Review: how psychedelics and ketamine may reshape brain connections in depression, PTSD and addiction

The question

Why do psychedelics and ketamine seem to help psychiatric symptoms for weeks after the drug has left the body? This review asks whether changes in the brain’s ability to rewire itself, known as neuroplasticity, can explain it.

What they did

The authors reviewed pre-clinical (laboratory and animal) and clinical research on psychedelics and related drugs. They traced the proposed chain of events from receptors on brain cells through to changes in nerve cells and behaviour. They compared serotonergic psychedelics, ketamine, ibogaine and MDMA.

What they found

The authors report that classic serotonergic psychedelics and ketamine appear to share a common cellular route: they activate glutamate-releasing neurons, which boosts BDNF-TrkB signalling (a growth-factor system that supports nerve cells) and promotes the formation of new connections between neurons via the mTOR pathway. Ibogaine is described as acting mainly through a different growth-factor pathway, which may relate to its reported effects in addiction. MDMA is presented as a paradox: it may support new connections through BDNF, yet the authors note evidence of harmful effects on growth-factor signalling in the hippocampus, a memory-related brain region. The review concludes that growth-factor changes plausibly contribute to reduced depressive symptoms, but their role in PTSD and addiction is less well understood.

The fine print

This is a narrative review, not a systematic review or meta-analysis, so studies were not pooled or formally graded and selection may be uneven. Much of the mechanistic evidence comes from animal and cell work, which does not always translate to people. No patient numbers, doses or clinical outcomes are reported in the abstract, and this summary is based on the abstract alone.

What it means

Researchers think that lasting symptom change after psychedelics or ketamine may involve the brain forming new connections, but the biology is still being worked out and differs between drugs. The mechanisms are a hypothesis under study, not settled science, and they do not by themselves show how well these treatments work.

Evidence grade: Very low. This is a narrative review of biological mechanisms that draws on both animal and human studies; it reports no new data and no pooled results.

This summary is based on the study’s published abstract.