Treating PTSD with MDMA: An Interview with Dr. Shveta Parekh
By Jinan Ibrahim
The current paradigm for treating post-traumatic stress disorder (PTSD) relies on the administration of antidepressants and anti-anxiety medications. Unfortunately, these medications may alleviate the symptoms of PTSD but do not address its underlying neurological mechanisms. (1) However, a potential shift is on the horizon as recent neuroscience research introduces a promising contender: 3,4-methylenedioxy-methamphetamine (MDMA), commonly known as Ecstasy or Molly, which might just have the answers scientists have been searching for.
MDMA shows significant promise in the clinical treatment of PTSD. This potential is substantiated by recent clinical trials that employed MDMA-assisted psychotherapy as a novel approach to addressing this psychiatric disorder. Notably, one clinical trial found that 75 percent of participants with chronic PTSD, who underwent MDMA-assisted psychotherapy, no longer met the criteria for PTSD diagnosis one year later. (1) These trials not only establish the effectiveness of this therapy but also suggest that MDMA plays a role in reducing anxiety associated with PTSD.
This outcome raises a critical question: What precisely occurs in the brain when MDMA is administered in these trials? To date, the molecular mechanisms underlying the effects ofMDMA on the PTSD-affected brain remain unknown; however, Dr. Shveta Parekh from the Department of Neuroscience and Psychology at the University of North Carolina at Chapel Hill has dedicated her research to answering this question.
Dr. Parekh, a Teaching Assistant Professor and researcher at the Lysle Lab, is actively engaged in pioneering research that delves into the molecular underpinnings of MDMA from a neuroimmune perspective. MDMA is recognized for its notable impact on neuroimmunology, particularly in reducing proinflammatory cytokine levels associated with stress. This implies that administering MDMA to an individual could result in a decrease in proinflammatory cytokines, which subsequently alleviates stress. (1)
At the Lysle Lab, Dr. Parekh’s work hones in on the preclinical implications of MDMA in the context of PTSD. In her 2022 study, it was discovered that animals given MDMA exhibited reduced fear learning, a finding supported by a decrease in defensive responses to stressful stimuli. (2) The Lysle Lab posits that this change in behavior can be attributed to the influence ofMDMA on proinflammatory cytokines within the brain. This research specifically focused on cytokines IL-1β and TNFα, revealing that MDMA effectively lowered the levels of IL-1β. It is proposed that this could serve as a potential mechanism through which MDMA offers assistance in the context of PTSD.
The research on MDMA has been primarily restricted to preclinical studies involving males, which is an area of significant concern for Dr. Parekh. She is resolute in her belief that “sex omission and sex bias in research is a major flaw of neuroscience research,” extending this critique to various other fields of study. This perspective is evidently manifested in her 2020study, where the absence of preclinical knowledge regarding distinctions in male and female responses significantly influenced her research within the context of PTSD. This paper utilized an animal model of PTSD and found significant sex differences in cytokine expression.
This preclinical data suggests a potential avenue for the successful development of a drug targeting these cytokines specifically for males with PTSD but not for females. Dr. Parekh stresses that this discovery is promising for the formulation of pharmacological interventions designed to address chronic PTSD in both male and female populations. She states that the differences seen in this paper are “starking” and only reaffirm the importance of preclinically assessing both sexes.
Dr. Parekh, deeply immersed in the up-and-coming field of neuroimmunology since her undergraduate years working with Autism and Parkinson’s disease, aspires to advance this line of research by directing attention towards neurogenesis and neuroplasticity. She points out thatMDMA has demonstrated the potential to influence synaptic plasticity within the hippocampus, a critical brain region involved in PTSD. Exploring neuroplasticity and neurogenesis in the brain could have profound implications for the use of MDMA in the treatment of PTSD as well as psychiatric conditions.
References:
Interview with Dr. Shveta Parekh, PhD, 9/29/232.
Parekh SV, Adams LO, Barkell GA, Lysle DT. MDMA Administration Attenuates Hippocampal IL-β Immunoreactivity and Subsequent Stress-enhanced Fear Learning: AnAnimal Model of PTSD. Brain Behav Immun Health. 2022; 26:100542. doi:10.1016/j.bbih.2022.100542.
Parekh SV, Adams LO, Barkell GA, Lysle DT. Sex-differences in Anxiety, Neuroinflammatory Markers, and Enhances Fear Learning Following Chronic HeroinWithdrawal. Psychopharmacology (Berl). 2023. doi: 10.1007/s00213-023-06310-0.