Changing your mind: neuroplastic mechanisms underlying the therapeutic effect of psychedelics in depression, PTSD, and addiction
Progress in Neuro-Psychopharmacology and Biological Psychiatry October 1, 2025 Marta L.c. Palhas, Rémi Corne, Raymond Mongeau 4 citations
Psychedelic treatments produce therapeutic effects within hours that persist beyond the drug's elimination, suggesting neuroplasticity-related mechanisms. Serotonergic psychedelics and ketamine recruit glutamatergic neurons to stimulate BDNF-trKB signaling, promoting synaptogenesis via the mTOR pathway, which may explain their efficacy in depression, anxiety, PTSD, and addiction. Ibogaine exerts effects through GDF-mediated mechanisms underlying its benefit in addiction. MDMA, used for PTSD, influences synaptogenesis via 5-HT2A-dependent effects on BDNF but appears to have deleterious effects on neurotrophic signaling in the hippocampus, impacting plasticity differently. The modulation of the neurotrophic system contributes to reducing depressive symptoms, but its role in PTSD and addiction remains less understood.