A single high dose of the short-acting psychedelic 5-MeO-DMT alters gene expression in specific brain regions of mice, including the anterior cingulate cortex, basolateral amygdala, ventral hippocampus CA1 region, and dentate gyrus. The compound changed mRNA levels of immediate early genes Arc and Zif268 in several regions and increased TRIP8b expression in the ventral hippocampus after five days. Behaviorally, treated mice showed mixed anxiety-reducing and anxiety-increasing effects in standard tests. However, when pre-treated mice were subjected to acute stress, they had lower corticosterone levels and robust anxiety-reducing effects. These findings suggest molecular actions of 5-MeO-DMT related to its potential anxiolytic effects.
The psychedelic 5-MeO-DMT increases delta power and decreases theta power in the hippocampus of freely moving rats, effects not explained by changes in locomotion. It also dose-dependently reduces slow and mid gamma power and theta phase modulation. The overall spectral profile of awake behavior after 5-MeO-DMT resembles electrophysiological states seen during slow-wave sleep and REM sleep. These findings suggest that classical psychedelics may integrate waking behaviors with sleep-like neural activity patterns.