Psychedelic-assisted therapy mechanisms

Psilocybin and MDMA have shown remarkable efficacy in clinical trials for depression and PTSD, but the precise mechanisms linking acute psychedelic experience to lasting therapeutic change remain unclear. Key open questions include the relative contributions of 5-HT2A receptor agonism, increased neural entropy and plasticity (via BDNF/TrkB), default mode network disruption, and the psychological content of the experience itself. Disentangling pharmacological from psychological mechanisms is essential for optimizing protocols and developing next-generation compounds.