Clinical TrialTreatment-Resistant Depression (TRD)PsilocybinRecruiting

An open-label study of the efficacy and feasibility of psilocybin-assisted psychotherapy for treatment-resistant depression (TRD)

Open-label, single-group Phase II study (n=15) of psilocybin-assisted psychotherapy for treatment-resistant depression: two 25 mg oral dosing sessions (6 weeks apart) with preparatory and integrative therapy over 12 weeks.

Target Enrollment
15 participants
Study Type
Phase II interventional
Design
Non-randomized

Detailed Description

This single-group, open-label study evaluates feasibility and efficacy of psilocybin-assisted psychotherapy in adults with treatment-resistant depression over a 12-week programme including two supervised 25 mg dosing sessions and nine non-drug therapy sessions.

Preparatory psychotherapy (3 sessions) precedes dosing; integrative psychotherapy (6 sessions total) follows dosing. Outcomes include change in depressive symptoms measured by QIDS self-rated and quality-of-life (WHO-QoL-Bref) at baseline, 3 weeks post-dose 1 and 2, and 20 weeks post-dose 2.

Dosing sessions occur at Swinburne University (Hawthorn campus) in a comfortable, living-room-like environment; vitals monitored and rescue benzodiazepines available for adverse psychological reactions.

Study Protocol

Preparation

3 sessions
60 min each

Dosing

2 sessions
420 min each

Integration

6 sessions
60 min each

Therapeutic Protocol

Manualized psychotherapy included

Study Arms & Interventions

Psilocybin-assisted psychotherapy

experimental

Two supervised psilocybin dosing sessions (25 mg each) delivered with preparatory and integrative psychotherapy.

Interventions

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

    Two 25 mg oral capsules administered in dosing sessions ~6 weeks apart; second session optional; supervised by two therapists; rescue benzodiazepines available.

Participants

Ages
18 – 65
Sexes
Male & Female

Inclusion Criteria

  • 1. Adults experiencing treatment-resistant unipolar depression, under the care of a psychiatrist, psychologist, physician, or GP.
  • 2. Proficient in English.
  • 3. Currently living full-time in Victoria.
  • 4. Experiencing severe depression as diagnosed by a trial therapist, with use of a clinical interview and the Montgomery-Åsberg Depression Rating Scale (MADRS).
  • 5. Experiencing depression that has not responded to two or more separate pharmacological interventions during the current depressive episode.
  • 6. Treating medical doctor can confirm patient has safely tapered and washed-out current antidepressant pharmacotherapy prior to baseline assessment.

Exclusion Criteria

  • 1. Contraindicated medical conditions including: cardiovascular conditions, major CNS disease, hepatic dysfunction, hypercalcaemia risk, epilepsy/seizures, renal insufficiency, diabetes, hypothyroidism.
  • 2. Females who are pregnant, breastfeeding, attempting to conceive or not using effective means of contraception.
  • 3. Weight <40 kg.
  • 4. Taking a contraindicated medication that cannot be ceased for an appropriate length of time during the trial (may include opioids, metabolic inducers or inhibitors, drugs with a low therapeutic index, and antidepressant medications).
  • 5. MRI contraindications.
  • 6. Any significant, uncorrected visual impairments required for cognitive and social processing tasks.
  • 7. Extremely severe depression/anxiety/suicidality symptoms warranting immediate hospitalisation, as determined by the screening psychiatrist in a clinical interview.
  • 8. Current, past history or 1st degree relative with schizophrenia, psychotic disorder (unless induced by substance or medical condition), or Bipolar I/II, as determined by the screening psychiatrist in a clinical interview.
  • 9. Current or past (5 year) history of alcohol or substance use disorder (excluding caffeine and nicotine), as determined by the screening psychiatrist and with the use of the DAST-10 and AUDIT.
  • 10. Current dissociative disorder, anorexia nervosa, bulimia nervosa or other condition judged to be incompatible with establishment of rapport or safe psilocybin administration as determined by the screening psychiatrist.

Primary Results(1 publication)

Participants

N = 7S. et al. 2025 →

Adverse Events (from all publications)

Arm / GroupnAny TEAESevereSeriousDiscont.
Psilocybin-assisted psychotherapyexperimental77(100.0%)—0(0.0%)0(0.0%)

* 7 participants completed the full treatment protocol. Table 4 shows 27 instances of adverse events across 7 participants. No serious adverse events were reported. One participant (ID 2) reported anxiety, insomnia, and suicidal ideation following the first dose.

Study Details

Locations

Unknown facility — Australia

Related Publications

Psilocybin with psychotherapeutic support for treatment-resistant depression: a pilot clinical trial

Published
Authors
Meikle, S., Carter, O., Liknaitzky, P., Johansen, L., Iyer, R., Strauss, N., Williams, M., Castle, D., Rossell, S. L., Ids, O.

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