BRIEF RESEARCH REPORT article
Front. Neurosci.
Sec. Neuropharmacology
Inflammatory biomarker outcomes associated with MDMA-Assisted Therapy: An open-label exploratory study
1. Oregon Health and Science University, Portland, United States
2. VA Portland Health Care System, Portland, United States
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Abstract
Background: Posttraumatic stress disorder (PTSD) is associated with elevated inflammation and risk for chronic illness, yet few studies have examined inflammatory biomarker outcomes of PTSD interventions. Rapid PTSD symptom reduction has been observed following 3,4-methylenedioxymethamphetamine (MDMA)-assisted therapy, which leverages MDMA as a prosocial adjunct to psychotherapy. No studies have evaluated inflammatory biomarker outcomes of MDMA-assisted therapy. This exploratory pilot study examined within-person changes in inflammatory biomarkers during MDMA-assisted group therapy for Veterans with PTSD (www.clinicaltrials.gov [NCT05961527]). Methods: Blood plasma samples were collected from 23 Veterans at baseline and end-of-intervention. Hedges' g effect sizes were calculated for interleukin-6 (IL-6), tumor necrosis factor alpha (TNF-α), and C-reactive protein (CRP). PTSD severity was assessed with the Clinician-Administered PTSD Scale for DSM-5 (CAPS-5) at baseline and 30-day follow-up. Spearman's rho correlations were calculated among biomarkers, PTSD symptoms, and change scores. Results: Small increases were observed in IL-6 (g = 0.24; 95% CI –0.25, 0.72) and CRP (g = 0.23; 95% CI –0.30, 0.74), and a small decrease in TNF-α (g = –0.24; 95% CI –0.69, 0.23). Baseline IL-6 and TNF-α were positively associated with baseline CAPS-5 scores (ρ = 0.45, 0.32). Higher baseline IL-6 weakly predicted symptom improvement (ρ = –0.25), and IL-6 change correlated with symptom change (ρ = 0.41). CRP showed weak negative associations with PTSD symptoms (ρ = –0.26). Conclusion: Findings suggest MDMA-assisted therapy may modulate inflammatory biomarkers and highlight biomarker–symptom relationships. Results are preliminary but may inform larger studies.
Summary
Keywords
crp, IL-6, Inflammation, Inflammatory markers, MDMA, posttraumatic stress disorder, TNF-α, Veterans
Received
30 September 2025
Accepted
19 February 2026
Copyright
© 2026 Kachmarik, Loftis and Stauffer. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
*Correspondence: Jenna E. Kachmarik
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