January 30, 2026
Makaela Weeda, Valeria Gazzola, Christian Keysers et al.
preprint
MDMA, also known as ecstasy, shows promise for treating mental disorders, but its therapeutic use remains unapproved partly because its neurobiological effects are not well understood. This review examines MDMA's effects on social behavior in humans and animals, focusing on empathy. The authors summarize current knowledge of the pharmacological and neurobiological mechanisms and brain circuits involved in MDMA's influence on social behavior, noting that scientific data on its social effects are ambiguous.
Journal of clinical epidemiology
January 23, 2026
Marija Franka Žuljević, Antonija Mijatović, Renata Orhanović et al.
4 citations
A cross-sectional analysis of 336 clinical trials on MDMA or psilocybin registered on ClinicalTrials.gov found that 17.6% made major changes to primary outcome measures and 28.6% changed eligibility criteria, most after recruitment began. Among completed trials, 72.0% did not post results on the registry, and most that did exceeded the one-year reporting window. Only 3 of 29 trials with both posted results and publications had fully concordant adverse event reporting; most showed qualitative and quantitative discrepancies. These inconsistencies undermine the credibility and safety evaluation of these trials, and the authors advise greater transparency and stricter adherence to reporting standards.
Neuropsychopharmacology
January 16, 2026
Philip D. Harvey, Charles B. Nemeroff
2 citations
Interest in psychedelic therapies is booming, yet no psychedelic treatment has been approved for any psychiatric condition. The one large-scale MDMA development program that reached the FDA was disapproved for reasons that could also apply to classical psychedelic trials. This review defines psychedelics, surveys current therapies, targeted conditions, compounds under investigation, and research strategies. Some interventions combine drugs with psychotherapy, bringing both benefits and challenges. Debate continues over whether the psychedelic experience itself is essential for therapeutic effect, complicating blinded trials. The review also addresses societal issues like deregulation of formerly illegal substances and regulatory hurdles, including alternatives to blinded trials and whether targets like adjustment disorder pose problems under current standards.
Frontiers in neuroscience
January 1, 2026
Jenna E Kachmarik, Jennifer M Loftis, Christopher S Stauffer
Posttraumatic stress disorder (PTSD) is linked to higher inflammation and chronic illness risk, but few studies have examined how PTSD interventions affect inflammatory biomarkers. In this pilot study, 23 Veterans with PTSD provided blood samples before and after MDMA-assisted group therapy. Small increases occurred in interleukin-6 (IL-6) and C-reactive protein (CRP), while tumor necrosis factor alpha (TNF-α) showed a small decrease. Higher baseline IL-6 and TNF-α were associated with more severe PTSD symptoms. IL-6 change correlated with symptom change, and higher baseline IL-6 weakly predicted symptom improvement. These preliminary results suggest MDMA-assisted therapy may influence inflammatory biomarkers and highlight relationships between biomarkers and PTSD symptoms.
Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology
January 1, 2026
Isabelle Straumann, Patrick Vizeli, Isidora Avedisian et al.
5 citations
In a double-blind, placebo-controlled crossover trial with 23 healthy adults, the acute effects of MDMA, its metabolite MDA, and two lysine-conjugated prodrugs were compared. MDA produced stronger and longer-lasting subjective drug effects (6.1 vs. 4.1 hours), greater stimulant effects, more negative effects, fear, and visual alterations than MDMA at equimolar doses. The lysine-conjugated prodrug of MDA (Lys-MDA) delayed the onset and peak of effects but otherwise acted similarly to MDA. Lys-MDMA did not release MDMA into the blood and produced no effects, indicating it is not a functional prodrug. The findings suggest MDA has a less favorable therapeutic profile than MDMA, and lysine conjugation can modulate the timing but not necessarily improve tolerability of effects.
Case Reports in Psychiatry
January 1, 2026
Ridhi J. Vyas, Ryan Hood, Jeremy Hsiang et al.
A 31-year-old woman with chronic PTSD and a history of childhood compulsions developed new-onset obsessive-compulsive disorder (OCD) after undergoing MDMA-assisted psychotherapy (MDMA-AP) in a clinical trial. Her PTSD had been resistant to multiple medications, and she reported significant improvements in flashbacks and suicidal ideation after the first session. Following a delayed second session, she experienced intrusive guilt, scrupulosity, and compulsive urges to confess, leading to a DSM-5 diagnosis of OCD. OCD symptoms persisted for over a year, with a Y-BOCS score of 17 indicating moderate severity, and improved with escitalopram. This case suggests that MDMA-AP may trigger obsessive-compulsive pathology in individuals with complex trauma and prior obsessive-compulsive tendencies, possibly through serotonergic effects on frontostriatal circuits, and highlights the need for screening and long-term monitoring in such protocols.
Open Science Framework
January 1, 2026
Christina Chwyl, M. Kati Lear, Sunjeev Kamboj et al.
Self-compassion is thought to be important for mental health, especially for people with social anxiety disorder. MDMA-assisted therapy may work by increasing self-compassion. This study will examine whether trait self-compassion rises during treatment and whether self-compassion felt during MDMA dosing sessions leads to lasting changes. It will also test if changes in self-compassion relate to improvements in social anxiety, depression, shame, functioning, and belonging. Five specific aims are outlined to explore these relationships across two dosing sessions.
Frontiers in pharmacology
January 1, 2026
Patricio Sáez-briones, Amanda Silva-Rodríguez, Michelle Morales-Vidal et al.
MDMA (Ecstasy) suppressed helping behavior in adult male rats at doses of 5 mg/kg and 10 mg/kg, fully eliminating the behavior, while lower doses (1 mg/kg and 0.5 mg/kg) caused partial inhibition only after the rats switched roles. The lowest dose (0.25 mg/kg) had no effect. Electrophysiological recordings showed that MDMA reinforced long-term depression in the nucleus accumbens core and increased long-term potentiation in the anterior cingulate cortex, with the latter depending on serotonin and oxytocin. These neuroplastic effects align with mechanisms thought to promote prosocial behavior, yet the drug disrupted helping behavior, suggesting MDMA may impair neural processes essential for executing helping actions without reducing the willingness to help.