Frontiers in pharmacology
January 1, 2023
Klemens Egger, Frederik Gudmundsen, Naja Støckel Jessen et al.
17 citations
Co-administration of harmine with DMT in rats increased brain DMT levels by inhibiting its metabolism to indole-3-acetic acid, yet no significant occupancy of serotonin 5-HT2A receptors by DMT was detected, even at brain DMT concentrations up to 11.3 µM. Low doses of DMT and/or harmine did not significantly alter brain glucose metabolism as measured by [18F]FDG-PET. These preliminary findings suggest that the role of MAO-A inhibition in potentiating DMT's psychedelic effects may be more complex than previously assumed, and further dose-response studies are needed.
May 28, 2024
Frederik Gudmundsen, Julia Czurylo, Camilla Trang Vo et al.
1 citation
preprint
Three serotonergic psychedelics—psilocybin, LSD, and 2C-B—produce distinct acute and long-term changes in rat brain metabolic activity and connectivity. Psilocybin uniquely alters connectivity between cortical regions including the orbitofrontal, medial prefrontal, and insula cortex, as well as with the dorsal striatum, thalamus, and hippocampus. LSD and 2C-B share more similar effects, centered on acute inhibition of the anterior cingulate cortex, increased activity and connectivity between the amygdala and hypothalamus, and heightened activity in dopamine-rich regions of the ventral tegmental area and substantia nigra. These distinct neural patterns may guide which psychedelic drug could be most beneficial for specific neuropsychiatric disorders.
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.