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

NCT03715127 | Completed Phase 2 DMC

• 1 other identifier: PSIDEPR128
• Study Type: interventional
• Target: 55
• Locations: 1 country
• Sites: 1

Brief Summary

Effects of serotonin 2A/1A receptor stimulation by psilocybin on mood and emotion processing in major depressive disorder: a randomized double-blind placebo-controlled study

Conditions

Depressive Disorder, Major

Keywords

Depression; 5HT-2A; Psilocybin; clinical efficacy; self; emotion regulation; placebo-controlled; proof-of-concept

Outcome Measures

Primary Outcomes (2)

• Montgomery Asberg Depression Scale

  observer-rated score for depression

  Day 32

• Beck Depression Inventory

  self-rated score for depression

  Day 32

Secondary Outcomes (2)

• Changes in BOLD signal over time as measured by fMRI

  Day 17, 20, 32

• 5 Dimensions- Altered States of consciousness(5D-ASC)

  Day 18

Study Arms (2)

Placebo

PLACEBO COMPARATOR

one oral dose of 100% mannitol (placebo)

Drug: Placebo oral capsule

Psilocybin

ACTIVE COMPARATOR

one oral dose of 0.215mg/kg psilocybin (verum)

Drug: Psilocybine oral capsule

Interventions

Psilocybine oral capsule DRUG

single dose of psilocybin (0.215mg / kg body weight)

Psilocybin

Placebo oral capsule DRUG

single dose of placebo (100% mannitol)

Placebo

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• 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, such as oral, injectable, or implantable contraceptives, or intrauterine contraceptive devices. Note: female participants who are surgically sterilised / hysterectomised or post-menopausal for longer than 2 years are not considered as being of child bearing potential.
• Have a family member or friend who can pick them up and stay with them overnight after the psilocybin administration sessions (driving is forbidden at drug treatment days)

You may not qualify if:

• 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

Sponsors & Collaborators

• University of Zurich: lead
• Schweizerischer Nationalfonds: collaborator

Study Sites (1)

Psychiatrische Universitätsklinik Zürich

Zurich, 8032, Switzerland

Location

Related Publications (2)

• Jungwirth J, von Rotz R, Dziobek I, Vollenweider FX, Preller KH. Psilocybin increases emotional empathy in patients with major depression. Mol Psychiatry. 2025 Jun;30(6):2665-2672. doi: 10.1038/s41380-024-02875-0. Epub 2024 Dec 18.

  PMID: 39695323 DERIVED

• von Rotz R, Schindowski EM, Jungwirth J, Schuldt A, Rieser NM, Zahoranszky K, Seifritz E, Nowak A, Nowak P, Jancke L, Preller KH, Vollenweider FX. Single-dose psilocybin-assisted therapy in major depressive disorder: A placebo-controlled, double-blind, randomised clinical trial. EClinicalMedicine. 2022 Dec 28;56:101809. doi: 10.1016/j.eclinm.2022.101809. eCollection 2023 Feb.

  PMID: 36636296 DERIVED

MeSH Terms

Conditions

Depressive Disorder, Major; Depression; Emotional Regulation

Interventions

Psilocybin

Condition Hierarchy (Ancestors)

Depressive Disorder; Mood Disorders; Mental Disorders; Behavioral Symptoms; Behavior; Self-Control; Social Behavior

Intervention Hierarchy (Ancestors)

Indole Alkaloids; Alkaloids; Heterocyclic Compounds; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Tryptamines; Indolizidines; Indolizines

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: quadruple-blind
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: placebo-controlled, quadruple-blind, randomized, mono-centric

Study Record Dates

• First Submitted: October 16, 2018
• First Posted: October 22, 2018
• Study Start: March 11, 2019
• Primary Completion: October 12, 2021
• Study Completion: April 12, 2022
• Last Updated: April 29, 2022

Record last verified: 2022-04

Locations

CH (1)