medRxiv Preprint Server
March 27, 2026
Brooke L. Sevchik, S. Parker Singleton, Analiese Lahey et al.
preprint
A living systematic review and meta-analysis of six randomized controlled trials with 286 participants found that MDMA-assisted therapy reduces PTSD symptoms more than control conditions (Hedges' g = -0.71). More dosing sessions and higher cumulative doses were linked to larger effects. MDMA also led to higher response (risk ratio 1.35) and remission (risk ratio 2.25) rates. Most studies had low risk of bias per Cochrane guidelines, though issues like expectancy and functional unblinding remain. The evidence was rated low certainty using GRADE, and the authors note more trials are needed.
Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology
March 27, 2026
Kade L Huckstep, Billi Newton, Grace Bailey et al.
Post-traumatic stress disorder and alcohol use often co-occur and worsen each other, but no medications specifically target trauma-driven increases in drinking. In rats predisposed to heavy alcohol use (inbred alcohol-preferring rats), a single dose of MDMA given before fear-extinction training prevented the rise in alcohol consumption that normally follows a stressful experience. MDMA did not improve long-term fear extinction memory in any group. The effect on drinking was specific to the genetically vulnerable rats and was not explained by prior alcohol history. MDMA's main benefit in this model was disrupting the link between trauma and escalated alcohol intake, not enhancing fear extinction.
Biomed Pharmacother
March 19, 2026
correction
This is a corrigendum (correction notice) for a previously published research article. It does not provide new findings or data. The original study investigated how Withania somnifera (ashwagandha) affected MDMA-induced hyperthermia, cognitive impairment, neurotoxicity, and neuroinflammation in mice.
Journal of analytical toxicology
March 15, 2026
Aurora Balloni, Sarah M R Wille, Giorgia Sprega et al.
MDMA (Ecstasy) is broken down and cleared from the body at different rates for its two mirror-image forms. In oral fluid from 161 samples, the S-(+)-enantiomer of MDMA was eliminated faster (half-life 3.3 hours) than the R-(-)-enantiomer (half-life 4.8 hours). Both reached peak levels within 1.75 hours after taking the drug. For the metabolite MDA, the second enantiomer cleared more quickly (half-life 9.6 hours) than the first (23.8 hours). The ratio of R to S MDMA increased over time, which could help estimate when the drug was taken. In roadside checks, 54.5% of cases had an R/S ratio above 1.5, suggesting use within the prior 24 hours.
Drug Testing and Analysis
March 15, 2026
Simon K. Wellenberg, Lea Wagmann, Matthias D. Kroesen et al.
Amino acid prodrugs of MDMA—MDMA-tryptophan, MDMA-lysine, and MDMA-glycine—are cleaved to release MDMA in zebrafish embryos, human liver S9 fraction, and human urine after microdosing, but not in human blood under the tested conditions. MDMA-tryptophan follows a stepwise bioactivation pathway involving hydroxylation and N-dealkylation before amide cleavage, unlike the other prodrugs which convert directly. Known MDMA metabolites also form in zebrafish and liver systems. Unique urine screening targets appear only for MDMA-tryptophan; biomarkers for the other prodrugs are MDMA and its known metabolites. Further studies of human pharmacokinetic profiles are needed.
Child and Adolescent Psychiatry and Mental Health
March 13, 2026
Marc-Antoine Crocq, Philippe Auby
The recent approval of esketamine for adults has renewed interest in psychedelic compounds for psychiatric use, but their relevance for children and adolescents is unclear. This review examines the rationale for investigating classic serotonergic psychedelics (e.g., psilocybin, LSD), the entactogen MDMA, and dissociative compounds like ketamine and esketamine in young populations. Ongoing and planned trials primarily involve adolescents aged 16 years and older, driven by unmet needs in child and adolescent psychiatry, where few medications are approved and therapeutic response is often unsatisfactory. Potential targets include anorexia nervosa, autism spectrum disorder symptoms, obsessive-compulsive disorder, resistant depression, and severe PTSD. Translation to pediatric populations requires caution due to developmental vulnerabilities and limited long-term safety data.
Journal of Traumatic Stress
March 12, 2026
Leslie A. Morland, B O Rothbaum, Lauren M. Sippel et al.
2 citations
MDMA-assisted psychotherapy for PTSD shows promising results in recent randomized controlled trials, with high response and remission rates, but the FDA declined to approve it in August 2024 due to insufficient evidence. This review examines the current scientific literature on MDMA-AT, covering proposed mechanisms, methodological strengths and limitations, evidence gaps, and clinical, ethical, and regulatory issues. Key limitations include challenges with blinding, lack of active comparator conditions, no head-to-head comparisons of different therapy models, inadequate safety monitoring, and limited sample generalizability. Emerging research integrates MDMA with established trauma-focused therapies like prolonged exposure and cognitive processing therapy to leverage MDMA's effects on cognitive behavioral mechanisms.
European Neuropsychopharmacology
March 12, 2026
Natalia E. Fares-Otero, Yuki Furukawa, Marit Sijbrandij et al.
A systematic review and meta-analysis of randomized controlled trials found that MDMA-assisted therapy (MDMA-AT) was associated with reductions in PTSD symptom severity and dissociative symptoms, and may improve functioning, compared with control conditions. No clear benefit was observed for depressive symptoms. The analysis included 8 trials with 298 participants for the primary outcome. However, the overall certainty of the evidence was very low due to high risk of bias in outcome measurement, deviations from intended interventions, small sample sizes, and lack of active controls in most studies. Larger, higher-quality trials with active controls and long-term follow-up are needed to determine efficacy.
Frontiers in Psychology
March 11, 2026
Filippo Dellanoce
1 citation
A novel therapeutic approach called 'amplified psychoanalysis' integrates MDMA-assisted therapy with traditional psychoanalytic treatment for obsessive-compulsive disorder (OCD). A single-case clinical narrative of a patient named Ygg illustrates how MDMA-induced altered states of consciousness may facilitate access to unconscious material and help overcome therapeutic impasses. The patient experienced more direct access to and processing of previously avoided memories and affects. The combination may be particularly promising for OCD, where traditional approaches often face limitations. Enhanced emotional processing, a strengthened therapeutic alliance, and improved access to traumatic memories are identified as putative processes of change. The approach requires systematic investigation with larger samples and formal outcome measures.
Psychedelic Medicine
March 10, 2026
Amy Lehrner, Miryam Sperka, Lauren Lepow et al.
1 citation
MDMA-assisted therapy for post-traumatic stress disorder has shown strong clinical effects, high response rates, and low dropout when using a principle-guided, patient-directed model that includes nondrug preparatory and integrative sessions. This perspective argues that embedding MDMA into highly structured, manualized cognitive-behavioral treatment protocols may misapprehend the therapy's synergistic nature, blunt its transformative effects, and potentially cause harm. The field should prioritize research on real-world evidence, treatment optimization, and mechanisms of action of this distinct patient-directed model rather than immediately adapting existing protocols.
bioRxiv (Cold Spring Harbor Laboratory)
March 8, 2026
Nitzan Geva, Sarah J. Jefferson, Emi Krishnamurthy et al.
MDMA increases spine density and the formation of new spines in the medial prefrontal cortex of mice, as shown by two-photon microscopy. Calcium imaging in the infralimbic cortex during fear extinction revealed that neural activity in this region became more correlated with the suppression of freezing behavior, indicating a strengthened role in extinction. Longitudinal cell registration showed accelerated representational drift across days in MDMA-treated mice, especially in neurons that suppressed activity to conditioned cues. These findings indicate that MDMA facilitates structural and functional neuroplasticity, which may underlie its enhancement of extinction learning.
Br J Psychiatry
March 6, 2026
No Summary
ACS Chem Neurosci
March 4, 2026
correction
A correction notice clarifies that two errors in the original paper do not affect the accuracy of the results, interpretations, or conclusions. The first correction addresses a presentation issue in Table 1, confirming the data are correct. The second correction clarifies that thigmotaxis, a measure of anxiety-like behavior, was evaluated in rats given SDA or SDMA compounds. Compared to saline, only the 10 mg/kg dose of SDA significantly increased thigmotaxis, meaning the rats spent less time in the center of the arena.
Psychopharmacology
March 4, 2026
Ava M. Mac, Srinivasu Kallakuri, Alixandria T. Mascarin et al.
Repeated low doses of MDMA (2.5 mg/kg) caused mild anxiety-like behavior in rats one day after exposure, but this effect was confounded by reduced movement and did not persist at 15 days. Higher doses (5 mg/kg) did not produce anxiety-like behavior. Sucrose preference, a measure of anhedonia, increased over time and was unaffected by MDMA or sex. Brain analysis showed reduced serotonin levels in the nucleus accumbens one day after both MDMA doses, but not in the prefrontal cortex or dorsal hippocampus. These transient effects suggest that low-dose MDMA used clinically may be tolerated without limiting therapeutic benefit.
American Journal of Health-System Pharmacy
March 4, 2026
Jennifer E. Thomas, Anna Dellarole, Robin J. Jacobs
Current literature most strongly supports MDMA and intravenous ketamine as treatments for PTSD. Under professional supervision, these agents may reduce PTSD symptoms and are generally well tolerated. However, findings require cautious interpretation because of limitations including treatment expectancy effects and potential inadequate blinding. Additional randomized controlled trials of other psychedelics, such as psilocybin and lysergic acid diethylamide, are necessary to evaluate their effectiveness for PTSD.
Drug and alcohol review
March 1, 2026
Jack Freestone, Harriet MacDonald, Stassi Kypri et al.
Drug alerts in Australia are triggered when MDMA pills contain at least 150 mg of free-base MDMA, a threshold experts consider reasonable despite its limitations. Nineteen such alerts were issued in 2024, raising concerns about diminishing impact. Fifteen experts who design and disseminate drug alerts completed a survey, and seven participated in a focus group. Most agreed 150 mg is a reasonable threshold because it enables rapid communication and addresses potential harm, though thresholds cannot account for evolving manufacturing or consumption trends. Limited capacity to monitor community perceptions means there is little evidence to justify changing the threshold. Notifying communities about high-dose MDMA remains a harm-reduction priority; improving monitoring and establishing a dosage database could enhance future risk communication.
Pharmacology, biochemistry, and behavior
March 1, 2026
Negar G Ardabili, Shira Tan, María Elisa Márquez De Prado Arrarás et al.
A history of exposure to the synthetic cathinone eutylone alters the rewarding but not the aversive effects of cocaine and MDMA in female rats. Adult female Sprague-Dawley rats were given prior eutylone or saline, then underwent conditioning where saccharin taste and a distinct compartment were paired with cocaine, MDMA, or eutylone. All three drugs produced taste avoidance. Prior eutylone reduced the taste avoidance caused by eutylone itself but did not affect avoidance caused by cocaine or MDMA. Eutylone history had no effect on place preferences for MDMA or eutylone but increased place preferences for cocaine. The dissociable effects on reward versus aversion suggest that the subjective effects of eutylone differ from those of MDMA and cocaine, and that the neural bases for these drug effects are separable.