Translational Psychiatry
June 13, 2025
Tom Ben-Tal, Ilana Pogodin, Alexander Botvinnik et al.
2 citations
Combining the psychedelic psilocybin with the NMDAR modulators D-serine or D-cycloserine reduced hallucinogenic-like effects and enhanced antipsychotic-like effects in male mice, while also promoting neuroplasticity-related synaptic protein expression. Psilocybin alone increased head twitch response, a surrogate for hallucinogenic effects, which was dose-dependently lowered by either modulator. The combinations also decreased MK-801-induced hyperactivity, modeling antipsychotic action. The psilocybin-D-serine combination increased GAP43 expression across four brain regions and overall synaptic protein levels in the hippocampus; psilocybin-D-cycloserine elevated PSD95 across all regions. These results suggest that pairing serotonergic psychedelics with NMDAR modulators may improve therapeutic potential by reducing adverse effects and enhancing neuroplasticity.
The International Journal of Neuropsychopharmacology
August 1, 2025
Bernard Lerer, T. Tal, Ilana Pogodin et al.
Combining psilocybin with NMDAR modulators D-serine or D-cycloserine may enhance therapeutic benefits while reducing adverse effects. In mice, psilocybin alone increased head twitch response, a proxy for hallucinogenic effects, but co-administration of D-serine or D-cycloserine reduced this response dose-dependently. The combinations also decreased MK-801-induced hyperactivity, modeling antipsychotic effects, whereas psilocybin alone did not. Additionally, psilocybin with D-serine boosted GAP43 protein expression across four brain regions and overall synaptic protein levels in the hippocampus, while psilocybin with D-cycloserine elevated PSD95 levels across all regions. These results suggest that such combinations could optimize psilocybin's therapeutic potential by mitigating side effects and enhancing neuroplasticity.
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.