Psilocybin for Treatment-Resistant Depression

NCT06230757 | Completed Phase 2 DMC FDA Drug

• 1 other identifier: 22-1681
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to evaluate the efficacy of psilocybin on the symptom of anhedonia in individuals with treatment-resistant major depressive disorder.

Conditions

Treatment Resistant Depression; Major Depressive Disorder; Anhedonia

Outcome Measures

Primary Outcomes (1)

• Change from baseline in self-reported anhedonia scores on the Dimensional Anhedonia Rating Scale (DARS).

  The DARS is a 17-item scale that captures multiple domains of anhedonia found in depression. Scores range from 0 to 68 with lower scores indicating greater anhedonia and 68 indicating no anhedonia.

  One week post-dosing

Secondary Outcomes (6)

• Change from baseline in self-reported anhedonia scores on the Dimensional Anhedonia Rating Scale (DARS).

  Eight weeks post-dosing

• Change from baseline in self-reported anhedonia scores on the Snaith-Hamilton Pleasure Scale (SHAPS).

  One week and eight weeks post-dosing

• Change from baseline in response bias for the high reward condition on the Probabilistic Reward Task (PRT)

  One and eight weeks post-dosing

• Change from baseline in nucleus accumbens neural activation during expectation of reward versus expectation of non-reward during the Monetary Incentive Delay Task (MID).

  One week post-dosing

• Change from baseline in depression scores of the clinician-rated Montgomery-Asberg Depression Rating Scale (MADRS).

  One and eight weeks post-dosing

Study Arms (2)

Psilocybin

EXPERIMENTAL

Participants receive Psilocybin 25mg capsule orally, administered with psychological support, on dosing day.

Drug: Psilocybin 25mg

Active Placebo

PLACEBO COMPARATOR

Participants receive Psilocybin 1mg capsule (identical to the Psilocybin 25mg capsule) orally, administered with psychological support, on dosing day.

Drug: Placebo (active placebo)

Interventions

Psilocybin 25mg DRUG

25mg psilocybin capsule

Psilocybin

Placebo (active placebo) DRUG

1mg psilocybin capsule

Also known as: Ultra Low Dose Psilocybin

Active Placebo

Eligibility Criteria

• Age: 21 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Adults ≥ 21 years of age at Screening
• Diagnosis of Major Depressive Disorder (MDD)
• Score of at least 12 (symptomatic depression) on administration of the Montgomery Asberg Depression Rating Scale (MADRS)
• Score of at least a 3 on question 8 on the MADRS evaluating loss of interest and ability to feel at both Screening and Baseline Visit 1
• The participant's Major depressive disorder meets the criteria for being treatment-resistant, defined as not experiencing a 50% improvement to two or more antidepressant treatments for adequate duration (6 weeks minimum) within the current episode, as determined by the Antidepressant Treatment Response Questionnaire (Desseilles et al., 2011; Posternak et al., 2004)
• Sufficiently competent in English Language
• Currently under the care of a psychiatric practitioner (MD, DO, NP, PA) OR under the consistent care of a clinician within the UCHealth/CUMedicine health system (for example, primary care provider, neurologist, therapist). Participants engaged in additional psychosocial treatments beyond seeing a psychiatric practitioner or regular therapist will be evaluated on a case by case basis.
• Right-handed
• Women of childbearing potential (WOCBP) must agree to practice an effective means of birth control throughout the duration of the study. A person of childbearing potential is anyone born female who has experienced menarche and who has not undergone surgical sterilization (eg, hysterectomy, bilateral salpingectomy, bilateral oophorectomy) or has not completed menopause. Menopause is defined clinically as 12 months of amenorrhea in a person over age 45 in the absence of other biological, physiological, or pharmacological causes.
• Have an identified support person and agree to be accompanied home (or to an otherwise safe destination) by the support person, or another responsible party, following dosing
• Written informed consent obtained from participant and ability for subject to comply with the requirements of the study.
• Ability to abstain from caffeine and nicotine for 2 hours prior to fMRI scan visits

You may not qualify if:

• Unstable medical conditions or serious abnormalities of complete blood count, chemistries, or EKG that in the opinion of the study physician would preclude safe participation in the trial. Some examples include:
• Congestive heart failure
• Clinically significant arrhythmias (e.g. ventricular fibrillation, torsades) or clinically significant EKG abnormality (i.e. QTC interval \> 450)
• Recent acute myocardial infarction or evidence of ischemia
• Malignant hypertension
• Congenital long QT syndrome
• Acute renal failure
• Severe hepatic impairment
• Respiratory failure
• Risk for hypertensive crisis defined as Screening, Baseline, and Medication Session (prior to dosing) Blood Pressure \>140/90 mmHg.
• High resting heart rate defined as Screening, Baseline, and Medication Session (prior to dosing) heart of rate of \>90 BPM
• Significant CNS pathology as determined by self-report and confirmed by a history and physical examination and review of medical records. Current and historical psychiatric disorders will be determined by the MINI. Specific examples include:
• Primary or secondary cerebral neoplasm
• Epilepsy
• History of stroke

Sponsors & Collaborators

• University of Colorado, Denver: lead

Study Sites (1)

University of Colorado Anschutz Medical Campus

Aurora, Colorado, 80045, United States

Location

MeSH Terms

Conditions

Depressive Disorder, Major; Anhedonia; Depressive Disorder, Treatment-Resistant

Interventions

Psilocybin

Condition Hierarchy (Ancestors)

Depressive Disorder; Mood Disorders; Mental Disorders; Neurobehavioral Manifestations; Neurologic Manifestations; Nervous System Diseases; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

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

Study Officials

• Andrew M Novick, MD, PhD

  University of Colorado, Denver

  PRINCIPAL INVESTIGATOR

Study Design

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

Study Record Dates

• First Submitted: January 19, 2024
• First Posted: January 30, 2024
• Study Start: July 8, 2024
• Primary Completion: May 8, 2026
• Study Completion: May 8, 2026
• Last Updated: May 22, 2026

Record last verified: 2026-05

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)