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

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Kobenhavns Universitet, Koebenhavns Universitet

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Psychiatry and Psychology [F] - Mental Disorders [F03]

Decision date (initial)

2026-03-24

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Efficacy, Therapy

To investigate the impact of support and music on acute and long-term clinical outcomes in psilocybin therapy for individuals with depression.

Secondary objectives 3

1. To evaluate the efficacy of a single dose of psilocybin with medical support + psychotherapy compared to psilocybin with medical support in patients diagnosed with moderate-severe MDD.
2. To evaluate the effects of music on the subjective drug experience.
3. To explore the interaction between psychotherapy and music during dosing session on the acute and long-term effects.

Conditions and MedDRA coding

Depression

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 6

1. Informed oral and written consent.
2. Meeting diagnostic criteria for moderate-severe MDD according to the International Classification of Diseases 10 (ICD-10) and The Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5).
3. A MADRS total score between 20-60 (both included).
4. Age 25 - 65 years (both included).
5. Being willing to abstain from other psychotherapeutic or antidepressant treatments until at least the 6-week primary endpoint.
6. Have an identified support person.

Exclusion criteria 18

1. Meeting ICD-10 diagnostic criteria for mental retardation, schizophrenia spectrum, or other psychotic disorders, and bipolar disorders.
2. No psychotic symptoms of depression or the like.
3. Immediate family history of psychotic disorders or bipolar disorders, including parents and siblings, but not offspring.
4. Any co-morbid psychiatric condition deemed to be incompatible with the safe administration of psilocybin, e.g., inability to establish rapport.
5. Meeting ICD-10 diagnostic criteria for substance use disorder and/or alcohol use disorders.
6. History of suicide attempt or: 1) active suicidal ideation with some intent to act without specific plan (C-SSRS item 4), 2) active suicidal ideation with specific plan and intent (C-SSRS item 5), 3) have a score of ≥ 5 on Item 10 (suicidal thoughts) on MADRS at screening, 4) have any suicidal ideation or thoughts, in the opinion of the study personnel, PI, the support person or close relatives, that present a serious risk of suicidal or self-injurious behavior at any time.
7. Present or former severe neurological disease, including epilepsy and head trauma with loss of consciousness > 30 min.
8. Concomitant treatment against depressive disorder including pharmacotherapies, electroconvulsive therapy, deep brain stimulation, and vagus nerve stimulation. Benzodiazepines and sleep medicine is allowed, except on the day of dosing.
9. Ongoing tapering off antidepressant or any other serotonergic medication. Prescribed medication must have been stopped at least 5 x elimination half-life. Study personnel will not encourage any tapering off.
10. Concomitant treatment with medication that modulates uridine diphosphate (UDP) or glucuronosyltransferase (UGT).
11. Use of any serotonergic psychedelic drug within the past 10 years or > 25 lifetime uses.
12. Cardiovascular disease, including a history of myocardial infarction, angina pectoris, heart failure (NYHA class ≥ III), prolonged QTc interval (>450 ms/470 ms men/women)
13. Uncontrolled hypertension (systolic blood pressure >150mm Hg, diastolic blood pressure >90 mm Hg*).
14. Females of childbearing potential who are pregnant, breastfeeding or have the intention of becoming pregnant within the next 12 weeks, or are not using contraceptives (during the whole study period) considered as highly effective (combined (oestrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation (oral, intravaginal, transdermal), progestogen-only hormonal contraception associated with inhibition of ovulation (oral, injectable, implantable) intrauterine device – IUD, IUS, bilateral tubal occlusion, vasectomised partner, sexual abstinence)
15. Pregnancy (serum human chorionic gonadotropin (hCG) > 3 U/L at inclusion).
16. Hypersensitivity to the active substance or any of the excipients
17. Unable to speak and/or understand Danish
18. Any condition that the investigator feels would interfere with trial participation.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. The primary endpoint of this study will be the change in depressive symptoms measured by the MADRS from baseline to the 6-week follow-up, assessed by a blinded rater.

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Kobenhavns Universitet

Sponsor organisation

Kobenhavns Universitet

Address

Oester Farimagsgade 5

City

Copenhagen K

Postcode

1353

Country

Denmark

Scientific contact point

Organisation

Koebenhavns Universitet

Contact name

Sarah Sonja Hugger

Public contact point

Organisation

Koebenhavns Universitet

Contact name

Sarah Sonja Hugger

Third parties 1

Koebenhavns Universitet

Sponsor organisation

Koebenhavns Universitet

Address

Oester Farimagsgade 2a

City

Copenhagen K

Postcode

1353

Country

Denmark

Scientific contact point

Organisation

Koebenhavns Universitet

Contact name

Sarah Sonja Hugger

Public contact point

Organisation

Koebenhavns Universitet

Contact name

Sarah Sonja Hugger

Locations

1 EU/EEA country · 1 investigational sites

By country

Investigational sites

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 8 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

1 submissions — initial application plus substantial / non-substantial modifications