None listed
Conditions
Brief summary
This is a 3-arm study using psilocybin-assisted psychotherapy. A randomised controlled, multi-arm design will be used with the same control group all the way through the 57 weeks of the study. Potential participants will be screened to ensure suitability for trial inclusion, and 160 participants will be accepted into the trial upon completion of informed consent. The schedule for all participants will consist of two courses of therapy separated by 4 weeks, each course is comprised of a dosing session plus preparatory and post-integrative psychotherapy sessions with a co-therapist dyad that will generally consist of one female and one male therapist. After the 3-month face to face follow-up session, a third course of therapy (preparatory, dosing, post-integrative) will occur. Participants randomly allocated to the treatment arm will receive an active dose of psilocybin during the first two dosing sessions. Participants in the treatment arm will then be randomly re-allocated to receive either active psilocybin (Arm 1) or an inactive placebo (Arm 2) for the third and final dosing session. Participants allocated to the control group (Arm 3) will receive an in-active placebo at all three dosing sessions. Self-report follow-up assessments will be conducted for all participants every 4 weeks after the first dose-session until 12 months after the second dosing session. Face to face follow-up sessions will occur at 3 months, 6 months and 12 months after the second dosing sessions.
Interventions
There will be two intervention arms and one control arm.
Arm 1: 3 dose-sessions of 25 mg oral psilocybin + psychotherapy
Arm 2: 2 dose-sessions of 25 mg oral psilocybin + psychotherapy, followed by 1 dose-session of oral inactive placebo + psychotherapy
Arm 3 (control): 3 dose-sessions of oral inactive placebo + psychotherapy
Each dose session will be 6-8 hours in length, and will occur at the following time points:
1: 1 week post baseline;
2: 5 weeks post baseline;
3: 18 weeks post baseline.
There will be two intervention arms and one control arm. Arm 1: 3 dose-sessions of 25 mg oral psilocybin + psychotherapy Arm 2: 2 dose-sessions of 25 mg oral psilocybin + psychotherapy, followed by 1 dose-session of oral inactive placebo + psychotherapy Arm 3 (control): 3 dose-sessions of oral inactive placebo + psychotherapy Each dose session will be 6-8 hours in length, and will occur at the following time points: 1: 1 week post baseline; 2: 5 weeks post baseline; 3: 18 weeks post baseline. Administration of psilocybin and inactive placebo will be by oral tablet with neutral excipient, and will occur under direct supervision of a medical practitioner at the study site. All psychotherapy associated with the intervention will be administered face-to-face by a trained co-therapist dyad consisting of one medically-trained health professional (psychiatrist, psychiatry registrar, GP, or physician) and one psychologist. Psychotherapy will involve 2 Preparatory Sessions prior to Dose Session 1, at which time participants will be provided with information relating to psilocybin and its psychotropic effects. Supportive psychotherapy provided on-site during Dose Sessions will consist of non-directive psychological support within the context of a largely non-interventional approach. Each Dose Session will be followed by 3 Integration Sessions, during which participants will be invited to discuss their experience during the Dose Session, and engage in analysis and meaning-making to consolidate any therapeutic outcomes accrued during the experience.
Sponsors
Swinburne University of Technology, Hawthorn
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
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
- Adults aged 18 to 65 years. - Those currently experiencing major depressive disorder (DSM-5) as determined by the SCID-5. - Those with current moderate to severe depression according to the MADRS. - Treatment-resistance using criteria adapted from current literature of research in major depression. - Under the care of a psychiatrist, psychologist, physician, or GP. - Proficiency in English. - Safe tapering and wash-out of current antidepressant pharmacotherapy prior to baseline assessment, as confirmed by treating GP, psychiatrist, or physician. - Abstinence from illicit or extra-medical drug and alcohol use for at least 2 days prior to each dose session. - Participants who agree to have their drug dosing sessions recorded to video for treatment fidelity and clinical supervision within the study team. - Participants who are able to swallow tablets.
Exclusion criteria
Key General Medical Exclusion Criteria: - Patients in treatment in another clinical trial involving an investigational product. - Any disorder with known CNS involvement, or other major CNS disease. - Hepatic dysfunction. - Known conditions putting participant at risk for hypercalcaemia, - Cardiovascular conditions: uncontrolled hypertension, angina, a clinically significant ECG abnormality (e.g., atrial fibrillation), TIA in the last 6 months, stroke, or cerebrovascular disease, peripheral or pulmonary vascular disease. - A diagnosis of epilepsy or previous seizures. - Renal insufficiency. - Insulin-dependent diabetes. - Females who are pregnant or nursing or are trying to get pregnant, or become pregnant during the study. - Current hypothyroidism. - Weight less than 40 kg. - Contraindicated medication (SSRIs, SNRIs, MAOIs), and either 1) do not wish to be tapered off this medication, or 2) it is deemed by trial psychiatrists or the participant’s usual treatment team that tapering the participant off their current medication would be inappropriate. - Use of any illicit or extra-medical drugs or alcohol within the 2 days prior to each psilocybin dosing. - Current use of any potent metabolic inducers or inhibitors - Significant, uncorrected visual impairments (to ensure that they can read all study material). Key Psychiatric Exclusion Criteria: - Current or past history of meeting DSM-5 criteria for Schizophrenia, Psychotic Disorder (unless substance-induced or due to a medical condition), Bipolar I or II Disorder, or Mania. - First degree relative with diagnosed Schizophrenia, Psychotic Disorder (unless substance-induced or due to a medical condition), Bipolar I or II Disorder or Mania. - Currently meets DSM-5 criteria for Dissociative Disorder, Anorexia Nervosa, Bulimia Nervosa, or any psychiatric conditions judged to be incompatible with establishment of rapport or safe exposure to psilocybin. - Unable to give adequate informed consent.
Outcome results
None listed