Functional imaging studies of acute administration of classic psychedelics, ketamine, and MDMA: Methodological limitations and convergent results
Basbaum, A., Corder, G., Dworkin, R. H., Edwards, R. R., Eickhoff, C. R., Larsen, I. B., Linguiti, S., McKinstry-Wu, A., Pines, A., Roalf, D. R., Satterthwaite, T. D., Scott, J. C., Sharma, V., Strain, E. C., Sydnor, V. J., Vogel, J. W., Wellman, N.
This systematic review (s=51) examines fMRI studies on the acute effects of psychedelics like psilocybin, LSD, and ketamine on the human brain. The review highlights significant methodological inconsistencies across studies, including 54% not meeting contemporary Type I error correction or motion artefact control standards. Despite these limitations, convergent findings indicate that psilocybin and LSD affect the connectivity architecture of the sensorimotor-association cortical axis, while ketamine 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.