Clinical TrialMajor Depressive Disorder (MDD)PsilocybinPlaceboCompleted

The Effect of Psilocybin on MDD Symptom Severity and Synaptic Density

The effect of psilocybin on major depressive disorder (MDD) symptom severity and synaptic density - a single dose randomized, double blind, placebo-controlled Phase IIb positron emission tomography study.

Target Enrollment
35 participants
Study Type
Phase II interventional
Design
Randomized, quadruple Blind

Detailed Description

Randomized, double-blind, parallel-group Phase 2b trial (n=35 actual) comparing a single 25 mg oral dose of psilocybin with a single 100 mg niacin active placebo in adults with MDD; primary outcome is change in MADRS score to Day 8.

Participants undergo MRI and PET with [11C]UCB-J to assess synaptic density at baseline and Day 15; one preparation session and three post-dose integration sessions are provided under a set-and-setting protocol with two facilitators present during dosing.

Safety measures and biological samples (CSF, blood) collected at baseline and Day 15; follow-up visits continue to Day 365 for clinical outcomes and safety.

Study Protocol

Preparation

1 sessions

Dosing

1 sessions

Integration

3 sessions

Therapeutic Protocol

support

Study Arms & Interventions

Psilocybin

experimental

Single oral 25 mg psilocybin dose

Interventions

  • Psilocybin25 mg
    via Oral• single dose• 1 doses total

Niacin (active placebo)

active comparator

Single oral 100 mg niacin active placebo

Interventions

  • Placebo100 mg
    via Oral• single dose• 1 doses total

    Niacin 100 mg active placebo to aid blinding

Participants

Ages
20 – 65
Sexes
Male & Female

Inclusion Criteria

  • Inclusion Criteria:
  • Individuals eligible to be randomized in this protocol are those who meet all of the following criteria:
  • 1. Are 20 to 65 years old at the time of written informed consent at the In-Person Screening visit
  • 2. Are able to read, speak, and understand Swedish
  • 3. Are able and willing to adhere to study requirements, including attending all study visits, preparatory and follow-up sessions, and completing all study evaluations
  • 4. Are able to swallow capsules
  • 5. Women of childbearing potential (WOCBP) must agree to practice an effective means of birth control throughout the duration of the study, from Screening through the Day 42 assessment
  • 6. Meet ICD-10 criteria for a diagnosis of remitting major depressive disorder and are currently experiencing a major depressive episode of at least 30 days and less than 5 years at time of Screening
  • 7. Have sustained moderate-severe depression symptoms at Screening and Baseline, as defined by a Screening MADRS total score ≥ 22 and ≤30% and ≤7 point improvement from web-screening to screening
  • 9. Have an identified support person and agree to be accompanied home after dosing

Exclusion Criteria

  • Exclusion Criteria:
  • 1. Women who are pregnant or nursing or intend to become pregnant during the study
  • 2. Current depressive episode lasting >5 years
  • 3. Unwilling or unable to discontinue formal psychotherapy
  • 4. Ongoing antidepressant drug treatment
  • 5. Prior DBS or VNS in current episode
  • 6. Currently receiving ECT or TMS
  • 7. Unable or unwilling to discontinue medications that are UDP or UGT modulators (eg valproate)
  • 8. Report psychedelic substance use ever (psilocybin, LSD, mescaline, DMT, 5-MeO-DMT, ibogaine, 2C compounds, MDMA, etc.)
  • 9. Specific cardiovascular conditions (coronary artery disease, prior MI, long QT, hypertrophy, ischemia, CHF), tachycardia (>100 bpm), clinically significant ECG abnormality (eg QTcF >450 ms), artificial heart valve
  • 10. Elevated blood pressure at Screening or Baseline per protocol thresholds
  • 11. History of stroke or TIA
  • 12. Moderate to severe hepatic impairment (Child-Pugh ≥7)
  • 13. Epilepsy
  • 14. Insulin-dependent diabetes or history of hypoglycaemia requiring intervention
  • 15. Inability to suspend certain medications/supplements (eg PDE5 inhibitors, niacin >20 mg) or positive urine drug test for specified substances
  • 16. Nicotine dependence preventing nicotine-free dosing period
  • 17. ICD-10 schizophrenia spectrum or other psychotic disorders, bipolar I/II or NOS
  • 18. Antisocial personality disorder
  • 19. Moderate or severe alcohol or drug use disorder within past 12 months
  • 20. Any psychiatric condition judged by PI to be more significant than MDD
  • 21. First-degree relative with schizophrenia spectrum/psychotic disorders or bipolar I
  • 22. Psychiatric condition incompatible with rapport or safe exposure to psilocybin
  • 23. Suicidal ideation per MADRS Item 10 ≥5 or any suicidal thoughts judged to present serious risk prior to randomization
  • 24. Any other physical or psychological condition making participant unsuitable

Study Details

Locations

Northern Stockholm Spychiatry Clinic — Stockholm, Sweden

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