Repeated low doses of psilocybin, similar to human microdosing, were tested in rats. The regimen was well tolerated, causing no signs of anhedonia, anxiety, or altered movement, and did not downregulate or desensitize 5-HT2A receptors. The treatment increased resilience to injection stress, reduced self-grooming (a proxy for compulsive actions), and raised 5-HT7 receptor expression and synaptic density in the paraventricular nucleus of the thalamus. These findings support anecdotal reports of benefits from psilocybin microdosing and suggest a possible physiological mechanism.
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.