CNSC-36. PSILOCYBIN INDUCES SUSTAINED GLIOMA GROWTH THROUGH SEROTONERGIC AND TRKB PATHWAYS
Neuro-Oncology November 1, 2025 Richard Drexler, Belgin Yalçın, Rebecca Mancusi et al.
High-grade gliomas integrate into serotonergic circuits via dorsal and median raphe projections, which drive calcium-mediated proliferation. Psilocybin, a serotonergic psychedelic selective for 5-HT2A with activity at TrkB, significantly increased proliferation in glioblastoma and DMG xenografts after a single dose, with effects persisting for at least two weeks. Calcium transients in glioma cells appeared within 30 minutes and remained detectable for two weeks. Genetic knockout of 5-HT2A nearly abolished psilocybin-induced proliferation, while TrkB knockout partially reduced it. These findings indicate that psilocybin promotes sustained glioma growth primarily through 5-HT2A activation, with a modulatory role for TrkB, suggesting caution for clinical use in brain tumor patients.