Neuroimaging Correlates of Treatment Response with Psychedelics in Major Depressive Disorder: A Systematic Review
Sarah Kuburi, Anne-Marie Di Passa, Vanessa K Tassone, Raesham Mahmood, Aleksandra Lalovic, Karim S Ladha, Katharine Dunlop, Sakina J. Rizvi, Ilya Demchenko, Venkat Bhat
Chronic Stress 2022 DOI: 10.1177/24705470221115342 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Systematic review Peer reviewed |
|---|---|
| Population | Patients with major depressive disorder |
| Interventions | psilocybin ayahuasca lysergic acid diethylamide |
| Topics | Depression |
| Keywords | Neuroimaging Clinical psychology |
| Citations | 14 |
| Key findings | Psilocybin, ayahuasca, and LSD produce neuroimaging changes—including amygdala and prefrontal cortex connectivity alterations and decreased brain network modularity—that correlate with antidepressant response in major depressive disorder. |
Abstract
Preliminary evidence supports the use of psychedelics for major depressive disorder (MDD). However, less attention has been given to the neural mechanisms behind their effects. We conducted a systematic review examining the neuroimaging correlates of antidepressant response following psychedelic interventions for MDD. Through MEDLINE, Embase, and APA PsycINFO, 187 records were identified and 42 articles were screened. Six published studies and one conference abstract were included. Five ongoing trials were included from ClinicalTrials.gov. Our search covered several psychedelics, though included studies were specific to psilocybin, ayahuasca, and lysergic acid diethylamide. Three psilocybin studies noted amygdala activity and functional connectivity (FC) alterations that correlated with treatment response. Two psilocybin studies reported that FC changes in the medial and ventromedial prefrontal cortices correlated with treatment response. Two trials from a single study reported global decreases in brain network modularity which correlated with antidepressant response. One ayahuasca study reported increased activity in the limbic regions following treatment. Preliminary evidence suggests that the default mode and limbic networks may be a target for future research on the neural mechanisms of psychedelics. More data is required to corroborate these initial findings as the evidence summarized in this review is based on four datasets.
Comparable studies
Other systematic reviews and meta-analyses on depression, most cited first.
Citations in the library
Cited by 10
- The Psychedelic Future of Post-Traumatic Stress Disorder Treatment Current Neuropharmacology January 5, 2024
- Role of Psychedelics in Treatment-Resistant Depression. Psychiatric Clinics of North America June 1, 2023
- Role of selective serotonin reuptake inhibitors, serotonin-norepinephrine reuptake inhibitors and psychedelics in the treatment of major depressive disorder: A perspective on mechanistic insight and current status. European Journal of Pharmacology August 15, 2025
- The serotonergic psychedelic N,N-dipropyltryptamine alters information-processing dynamics in in vitro cortical neural circuits. Network Neuroscience December 10, 2024
- Use of psychedelic treatments in psychiatric clinical practice: an EPA policy paper European Psychiatry 2025
and 5 more in the library
Cites 38
- Trial of Psilocybin versus Escitalopram for Depression New England Journal of Medicine April 14, 2021
- Neural correlates of the psychedelic state as determined by fMRI studies with psilocybin Proceedings of the National Academy of Sciences January 23, 2012
- Psilocybin induces schizophrenia-like psychosis in humans via a serotonin-2 agonist action Neuroreport December 1, 1998
- Neural correlates of the LSD experience revealed by multimodal neuroimaging. Proceedings of the National Academy of Sciences April 11, 2016
- Psilocybin for treatment-resistant depression: fMRI-measured brain mechanisms. Scientific Reports October 13, 2017
and 33 more in the library