Psilocybin for Prolonged Grief Disorder

NCT06724289 | Recruiting Early Phase 1 FDA Drug

• 1 other identifier: HSR231647
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 1

Brief Summary

The primary purpose of this study is to explore the feasibility of conducting a clinical trial on the effects of psilocybin for individuals with prolonged grief disorder (PGD).

Conditions

Prolonged Grief Disorder

Keywords

prolonged grief disorder; psilocybin; psychedlic-assisted treatment; psilocybin-assisted therapy; grief; grief disorder

Outcome Measures

Primary Outcomes (2)

• Recruitment Rate

  Number of participants enrolled divided by number screened over the recruitment period.

  Through end of enrollment period

• Dropout Rate

  Proportion of enrolled participants who withdraw or are lost to follow-up prior to completing the 6-month assessment.

  Baseline to 6-month Follow-up

Secondary Outcomes (11)

• Change in Prolonged Grief Disorder Symptoms (ICG)

  Baseline (Visit 0 - Screening) to 6-month Follow-up

• Change in PTSD Symptoms (DTS)

  Baseline (Visit 0 Screening) to 6-month Follow-up

• Mystical Experience (MEQ)

  Baseline (Visit 3 - Treatment Visit) to 6-month Follow-up

• Altered States of Consciousness (5-D ASC)

  Baseline (Visit 3 - Treatment Visit) to 6-month Follow-up

• Awe Experience (AWE-S)

  Baseline (Visit 3 - Treatment Visit) to 6-month Follow-up

Study Arms (1)

Open-label, single arm trial

EXPERIMENTAL

25 mg psilocybin administered to each participant

Drug: Psilocybin 25 mg; Diagnostic Test: Functional Magnetic Resonance Imaging (fMRI)

Interventions

Psilocybin 25 mg DRUG

25 mg psilocybin administered to each participant in single arm, open-label trial

Open-label, single arm trial

Functional Magnetic Resonance Imaging (fMRI) DIAGNOSTIC_TEST

There are two "fMRIs" (functional magnetic resonance imaging) that take place 1-14 days before and 1-14 days after psilocybin administration.

Open-label, single arm trial

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Ages 18 years old up to and including 65 years of age
• Negative UDS results for illicit drugs at screening and prior to each drug administration session
• Consent to all study procedures
• Have an existing diagnosis of Prolonged Grief Disorder. May also be determined to have Complicated Grief Disorder without official diagnosis as determined by PI or designate based on DSM V criteria
• Score of greater than 25 on the Inventory of Complicated Grief
• Agree to abstain from any psychoactive drugs on the day prior to and the day of the drug administration session
• People of childbearing potential that are sexually active must agree to continue or initiate practice of a highly effective means of birth control, alone or in combination with another, throughout the study. Highly effective options are: implants, intrauterine devices (IUD), and sterilization. Exclusive use of condoms is not effective.
• Be judged by study team clinicians to be at low risk for suicidality as determined by MINI, Columbia Suicide Severity Scale, and the Patient Health Questionnaire-9.
• Concurrent psychotherapy or pharmacotherapy with SSRIs, SNRIs, and/or bupropion (\< 300 mg bupropion) is allowed if the type and frequency of the therapy has been stable for at least two months prior to screening and is expected to remain stable during participation in the study
• Be otherwise medically stable as determined by screening for medical problems via a personal interview, a medical questionnaire, a physical examination, an electrocardiogram (ECG), urine beta-HCG, and urine toxicology screen
• Participant must agree to consume approximately the same amount of caffeine-containing beverage (e.g., coffee, tea) that they consume on a usual morning, before arriving at the research unit on the mornings of drug session days. If the participant does not routinely consume caffeinated beverages, they must agree not to do so on session days
• Agree not to take any PRN medications on the mornings of drug sessions
• Agree not to take sildenafil (Viagra®), tadalafil, or similar medications within 72 hours of each drug administration
• Agree that for one week before each drug session, participant will refrain from taking any nonprescription medication, nutritional supplement, or herbal supplement except when approved by the study investigators. Exceptions will be evaluated by the study investigators and will include acetaminophen, non-steroidal anti-inflammatory drugs, and common doses of vitamins and minerals
• Willingness and ability to remain within the observation room for the duration of the study visits up to 10 hours

You may not qualify if:

• Person who is pregnant, nursing, or planning to get pregnant determined at screening and before drug session by urine test or self-report
• People of childbearing potential that are sexually active who are not practicing an effective means of birth control
• Cardiovascular conditions: coronary artery disease, stroke, angina, a clinically significant ECG abnormality (e.g., atrial fibrillation), prolonged QTc interval (i.e., QTc \> 450 msec), heart valve, or TIA in the past year.
• History of head trauma with neurological deficit; seizures, or neurologic disorders including cerebrovascular disease, epilepsy, or neurogenerative diseases
• Type 1 diabetes
• BMI \<18
• Currently taking on a regular (e.g., daily) basis any antidepressant medications other than SSRIs, SNRIs, or bupropion, or any other medications that have a primary centrally-acting serotonergic effect, including MAOIs. Bupropion dosage must be \< 300 mg in order to be included
• Nicotine dependence that would be incompatible with remaining in study area for the entirety of the visit
• Prescribed or illicit use of benzodiazepines or opioids within 4 weeks prior to screening
• Baseline blood pressure greater than 139/79 (after repeat measures) unless stable with medication as determined by PI or PI designate
• Taking any muscle relaxers, antihistamines, or other medications known to cause lethargy or impair cognitive ability within one day prior to psilocybin session
• Serious medical comorbidity requiring medical intervention or close supervision
• History of claustrophobia
• Any court mandated or legal restrictions that would impair the participant from attending all visits
• Inability to follow and comply with all study procedures

Sponsors & Collaborators

• University of Virginia: lead
• Tiny Blue Dot Foundation: collaborator
• Texas Tech University: collaborator

Study Sites (1)

University of Virginia

Charlottesville, Virginia, 22903, United States

RECRUITING

MeSH Terms

Conditions

Prolonged Grief Disorder

Interventions

Psilocybin; Magnetic Resonance Imaging

Condition Hierarchy (Ancestors)

Trauma and Stressor Related Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Indole Alkaloids; Alkaloids; Heterocyclic Compounds; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Tryptamines; Indolizidines; Indolizines; Tomography; Diagnostic Imaging; Diagnostic Techniques and Procedures; Diagnosis

Study Officials

• Jennifer K Penberthy, PhD

  University of Virginia

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Fatma Wise, PhD

CONTACT

(434) 243-0568; uvagrieftrial@uvahealth.org

Madison Focht

CONTACT

uvagrieftrial@uvahealth.org

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: PhD, ABPP

Model Details: All eligible participants will receive 25 mg of psilocybin.

Study Record Dates

• First Submitted: December 4, 2024
• First Posted: December 9, 2024
• Study Start: March 1, 2026
• Primary Completion (Estimated): August 1, 2027
• Study Completion (Estimated): August 1, 2027
• Last Updated: March 3, 2026

Record last verified: 2026-03

Locations

US (1)