Clinical TrialTreatment-Resistant Depression (TRD)PsilocybinPsilocybinNot yet recruiting

Exploratory trial to assess the efficacy and safety of Psilocybin-Assisted Psychotherapy (PAP) involving family-members compared to standard PAP in adults with treatment-resistant major depressive disorder (TRMDD)

Randomised interventional trial (n=60) comparing psilocybin-assisted psychotherapy with family-member involvement versus PAP with therapists only; two 25 mg oral psilocybin sessions 3 weeks apart in adults with treatment‑resistant MDD.

Target Enrollment
60 participants
Study Type
Phase NA interventional
Design
Randomized

Detailed Description

This randomised controlled trial enrols adults (18–65) with treatment‑resistant major depressive disorder to test whether involving a family member in Psilocybin‑Assisted Psychotherapy improves outcomes compared with therapist‑only PAP. All participants receive two 25 mg oral psilocybin doses given three weeks apart with therapist support.

Dosing sessions require an 8‑hour fast and monitoring by two clinical psychologists plus medically qualified staff for a minimum of six hours; primary outcome assessed using MADRS/HAM‑D instruments with safety monitoring and contraception/pregnancy testing as specified.

Study Protocol

Preparation

1 sessions
150 min each

Dosing

2 sessions
360 min each

Integration

sessions

Therapeutic Protocol

support

Study Arms & Interventions

PAP + family

experimental

Psilocybin-assisted psychotherapy with a supporting family member present during preparation; two dosing sessions (25 mg each) with therapist-led integration.

Interventions

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

    Two 25 mg oral capsules given 3 weeks apart; fast 8 h prior; monitored ≥6 h by therapists and medical staff.

PAP only

active comparator

Psilocybin-assisted psychotherapy without family member present during dosing (therapists only); same dosing schedule.

Interventions

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

    Two 25 mg oral capsules given 3 weeks apart; fast 8 h prior; monitored ≥6 h by therapists and medical staff.

Participants

Ages
18 – 65
Sexes
Male & Female

Inclusion Criteria

  • Participant must be over 18 years of age inclusive, up to 65 years old at the time of signing informed consent.
  • Participant is able to read, understand and agree with study procedures.
  • Diagnosed with major depressive disorder with moderate to severe depression (HAM-D17 ≥17).
  • Failed to respond to two adequate antidepressant courses of different pharmacological classes lasting at least 6 weeks within the current depressive episode and not subject to ECT within 6 months prior to study.
  • Participant can confirm involvement and willingness of a family member during PAP sessions and study duration.
  • Male participants must agree to specified contraception/abstinence requirements for duration of study and 3 months after last dose; female participants of childbearing potential must use highly effective contraception and have a negative pregnancy test at screening and prior to each psilocybin administration.
  • Consent for study team to contact participant’s healthcare provider for follow-up arrangements if needed.

Exclusion Criteria

  • Unable to provide written informed consent.
  • History of current or previously diagnosed psychotic disorder or bipolar disorder.
  • Immediate family member with a diagnosed psychotic disorder.
  • Pregnant or breastfeeding, positive pregnancy test at screening/prior to dosing, or refusal to have on-site pregnancy test.
  • Participants with sexual contact without contraceptive measures with a person who may become pregnant during or within 90 days of psilocybin cessation.
  • History of serious suicide attempts or current C-SSRS positive (YES) for questions 4,5 or 6, or deliberate self-harm within last year.
  • Cluster B personality disorders (e.g., borderline, histrionic, antisocial, narcissistic).
  • Eating disorders (anorexia, bulimia, binge eating disorder, other specified feeding/eating disorders).
  • Receiving SSRIs within last 4 weeks (washout 4 weeks; 5 weeks for fluoxetine) or MAOIs or other agents that may precipitate serotonin syndrome within 4 weeks prior to enrolment.
  • Known history of serotonin syndrome, neuroleptic malignant syndrome or malignant hyperthermia.
  • Moderate to severe hypertension or uncontrolled mild hypertension, prior hypertensive crisis, known/suspected aneurysm or intracerebral haemorrhage.
  • Evidence of moderate to severe hepatic impairment (Child–Pugh A–C) or renal impairment (eGFR <70 mL/min).
  • Hypersensitivity to study interventions or constituents.
  • Clinically significant abnormal ECG or known prolonged QT syndrome or concomitant QT-prolonging medications.
  • Current substance use disorder (excluding nicotine or caffeine) within last year; inability to refrain from smoking/vaping for 12 hours.
  • Any other medical or clinical condition judged by Investigator to affect safety or study conduct.
  • Employees of the clinical study site or immediate family of site staff; prisoners or legally institutionalised individuals; other situations raising ethics concerns.

Study Details

Locations

Unknown facility — Australia

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