AuthorisedTherapeutic exploratory (Phase II)Interventional

The Acute and Long-term Impact of Support in Psilocybin Therapy for Depression: The Psilocybin Setting Trial (PSISET)

Depression is a common condition that can be difficult to treat. Psilocybin is an active compound originally found in certain mushrooms that has shown promise in lifting depressive symptoms. However, scientists need to know what kind of psychological support is necessary to get the best results safely. This Phase II study, called PSISET, looks at whether full psychotherapy makes psilocybin treatment more effective compared to basic emotional support or standard medical care. Participants take a single dose of psilocybin in a quiet, hospital setting with trained professionals present. Researchers will measure changes in mood, anxiety, sleep, and overall quality of life at 10 weeks, with long-term check-ups continuing for up to 52 weeks. The goal is to help healthcare providers understand how to combine psychedelic medicine with the right level of psychological support in the future.

At a glance

Status

Authorised

Phase

Therapeutic exploratory (Phase II)

Sponsor

Kobenhavns Universitet, Koebenhavns Universitet

Enrolment target

180

Start

03 Jul 2026

Depression

What is this study about?

Depression can have a profound impact on everyday life, making simple daily tasks feel overwhelming. While existing treatments like antidepressants and talking therapies work for many, they do not help everyone. Because of this, scientists are investigating new approaches, including psilocybin. Psilocybin is a substance that temporarily changes how brain cells communicate with each other, which may help break repetitive patterns of negative thinking.

However, taking psilocybin is only one part of the treatment. Many experts believe that the environment and psychological guidance given to a patient—often called the "setting"—are just as important as the medicine itself. The PSISET trial was designed to test this theory. It compares people who receive intensive talking therapy alongside psilocybin with those who receive basic support, as well as those receiving usual care.

Over the course of the study, researchers will track how depressive symptoms change using standard rating scales. They will also look at anxiety, sleep, quality of life, and biological markers in the blood to understand the broader effects on the body and mind. Patients will be monitored closely for a full year to see if improvements last.

By comparing these different levels of care, the study aims to find the safest and most practical way to offer psychedelic therapy in mainstream healthcare, ensuring patients receive the right kind of help without unnecessary burden.

Key takeaways

Tests 25mg psilocybin capsules for adults diagnosed with depression.
Explores whether full psychological therapy improves outcomes compared to basic support.
The medicine is taken in a safe, monitored clinic with trained staff present.
Participants are followed up regularly for up to one year (52 weeks).
Joining is voluntary, and you can withdraw at any time without losing your standard care.

Who may be eligible?

This trial is open to adults aged 18 and over who are currently living with depression. Men and women of any background can take part, provided they meet the medical criteria set by the study team.

Because psilocybin causes strong emotional and sensory experiences, it is not safe for everyone. People with a personal or close family history of certain psychiatric conditions, such as psychosis or bipolar disorder, are usually unable to join. You may also need to review your current medications, as some antidepressants cannot be safely taken alongside psilocybin.

A doctor from the study team will carry out a thorough health check before you join. This includes discussing your mental health history, reviewing your physical health, and ensuring you feel comfortable and ready for the experience.

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 am currently experiencing depression.
I do not have a personal or family history of psychosis or schizophrenia.
I am able to attend appointments at the study clinic over a 12-month period.
I am willing to take a trial medication and discuss my feelings with healthcare staff.

Answer every question to see your result.

What does participation involve?

Taking part lasts for about one year (52 weeks) in total. First, you will attend a screening appointment to check your health and suitability. If you join, you will be placed into a group receiving psilocybin (a 25mg capsule) alongside either full psychotherapy, basic emotional support, or standard care. On the dosing day, you will take the capsule in a calm, private room with trained professionals present throughout to guide and support you. You will stay for several hours until the effects wear off. Over the following weeks and months, you will attend follow-up visits and complete surveys about your mood, anxiety, and sleep. Key reviews take place at 10, 26, and 52 weeks, and you may also have occasional blood tests.

Potential risks and benefits

Taking part may help reduce your depressive symptoms, and the findings will help doctors improve depression care for others. However, an improvement in your symptoms cannot be guaranteed. Psilocybin can cause short-term side effects including anxiety, emotional distress, dizziness, headaches, nausea, or changes in blood pressure during the session. Trained staff will be with you to keep you safe and comfortable. Taking part is completely voluntary, and you can change your mind and leave the study at any time without your regular NHS care being affected.

Locations (1)

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

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Unverified
Denmark

Common questions

Is psilocybin legal in this clinical trial?

Yes. While psilocybin is normally a controlled substance in the UK, this trial has special regulatory and ethical approvals to use medical-grade psilocybin safely in a research setting.

Will I be left on my own after taking the capsule?

No. You will be looked after by trained healthcare professionals in a comfortable room for the entire duration of the medicine's effects.

How long do the effects of the capsule last?

The active effects typically last between 4 and 6 hours. You will spend most of the day at the clinic and will need someone to help you get home safely.

Can I stay on my regular antidepressants?

Some medications can interfere with psilocybin. The study doctors will carefully check your prescriptions and advise you on what is safe before you take part.

Does it cost anything to join the study?

No. Treatment and assessments in clinical trials are provided free of charge, and travel expenses are usually reimbursed.