Five-hour fMRI mapping after oral psilocybin reveals distinct psilocin-dependent changes in resting state functional connectivity
Resting-state functional connectivity (RSFC) studies demonstrate effects after iv psilocybin but oral psilocybin RSFC effects and relations with plasma psilocin levels (PPL) remain unknown. Methods Eleven healthy volunteers (age (SD): 33.3 (10.3) years; four females) participated. Resting state fMRI data was acquired before and 40, 80, 130 and 300 minutes after oral psilocybin (dose: 0.2 (n=4) and 0.3 (n=7) mg/kg). PPL was determined from blood samples. Average within- and between-network RSFC was estimated for seven networks (DMN; dorsal attention (DAN), executive control (ECN), salience (SAN), auditory, visual and sensorimotor).
PPL correlated negatively with DMN RSFC (pFWER=0.04) and positively with global RSFC (pFWER=0.002). As a function of PPL, DMN showed increased RSFC with DAN, ECN and SAN (pFWER<0.02), and the DAN exhibited increased RSFC with DMN, auditory, sensorimotor (pFWER=<0.02) and with visual network (pFWER=0.06). Conclusion For the first time, we evaluated RSFC after oral psilocybin and assessed relations between PPL and RSFC. We replicate decreased DMN RSFC and increased global RSFC after psilocybin. Also, our results suggest a role for the DAN in psilocybin effects. Funding. The study was supported by Innovation Fund Denmark (grant ID 4108-00004B), Independent Research Fund Denmark (grant ID 6110-00518B), and Ester M. og Konrad Kristian Sigurdssons Dyreværnsfond (grant ID 850-22-55166-17-LNG). M.K.M. was supported through a scholarship stipend from Rigshospitalet’s Research Council (grant ID R130-A5324). A.A. and M.M-J was supported by a scholarship stipend from the Lundbeck Foundation. B.O. was supported by the Lundbeck foundation (grant ID R231-2016-3236) and Marie-Curie-NEUROMODEL (Grant ID 746850).
Martin K. Madsen is a medical doctor, pursuing a PhD at the Neurobiology Research Unit, Copenhagen, Denmark. The research includes utilizing PET and fMRI to gain a better understanding of psilocybin brain effects and of the role of the 5-HT2AR.