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Home/Research/MDMA/Depressive Disorders

MDMA for Depressive Disorders

99 papers and 10 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

99 papers
Open Accessindividual

Psychedelic-assisted therapy: a survey on the clinical methods of Swiss physicians

This survey study (n=41) examined how Swiss physicians provide psychedelic-assisted therapy under legal exemptions, mainly for depression, anxiety, PTSD and chronic pain. It found wide variation in practice, with psilocybin, MDMA and LSD commonly used, music often played during sessions, and adverse effects usually including disorientation, feeling cold, anxiety and nausea.

Published
May 20, 2026
Journal
Therapeutic Advances in Psychopharmacology
Authors
Beichmann, K., Catzeflis, P., Aicher, H. D., Seragnoli, F., Calder, A., Amrani, A., Hasler, G.
Paywallindividual

From trials to clinics: investigators' perspectives on translating psychedelic research into clinical care

This qualitative study (n=21) interviewed US psychedelic clinical investigators about how treatments such as MDMA and psilocybin might move from trials into routine care. They saw major challenges in the role of psychotherapy, treatment cost and scalability, and the effects of hype and stigma on uptake.

Published
May 19, 2026
Authors
Mitchell, J., Neitzke-Spruill, L., Mathai, D. S., Robinson, J. O., Kavan, Z., Averil, L. A., McGuire, A. L.
Open Accessindividual

Age moderates the relationship between psychedelics use and mental health in naturalistic settings

This cross-sectional survey (n=1,088) found that age significantly moderates the relationship between lifetime psychedelic use and mental health, with classic psychedelics such as psilocybin being associated with lower depression and anxiety in younger adults, but these benefits diminish with age and even reverse for anxiety in older participants.

Published
March 10, 2026
Journal
Research Square
Authors
Gregorio, G. D., Basset, S., Manmohan, H., Nixon, W. C., Pogaku, A., Zhou, J., Sanderson, D. J., Lengieza, M. L., Bocchio, M.
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.
Open Accessindividual

Efficacy and Safety of the Neuroplastogen TSND-201 for the Treatment of PTSD A Randomized Clinical Trial

In a multicentre, double‑blind, placebo‑controlled phase 2 trial of 65 adults with chronic PTSD, once‑weekly oral TSND‑201 produced significantly greater reductions in clinician‑rated PTSD severity (CAPS‑5; LS mean difference 9.64, P = .01) and improvements in self‑reported symptoms, functioning and depression versus placebo. TSND‑201 was generally well tolerated — common adverse events included headache, decreased appetite, nausea, dizziness and transient blood‑pressure increases — supporting its potential as a rapid‑acting, durable treatment for PTSD.

Published
February 18, 2026
Journal
JAMA Psychiatry
Authors
Jones, A., Warner-Schmidt, J., Kwak, H., Stogniew, M., Mandell, B., Ching, T. H., Stein, M. B., Kelmendi, B.
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.

Clinical Trials

10 trials
CompletedPhase II

A Study to Assess the Use of Methylone in the Treatment of PTSD (IMPACT-1)

This Phase II, two-part, multicentre trial (n=64) will assess methylone as a treatment for adults with post-traumatic stress disorder (PTSD). It is designed to evaluate the drug’s safety, tolerability, and efficacy in participants aged 18–65 years in the UK, including people who have previously tried at least one PTSD treatment without sufficient benefit.

Type
interventional
Blinding
double
Randomized
Yes
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

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
ACTRN12622000883718
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

Explore further

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