AuthorisedTherapeutic exploratory (Phase II)Interventional

A Randomized, Delayed-Treatment Controlled, Phase 2 Pilot Study of Manualized MDMA-Assisted Therapy for Young Adults with Chronic Treatment-Resistant Major Depressive Disorder

Major depression can be exhausting and difficult to live with, particularly when standard options like antidepressants or routine counselling have not helped. This clinical trial is exploring an experimental approach called MDMA-assisted therapy for adults with chronic, treatment-resistant depression. Midomafetamine (MDMA) is given in a quiet, medically supervised clinic alongside structured support from trained therapists. In this study, some participants will receive the treatment right away, while others will receive it after a short waiting period. This helps researchers compare the results fairly. The main aim is to check how safe the treatment is, watch for any side effects, and see how well participants manage the programme. Researchers will also measure whether the therapy helps lift low mood and makes everyday tasks easier. Taking part is entirely voluntary, and your standard healthcare continues regardless of your decision.

At a glance

Status

Authorised

Phase

Therapeutic exploratory (Phase II)

Sponsor

Ostfold Hospital Trust

Enrolment target

Start

03 Jul 2026

Major Depressive Disorder

What is this study about?

Living with long-term depression can have an overwhelming impact on your health, relationships, and daily life. For many people, common treatments like standard antidepressant tablets or regular talking therapies provide good relief. However, for others, these options do not work well enough. When depression continues despite trying several treatments, doctors call it 'treatment-resistant' depression. Finding new, safe ways to help people in this situation is an urgent priority.

This clinical trial is testing a combination of a medicine called midomafetamine (MDMA) and specialised psychological therapy. In daily life, MDMA is known as a controlled substance, but in this medical study, a pure, carefully measured dose is given in a secure, calm setting. The medicine is not taken alone at home. Instead, it is used during in-depth therapy sessions with trained professionals who guide and support you throughout the experience. Scientists believe this may help people process painful emotions and change unhelpful patterns of thinking.

Because this is a Phase 2 pilot study, the primary focus is on safety and practical delivery. Doctors want to understand how well patients tolerate the treatment, monitor any side effects, and see if people are able to complete all the planned sessions. They will also look closely at whether the treatment reduces depression scores and helps people get back to enjoying everyday life.

The trial uses a 'delayed-treatment' design. This means half the people receive the treatment straight away, while the other half wait for a set period before receiving it. Comparing both groups helps researchers know whether any improvements are truly due to the therapy.

Key takeaways

The study tests MDMA combined with psychological therapy for severe, hard-to-treat depression.
It is a Phase 2 trial focused on safety, side effects, and symptom relief.
Treatment takes place in a controlled clinic setting with trained therapists present throughout.
Participants may receive treatment immediately or after a short waiting period.
Taking part is voluntary, and you can withdraw at any time without affecting your standard care.

Who may be eligible?

This trial is designed for adults aged 18 and older who have been diagnosed with chronic major depressive disorder that has not improved after trying standard treatments. The study specifically looks at young adults and older adults who continue to experience significant distress despite past medical care.

To ensure participant safety, there are several health checks before joining. MDMA can temporarily raise blood pressure and heart rate, so people with certain heart problems or blood pressure issues may not be eligible. People with particular mental health conditions, such as psychosis or bipolar disorder, or those who are currently at high risk of self-harm, will usually not be able to join.

Certain prescription medicines can also interact unsafely with MDMA. The study team will review your full medical history and current medications in detail to make sure that taking part would be completely safe for you.

Could this study suit you?

Answer these quick questions to see if you may be eligible. This is a guide only — the research team makes the final call.

I am aged 18 or older.
I have a formal diagnosis of major depressive disorder.
My depression has lasted a long time and has not responded well to past treatments.
I am able to attend regular in-person hospital or clinic appointments.
I do not have a history of serious heart disease or uncontrolled high blood pressure.

Answer every question to see your result.

What does participation involve?

Taking part in this study involves several stages over a number of weeks. First, you will attend screening visits where doctors check your physical health, blood pressure, and mental health history. If you are eligible, you will have preparatory talking sessions with two study therapists to build trust, discuss your background, and learn what to expect.

Next, you will take part in the dosing sessions. On these days, you will take the medicine in a comfortable clinic room with the therapists staying with you the whole time. You may listen to music, rest with an eye mask, or talk through feelings as they arise. After these sessions, you will return for 'integration' therapy visits to talk about what you experienced and how to apply any insights to daily life. Depending on which group you are placed in, your active treatment may start immediately or after a waiting period. You will also have regular check-ups, questionnaires, and follow-up phone calls to monitor your progress and wellbeing.

Potential risks and benefits

Taking part may help improve your depression symptoms and provide dedicated emotional support from specialised professionals. Your participation also helps researchers understand whether this approach could benefit others with hard-to-treat depression in the future. However, there are risks to consider. MDMA can cause temporary physical side effects such as nausea, jaw clenching, sweating, headache, or a fast heartbeat. It can also bring up intense or distressing emotions during and after therapy sessions. You will be monitored closely by medical staff at all times to manage any problems. Taking part is completely voluntary, and you are free to leave the trial at any time without giving a reason and without losing any of your normal medical care.

Locations (1)

Some site locations are approximate. We're improving this — please verify with the trial team before travelling.

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Unverified
Norway

Common questions

What is MDMA-assisted therapy?

It is a treatment where a pure, pharmaceutical dose of MDMA is given under close medical supervision alongside guided sessions with trained mental health professionals.

Is this the same as taking recreational drugs?

No. The medicine used is pure, carefully measured, and given in a safe medical clinic under constant supervision, combined with professional therapy.

What does 'delayed-treatment' mean?

It means participants are put into two groups at random. One group receives the treatment immediately, while the other group waits a short time before receiving the same treatment.

Will I have to stop taking my current antidepressants?

Certain medications cannot be taken with MDMA for safety reasons. The trial doctors will discuss whether safely pausing or tapering your current medication is appropriate for you.

Do I have to pay to take part?

No, taking part in clinical trials in the UK is free, and trial teams often help cover reasonable travel expenses.