Clinical TrialAnxiety DisordersPsilocybinPsilocybinRecruiting

A clinical trial of 5 mg psilocybin plus psychological support vs 25 mg psilocybin plus psychological support in adults with generalised anxiety disorder

Phase IIb randomised, double-blind trial (n=96) comparing two doses of psilocybin (25 mg vs 5 mg) plus psychological support; two doses given one month apart with outcomes over 33 weeks in adults with severe GAD.

Target Enrollment
96 participants
Study Type
Phase II interventional
Design
Randomized, double Blind

Detailed Description

Multicentre, randomised, double-blind parallel-group trial comparing efficacy and safety of two oral psilocybin doses (25 mg vs 5 mg) given in two dosing sessions one month apart, with stratification by SSRI status and follow-up to 33 weeks.

Primary outcome is change in HAM-A at week 8; secondary outcomes include GAD-7, PHQ-9, SDS, WEMWBS, healthcare utilisation, EEG/ECG measures (resting-state, emotional faces, oddball), and safety/tolerability across acute and follow-up visits.

Participants may be taking permitted stable SSRIs; capsules are matched for appearance and masking efficacy will be assessed at each dosing session.

Study Protocol

Preparation

sessions

Dosing

2 sessions

Integration

sessions

Therapeutic Protocol

support

Study Arms & Interventions

25 mg psilocybin

experimental

High-dose arm receiving two oral 25 mg psilocybin capsules with psychological support, one month apart.

Interventions

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

    Two doses, one month apart; capsules matched for weight/appearance with 5 mg.

5 mg psilocybin

active comparator

Low-dose comparator receiving two oral 5 mg psilocybin capsules with psychological support, one month apart.

Interventions

  • Psilocybin5 mg
    via Oral• two sessions• 2 doses total

    Two doses, one month apart; capsules matched for weight/appearance with 25 mg.

Participants

Ages
18 – 70
Sexes
Male & Female

Inclusion Criteria

  • 1. Aged 18 - 70 years
  • 2. Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5)/International Classification of Diseases 11th Revision (ICD-11) defined GAD as the primary diagnosis, with severity indicated by a HAM-A score >25
  • 3. Any sex or gender
  • 4. Body Mass Index 18 - 35 kg/m²
  • 5. Medically suitable as determined by screening including a past medical history, family history, drug history, social history, physical examination and investigations, including an electrocardiogram (EEG) and blood tests.
  • 6. Refrain from taking contraindicated or excluded medications, including herbal, complementary or over-the-counter medications, or have safely tapered and washed out from excluded medications in accordance with the washout period specified in the protocol.

Exclusion Criteria

  • 1. Any clinically significant, untreated or unstable illness (e.g., hepatic, renal or cardiovascular functions)
  • 2. Type 1 diabetes or insulin dependent type 2 diabetes
  • 3. A diagnosis of epilepsy or at significant risk of seizures based on medical history
  • 4. Positive urine drug test for psychoactive substances at in-clinic screening visit or dosing visits
  • 5. Positive alcohol breathalyser test at the in-clinic screening visit or dosing visits
  • 6. Female participants who are pregnant, breastfeeding or of childbearing potential who are unwilling or unable to use a highly effective method of contraception
  • 7. Participation in another clinical trial of an investigational drug within 30 days or 5 half-lives of the drug (whichever is longest) prior to screening
  • 8. Allergy, hypersensitivity or other Adverse Reaction (AR) to previous use of psilocybin, other hallucinogens, rescue medication and their excipients microcrystalline cellulose
  • 9. Anyone with organic brain injury
  • 10. Treatment with any other antidepressant medication other than a currently prescribed permitted SSRI which must be a stable dose (constant for at least 6 months with no plan to increase)
  • 11. Diagnosed with or having a first degree-relative family history of any of the following psychiatric disorders: schizophrenia or prodromal symptoms, any bipolar disorder, or other psychotic disorder as assessed during screening
  • 12. Any history of suicide attempts or behaviours as indicated by reporting "yes" on any item of the Suicide Behaviour Section of the Columbia Suicide Severity Rating Scale (C-SSRS) within the last 5 years
  • 13. History of suicidal ideation with some intent to act within the last 12 months prior to screening; the participant scores "yes" on item four or item five of the Suicidal Ideation section of the C-SSRS
  • 14. Judged to be of high suicide or self-harm risk following psychological assessment at screening or baseline
  • 15. Judged to be unfit for psilocybin-assisted therapy based on assessments made during psychological support sessions prior to first dosing session
  • 16. Current or recent treatment with prohibited medications
  • 17. History of hallucinogen use disorder, or any use in the past 1 year, or >25 lifetime uses
  • 18. History of electroconvulsive treatment (ECT) or transcranial magnetic stimulation treatment, ketamine, or vagal nerve stimulation
  • 19. Current (within 12 months) alcohol or drug abuse identified as moderate or severe during screening through medical history and the Mini International Neuropsychiatric Interview (MINI) 7.0.2

Study Details

  • Status
    Recruiting
  • Phase
    Phase II
  • Type
    interventional
  • Design
    Randomizeddouble Blind
  • Target Enrollment96 participants
  • Timeline
    Start: 2026-04-01
    End: 2027-04-30
  • Compounds
    PsilocybinPsilocybin
  • Topic
    Anxiety Disorders

Locations

Unknown facility — England

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