MDMA for Depressive Disorders

26 papers and 5 clinical trials exploring mdma as a treatment for depressive disorders.

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

IndicationApproximately 260 million people worldwide are affected by depression.

Depressive Disorders

Depressive disorders, particularly major depressive disorder (MDD), are significant contributors to global mental health issues. Research into the therapeutic potential of psychedelics, such as psilocybin and ketamine, offers promising avenues for treatment, especially for cases that are resistant to conventional therapies.

Full Depressive Disorders profile

Academic Research

26 papers

Paywallindividual

MDMA-Assisted Therapy for Major Depressive Disorder: A Seven-Month Follow-Up Proof of Principle Trial

This long-term follow-up (n=12) of participants with moderate-to-severe major depressive disorder who received MDMA-assisted therapy (two dosing sessions integrated with nine psychotherapy sessions) found significant reductions in depression severity and functional impairment at seven months compared to baseline, with improvements maintained from the post-treatment assessment and no increases in suicidal ideation.

Published: February 1, 2026
Journal: Journal of Psychiatric Research
Authors: Kvam, T. M., Goksøyr, I. W., Rog, J., van de Vooren, I. T. J., Stewart, L. H., Autran, I., Berthold-Losleben, M., Mørch-Johnsen, L., Holst, R., Røssberg, J. I., Clausen, I., Andreassen, O. A.

Open Accessindividual

Naturalistic psychedelic use and changes in depressive symptoms

This longitudinal observational study (n=12,345) of U.S. residents found that naturalistic psychedelic use (n=505, 4.1% of participants) was associated with modest increases in depressive symptoms, particularly when occurring in 'risk contexts' characterised by negative mindset and lack of psychological support, with challenging psychedelic experiences mediating this relationship and suggesting that unsupervised psychedelic use may not be generally therapeutic and could worsen depression under certain circumstances.

Published: December 1, 2025
Journal: Journal of Affective Disorders
Authors: Goldberg, S. B., Hendricks, P. S., Osika, W., Simonsson, O., Swords, C. M.

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: Belahda, D., Graux, C., Igounenc, N., Luquiens, A., Mura, T., Rochefort, P., Sergent, F., Serrand, C.

Open Accessindividual

MDMA-assisted therapy as a treatment for major depressive disorder: proof of principle study

In an open‑label proof‑of‑principle study of 12 participants with moderate–severe major depressive disorder, two MDMA‑assisted therapy sessions plus psychotherapy were feasible, well tolerated and produced large, statistically significant reductions in depressive symptoms (mean MADRS change −19.3) and functional impairment. No unexpected or serious adverse events occurred, and the authors conclude that randomised trials are needed to confirm efficacy.

Published: July 11, 2025
Journal: British Journal of Psychiatry
Authors: Andreassen, O. A., Autran, I., Berthold-Losleben, M., Clausen, I., Goksøyr, I. W., Holst, R., Jentoft van de Vooren, I.-T., Kvam, T-M., Mørch-Johnsen, L., Rog, J., Stewart, L. H.

Open Accessindividual

Negative Affect Circuit Subtypes and Neural, Behavioral, and Affective Responses to MDMA: A Randomized Clinical Trial

In a double‑blind, placebo‑controlled within‑participant randomised trial of 16 adults stratified by baseline nonconscious‑threat–evoked amygdala activity, 120 mg MDMA acutely reduced amygdala and subgenual ACC activity, increased sgACC–amygdala connectivity, and raised likability of threat expressions in the high‑reactivity subgroup (NTNA+) versus the low‑reactivity subgroup. These results indicate that baseline neuroimaging of negative affect circuitry can identify biomarkers to personalise MDMA‑based therapies.

Published: April 30, 2025
Journal: JAMA Network Open
Authors: Bertrand, C., Deisseroth, K., Gray, N. J., Hack, L. M., Heifets, B. D., Hilton, R., Knutson, B., Laudie, J., Rodriguez, C. I., Roessell, P. J. V., Suppes, T., Williams, L. M., Zhang, X.

Open Accessindividual

Trauma Under Psychedelics: MDMA Shows Protective Effects During the Peritraumatic Period

In a naturalistic cohort of 772 survivors of the October 7 Supernova festival attack, participants who were under the influence of MDMA during the trauma reported lower psychological distress, fewer PTSD symptoms, greater social interaction and better sleep in the one to four months post-attack compared with those who were sober, whereas cannabis and/or alcohol use was associated with worse outcomes. These novel findings suggest a putative protective role for MDMA during the peritraumatic period and warrant mechanistic and longitudinal investigation.

Published: March 31, 2024
Journal: Biorxiv
Authors: Admon, R., Gross, R., Magal, N., Netzer, O., Polinsky, T., Salomon, R., Stern, Y.

Clinical Trials

5 trials

RecruitingPhase II

A double-blind, randomised trial of methylphenidate-assisted versus MDMA-assisted therapy for mood and anxiety symptoms in advanced-stage cancer patients

This double-blind, randomised, parallel Phase II trial (n=32) compares single-dose MDMA-assisted therapy (120 mg, optional 60 mg supplemental) versus methylphenidate-assisted therapy (20 mg, optional 10 mg supplemental) for depressive and anxiety symptoms in people with advanced-stage cancer.

Started: July 31, 2023
Type: interventional
Blinding: single
Randomized: Yes
Registry ID: ACTRN12619001334190

RecruitingPhase II

MDMA-assisted Therapy for Adjustment Disorder (AD) in Dyads of Patients With Cancer and a Concerned Significant Other

This open-label single-group assignment trial (n=20) aims to evaluate the feasibility, tolerability, and preliminary effectiveness of MDMA-assisted therapy for adjustment disorder (AD) in 10 dyads of cancer patients and their concerned significant others (CSOs).

Started: October 6, 2022
Type: interventional
Blinding: none
Randomized: No
Registry ID: NCT05584826

WithdrawnPhase II

Brain Activity Effects of Psychedelic Medicines in Healthy Volunteers

This open-label Phase II trial (n=200) evaluated the safety and efficacy of psilocybin for depression post-traumatic stress disorder.

Started: August 22, 2022
Type: interventional
Blinding: none
Randomized: Yes
Registry ID: 12622000883718

WithdrawnPhase II/III

Brain Activity Effects of Psychedelic Medicines in Healthy Volunteers

This interventional trial (n=0, withdrawn) aimed to investigate the brain activity effects of psychedelic medicines, specifically psilocybin or MDMA, in healthy volunteers.

Started: August 22, 2022
Type: interventional
Blinding: none
Randomized: No
Registry ID: ACTRN12622000883718p

CompletedPhase I

Effects of Methylphenidate, Modafinil, and MDMA on Emotion-processing in Humans: A Pharmaco-fMRI Study

Randomised, quadruple-blind, placebo-controlled crossover fMRI study (n=24) administering single doses of methylphenidate 60 mg, modafinil 600 mg, MDMA 125 mg, and placebo to healthy volunteers to assess emotion-processing and cognitive performance.

Started: January 10, 2013
Type: interventional
Blinding: quadruple
Randomized: Yes
Registry ID: NCT01951508

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Search all MDMA papers Search all Depressive Disorders trials Full MDMA profile Full Depressive Disorders profile

MDMA for Depressive Disorders

MDMA

Depressive Disorders

Academic Research

MDMA-Assisted Therapy for Major Depressive Disorder: A Seven-Month Follow-Up Proof of Principle Trial

Naturalistic psychedelic use and changes in depressive symptoms

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

MDMA-assisted therapy as a treatment for major depressive disorder: proof of principle study

Negative Affect Circuit Subtypes and Neural, Behavioral, and Affective Responses to MDMA: A Randomized Clinical Trial

Trauma Under Psychedelics: MDMA Shows Protective Effects During the Peritraumatic Period

Clinical Trials

A double-blind, randomised trial of methylphenidate-assisted versus MDMA-assisted therapy for mood and anxiety symptoms in advanced-stage cancer patients

MDMA-assisted Therapy for Adjustment Disorder (AD) in Dyads of Patients With Cancer and a Concerned Significant Other

Brain Activity Effects of Psychedelic Medicines in Healthy Volunteers

Brain Activity Effects of Psychedelic Medicines in Healthy Volunteers

Effects of Methylphenidate, Modafinil, and MDMA on Emotion-processing in Humans: A Pharmaco-fMRI Study

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