Pharmacokinetic and Pharmacodynamic Interaction of the Ayahuasca Constituents Harmine and Dimethyltryptamine (DMT) in the Rat Brain
January 4, 2023 Klemens Egger, Frederik Gudmundsen, Naja Støckel Jessen et al. preprint
Co-administration of harmine with N,N-dimethyltryptamine (DMT) in rats inhibited the formation of the DMT metabolite indole-3-acetic acid in the brain and increased cerebral availability of DMT, confirming harmine's role in making oral DMT bioavailable. However, no significant occupancy by DMT at serotonin 5-HT2A receptors was detected ex vivo, despite brain DMT concentrations reaching 11.3 µM at moderate doses. Low doses of DMT and/or harmine did not strongly influence brain glucose metabolism measured with [18F]FDG-PET. The results call for further experiments on dose-dependent effects of harmine/DMT on receptor occupancy and cerebral metabolism.