ACS Chemical Neuroscience
January 6, 2022
D. Kelley, Katy Venable, Aspasia Destouni et al.
41 citations
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.
Research Square
June 15, 2021
D. Parker Kelley, Katy Venable, Gerald Billac et al.
1 citation
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.
SSRN Electronic Journal
January 1, 2026
Dennis Parker Kelley, Gabriel Sturm, Katy Venable et al.
Serotonergic psychedelics show therapeutic effects across diverse neuropsychiatric, inflammatory, and cardiometabolic disorders, effects mediated largely by the serotonin 5-HT2A receptor. These drugs are exceptionally context-dependent, able to be anti-inflammatory or pro-inflammatory depending on setting. Each target pathology is linked to elevated stress exposure, which drives mitochondrial and allostatic dysregulation. The authors propose that psychedelics act as super-normal stimuli for the adaptive 5-HT2A receptor stress response, inducing a process called allostatic recalibration (AR). AR involves three phases: destabilizing, recalibrating, and consolidating updated allostatic programs. This recalibration replaces entrenched pathological allostatic programs with ones tuned to the safe context of psychedelic therapy, explaining their transdiagnostic effects.