POSITRON - PsilOcybin with pSychologIcal supporT foR cOcaiNe: a randomised controlled pilot feasibility trial of psilocybin with psychological support for cocaine use disorder

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Trinity College Dublin

Participant type

Patients

Age range

18-64 years

Gender

Male and Female

Therapeutic area

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

Decision date (initial)

2026-02-27

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

Health Research Board, IRELAND (HRB)

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Therapy, Efficacy

The primary objective is to assess the feasibility of a trial of psilocybin with psychological support for the treatment of DSM-5 powder/intranasal cocaine use disorder (CUD) by conducting a randomised double-blind controlled pilot trial of a single dose of psilocybin (25mg) versus diphenhydramine 100mg (1:1) with 6 sessions of psychological support, to inform a future definitive trial.

Secondary objectives 2

1. To assess psilocybin 25mg versus diphenhydramine 100mg (1:1) for the following: Percentage of days abstinent from cocaine assessed by the self-report Timeline Followback method and urine drug test from the psilocybin administration session, Sustained/complete abstinence (defined as percentage of participants who report complete abstinence from cocaine from the psilocybin administration session), Time to first relapse (defined as first cocaine use after the psilocybin administration session assessed by the self-report Timeline Followback method and urine drug test, or dropout), Cocaine craving (Cocaine Craving Questionnaire-Brief), Mood and anxiety (DASS-21), Functionality (Sheehan Disability Scale, EQ-5D-5L), Psychedelic experience (5D-ASC, CEQ), Treatment expectancy (SETS), Blinding assessment
2. As Safety Objectives, to assess psilocybin 25mg versus diphenhydramine 100mg (1:1) for the following: Number of Adverse Events (AEs) and number of Serious Adverse Events (SAEs), ECG (emergence of serious ECG abnormalities (e.g., evidence of ischemia, myocardial infarction, QTc prolongation (QTc > 450 milliseconds for men, QTc > 470 milliseconds for women), Clinically significant changes in Blood pressure and heart rate during dosing session (15 minutes before drug administration, and one, three, and six hours after drug administration), Clinically significant changes in clinical laboratory tests (full blood count, liver function tests and urea and electrolytes).

Conditions and MedDRA coding

Cocaine addiction

Regulatory references

Plan to share IPD

No

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 12

1. DSM-5 cocaine use disorder (powder/intranasal, at least moderate)
2. If female of childbearing potential, are willing to use approved form of contraception (contraception pills, intrauterine device, bilateral tubal occlusion) from screening until study completion
3. Seeking treatment
4. ≥4 on the Severity of Dependence Scale
5. Cocaine use on at least 4 separate days in the past month
6. Aged 21-65 years at the time of signing informed consent
7. Able to give informed written consent
8. Able to speak English
9. Clinically acceptable laboratory and ECG findings
10. Negative urine test for cocaine at least the day before psilocybin dosing and on dosing day
11. Availability of a friend or family member into whose care the participant can be released following their psilocybin administration session and ensures they return home safely after the psilocybin administration session
12. Female subjects' serum pregnancy test performed at the screening visit and urine pregnancy test performed at the baseline visit must be negative.

Exclusion criteria 15

1. DSM-5 diagnoses (ascertained by the MINI V.7.0 and confirmation by a psychiatrist) of bipolar affective disorder type 1 or type 2, any psychotic disorder
2. Dementia
3. First degree relatives with psychotic disorders
4. Current suicidal or homicidal ideation
5. Exhibiting significant suicide risk, as defined by: suicidal ideation as indicated by items 4 or 5 on the Columbia-Suicide Severity Rating Scale (C-SSRS) within the past six months, at Screening, during the Screening Period, or the day before dosing; demonstrating suicidal behaviours or non-suicidal self-injury within the past six months, or; clinical assessment of significant suicidal risk or risk of self-injury during participant interview
6. Psychiatric inpatient within the past six months prior to screening
7. Current severe Alcohol use disorder (DSM-5) (ascertained by the MINI V.7.0)
8. Current heroin use
9. Tricyclic antidepressants, lithium, MAO-Is, antipsychotics, (greater than 25% of the max recommended dose), Aldehyde dehydrogenase (ALDH) inhibitors, Alcohol dehydrogenase (ADH) inhibitors, Uracil-DNA Glycosylase (UDG)
10. Psychedelic use within the last 12 months
11. ≥ 25 lifetime uses of Psychedelics
12. Other personal circumstances and behaviour judged to be incompatible with the establishment of rapport or safe exposure to psilocybin
13. Active legal problems with the potential to result in incarceration
14. Psychological/behavioural therapies that have been initiated within 30 days prior to screening and/or will not remain stable for the duration of the study.
15. General Medical Exclusion Criteria (refer to protocol)

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. To assess feasibility of the clinical trial using psilocybin 25mg versus diphenhydramine 100mg (1:1) for the following: Recruitment methods and rate, Rate of willingness to be randomised, Randomisation, Adherence to follow-up, Reasons for drop-out from treatment and follow-up

Secondary endpoints 2

1. Outcomes include: percentage of days abstinent (Timeline Followback & urine), sustained abstinence, time to relapse, cocaine craving (CCQ-Brief), mood/anxiety (DASS-21), functionality (Sheehan, EQ-5D-5L), psychedelic experience (5D-ASC, CEQ), treatment expectancy (SETS), blinding assessment, and meaning in life (MLQ).
2. Safety outcomes include: number of AEs and SAEs, ECG abnormalities (e.g., ischemia, MI, QTc >450ms for men, >470ms for women), clinically significant changes in blood pressure and heart rate during dosing (pre-dose, 1h, 3h, 6h), and lab tests (FBC, LFTs, U&E).

Investigational products

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

Test 1

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Trinity College Dublin

Sponsor organisation

Trinity College Dublin

Address

College Green

City

Dublin 2

Postcode

D02 PN40

Country

Ireland

Scientific contact point

Organisation

Trinity College Dublin

Contact name

Head of Clinical Sponsorship Oversight

Public contact point

Organisation

Trinity College Dublin

Contact name

Head of Clinical Sponsorship Oversight

Locations

1 EU/EEA country · 2 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