Clinical psychopharmacology and neuroscience : the official scientific journal of the Korean College of Neuropsychopharmacology
May 31, 2026
Yong Yue, Yi Cai, Rumi Murayama et al.
Gut bacteria contribute to baseline central oxytocin signaling in rats, but are not necessary for the acute oxytocin release triggered by MDMA. Male rats given broad-spectrum antibiotics for seven days showed enlarged ceca, confirming microbiome disruption, yet maintained stable body weight. Baseline oxytocin expression in the paraventricular and supraoptic nuclei of the hypothalamus was significantly reduced after antibiotic treatment, while peripheral oxytocin levels remained unchanged. MDMA administration increased central oxytocin expression similarly in both antibiotic-treated and control rats, and MDMA-induced peripheral oxytocin levels also did not differ between groups. The findings indicate that gut microbiota help maintain central oxytocin under normal conditions but are not required for MDMA's oxytocin-activating effects.
Clinical Pharmacology & Therapeutics
May 28, 2026
Gia Han Le, Sabrina Wong, Danica E. Johnson et al.
The serotonin 5-HT2B receptor sits at a crossroads between potential antidepressant effects in the brain and serious heart valve risks when activated peripherally. This narrative review of preclinical and clinical literature finds that peripheral activation of 5-HT2B receptors causes valvular heart disease through cell proliferation and scarring, as seen with older drugs like fenfluramine and some dopamine agonists. In the brain, the receptor's effects are mixed: astrocytic activation may support metabolism and plasticity, while neuronal blockade can normalize dopamine and glutamate activity. Several approved antidepressant adjuncts (aripiprazole, brexpiprazole, cariprazine) antagonize this receptor without observed heart valve problems. The authors propose developing centrally selective, periphery-sparing 5-HT2B antagonists for treatment-resistant depression, with early cardiac monitoring to ensure safety.
European neuropsychopharmacology : the journal of the European College of Neuropsychopharmacology
May 28, 2026
L Belinger, N M Rieser, E J E Engeli et al.
In a double-blind randomized trial with 120 healthy volunteers who received psilocybin, MDMA, or methylphenidate (active placebo), overall blinding was insufficient. Psilocybin had the highest rates of functional unblinding, MDMA moderate levels, and methylphenidate the lowest. As an active placebo, methylphenidate provided more effective blinding for MDMA than for psilocybin. Incorporating certainty levels of substance guesses revealed a more differentiated pattern with lower functional unblinding rates. Decision factors and subjective substance experiences were associated with phenomenological effects. Prior substance experiences did not influence accuracy of forced-choice guesses. These findings offer empirical guidance for designing and reporting blinding procedures in psychedelic trials.
Translational psychiatry
May 21, 2026
Francesco Bavato, Andrea Steuer, Anna M Jacobsen et al.
Chronic users of methamphetamine (METH) and MDMA (Ecstasy) show distinct alterations in blood levels of tryptophan-related metabolites, which may help explain their different clinical effects. In a study of 36 chronic MDMA users, 33 chronic METH users, and 71 healthy controls, METH use was linked to depleted serum tryptophan and serotonin and broad activation of kynurenine pathways, whereas MDMA use was associated with selective activation of the OH-kynurenine branch. These metabolite changes correlated with the severity of depression and psychosis symptoms. The findings suggest that persistent changes in peripheral tryptophan metabolism may contribute to the substances' contrasting addiction and psychiatric profiles.
Brain
May 15, 2026
The authors argue that the consequences of MDMA use cannot be easily separated from the effects of other drug use or lifestyle factors, highlighting the difficulty in attributing specific outcomes solely to MDMA.
Psychoactives
May 12, 2026
Sean M. Viña
Analyzing 2008–2019 National Survey on Drug Use and Health data, lifetime psychedelic use is not independently linked to lower odds of missing needed mental health treatment after accounting for psychological distress. However, psychedelic exposure weakens the link between distress and missed care: as distress rises, those who have used psychedelics—especially men—show a smaller increase in unmet treatment needs compared to non-users. Among women, only MDMA shows a similar buffering effect. The findings indicate that psychedelic use does not uniformly improve care engagement but reveals gendered patterns in how distress leads to disengagement, with women experiencing diminished benefits despite comparable distress levels.
BMJ open
May 11, 2026
Julia Colcott, Alexandre A Guerin, Olivia Carter et al.
A new tool, the MDMA-Assisted Psychotherapy Side Effects Tool (M-SET), was developed to systematically capture side effects during MDMA-assisted psychotherapy. Experts in MDMA-AP and neuropsychopharmacology participated in a two-round online Delphi process to refine a list of 165 items across four questionnaires covering screening, baseline, medication session days, and follow-up. The tool aims to improve safety monitoring and build a more robust evidence base on the tolerability of MDMA-AP for research and clinical use.
ACS chemical neuroscience
May 6, 2026
Maxemiliano V Vargas, Cassandra J Hatzipantelis, Lee E Dunlap et al.
A safer analogue of MDMA, called R-MDDMA, shows promise for treating PTSD and depression without the abuse potential of MDMA. Unlike MDMA, R-MDDMA does not activate 5-HT2B receptors, induce serotonin release, cause head-twitch responses, affect body temperature, or increase locomotion at therapeutic doses. However, it still promotes structural neuroplasticity in cortical neurons, facilitates fear extinction learning, and produces sustained antidepressant-like effects. These results suggest that R-MDDMA might be a safer MDMA analogue with similar therapeutic properties.
Neurochemical research
May 6, 2026
Oyedayo Phillips Akano, Goodness Olatinwo, Moses Agbomhere Hamed et al.
In male Wistar rats given MDMA (ecstasy) orally for 56 days, the drug caused oxidative damage, inflammation, neurotransmitter imbalances, and cell death in the brain, especially in the hippocampus. Co-administration of the antioxidant glutathione partially reversed these harmful effects at moderate MDMA doses by restoring antioxidant defenses, reducing inflammation, and preserving hippocampal structure. However, at higher MDMA doses, glutathione's protective effects were much weaker, indicating that additional treatments are needed to address excitotoxicity and mitochondrial dysfunction.
medRxiv Preprint Server
May 5, 2026
Nicholas C. Borgogna, D. Drew Whittington, Tyler Owen et al.
preprint
MDMA-assisted therapy (MDMA-AT) shows a moderate-to-large reduction in psychological symptoms compared to control conditions, based on a meta-analysis of eight controlled trials with 295 participants. The effect was larger against inert placebos than active controls. Trauma symptoms improved strongly, while depression showed a smaller, non-significant effect. Only 23% of publications met high-quality standards for reporting harms. Small samples and mediocre harm reporting underscore the need for larger, more transparent trials.
May 4, 2026
Victoria Burmester, Laura Aggett, David J Nutt et al.
preprint
MDMA reliably enhances subjective social feelings such as sociability, emotional openness, closeness, and emotional empathy, but these changes do not consistently translate into observable prosocial behaviors like cooperation or trust, which remain highly context dependent. The most robust social effect is a reduction in the processing of social threat, including diminished sensitivity to negative social cues and impaired recognition of fear and anger. This divergence between felt and enacted social effects helps explain variability in laboratory findings and underscores the importance of context and measurement. These mechanisms may inform MDMA's therapeutic use for conditions involving heightened social threat and avoidance.
Cureus
May 1, 2026
Pierre-Henri Woitrin, Pascale Lievens
MDMA toxicity, once stereotyped as affecting only young people in nightclubs, may now appear in older individuals using the drug for self-directed therapy, creating a diagnostic trap for emergency physicians. A 55-year-old woman developed life-threatening hyponatremic encephalopathy after taking MDMA in a private home, not a rave. Her severe hyponatremia and neurological decline were initially puzzling because her age and setting did not match the expected profile. The case underscores that representativeness bias—judging based on a stereotypical category—can cause clinicians to overlook MDMA as a cause of unexplained hyponatremia with altered mental status, regardless of patient age or social context.