Functional imaging studies of acute administration of classic psychedelics, ketamine, and MDMA: Methodological limitations and convergent results.

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.

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Declaration of Competing Interest Robert H. Dworkin, PhD, has received in the past 5 years research grants and contracts from the US Food and Drug Administration and the US National Institutes of Health, and compensation for serving on advisory boards or consulting on clinical trial methods from Abide, Acadia, Adynxx, Analgesic Solutions, Aptinyx, Aquinox, Asahi Kasei, Astellas, Beckley, Biogen, Biohaven, Biosplice, Boston Scientific, Braeburn, Cardialen, Centrexion, Chiesi, Chromocell, Clexio, Collegium, CoimbiGene, Confo, Decibel, Editas, Eli Lilly, Endo, Ethismos (equity), Eupraxia, Exicure, GlaxoSmithKline, Glenmark, Gloriana, Hope, Juca, Kriya, Lotus, Mainstay, Merck, Mind Medicine (also equity), Neumentum, Neurana, NeuroBo, Novaremed, Novartis, OliPass, Orion, Oxford Cannabinoid Technologies, Pfizer, Q-State, Reckitt Benckiser, Regenacy (also equity), Rho, Sangamo, Sanifit, Scilex, Semnur, SIMR Biotech, Sinfonia, SK Biopharmaceuticals, Sollis, SPM Therapeutics, SPRIM Health, Teva, Theranexus, Vertex, Vizuri, and WCG. Over the last three years, Eric Strain has had grant funding to his institution from NIH; editing payments from: Wolters-Kluwer, Elsevier (ended); consulting fees from: Pear Therapeutics (ended), Fast Track Drugs and Biologics, Otsuka Pharmaceutical Development and Commercialization, Inc., Cerevel; honoraria for talks: Rutgers University; medical devices supplied to his institution for his research: Masimo; and medical-legal consultations. He also has served on the board of directors (unpaid) for a treatment program: Ashley Addiction Treatment.