Pharmahuasca Reduces ROS Production and inflammatory Gene Expression in the Brain in a Model of PTSD: Exploration by RNA Sequencing
D. Parker Kelley, Katy Venable, Gerald Billac, Aspasia Destouni, Philip J. Ebenezer, Krisztian Stadler, Charles D. Nichols, Steven A. Barker, Joseph Francis
Research Square June 15, 2021 DOI: 10.21203/rs.3.rs-602961/v1 via OpenAlex
Summary
AI-generated from the abstractIn 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.
Study at a glance
| Characteristics | Animal study Peer reviewed |
|---|---|
| Population | Rats exposed to predator and psychosocial stress (PTSD model) |
| Interventions | DMT harmaline |
| Dose | 2 mg/kg IP DMT, 1.5 mg/kg IP harmaline |
| Duration | Every other day for 5 days |
| Keywords | Harmaline Oxidative stress Neuroprotection Pharmacology Reactive oxygen species |
| Citations | 1 |
| Key finding | DMT and pharmahuasca reduced ROS production in the prefrontal cortex and hippocampus and altered gene expression related to ROS, inflammation, and neuroplasticity in a rat PTSD model. |
Abstract
Abstract Post-traumatic stress disorder (PTSD) is associated with cognitive deficits, oxidative stress and inflammation. N,N-dimethyltryptamine (DMT) is a known neuroprotective, antioxidant, anti-inflammatory, and psychoplastogen with antidepressant effects. Therefore, we tested the capacity of DMT, the monoamine oxidase inhibitor (MAOI) harmaline, and “pharmahuasca” (DMT + harmaline) to reduce reactive oxygen species (ROS) production and inflammatory gene expression and modulate neuroplasticity-related gene expression in a predator exposure and psychosocial stress rat model of PTSD. We administered DMT (2 mg/kg IP), harmaline (1.5 mg/kg IP), or pharmahuasca every other day for 5 days. We measured ROS production in the prefrontal cortex (PFC) and hippocampus (HC) by electron paramagnetic resonance spectroscopy (EPR) and extracted total RNA from the PFC for sequencing. We also performed in vitro assays to measure the affinity and efficacy of DMT and harmaline at the 5HT2AR. DMT and pharmahuasca reduced ROS production in the PFC and HC, while harmaline had mixed effects. RNA sequencing implicated genes related to ROS production, inflammation, neurotransmission, and neuroplasticity. DMT, but not harmaline exhibits both affinity and efficacy at the human 5HT2AR. DMT and pharmahuasca exhibit broad effects that may facilitate the treatment of PTSD by reducing ROS production and inflammatory gene expression, and inducing neuroplasticity.