Antidepressant effects of psilocybin without the psychedelic serotonin experience: A dimensional approach using functional neuroimaging.

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Fundacio Institut De Recerca De L'Hospital De La Santa Creu I Sant Pau

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)

2026-05-04

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: Pharmacodynamic

Evaluate which changes in resting-state network functional connectivity (rsNFC) induced by psilocybin are associated with the psychedelic experience by comparing functional magnetic resonance imaging (fMRI) data from patients with major depressive disorder (MDD) treated with psilocybin + pimavanserin and those treated with psilocybin + placebo across scans 1, 2, and 3.

Conditions and MedDRA coding

Major depressive disorder

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 4

1. Adults diagnosed with a non-psychotic MDD according to DSM-5 criteria and who are experiencing a current major depressive episode resistant to at least one previous adequate attempt of antidepressant treatment.
2. Patients will be men and women aged between 18 and 65 years.
3. Patients with a score of ≥ 14 on the 24-HDRS.
4. Individuals who have the legal capacity to personally provide informed consent and who do so.

Exclusion criteria 14

1. Current or past comorbidity with another severe mental disorder or substance use disorder, except for nicotine dependence.
2. Clinically relevant impairment of renal or hepatic function.
3. In the case of individuals capable of becoming pregnant, a) a negative pregnancy test will be required during the week prior to recruitment and again on the day of recruitment, and b) the use of two highly effective contraceptive methods, one of which must be a barrier method, throughout participation in the study.
4. Anticipated lack of availability to attend all study visits and procedures.
5. Active suicidal ideation.
6. A first-degree relative with a history of any psychotic disorder.
7. Current or past presence of serious medical conditions that pose a health risk or that interfere, either directly or due to their treatment, with the interpretation of the study.
8. History of electroconvulsive therapy, esketamine, or experimental medications or interventions in the last month, along with lifetime use of serotonergic psychedelic drugs.
9. Current use of other substances (medications or drugs) that may interfere with the study products.
10. Contraindication for psilocybin or pimavanserin.
11. Contraindication for magnetic resonance imaging (MRI).
12. Pregnancy or breastfeeding.
13. Subjects with a history of rhythm disorders or other cardiac conditions, with baseline QTc values >450 ms (men) or >470 ms (women), or with electrolyte abnormalities of any cause.
14. Subjects who are taking concomitant medications during the study with a known risk of QTc prolongation (e.g., macrolides, fluoroquinolones, antipsychotics, ondansetron, droperidol, amiodarone, sotalol, quinidine, or others); any concomitant medication taken by the subjects will be verified for this purpose by consulting the corresponding Summary of Product Characteristics (SmPC).

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Brain connectivity assessments using MRI: A resting-state functional sequence. A T1-weighted anatomical sequence. Using a brain rsNFC study model, beta measurement values will be obtained from the images. Statistically significant changes in these beta measures will be considered relevant to the study results.

Investigational products

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

Test 2

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Fundacio Institut De Recerca De L'Hospital De La Santa Creu I Sant Pau

Sponsor organisation

Fundacio Institut De Recerca De L'Hospital De La Santa Creu I Sant Pau

Address

Calle Sant Quinti 77-79

City

Barcelona

Postcode

08041

Country

Spain

Scientific contact point

Organisation

Fundacio Institut De Recerca De L'Hospital De La Santa Creu I Sant Pau

Contact name

Rosa M. Antonijoan Arbos

Public contact point

Organisation

Fundacio Institut De Recerca De L'Hospital De La Santa Creu I Sant Pau

Contact name

Rosa M. Antonijoan Arbos

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 5 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