Pharmahuasca Reduces ROS Production and inflammatory Gene Expression in the Brain in a Model of PTSD: Exploration by RNA Sequencing
Dennis 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 preprint DOI: 10.21203/rs.3.rs-602961/v1 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Animal study |
|---|---|
| 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 |
| Topics | PTSD |
| Keywords | Harmaline Oxidative stress Neuroprotection Pharmacology Reactive oxygen species Gene expression Prefrontal cortex Biochemistry Cognition |
| Citations | 1 |
| Key points | 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.
Comparable studies
Other preclinical and animal studies on PTSD, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| Pharmahuasca and DMT Rescue ROS Production and Differentially Expressed Genes Observed after Predator and Psychosocial Stress: Relevance to Human PTSD. Rats exposed to a 30-day stress regimen | 2022 | Preclinical animal study with in vitro assays | |
| Ketamine ameliorates post-traumatic social avoidance by erasing the traumatic memory encoded in VTA-innervated BLA engram cells. Mice | 2024 | Experimental animal study | |
| Psilocybin Facilitates Fear Extinction: Importance of Dose, Context, and Serotonin Receptors Male and female mice | 2024 | Experimental study | |
| Molecular signatures of astrocytes and microglia maladaptive responses to acute stress are rescued by a single administration of ketamine in a rodent model of PTSD. Rats | 2024 | Animal study | |
| Psilocybe cubensis extract potently prevents fear memory recall and freezing behavior in short- but not long-term in a rat model of posttraumatic stress disorder. Male rats | 2024 | Preclinical study |
Citations in the library
Cites 24
- Rapid antidepressant effects of the psychedelic ayahuasca in treatment-resistant depression: a randomized placebo-controlled trial Psychological Medicine June 15, 2018
- Antidepressant effects of a single dose of ayahuasca in patients with recurrent depression: a preliminary report Brazilian Journal of Psychiatry March 1, 2015
- Psychedelics as Medicines: An Emerging New Paradigm Clinical Pharmacology & Therapeutics November 4, 2016
- Ayahuasca-Assisted Therapy for Addiction: Results from a Preliminary Observational Study in Canada Current Drug Abuse Reviews June 1, 2013
- Antidepressive, anxiolytic, and antiaddictive effects of ayahuasca, psilocybin and lysergic acid diethylamide (LSD): a systematic review of clinical trials published in the last 25 years Therapeutic Advances in Psychopharmacology March 18, 2016
and 19 more in the library