Psilocybin enhances conditioned place preference learning in planarians.

Psilocybin has emerged as a promising therapeutic agent, with clinical benefits attributed to enhanced neuroplasticity rather than acute pharmacological effects. However, the fundamental mechanisms underlying these effects remain poorly understood. Using planarians as a model system, we investigated whether psilocybin enhances associative learning using a conditioned place preference paradigm. Following a single exposure to 5 µM psilocybin, planarians underwent 5 days of conditioning in which light was paired with sucrose. Psilocybin-treated planarians showed a significantly greater shift in light preference compared to controls (time × group × drug interaction: F(2,38) = 3.3, P < 0.05), with effects persisting at least 6 days post-administration. These findings demonstrate that psilocybin enhances appetitive associative learning in an invertebrate model, supporting the hypothesis that psychedelic-induced neuroplasticity operates through evolutionarily conserved serotonergic mechanisms.