Clinical TrialMajor Depressive Disorder (MDD)PsilocybinPlaceboNot yet recruiting

A Double-Blind Randomised Controlled Trial of the Efficacy of Microdosing with Psilocybin to treat Moderate Depression

Double-blind, randomised, parallel Phase II trial (n=293) of oral psilocybin microdosing (4 mg, 11 doses over six weeks) versus caffeine (60 mg) for moderate major depressive disorder.

Target Enrollment
293 participants
Study Type
Phase II interventional
Design
Randomized, single Blind

Detailed Description

This is a double-blind, randomised, parallel-group Phase II trial assessing low-dose oral psilocybin (WP001) taken onsite 11 times over six weeks (every 3–4 days) in participants with moderate major depressive disorder; the active comparator arm receives caffeine 60 mg in identical capsules.

Participants are monitored by a psychiatrist throughout; dosing may be titrated down to 2 mg for safety. A nested neuroimaging (MEG) substudy will recruit up to 80 participants (baseline and first-dose scan), with every third participant invited to participate.

Study Protocol

Preparation

sessions

Dosing

11 sessions

Integration

sessions

Study Arms & Interventions

Psilocybin microdose

experimental

Oral low-dose psilocybin (WP001) capsules given on-site every 3–4 days over six weeks.

Interventions

  • Psilocybin4 mg
    via Oral• every 3-4 days• 11 doses total

    Dose may be titrated down to 2 mg if participant shows impairment; dosing supervised on-site; adherence confirmed by staff.

Caffeine comparator

active comparator

Identical capsules containing caffeine administered on the same schedule as experimental arm.

Interventions

  • Placebo60 mg
    via Oral• every 3-4 days• 11 doses total

    Caffeine 60 mg in identical capsules (active comparator labelled in protocol as control/placebo).

Participants

Ages
18 – 99
Sexes
Male & Female

Inclusion Criteria

  • Participants may be included in the study if they meet all of the following inclusion criteria.
  • 1. Age greater than or equal to 18 years at the time of screening
  • 2. Self-reported fluency in English
  • 3. Meets the definition of moderate depression, defined as a score of between 15 and 23 on the Hamilton Rating Scale for Depression
  • 4. Diagnosis of major depressive disorder, as assessed by the Mini International Neuropsychiatric Interview (MINI)
  • 5. Able to swallow WP001 or Caffeine capsules
  • 6. Has a body weight between 50kg and 120kg, and BMI above 16.
  • 7. Refrains from the use of any psychoactive medication not approved by the research team from baseline through Study Termination.
  • 8. Agrees to abstain from herbal, complementary or over the counter medications with serotonergic effects including, but not limited to, St John’s Wort, S-adenosyl methionine (SAM-e), 5-hydroxytryptophan (5-HTP) and L-tryptophan.
  • 9. Agrees to comply with contraception requirements:
  • a. Women of childbearing potential must have a negative urine or serum pregnancy test at screening and baseline and be non-lactating. During the study, women of childbearing potential must agree to use a highly effective method of birth control up to 7 days after the last dose.
  • b. Male participants must agree to use highly effective method of birth control during the participation in the study up to 7 days after the last dose.
  • 10. Able and willing to comply with all scheduled visits, treatment plan, laboratory tests, lifestyle considerations and other study procedures
  • 11. Agrees to study investigators communicating directly with all of their External Health Practitioners.
  • 12. Provides a contact (relative, spouse, close friend or other Support Person) who is willing and able to be reached by the investigators in the event of a participant becoming unreachable.
  • 13. Must agree not to operate heavy machinery, any motorised vehicle or perform tasks that might endanger oneself or others, such as those requiring fine motor control, fast response times or real-time planning for three hours following each dosing session.

Exclusion Criteria

  • Participants will be excluded from the study if they meet any of the following exclusion criteria:
  • 1. Recently started new psychological therapies and/or sessions with health professionals within 30 days of consent (such as counsellor, psychotherapists). Participants with a stable regimen may be included in this study if they agree to continue with the psychological therapies and/or counselling sessions as is (frequency of the therapy and/or sessions should not change)
  • 2. Use of antidepressant or antipsychotic medication in the prior 3 months, or plans to start new antidepressant or antipsychotic medication in the upcoming 2 months
  • 3. Current diagnosis of psychotic disorder, bipolar disorder, personality disorder, post-traumatic stress disorder, or substance use disorders.
  • 4. Identification of a primary mental health diagnosis apart from Major Depressive Disorder on the Mini International Neuropsychiatric Interview.
  • 5. Any participant presenting current serious suicide risk, as determined through psychiatric interview, responses to Columbia Suicide Severity Rating Scale (C-SSRS), and clinical judgment of the investigator will be excluded. Any participant who is likely to require hospitalisation related to suicidal ideation and behaviour, in the judgment of the investigator, will not be enrolled.
  • 6. Poorly controlled hypertension or other cardiac abnormalities.
  • 7. History of psychosis, bipolar disorder, stroke, epilepsy, brain injury or head trauma.
  • 8. History of serious liver (Child-Pugh B or C), kidney disease (eGFR<60ml/min).
  • 9. First degree relative with psychotic disorder.
  • 10. Pregnant, or trying to get pregnant, or breastfeeding
  • 11. Use of any psychotropic drug (excluding alcohol, nicotine and caffeine) within the last 3 months from date of consent
  • 12. Moderate to severe cannabis or alcohol use disorder in the prior 12 months
  • 13. An illicit or prescription drug use disorder of any severity in the prior 12 months
  • 14. Baseline 12-lead ECG that demonstrates clinically relevant abnormalities that may affect participant safety or interpretation of study results
  • 15. Significantly abnormal laboratory blood test defined as outside the normal range and deemed clinically significant by an investigator with expertise in this field
  • 16. Resting blood pressure exceeding 160mmHg systolic and 100mmHg diastolic
  • 17. Currently taking part in another clinical trial involving interventions such as an investigational drug, device, or psychotherapy
  • 18. Current evidence of, or a history of, any condition, therapy or abnormal laboratory assessment or other events that, in the opinion of the investigator, may affect safety, and/or disrupt their participation for the duration of the study.

Study Details

Locations

Unknown facility — Australia

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