Comparing gene expression in the prefrontal cortex of a rat stress model and the dorsolateral prefrontal cortex of humans with PTSD reveals 20 overlapping differentially expressed genes, 85% of which change in the same direction. The psychedelic compound N,N-dimethyltryptamine (DMT), alone or combined with the monoamine oxidase inhibitor harmaline (pharmahuasca), reduces reactive oxygen species production in the prefrontal cortex and hippocampus and normalizes expression of genes involved in oxidative stress, inflammation, growth factor signaling, neurotransmission, and neuroplasticity. Harmaline alone has mixed effects on reactive oxygen species.
In a rat model of post-traumatic stress disorder (PTSD), N,N-dimethyltryptamine (DMT) and the combination of DMT with the monoamine oxidase inhibitor harmaline (pharmahuasca) reduced reactive oxygen species (ROS) production in the prefrontal cortex and hippocampus, while harmaline alone had mixed effects. RNA sequencing of the prefrontal cortex showed that DMT and pharmahuasca altered expression of genes related to ROS production, inflammation, neurotransmission, and neuroplasticity. DMT, but not harmaline, showed both affinity and efficacy at the human 5HT2A receptor. The findings suggest DMT and pharmahuasca may help treat PTSD by reducing oxidative stress and inflammation and promoting neuroplasticity.