A spatiotemporal gating hypothesis for psilocybin plasticity: reconciling the 5-HT₂A-TrkB mechanistic paradox.
Cell Discov May 29, 2026 DOI: 10.1038/s41421-026-00906-4 (opens in new tab) via PubMed Central
Summary
AI-generated from the abstractThe authors propose a spatiotemporal gating hypothesis to resolve a paradox in how psilocybin produces lasting neural plasticity. Psilocybin activates 5-HT₂A receptors, but the plasticity it induces requires TrkB signaling, even though psilocybin does not directly bind TrkB. The hypothesis suggests that 5-HT₂A activation creates a specific pattern of neural activity—a spatiotemporal gate—that indirectly engages TrkB signaling, reconciling the two mechanisms. This framework aims to explain how a brief psychedelic experience can lead to sustained changes in brain structure and function.
Study at a glance
| Characteristics | Theoretical or philosophical paper Peer reviewed |
|---|---|
| Key finding | Proposes that psilocybin's paradoxical activation of both 5-HT₂A and TrkB receptors is reconciled by a spatiotemporal gating mechanism that coordinates their signaling to produce neuroplasticity. |
Abstract
A spatiotemporal gating hypothesis for psilocybin plasticity: reconciling the 5-HT₂A-TrkB mechanistic paradox.