Clinical TrialAnxiety DisordersPsilocybinPlaceboRecruiting

Safety and efficacy of psilocybin-assisted psychotherapy for Generalised Anxiety Disorder [Psi-GAD-1]: a randomised triple-blind active-placebo-controlled trial

Randomised, parallel-group Phase II trial (n≈72) of two-dose psilocybin-assisted psychotherapy (25 mg, optional escalation to 30 mg) versus diphenhydramine active-placebo (75 mg, optional escalation to 100 mg) in adults with GAD; two dosing sessions three weeks apart with preparatory and integrative therapy.

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

Detailed Description

This is a randomised, parallel-group, active-placebo-controlled trial testing a two-dose psilocybin-assisted psychotherapy intervention for adults with Generalised Anxiety Disorder. Participants receive preparatory psychotherapy, two supervised 8-hour dosing sessions three weeks apart, and integration psychotherapy sessions after each dosing.

Psilocybin dosing begins at 25 mg with a prespecified option to increase the second dose to 30 mg if the acute subjective response is judged limited without substantial adverse effects. The comparator arm uses diphenhydramine (75 mg; optional increase to 100 mg) as an active placebo, with identical psychological support.

Safety monitoring includes continuous observation during dosing, vital signs (heart rate, blood pressure), availability of rescue medications, and recording of adverse events/serious adverse events using CTCAE-aligned forms; primary outcome is change in HAM-A at study conclusion.

Study Protocol

Preparation

5 sessions
90 min each

Dosing

2 sessions
480 min each

Integration

6 sessions
90 min each

Therapeutic Protocol

support

Study Arms & Interventions

Psilocybin + therapy

experimental

Two oral psilocybin dosing sessions combined with preparatory and integrative psychotherapy; second dose may be escalated to 30 mg if first-session response limited.

Interventions

  • Psilocybin25 - 30 mg
    via Oral• two sessions• 2 doses total

    Dose 1 = 25 mg; Dose 2 = 25 mg (or increased to 30 mg per predefined response criteria).

Diphenhydramine + therapy

active comparator

Active-placebo comparator with diphenhydramine plus identical preparatory and integration psychotherapy.

Interventions

  • Placebo75 - 100 mg
    via Oral• two sessions• 2 doses total

    Diphenhydramine 75 mg; second dose may be increased to 100 mg if limited acute response.

Participants

Ages
18 – 75
Sexes
Male & Female

Inclusion Criteria

  • Adults experiencing severe GAD.
  • Proficiency in English.
  • Provide a contact (relative, spouse, close friend or other support person) who can transport and provide support following dosing sessions.
  • Taper and cease certain excluded medications as appropriate and under supportive care; successful taper confirmed following preliminary enrolment (taper not required prior to preliminary enrolment).
  • Agree to all study-related requirements.

Exclusion Criteria

  • Contraindicated medical conditions including cardiovascular conditions, major CNS disease, hepatic dysfunction, hypercalcaemia risk, epilepsy/seizures, renal insufficiency, diabetes, and hypothyroidism.
  • Weigh less than 48 kilograms or BMI < 17.
  • Pregnant or nursing, or able to become pregnant and not practising permanent or double-barrier birth control methods.
  • Taking a contraindicated medication that cannot be ceased for an appropriate length of time during the trial.
  • Extremely severe depression, anxiety, suicidality or other psychiatric symptoms that would warrant hospitalisation, as determined by the screening psychiatrist in a clinical interview.
  • Current or past history of meeting DSM-5 criteria for certain excluded psychiatric indications.

Study Details

  • Status
    Recruiting
  • Phase
    Phase II
  • Type
    interventional
  • Design
    Randomizedsingle Blind
  • Target Enrollment72 participants
  • Timeline
    Start: 2022-01-10
    End: 2023-12-31
  • Compounds
    PsilocybinPlacebo
  • Topic
    Anxiety Disorders

Locations

Unknown facility — Australia

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