Effects of Psilocybin With Psychological Support... — Clinical Trial Details

This Phase II randomised, quadruple‑blind, parallel study evaluates whether a single 25 mg oral dose of psilocybin plus psychological support reduces anhedonia in participants with treatment‑resistant major depressive disorder compared with an ultra‑low (1 mg) active‑placebo.

Primary efficacy is measured with MADRS (including item 8 for interest/ability to feel); secondary assessments include safety labs, ECG, adverse events, and neuroimaging (fMRI) outcomes. Psychological support is provided pre, during and post dosing.

Participants

Ages

21 – 75

Sexes

Male & Female

BMI

Psychosis History

Excluded

Inclusion Criteria

Inclusion Criteria:
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
Right-handed
Women of childbearing potential must agree to practice effective birth control throughout the study
Have an identified support person and agree to be accompanied home following dosing
Written informed consent obtained and ability to comply with study requirements
Ability to abstain from caffeine and nicotine for 2 hours prior to fMRI scan visits

Exclusion Criteria

Exclusion Criteria:
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 (examples: congestive heart failure; clinically significant arrhythmias or EKG abnormality, e.g. QTc > 450; recent acute myocardial infarction; malignant hypertension; congenital long QT syndrome; acute renal failure; severe hepatic impairment; respiratory failure)
Risk for hypertensive crisis defined as BP >140/90 mmHg at Screening, Baseline, or prior to dosing
High resting heart rate defined as >90 BPM at Screening, Baseline, or prior to dosing
Significant CNS pathology (e.g., neoplasm, epilepsy, history of stroke, cerebral aneurysm, dementia, delirium)
Current or lifetime primary psychotic disorder, bipolar affective disorder, affective disorder with psychotic features (e.g., schizophrenia spectrum, schizoaffective, bipolar I/II, history of mania)
Family history of first-degree relative with psychotic or serious bipolar spectrum illness
High risk of adverse emotional or behavioural reaction based on investigator assessment (e.g., agitation, violent behaviour)
Active substance use disorders (DSM-5 moderate/severe) in past year (excluding caffeine/nicotine)
Extensive recent or heavy use of serotonergic hallucinogens (any use in last 6 months or >25 lifetime uses)
History of hallucinogen persisting perception disorder (HPPD)
Women who are pregnant or nursing or intend to become pregnant during the study
History of severe suicide attempt requiring hospitalization in the past year
Any suicidal ideation or thoughts judged to present serious risk of imminent suicidal or self-injurious behaviour
Use of drugs or supplements that may interfere with study drug (examples listed in protocol); certain prescribed meds allowed at PI discretion with washout of 5 half-lives as required
Psychiatric condition incompatible with rapport or safe exposure to psilocybin per PI
Allergy or intolerance to study product materials
Positive urine drug screen for listed substances (exceptions noted for stable prescribed benzodiazepines)
Claustrophobia, lack of internet access, weight over 300 pounds, metal unsafe for MRI, or other contraindications to MRI
Known contraindication to clonidine, diazepam, or olanzapine (examples listed in protocol)

Company

Product

Legal

Effects of Psilocybin With Psychological Support on Anhedonia in Treatment-resistant Depression: a Randomized Controlled Pilot Trial

Detailed Description

Study Protocol

Preparation

Dosing

Locations

Integration

Therapeutic Protocol

Study Arms & Interventions

Psilocybin 25mg

Interventions

Active placebo 1mg

Interventions

Participants

Inclusion Criteria

Exclusion Criteria

Study Details

Study Team

Sponsors & Collaborators