Systematic review · 2025
Review of brain imaging studies on psychedelics and ketamine for depression
- Original title
- Psychedelics and ketamine/esketamine in depressive disorders: biological mechanisms and associated neuroimaging and clinical changes.
- Authors
- d'Andrea G, Chiappini S, Ciavoni L, et al.
- Journal
- Translational psychiatry, 2025
- Molecules
- Ketamine, Esketamine, Psilocybin, LSD, DMT, Ayahuasca
- Conditions
- Depression, Treatment-resistant depression
- Evidence grade
- Low
- Source
- Read the original paper
The question
What do brain imaging studies show about how psychedelics and ketamine or esketamine change brain activity in people with depression?
What they did
The authors searched three research databases (PubMed, Web of Science, Scopus) for human studies published up to March 2022 that used brain scanning techniques such as functional MRI, PET or SPECT. They looked for studies of LSD, psilocybin, ayahuasca, DMT, ketamine or esketamine in people with depressive disorders. They followed a standard checklist for systematic reviews (PRISMA).
What they found
The search produced 49 articles. Most, 44 of them, involved ketamine or esketamine; only 5 involved classic psychedelics (one on ayahuasca and four on psilocybin). By design, there were 9 randomized controlled trials, 25 open-label studies, 4 double-blind trials, 8 observational studies and 3 cross-over studies. The authors concluded that psilocybin appears to “reset” activity in the default mode network, a set of brain regions active during self-focused thought, while ketamine acts more specifically on prefrontal networks that influence the default mode network indirectly, which the authors link to its effects on anhedonia (loss of pleasure) and control over emotional stimuli.
The fine print
The review did not combine results statistically, so the conclusions are interpretive rather than measured effects. The evidence base is lopsided: nearly all studies involved ketamine or esketamine, and only five involved classic psychedelics, so statements about psilocybin rest on very few studies. Most included studies were open-label or observational, the search stopped at March 2022, and the number of people scanned across all studies is not reported in the abstract. This summary is based on the abstract only.
What it means
Brain imaging research in depression is currently dominated by ketamine, with only a handful of studies on classic psychedelics, and the proposed mechanisms remain provisional rather than settled.
Evidence grade: Low. A systematic review that counted and described 49 studies without pooling results, and most of the included studies were open-label or observational rather than randomized.
This summary is based on the study’s published abstract.