None listed
Conditions
Brief summary
This is a phase 2b, multi-centre, double-blind randomised controlled trial evaluating psilocybin-assisted psychotherapy (PAT) for methamphetamine use disorder (MAUD). One hundred and twenty treatment-seeking adults with MAUD will be randomised 1:1 to receive either PAT with a single 25 mg oral dose of psilocybin or PAT with a single 5 mg oral dose of psilocybin, with both groups receiving the same structured preparatory and integration psychotherapy. The primary outcome is the number of days of methamphetamine use in the 28 days prior to week 12 post-randomisation, assessed using Timeline Follow Back methodology and supported by urine drug testing. Secondary outcomes include methamphetamine abstinence and remission, other substance use, craving, mental health, sleep, quality of life, functional impairment, safety, acceptability, feasibility and cost-effectiveness. Participants will be followed to 52 weeks, with an optional open-label 25 mg psilocybin-assisted psychotherapy treatment offered after the week 16 assessment.
Interventions
Intervention: Psilocybin-assisted psychotherapy (PAT-25)
International Non-proprietary Name (INN): Psilocybin
Dose: Single 25 mg oral dose of psilocybin.
Duration of treatment: Approximately five weeks. Participants receive three 90-minute preparatory psychotherapy sessions during the two weeks preceding psilocybin administration, followed by a single supervised 6–8-hour psilocybin dosing session. Three 90-minute integration psychotherapy sessions are then provided after dosing: the first occ
Intervention: Psilocybin-assisted psychotherapy (PAT-25) International Non-proprietary Name (INN): Psilocybin Dose: Single 25 mg oral dose of psilocybin. Duration of treatment: Approximately five weeks. Participants receive three 90-minute preparatory psychotherapy sessions during the two weeks preceding psilocybin administration, followed by a single supervised 6–8-hour psilocybin dosing session. Three 90-minute integration psychotherapy sessions are then provided after dosing: the first occurs in the same week as the dosing session, and the second and third occur at approximately weekly intervals over the subsequent two weeks. Psychotherapy and mode of delivery: Psychotherapy is delivered by trained study therapists who are clinical psychologists, psychotherapists or psychiatrists, using a lead therapist and co-therapist model. The lead therapist delivers the three preparatory psychotherapy sessions and the three post-dose integration psychotherapy sessions, providing continuity of therapeutic care across the intervention. The co-therapist joins the lead therapist for one of the preparation sessions, the psilocybin dosing session and one of the integration sessions. The three preparatory sessions occur before psilocybin administration and focus on establishing the therapeutic relationship, preparing the participant for the dosing experience, discussing expectations and concerns, and developing strategies for managing potentially challenging experiences. Participants then receive a single 25 mg oral dose of psilocybin during a supervised 6–8-hour dosing session in a controlled clinical setting. Both the lead therapist and co-therapist are present throughout the dosing session to provide psychological support and monitoring. Following psilocybin administration, the lead therapist conducts three 90-minute integration psychotherapy sessions. The first occurs in the same week as the dosing session, with the second and third occurring at approximately weekly intervals over the subsequent two weeks. Integration sessions support participants to reflect on and make meaning of their dosing experience and consider how experiences or insights arising from the session may relate to their treatment goals, including methamphetamine use and recovery. Adherence: Psilocybin is administered directly by authorised study personnel at the study site, with administration documented in investigational product accountability records. Attendance at psychotherapy sessions is monitored and recorded. As the investigational product is administered as a single supervised dose, participant self-administration and medication adherence monitoring are not required. Optional open-label treatment: Participants will be followed for 52 weeks. Following completion of the Week 16 assessment, participants may elect to receive an optional open-label 25 mg psilocybin-assisted psychotherapy treatment. Receipt of the open-label treatment is conditional on the participant choosing to proceed and remaining clinically suitable for further psilocybin-assisted treatment. Participants will not proceed where there have been significant safety concerns, including a serious adverse event (SAE) that raises concern regarding further treatment, or where the participant's therapy dyad identifies clinical or safety concerns regarding further treatment. The optional open-label treatment occurs after completion of the randomised comparison period. Outcomes following the open-label treatment will be analysed separately from the primary randomised comparison and will not be combined with the blinded treatment period when estimating the effect of the randomised PAT-25 versus comparator intervention.
Sponsors
University of New South Wales
Study design
Allocation
Randomised controlled trial
Intervention model
Parallel
Primary purpose
Treatment
Masking
Blinded (masking used) (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
All
Age
25 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Aged 25 years or older. Meets DSM-5 criteria for methamphetamine use disorder (MAUD). Methamphetamine use on 6–28 days during the 28 days prior to screening. Independent verification of recent methamphetamine use within 28 days of trial registration (e.g. positive urine drug screen or written confirmation from an external therapist/treatment facility). Currently seeking treatment for MAUD and engaged with a therapist external to the study, with intention to continue treatment/support following completion of week 12. In good general health, as determined by medical history and physical examination. Able to abstain from illicit or extra-medical drug and alcohol use for at least 2 days prior to psilocybin dosing. Able to engage with psychotherapy and establish adequate therapeutic alliance with the study therapy team prior to dosing. Has an available friend or family member and suitable home-like environment to provide support for the 24 hours following psilocybin dosing. Able to complete study follow-up, read and write in English, and swallow capsules.
Exclusion criteria
Pregnant or breastfeeding, or of childbearing potential and unwilling to avoid pregnancy during the study. History of bipolar I or II disorder. History of anorexia nervosa or bulimia nervosa. First- or second-degree relative with a history of a psychotic disorder or bipolar I or II disorder. Suicidal or homicidal behaviours within the previous 6 months, as assessed using the Columbia-Suicide Severity Rating Scale (C-SSRS). History of drug-induced psychosis resulting in presentation to an emergency department or acute mental health facility, or hospital admission. Severe psychiatric illness other than substance use disorder requiring acute hospitalisation within the previous 4 years, or another psychiatric condition considered to compromise participant safety. Current dexamphetamine or lisdexamfetamine treatment. Uncontrolled hypertension, defined as >140/90 mmHg despite treatment with a single antihypertensive. Medically significant illness considered by the study medical officer to make participation unsuitable, including unstable diabetes, epilepsy, severe cardiovascular disease, significant hepatic disease or renal failure requiring dialysis. Current use of contraindicated medications, including monoamine oxidase inhibitors, antipsychotics, St John’s Wort, or other medications considered unsuitable by the study medical officer. Illicit drug use, extra-medical benzodiazepine or opioid use within 2 days before psilocybin administration. Participants receiving opioid substitution therapy may be included if otherwise eligible. Use of a classical hallucinogen (including LSD, DMT, psilocybin, mescaline, salvia divinorum or ibogaine) within 28 days before screening. Unstable housing or homelessness. Anticipated inability to complete follow-up, for example planned relocation, extended travel or likely imprisonment.
Outcome results
None listed