MDMA

What is MDMA?

MDMA is a synthetic molecule related to the amphetamines. In regulatory documents it appears under its international non-proprietary name, midomafetamine [1].

It belongs to the entactogens. Compared with classic psychedelics, the state it produces is shorter and easier to tolerate, with emotional openness and a feeling of connection with others [2].

MDMA bought on the illicit market has uncertain content and strength. That use cannot be compared with controlled administration in trials [2].

What is MDMA-assisted therapy?

MDMA-assisted therapy is an experimental treatment. The drug is taken only a few times, in long sessions attended by therapists, as part of a psychotherapy programme.

The idea is that MDMA makes traumatic memories easier to revisit without the person being overwhelmed by fear. What is being tested is the combination with psychotherapy, not the drug on its own [3].

For now the model exists only in clinical trials or in special access schemes such as Australia’s [4].

How does MDMA-assisted therapy work in trials?

In the phase 3 trials, treatment took about 18 weeks and alternated drug-free sessions with MDMA or placebo sessions. A two-person therapy team was present throughout [11] [12].

• Preparation. Drug-free sessions to build trust and prepare for the memories and feelings that may come up [11].
• MDMA or placebo sessions. Three sessions of about eight hours, roughly a month apart; vital signs were checked before discharge [11].
• Integration. Psychotherapy sessions after each drug session, to make sense of the experience [12].

Psychiatric medicines were stopped beforehand under medical supervision. Symptoms were rated by independent assessors who did not know which group each participant was in [11].

Which conditions is it being researched in?

Post-traumatic stress disorder is the only condition with phase 3 trials. The other areas are exploratory and rest on small studies.

PTSD. In the phase 3 trials, symptoms fell more with MDMA than with placebo, and both groups received the same psychotherapy [11] [12]. By the end of the second trial, more participants in the MDMA group no longer met diagnostic criteria [12].

Other areas. Small studies reported improvements in couples where one partner had PTSD and in social anxiety in autistic adults [20] [21]. In alcohol use, the main aim was to assess safety [22]. Larger controlled studies are still needed.

What are the known risks?

In the trials, with selected participants in controlled settings, the most common adverse effects were short-lived: muscle tightness, reduced appetite, nausea, sweating and feeling cold [11]. Teeth grinding, restlessness and blurred vision were also reported [12].

• Heart. MDMA briefly raises blood pressure and heart rate; the trials excluded uncontrolled hypertension and arrhythmias [11].
• Temperature. Small, transient rises occurred in the trials [11]; outside clinical settings, severe hyperthermia is a recognised complication [23].
• Blood sodium. MDMA can cause hyponatraemia, which is rare but can be fatal, and is more frequent and more severe in women [24].
• Interactions. With monoamine oxidase inhibitors it can cause serotonin syndrome, and deaths have been reported [25] [26]. Selective serotonin reuptake inhibitors blunt its effects [18].
• Illicit products. Samples tested in several European countries, Portugal among them, showed variable purity and new psychoactive substances mixed in [27].

The trials excluded people with psychotic disorders, bipolar I disorder, pregnancy or active substance use disorders [11]. Their findings do not apply to these groups.

What is the legal status of MDMA?

No medicine containing MDMA is authorised in the European Union or in Portugal [28]. Internationally, MDMA is under the strictest level of control.

• United Nations. Schedule I of the 1971 Convention on Psychotropic Substances [7].
• Portugal. Listed in schedule II-A of Decree-Law 15/93; outside authorised research, its use has no standing as a treatment [29] [30].
• Australia. Since 1 July 2023, authorised psychiatrists may prescribe it for PTSD with ethics committee approval; the regulator stresses that it has not evaluated any MDMA product [4].
• United States. MDMA remains in federal Schedule I and is not FDA-approved [31] [14]. In August 2026 it was reported that the sponsor had resubmitted its application to the FDA without a new phase 3 trial; the company has not confirmed this publicly and the FDA has not announced a decision [16] [17].

What is still being researched

Research is now focused on the questions the FDA and its advisory committee raised in 2024 [14] [13]. The answers will help to show what place, if any, MDMA-assisted therapy can have.

• Blinding and expectation. MDMA’s effects are easy to recognise, and most participants could tell which group they were in [12]. New trial designs aim to measure expectation from the outset [14].
• Durability. How long the benefit lasts and whether treatment needs repeating [14].
• Safety data. Complete recording of adverse events, laboratory tests and cardiac assessment [14].
• Misuse potential. Proper recording of effects experienced as “positive”, which are needed to assess this risk [14].
• The role of psychotherapy. How much of the benefit comes from MDMA and how much from psychotherapy; committee members suggested a factorial design to separate them [13].
• Who takes part. Many participants had used MDMA before, which limits generalisability; the FDA suggested keeping that number low [14].

The FDA set out a path: a new randomised, double-blind trial with longer follow-up [14]. Until then, MDMA-assisted therapy remains an investigational treatment.