A Study of Psilocybin for Major Depressive Disorder (MDD)
Condition: Depressive Disorder, Major
MeSH terms: Depressive Disorder; Depression; Depressive Disorder, Major
Study type: Interventional
Phase: Phase 2

Summary: 
      One hundred participants, ages 21 to 65, who meet Diagnostic and Statistical Manual of Mental
      Disorders (DSM-5) criteria for major depressive disorder (MDD) will be stratified by study
      site and randomized with a 1-to-1 allocation under double-blind conditions to receive a
      single 25 mg oral dose of psilocybin or a single 100 mg oral dose of niacin. Niacin will
      serve as an active placebo.

      The purpose of this study is to evaluate the potential efficacy of a single 25 mg oral dose
      of psilocybin for MDD compared to the active placebo in otherwise medically-healthy
      participants, assessed as the difference between groups in changes in depressive symptoms
      from Baseline to Day 43 post-dose.
    

Detailed description: 
      Major depressive disorder (MDD) has become a health crisis of epidemic proportions in the
      modern world. One in six individuals in the United States will experience an episode of major
      depression in his or her lifetime, and it is estimated that major depression will rank second
      after cardiac disease as a cause of international medical morbidity by the year 2020.
      Depression is associated with greater disability than are most other chronic illnesses and is
      a risk factor for mortality. Additionally, depression predicts the later development of a
      number of medical conditions, including cardiac and cerebrovascular disease, hypertension,
      diabetes, obesity, metabolic syndrome, dementia, and cancer. Unfortunately, most patients
      with depression do not experience a complete resolution of symptoms with antidepressant
      treatment. Partial-but incomplete-response to antidepressants is associated with an increased
      risk of full symptomatic relapse (even when on therapy) and a worse long-term disease course.
      Combined with the high prevalence and significant disability associated with MDD, the fact
      that currently available treatments are not fully adequate highlights the tremendous need to
      identify novel treatment strategies.

      Data suggest that psilocybin may have behavioral effects relevant to the treatment of
      depression and recent studies also suggest that psilocybin may possess antidepressant
      properties. To further assess the effects of psilocybin on MDD signs and symptoms, this trial
      will enroll 100 participants, ages 21 to 65, who meet criteria for MDD. Participants will be
      stratified by study site and randomized with a 1-to-1 allocation under double-blind
      conditions to receive a single 25 mg oral dose of psilocybin or a single 100 mg oral dose of
      niacin. Niacin will serve as an active placebo.

      To enhance participant safety, a Set and Setting (SaS) protocol will be utilized similar to
      the protocol that has been used in all modern studies of psilocybin. The SaS protocol for
      this study includes: 1) a period of preparation with session Facilitators prior to dosing; 2)
      administration of study medications in an aesthetically pleasing room under the supervision
      of two Facilitators who are present throughout the session; and 3) three post-dose
      integration sessions during which participants are encouraged to discuss their intervention
      experience with the Facilitators. The SaS protocol will be identical for those randomized to
      psilocybin or active placebo.

      The primary objective of this study is to evaluate the potential efficacy of a single 25 mg
      oral dose of psilocybin for MDD compared to the active placebo (niacin), assessed as the
      difference between groups in changes in depressive symptoms from Baseline to Day 43
      post-dose.
    

Intervention name(s): Psilocybin; Niacin; Set and Setting (SaS) Protocol
Intervention type(s): Drug; Drug; Other
Intervention description(s): The psilocybin used in this study is synthetically manufactured in a laboratory and meets quality specifications suitable for human research use. The active drug is encapsulated using a hydroxypropyl methylcellulose (HPMC) capsule and contains 25 mg of psilocybin.; The active placebo is encapsulated using a HPMC capsule and contains 100 mg of pharmaceutical grade niacin.; The SaS Protocol prescribes 6-8 hours of preparatory meetings with two facilitators prior to dosing, a 7-10 hour dosing session in a comfortable room under the supervision of the same two facilitators, and 4 hours of post-dose integration sessions with facilitators. During the dosing session participants are encouraged to wear eyeshades and listen to a curated playlist on headphones.
Other intervention name(s): Psilocybine, Psilocibin, Indocybin; Vitamin B3
Intervention MeSH terms: Niacin; Psilocybin
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Primary purpose: Treatment
Keywords: Psilocybin, Psychedelics, Depression, MDD