or D-cycloserine reduces hallucinogenic-like effects and enhances neuroplasticity in mice. Psilocybin alone increased head twitch response, a surrogate for hallucinogenic effects, which was dose-dependently reduced by either modulator. The combinations also decreased MK-801-induced hyperactivity, modeling antipsychotic effects. The psilocybin-D-serine combination increased GAP43 expression across all four brain regions examined and overall synaptic protein expression in the hippocampus, while psilocybin-D-cycloserine elevated PSD95 levels in all four regions, indicating synaptogenic synergy. These results suggest that pairing serotonergic psychedelics with NMDAR modulators may improve therapeutic efficacy and safety.