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

INTERVENTION: Product Name: Nytol One‐A‐Night 50 mg Tablets, Product Code:PRD12062272, Pharmaceutical Form: CAPSULE, Other descriptive name: , Strength: , Pharmaceutical form of the placebo: CAPSULE , Product Name: PSILOCYBIN (PEX010), Product Code:PRD12060449, Pharmaceutical Form: CAPSULE, Other descriptive name: , Strength: CONDITION: Cocaine addiction ; MedDRA version: 21.1Level: LLTClassification code: 10009815Term: Cocaine addiction Class: 10037175 Therapeutic area: Psychiatry and Psychology [F] ‐ Mental Disorders [F03] SECONDARY OUTCOME: Secondary end point(s):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). Secondary end point(s):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). INCLUSION CRITERIA: DSM‐5 cocaine use disorder (powder/intranasal, at least moderate), Negative urine test for cocaine at least the day before psilocybin dosing and on dosing day, 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, Female subjects' serum pregnancy test performed at the screening visit and urine pregnancy test performed at the baseline visit must be negative., 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, Seeking treatment, =4 on the Severity of Dependence Scale, Cocaine use on at least 4 separate days in the past month, Aged 21‐65 years at the time of signing informed consent, Able to give informed written consent, Able to speak English, Clinically accepta PRIMARY OUTCOME: Main Objective: 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. Primary end point(s): 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 Objective: 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, 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).