Functional imaging studies of acute administration of classic psychedelics, ketamine, and MDMA: Methodological limitations and convergent results.
Sophia Linguiti, Jacob W Vogel, Valerie J Sydnor, Adam R Pines, Nick Wellman, Allan I. Basbaum, Claudia R Eickhoff, Simon B. Eickhoff, Robert R Edwards, Bart Larsen, Andrew McKinstry-Wu, J Cobb Scott, David R. Roalf, Vaishnavi Sharma, Eric C. Strain, Gregory Corder, Robert H. Dworkin, Theodore D. Satterthwaite
Neuroscience & Biobehavioral Reviews November 1, 2023 DOI: 10.1016/j.neubiorev.2023.105421 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Systematic review Peer reviewed |
|---|---|
| Sample size | 91 |
| Population | fMRI studies examining acute responses to experimentally administered psychedelics |
| Interventions | Psilocybin LSD Ketamine |
| Topics | Ketamine LSD MDMA Psilocybin Esketamine |
| Keywords | FMRI Psychedelics hallucinogens Entheogens Neuroscience brain research Neural activity Brain function Neurology Brain imaging |
| Citations | 15 |
| Key findings | Psilocybin and LSD consistently modulate connectivity along the sensorimotor-association cortical axis, and ketamine consistently increases activation in the dorsomedial prefrontal cortex. |
Abstract
Functional magnetic resonance imaging (fMRI) is increasingly used to non-invasively study the acute impact of psychedelics on the human brain. While fMRI is a promising tool for measuring brain function in response to psychedelics, it also has known methodological challenges. We conducted a systematic review of fMRI studies examining acute responses to experimentally administered psychedelics in order to identify convergent findings and characterize heterogeneity in the literature. We reviewed 91 full-text papers; these studies were notable for substantial heterogeneity in design, task, dosage, drug timing, and statistical approach. Data recycling was common, with 51 unique samples across 91 studies. Fifty-seven studies (54%) did not meet contemporary standards for Type I error correction or control of motion artifact. Psilocybin and LSD were consistently reported to moderate the connectivity architecture of the sensorimotor-association cortical axis. Studies also consistently reported that ketamine administration increased activation in the dorsomedial prefrontal cortex. Moving forward, use of best practices such as pre-registration, standardized image processing and statistical testing, and data sharing will be important in this rapidly developing field.
Comparable studies
Other systematic reviews and meta-analyses on MDMA, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| A review of the acute subjective effects of MDMA/ecstasy | 2006 | Systematic review | |
| Adverse events in clinical treatments with serotonergic psychedelics and MDMA: A mixed-methods systematic review Patients in clinical trials with MDMA or serotonergic psychedelics | 2022 | Systematic review | n = 598 |
| Treating posttraumatic stress disorder with MDMA-assisted psychotherapy: A preliminary meta-analysis and comparison to prolonged exposure therapy Patients with PTSD | 2016 | Meta-analysis | |
| The neuropsychology of ecstasy (MDMA) use: a quantitative review MDMA users | 2007 | Meta-analysis | |
| Drug-drug interactions between psychiatric medications and MDMA or psilocybin: a systematic review | 2022 | Systematic review |
Citations in the library
Cited by 15
- Synergistic, multi-level understanding of psychedelics: three systematic reviews and meta-analyses of their pharmacology, neuroimaging and phenomenology. Translational Psychiatry December 4, 2024
- Psychedelics, entactogens and psychoplastogens for depression and related disorders British Journal of Pharmacology June 15, 2025
- Classic Psychedelics in Pain Modulation: Mechanisms, Clinical Evidence, and Future Perspectives ACS Chemical Neuroscience June 6, 2025
- An international mega-analysis of psychedelic drug effects on brain circuit function Nature Medicine April 1, 2026
- What fMRI studies say about the nature of the psychedelic effect: a scoping review Frontiers in Neuroscience July 1, 2025
and 10 more in the library
Cites 37
- 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
- Psychedelics Promote Structural and Functional Neural Plasticity Cell Reports June 1, 2018
- MDMA-assisted therapy for severe PTSD: a randomized, double-blind, placebo-controlled phase 3 study. Nature Medicine June 1, 2021
- Psilocybin for treatment-resistant depression: fMRI-measured brain mechanisms. Scientific Reports October 13, 2017
and 32 more in the library