Opioid use disorder Mental and Behavioural Disorders
Conditions
Interventions
This is a two-arm, single-dose, double-blind, randomised, controlled, Phase IIa trial investigating psilocybin therapy in participants with opioid use disorder (OUD) in early abstinence. Participants
Sponsors
Imperial College London
Eligibility
Sex/Gender
All
Age
18 Years to 64 Years
Inclusion criteria
Inclusion criteria: 1. Current opioid use disorder of moderate to severe severity as diagnosed by an appropriate medical professional using DSM-5 diagnostic criteria 2. Within 3 months of detoxification or cessation from using opioids 3. Previously dependent on heroin or other illicit street opioids 4. Aged 18-64 years 5. Willing and able to comply with the requirements of the study 6. Able to read, comprehend and record information written in English 7. Capable of giving written informed consent, which includes compliance with the requirements and restrictions listed in the consent form 8. Be under the care of a primary care provider 9. People of childbearing potential and fertile males must be willing to use an adequate method of contraception from the time of enrolment until 28 days after dosing of the study drug 10. Willing to provide consent for authorised individuals to access their Summary Care Record and/or medical records to support the process of assessing eligibility
Exclusion criteria
Exclusion criteria: 1. Current or previously diagnosed psychotic disorder or bipolar disorder I. 2. Immediate family member with a diagnosed psychotic disorder. 3. History of suicide attempts requiring hospital admissions or any suicidal ideation with intent within the past 6 months indicated by an answer “yes” to question 4 or 5 in the Columbia Suicide Severity Rating Scale (C-SSRS) at screening, as well as clinician judgement. 4. Emotionally unstable personality, or other psychiatric problem that the screening clinician feels may jeopardise the therapeutic alliance and/or safe exposure to psilocybin. 5. Current ongoing moderate to severe (DSM-5) substance use disorder (including alcohol but excluding opioid, nicotine and cannabis). Lifetime history of dependence will be allowed given very high incidence of comorbidity. 6. Positive breath alcohol at screening visit, or at Day -1 or Day 0 (i.e. BAC above 0.08%) that, in the opinion of the study clinician, indicates intoxication incompatible with participation in the visit. If positive on one of these visits, the visit may be rescheduled, at the discretion of the research team (updated 27/02/2026 and 24/04/2026, originally: Positive breath alcohol at screening visit, or at Day -1 or Day 0 (i.e. BAC above 0.08%). If positive at screening, the screening may be rescheduled, at the discretion of the research team). 7. Positive urine drug screen for opioids on Day -1 or Day 0 that, in the opinion of the study clinician, indicates recent opioid use incompatible with participation in the visit. If a urine drug screen is positive on one of these visits, the session may be rescheduled at the discretion of the research team (updated 24/04/2026, originally: Positive urine drug screen for opioids on Day -1 or Day 0. If a urine drug screen is positive on one of these visits, the session may be rescheduled at the discretion of the research team). 8. Psychedelic use in the past 6 months, at the discretion of the research team. 9. Clinically significant co-morbidities that would interfere with participant safety during the study, or with the integrity of the results such as current cardiac problems (e.g., ischemic heart disease, conduction defects, acute coronary syndrome or angina) or a clinically significant neurological condition (e.g. epilepsy, head injury) that in the opinion of the investigators, contraindicates their participation. Untreated hypertension – i.e., systolic blood pressure over 140, diastolic blood pressure over 90. 10. Tachycardia (heart rate >100 bpm) 11. Clinically significant abnormal biochemistry or haematological results on screening (e.g. hepatic or renal failure). Blood tests or other diagnostic tests will be undertaken, where it is deemed clinically necessary e.g., if a participant has a history of kidney/hepatic impairment that requires confirmation of current status. These can occur at the request of the clinical service or via the participant’s GP, with their consent. 12. Clinically significant abnormality on ECG such that the QT measurement is not suitable (e.g., poorly defined termination of the T-wave) and/or presents other abnormalities which, in the opinion of the study physician, represent risk. If a participant has a QT interval corrected using Fridericia’s formula (QTcF) value >440 ms for males and >470 ms for females, an exclusion decision will be made based on triplicate (3) ECG tracings obtained at least 1 minute apart. An average value for these 3 measurements will be u
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| The primary endpoint is time to first opioid use within 3 months following psilocybin administration. This will be measured using the self-report modified Time Line Follow Back (mTLFB) between Investigational Medicinal Product (IMP) dosing and 3 months (12 weeks). | — |
Secondary
| Measure | Time frame |
|---|---|
| The frequency, amount, and/or duration of opioid use will be characterised using TLFB and summarised by dose. Specifically, the following measures will be used: 1. Total number of days using opioids between IMP dosing and 12-week primary endpoint summarised by type of opioid (either illicit opioid or prescribed OST). 2. Incidence of return to OST between IMP dosing and 12 weeks, where a return to OST is defined as any use of prescribed OST. 3. Number of lapses between IMP dosing and 12 weeks, where a lapse is defined as any use of illicit/street opioids (not including prescribed OST). 4. Number of relapses between IMP dosing and 12 weeks, where a relapse is defined as use of illicit/street opioids for 3 or more consecutive days (not including prescribed OST). 5. Average duration of lapse/relapse measured as number of consecutive days of illicit opioid use between IMP dosing and the 12-week primary endpoint 6. % of opioid free weeks, where an opioid-free week is defined as 7 consecutive days without the use of any opioid (illicit or prescribed OST) as measured using TLFB. Improvements in health and wellbeing will be assessed using the following, summarised by dose: 1. Substance Use Recovery Evaluator (SURE) total score between baseline (Day -1) and the primary endpoint (12 weeks) 2. Craving, assessed using Opioid Craving Scale at baseline (day -1) and the 12-week primary endpoint (Updated 21/10/2025, previously: Craving, assessed using Minnesota Craving Scale at baseline (day -1) and the 12-week primary endpoint) 3. Patient impression, assessed using Patient Reported Outcomes (PRO-I / S) collected at baseline (day -1) and the 12-week primary endpoint 4. Mental wellbeing (over last 2 weeks) using the Warwick-Edinburgh Mental Wellbeing Scale (WEMWBS) between baseline (Day -1), and 12-week primary endpoint 5. Assessment of Recovery Capital (ARC) total score between baseline (Day -1), and the primary endpoint at 12 weeks (Updated 02/02/2026, previously: Drug Abstine | — |
Countries
England, United Kingdom
Contacts
Public ContactHannah Thurgur
Outcome results
None listed