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Home/Research/MDMA/Substance Use Disorders (SUD)

MDMA for Substance Use Disorders (SUD)

71 papers and 13 clinical trials exploring mdma as a treatment for substance use disorders (sud).

Compoundempathogen

MDMA

MDMA is a synthetic empathogen that enhances monoamine release, producing prosocial and anxiolytic effects without frank hallucinosis. Two Phase III trials demonstrated significant PTSD symptom reductions, though FDA review raised concerns about blinding, durability, and safety characterisation.

Full MDMA profile
IndicationOver 2% of the global population is affected by some form of substance use disorder, contributing to nearly 12 million deaths annually.

Substance Use Disorders (SUD)

Substance use disorders (SUDs) are complex conditions marked by compulsive substance use despite negative consequences. Recent research is exploring the therapeutic potential of various psychedelics, including LSD, psilocybin, and MDMA, in treating these disorders to provide novel, effective treatment options.

Full Substance Use Disorders (SUD) profile

Academic Research

71 papers
Open Accessmeta

Psychedelic medicine: mechanisms, evidence, and translation to practice

This review (2026) summarises the rapidly growing evidence for psychedelic-assisted therapies, finding the strongest support for psilocybin in treatment-resistant depression (TRD) and MDMA in post-traumatic stress disorder (PTSD). It also highlights that while these treatments are generally well tolerated in controlled settings, major challenges remain around unclear mechanisms, trial limitations, scalability, and translation into routine practice.

Published
February 23, 2026
Journal
BMJ
Authors
Jacobs, E., Zahid, Z., Hinkle, J., Nayak, S., Yaden, D. B.
Paywallindividual

The effect of methamphetamine and 3,4-methylenedioxymethamphetamine on peripheral endocannabinoid concentrations: a study in healthy adults

This within-subject, double-blind study (n=22) found that acute administration of methamphetamine (14 mg/70 kg) significantly lowered plasma 2-arachidonoylglycerol concentrations compared to placebo at 150-180 minutes post-administration, whilst MDMA (100 mg) did not affect endocannabinoid levels, and higher anandamide concentrations during the placebo condition correlated with disliking the 'drug effects'.

Published
October 6, 2025
Journal
Psychopharmacology
Authors
Mayo, L. M., Haggarty, C. J., Petrie, S. R., Hill, M. N., Bershad, A. K., de Wit, H., Deutch, A. Y.
Paywallindividual

Psilocybin in alcohol use disorder and comorbid depressive symptoms: Results from a feasibility randomized clinical trial

In this double‑blind, randomised pilot trial of recently detoxified patients with severe alcohol use disorder and comorbid depression, two 25 mg psilocybin‑assisted psychotherapy sessions (versus 1 mg control) were feasible, acceptable and safe. At 12 weeks the 25 mg group showed higher abstinence (55% vs 11%) and significant reductions in percent drinking days and craving frequency, although blinding was imperfect and the study was small and preliminary.

Published
July 24, 2025
Journal
Addiction
Authors
Luquiens, A., Belahda, D., Graux, C., Igounenc, N., Serrand, C., Rochefort, P., Mura, T., Sergent, F.
Open Accessindividual

MDMA-assisted psychotherapy for AUD: Bayesian analysis of WHO drinking risk level and exploratory analysis of drinking behavior and psychosocial functioning at 3 months follow-up

In an open‑label feasibility study of 14 recently detoxified participants, Bayesian analysis estimated a 55–63% probability that MDMA‑assisted psychotherapy produced a two‑level reduction in WHO drinking‑risk at 3‑month follow‑up, with preliminary reductions in alcohol craving and improvements in sleep and psychosocial functioning. The paper frames a harm‑reduction endpoint for AUD and provides early evidence that MDMA‑assisted psychotherapy may improve quality of life alongside reduced drinking.

Published
June 9, 2025
Journal
Alcohol and Alcoholism
Authors
Thurgur, H., Sessa, B., Higbed, L., O'brien, S., Durant, C., Wilson, S., Szigeti, B., Morgan, C. J. A., Nutt, D. J.
Open Accessindividual

Self-compassion mediates treatment effects in MDMA-assisted therapy for posttraumatic stress disorder

This secondary analysis (n=82) of a Phase III RCT of MDMA-assisted therapy found significant improvements in both uncompassionate self-responding and compassionate self-responding across all six Self-Compassion Scale subscales, most with large effect sizes. Changes in self-compassion fully mediated the reductions in PTSD severity and depressive symptoms observed with MDMA-AT versus placebo plus therapy, though no significant effects were seen for alcohol or substance use outcomes.

Published
May 7, 2025
Journal
European Journal of Psychotraumatology
Authors
Agin-Liebes, G. I., Zeifman, R. J., Mitchell, J.
Open Accessindividual

Dissociable effects of LSD and MDMA on striato-cortical connectivity in healthy subjects

In healthy volunteers, acute MDMA and LSD did not alter within-network connectivity of associative, limbic or sensorimotor striatal seeds but produced distinct striato‑cortical changes: MDMA reduced limbic striatum–amygdala coupling, while LSD increased associative striatum connectivity with frontal, sensorimotor and visual cortices. These drug-specific effects mainly occurred outside standard striatal networks, consistent with reduced network modularity and increased cross‑network connectivity under psychedelics.

Published
February 8, 2025
Journal
Biorxiv
Authors
Ertl, N., Ashraf, I., Azizi, L., Roseman, L., Erritzoe, D., Nutt, D. J., Carhart-Harris, R. L., Wall, M. B.

Clinical Trials

13 trials
RecruitingPhase II

MDMA for Co-occurring PTSD and OUD After Childbirth

This open-label trial (n=15) will assess feasibility, safety and preliminary efficacy of MDMA-assisted therapy (three monthly MDMA sessions with preparatory and integrative therapy) for postpartum people with co-occurring PTSD and Opioid Use Disorder.

Started
March 1, 2024
Type
interventional
Blinding
none
Randomized
No
Registry ID
NCT05219175
RecruitingPhase II

MDMA-assisted Prolonged Exposure Therapy for Comorbid Alcohol Use Disorder and Post-traumatic Stress Disorder (MPATHY)

This Phase II interventional trial (n=120) explores the effectiveness of MDMA-assisted (80–160 mg per session, with possible supplemental doses) prolonged exposure therapy (COPE) versus niacin control in individuals with comorbid PTSD and alcohol use disorder.

Started
September 19, 2023
Type
interventional
Blinding
double
Randomized
Yes
Registry ID
NCT05709353
RecruitingPhase II

MDMA for AUD/PTSD Comorbidity (MDMA)

This open-label, Phase II trial (n=18) will investigate the safety and preliminary effectiveness of MDMA-assisted therapy (MDMA-AT) in military veterans with co-occurring Alcohol Use Disorder (AUD) and Post-Traumatic Stress Disorder (PTSD).

Started
September 1, 2023
Type
interventional
Blinding
none
Randomized
No
Registry ID
NCT05943665
Unknown statusPhase I

Abuse Potential and Human Pharmacology of Methylone

Double-blind, randomised, placebo-controlled crossover Phase I study (n=17) comparing single oral methylone 200 mg, MDMA 100 mg, and placebo in healthy volunteers to assess abuse potential, subjective and physiological effects, and pharmacokinetics.

Started
December 1, 2021
Type
interventional
Blinding
quadruple
Randomized
Yes
Registry ID
NCT05488171
Unknown statusPhase II

Open-Label Proof of Concept Feasibility Study to Explore the Safety, Tolerability and Potential Role of MDMA-Assisted Psychotherapy for the Treatment of Detoxified Patients with Alcohol Use Disorder

Open-label proof-of-concept feasibility study (n=20) assessing safety, tolerability, and acceptability of MDMA-assisted psychotherapy (oral MDMA capsules) in detoxified patients with alcohol use disorder.

Started
January 3, 2017
Type
interventional
Blinding
none
Randomized
No
Registry ID
2016-002547-42
CompletedPhase I

Abuse Liability and Human Pharmacology of Mephedrone

Randomised, double-blind, crossover Phase I study (n=12) comparing single oral mephedrone 200 mg, MDMA 100 mg, and placebo in healthy male volunteers to assess abuse liability and human pharmacology.

Started
September 1, 2014
Type
interventional
Blinding
double
Randomized
Yes
Registry ID
NCT02232789

Explore further

Search all MDMA papers Search all Substance Use Disorders (SUD) trials Full MDMA profile Full Substance Use Disorders (SUD) profile