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Pharmahuasca and DMT Rescue ROS Production and Differentially Expressed Genes Observed after Predator and
D Parker Kelley1, Katy Venable1, Aspasia Destouni1
1Comparative Biomedical Sciences, Louisiana State University School of Veterinary Medicine, Baton Rouge, Louisiana 70803, United States.
ACS Chemical Neuroscience
|January 6, 2022
Summary
This study found that N,N-dimethyltryptamine (DMT) and pharmahuasca treatments reduced oxidative stress and inflammation in a post-traumatic stress disorder (PTSD) animal model, normalizing gene expression related to neuroplasticity.
Area of Science:
- Neuroscience
- Pharmacology
- Genetics
Background:
- Post-traumatic stress disorder (PTSD) is linked to cognitive deficits, oxidative stress, and inflammation.
- Existing animal models of PTSD show promise, but direct comparison of gene expression with human PTSD is lacking.
- Differentially expressed genes (DEGs) in the prefrontal cortex (PFC) of a stress model partially overlap with human PTSD DEGs.
Purpose of the Study:
- To compare DEGs in the PFC of a rat stress model with DEGs in the human dorsolateral PFC (dlPFC) of PTSD patients.
- To investigate the therapeutic potential of N,N-dimethyltryptamine (DMT), harmaline, and pharmahuasca in mitigating PTSD-related molecular changes.
- To assess the effects of these compounds on oxidative stress, inflammation, and neuroplasticity in the animal model.
Main Methods:
- Comparative RNA sequencing of rat PFC DEGs against human dlPFC PTSD DEGs.
- Administration of DMT, harmaline, or pharmahuasca to a 30-day stress-exposed rat model.
- Measurement of reactive oxygen species (ROS) via electron paramagnetic resonance spectroscopy and total mRNA sequencing in the PFC and hippocampus (HC).
- In vitro assays to determine the binding affinity and efficacy of DMT and harmaline at 5HT2A receptors.
Main Results:
- Significant enrichment of rat DEGs in human PTSD, with 20 overlapping DEGs (17 concordant).
- DMT and pharmahuasca significantly reduced ROS production in the PFC and HC.
- Treatments modulated overlapping DEGs involved in ROS, inflammation, growth factor signaling, neurotransmission, and neuroplasticity.
Conclusions:
- DMT and pharmahuasca show potential for treating PTSD by reducing oxidative stress and inflammation.
- These compounds may normalize gene expression related to neuroplasticity, offering a novel therapeutic avenue.
- The study highlights the utility of comparative transcriptomics in validating animal models for PTSD research.
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