Clinical TrialMajor Depressive Disorder (MDD)PsilocybinPlaceboCompleted

Clinical, Neurocognitive, and Emotional Effects of Psilocybin in Depressed Patients – Proof of Concept

Randomized double-blind placebo-controlled parallel Phase II study (n=55) of a single oral moderate dose psilocybin (0.215 mg/kg) plus short-term focused psychotherapy versus placebo in adults with mild-to-moderate MDD.

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

Detailed Description

Randomized, double-blind, placebo-controlled parallel trial testing a single oral dose of psilocybin (0.215 mg/kg) combined with short-term focused psychotherapy versus placebo in adults with mild-to-moderate major depressive disorder; mono-centric at Zurich.

Primary objectives include reduction in depressive symptoms and change in negative emotion processing bias assessed by fMRI; secondary measures include functional connectivity (e.g., amygdala–prefrontal) and plasma BDNF as a neuroplasticity biomarker.

Eligibility included adults 18–60, right-handed, drug-free, not at high suicide risk; exclusions included lifetime psychosis or bipolar disorder, recent substance dependence, abnormal ECG, BMI <17 or >35, and MRI contraindications.

Study Protocol

Preparation

sessions

Dosing

1 sessions

Integration

sessions

Therapeutic Protocol

support

Study Arms & Interventions

Psilocybin

experimental

Single oral moderate dose psilocybin (0.215 mg/kg) plus short-term focused psychotherapy.

Interventions

  • Psilocybin0.215 mg/kg
    via Oral• single dose• 1 doses total

    Single dose 0.215 mg/kg psilocybin (oral)

Placebo

inactive

Single oral placebo (100% mannitol) plus psychotherapy.

Interventions

  • Placebo
    via Oral• single dose• 1 doses total

    One oral dose of 100% mannitol (placebo)

Participants

Ages
18 – 60
Sexes
Male & Female

Inclusion Criteria

  • Capable of giving informed consent
  • Informed consent as documented by signature
  • Male and female in- and outpatients 18 years to 60 years of age
  • Right-handedness
  • DSM-IV-diagnosis of mild or moderate major depressive episode without psychotic features (based on clinical assessment and confirmed by the SCID Interview)
  • Score of ≥ 10 and ≤ 40 on the Montgomery-Asberg Depression Rating Scale (MADRS) at both screening and baseline visits.
  • Drug free from any psychotropic medication for at least two weeks (or five weeks for fluoxetine) before enrolling in the study
  • Judged clinically not to be a serious suicide risk
  • Good physical health with no unstable medical conditions, as determined by medical history, physical examination, routine blood labs, electrocardiogram, urineanalysis, and urine toxicology
  • Normal level of language comprehension and German or Swiss-German as first language
  • Willing to refrain from drinking alcohol the day before testing days, from drinking alcohol and caffeinated drinks during the testing days and from consuming psychoactive substances 2 weeks before enrolling in the study and for the remainder of the study
  • Women of childbearing potential must be using an effective, established method of contraception for the entire study duration
  • Have a family member or friend who can pick them up and stay with them overnight after the psilocybin administration sessions

Exclusion Criteria

  • Lifetime history of bipolar disorder (I, II, not otherwise specified)
  • Lifetime history of schizophrenia, schizoaffective disorder, or psychosis not otherwise specified
  • History of DSM-IV drug or alcohol dependence or abuse (except for caffeine or nicotine) within three months prior to enrollment
  • Comorbid Axis I anxiety disorder diagnoses will be permitted if they do not require current treatment
  • Family history of schizophrenia or schizoaffective disorder, or bipolar disorder type 1 (first or second degree relatives)
  • Lifetime history of hallucinogen use on more than 10 occasions
  • Getting psychotherapeutic or psychological treatment from third parties during the study is forbidden
  • Abnormal electrocardiogram
  • Any unstable illness as determined by history or laboratory tests
  • BMI <17 or >35
  • Uncorrected hypo- or hyperthyroidism
  • Women who are pregnant or breast feeding, or have the intention to become pregnant during the course of the study
  • Contraindications to magnetic resonance imaging (MRI safety form)
  • During the study, new use or dose changes of already existing concomitant medication without prior informing the investigators is forbidden
  • Allergy, hypersensitivity, or other adverse reaction to previous use of psilocybin or other hallucinogens
  • High risk of adverse emotional or behavioral reaction based on investigator's clinical evaluation (e.g., evidence of serious personality disorder, antisocial behavior, serious current stressors, lack of meaningful social support)
  • Participation in another study with investigational drug within the 30 days preceding and during the present study

Study Details

Locations

Psychiatrische Universitätsklinik Zürich — Zurich, Switzerland

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