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Inflammatory biomarker outcomes associated with MDMA-assisted therapy: an open-label exploratory study.

Jenna E Kachmarik, Jennifer M Loftis, Christopher S Stauffer

Frontiers in neuroscience January 1, 2026 Peer reviewed DOI: 10.3389/fnins.2026.1716817 via PubMed

Summary

MDMA-assisted therapy for Veterans with PTSD was associated with small changes in inflammatory biomarkers. Specifically, there were small increases in interleukin-6 (IL-6) and C-reactive protein (CRP), and a small decrease in tumor necrosis factor alpha (TNF-α). The study involved 23 Veterans, with blood samples collected before and after the intervention. The findings suggest potential modulation of inflammatory markers linked to PTSD symptoms, although results are preliminary and warrant further investigation.

Study at a glance

Design pilot study
Sample size 23
Population Veterans with PTSD
Key finding MDMA-assisted therapy may modulate inflammatory biomarkers, showing small increases in IL-6 and CRP, and a decrease in TNF-α.

Abstract

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). 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. 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). Findings suggest MDMA-assisted therapy may modulate inflammatory biomarkers and highlight biomarker-symptom relationships. Results are preliminary but may inform larger studies.

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