Prolonged Grief DisorderEarly Phase 1NCT06724289
Psilocybin for Prolonged Grief Disorder
A Early Phase 1 study testing Psilocybin 25 mg and Functional Magnetic Resonance Imaging (fMRI) in people with Prolonged Grief Disorder, run by University of Virginia at 1 site in United States.
Trial 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). Read more about this study
- Who is it for?
- Ages 18 to 65 yearsHealthy volunteers can take part
- Conditions the study is for
- Prolonged Grief Disorder
- What is being tested?
- Psilocybin 25 mg and Functional Magnetic Resonance Imaging (fMRI)
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 12 participants
- Where
- 1 siteUnited States
- Study dates
- 24 Mar 2026to Aug 2027
- Phase
- Early Phase 1
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 65 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- 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
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- 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
- Willingness and ability to follow study protocol as directed by research staff
- Willing and able to attend all sessions in the study and complete follow up assessments
- Fluent in English
- Ability to provide one photo of a deceased loved one and one photo of a living loved one, as required for the grief elicitation task.
Who cannot join
- General medical exclusion criteria:
- Previous use of a psychedelic drug may be exclusionary depending on frequency, context, and participant safety as determined by the PI or designate.
- 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
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- 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
- Deemed unable to meaningfully or safely participate in the study
- Any legal judgement toward subject determined to interfere with study attendance or jeopardize compliance with study protocol determined by PI or designate
- Individuals who are unable to undergo MRI as determined by MRI pre-screening.
- General psychiatric exclusion criteria:
- Score of less than 25 on the Inventory of Complicated Grief
- Severe psychiatric disorder (other than depression) within 6 months or lifetime history of serious psychiatric or neurological disorders, including bipolar disorder, or active psychosis
- Clinically significant suicidal ideation (e.g., with strong intent or means) within past 6 months or lifetime history of suicide attempt based on the MINI, Patient Health Questionnaire-9 or Columbia-Suicide Severity Scale. At any point during the study, a participant may be withdrawn from the study for concerns of suicidality and provided follow-up care by our team or a referral to care if needed.
- Current or past history of meeting DSM-5 criteria for schizophrenia spectrum or other psychotic disorders, or bipolar I disorder
- Current or previous history within one year of meeting DSM-5 criteria for a moderate or severe alcohol, or other drug use disorder (excluding tobacco, caffeine, and cannabis)
- Nicotine dependence that would be incompatible with an individual to be nicotine free for 8-10 hours on a psilocybin session day
- Have a first degree relative with schizophrenia or other psychotic disorders (except substance/medication-induced or due to another medical condition), or bipolar I disorder
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Madison Focht contact
United States1 site, 1 recruiting
- Recruiting
University of Virginia
Charlottesville, Virginia, 22903
About this study
Official title: Psilocybin-Assisted Therapy for Prolonged Grief
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).
Read the detailed description
The study aims to investigate whether a single dose of 25 mg psilocybin can reduce the symptoms of grief and trauma associated with Prolonged Grief Disorder (PGD). It is hypothesized that psilocybin will significantly reduce the symptoms of PGD, and that the treatment will facilitate subjective mystical, spiritual, or insightful experiences, which in turn may contribute to the alleviation of grief and trauma symptoms. Neuroimaging will be used to help researchers better understand the relationship between grief and brain functions, comparing pre- and post-dose scans. Participants will undergo two MRI (magnetic resonance imaging) where they are asked to look at images (this is called a functional MRI or fMRI).
- Conditions
- Prolonged Grief Disorder
- Being tested
- Psilocybin 25 mg, Functional Magnetic Resonance Imaging (fMRI)
- Keywords
- prolonged grief disorder, psilocybin, psychedlic-assisted treatment, psilocybin-assisted therapy, grief, grief disorder
- Medical subject headings
- Prolonged Grief Disorder
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Psilocybin 25 mgDrug
25 mg psilocybin administered to each participant in single arm, open-label 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.
| Study group | Role | What they receive |
|---|---|---|
| Open-label, single arm trial | Experimental | 25 mg psilocybin administered to each participant Receives: Drug: Psilocybin 25 mg; Diagnostic Test: Functional Magnetic Resonance Imaging (fMRI) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Recruitment Rate
Number of participants enrolled divided by number screened over the recruitment period.
Measured: 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.
Measured: Baseline to 6-month Follow-up
Secondary outcomes (11)
Change in Prolonged Grief Disorder Symptoms (ICG)
Change in the Inventory of Complicated Grief (ICG) is a 19-item scale assessing prolonged grief symptoms. Scores range from 0 to 76, with higher scores indicating greater symptom severity.
Measured: Baseline (Visit 0 - Screening) to 6-month Follow-up
Change in PTSD Symptoms (DTS)
Change in Davidson Trauma Scale (DTS) total score; range 0-136; higher scores indicate more severe PTSD symptoms.
Measured: Baseline (Visit 0 Screening) to 6-month Follow-up
Mystical Experience (MEQ)
Change in Mystical Experiences Questionnaire (MEQ-30) mean score; range 0-5; higher scores indicate greater mystical-type experience.
Measured: Baseline (Visit 3 - Treatment Visit) to 6-month Follow-up
Altered States of Consciousness (5-D ASC)
Change in 5-Dimensions of Altered States of Consciousness score; range 0-100%; higher percentages indicate greater altered-state intensity.
Measured: Baseline (Visit 3 - Treatment Visit) to 6-month Follow-up
Awe Experience (AWE-S)
Change in Awe Experience Scale mean score; range 1-7; higher scores indicate greater awe.
Measured: Baseline (Visit 3 - Treatment Visit) to 6-month Follow-up
Challenging Experiences (CEQ)
Change in Challenging Experiences Questionnaire mean score; range 0-5; higher scores indicate more intense challenging experiences.
Measured: Baseline (Visit 3 - Treatment Visit) to 6-month Follow-up
Psychological Flexibility (AAQ-II)
Change in Acceptance and Action Questionnaire-II total score; range 7-49; higher scores indicate greater psychological inflexibility.
Measured: Baseline (Visit 2 - Preparation for Treatment) to 6-month Follow-up
Closeness to Others (IOS)
Change in Inclusion of Others in the Self single-item score; range 1-7; higher scores indicate greater perceived interpersonal closeness.
Measured: Baseline (Visit 0 - Screening) to 6-month Follow-up
Meaning in Life (MIL)
Change in Meaning in Life Questionnaire Presence and Search subscales; each subscale range 5-35; higher scores indicate greater presence of meaning (Presence) or search for meaning (Search).
Measured: Baseline (Visit 2 - Preparation for Treatment) to 6-month Follow-up
Psychological Insight (PIQ)
Change in Psychological Insight Questionnaire mean score; range 0-5; higher scores indicate greater psychological insight.
Measured: Baseline (Visit 3 - Treatment Visit) to 6-month Follow-up
Personality Traits (NEO-FFI)
Change in the NEO Five-Factor Inventory (NEO-FFI) is a 60-item measure assessing five personality domains: Neuroticism, Extraversion, Openness, Agreeableness, and Conscientiousness. Each domain score ranges from 0-48, with higher scores indicating greater expression of the corresponding personality trait.
Measured: Baseline (Visit 2 - Preparation for Treatment) to 6-month Follow-up
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Dec 2024
- Study start24 Mar 2026
- Primary completionAug 2027 (estimated)
- Study completionAug 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Prolonged Grief DisorderStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Early Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Model description
- All eligible participants will receive 25 mg of psilocybin.
- Masking
- None (open label)
- Enrolment
- 12 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of Virginia
- Sponsor type
- University, hospital or other
- Collaborators
- Tiny Blue Dot Foundation, Texas Tech University
- Responsible party
- Principal investigator, Jennifer Kim Penberthy, University of Virginia
- Investigators
- Jennifer K Penberthy, PhD, Principal investigator, University of Virginia
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06724289
- Sponsor's protocol ID
- HSR231647
- Status last verified
- Jun 2026
- First submitted
- 4 Dec 2024
- Last updated
- 23 Jun 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 23 Jun 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Psilocybin-Assisted Therapy for Prolonged Grief
- ClinicalTrials.gov ID
- NCT06724289
- Acronym / sponsor ID
- HSR231647
- Conditions
- Prolonged Grief Disorder
- Keywords
- prolonged grief disorder, psilocybin, psychedlic-assisted treatment, psilocybin-assisted therapy, grief, grief disorder
- Phase
- Early Phase 1
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 12 participants (estimated)
- Lead sponsor
- University of VirginiaUniversity, hospital or other
- Collaborators
- Tiny Blue Dot Foundation, Texas Tech University
- Study start
- 24 Mar 2026 (actual)
- Primary completion
- Aug 2027 (estimated)
- Study completion
- Aug 2027 (estimated)
- First posted
- 9 Dec 2024 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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).
Detailed description
The study aims to investigate whether a single dose of 25 mg psilocybin can reduce the symptoms of grief and trauma associated with Prolonged Grief Disorder (PGD). It is hypothesized that psilocybin will significantly reduce the symptoms of PGD, and that the treatment will facilitate subjective mystical, spiritual, or insightful experiences, which in turn may contribute to the alleviation of grief and trauma symptoms. Neuroimaging will be used to help researchers better understand the relationship between grief and brain functions, comparing pre- and post-dose scans. Participants will undergo two MRI (magnetic resonance imaging) where they are asked to look at images (this is called a functional MRI or fMRI).
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- All eligible participants will receive 25 mg of psilocybin.
| Arm | Type | Receives |
|---|---|---|
| Open-label, single arm trial | Experimental | Drug: Psilocybin 25 mg, Diagnostic Test: Functional Magnetic Resonance Imaging (fMRI)25 mg psilocybin administered to each participant |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (19 listed)
- 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
Key exclusion criteria (28 listed)
- Previous use of a psychedelic drug may be exclusionary depending on frequency, context, and participant safety as determined by the PI or designate.
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Psilocybin 25 mg25 mg psilocybin administered to each participant in single arm, open-label trial | Drug | Open-label, single arm trial |
| Functional Magnetic Resonance Imaging (fMRI)There are two "fMRIs" (functional magnetic resonance imaging) that take place 1-14 days before and 1-14 days after psilocybin administration. | Diagnostic test | Open-label, single arm trial |
Primary outcome
Recruitment Rate
Time frame: Through end of enrollment period
Number of participants enrolled divided by number screened over the recruitment period.
Dropout Rate
Time frame: Baseline to 6-month Follow-up
Proportion of enrolled participants who withdraw or are lost to follow-up prior to completing the 6-month assessment.
11 secondary outcomes
Change in Prolonged Grief Disorder Symptoms (ICG)
Time frame: Baseline (Visit 0 - Screening) to 6-month Follow-up
Change in PTSD Symptoms (DTS)
Time frame: Baseline (Visit 0 Screening) to 6-month Follow-up
Mystical Experience (MEQ)
Time frame: Baseline (Visit 3 - Treatment Visit) to 6-month Follow-up
Altered States of Consciousness (5-D ASC)
Time frame: Baseline (Visit 3 - Treatment Visit) to 6-month Follow-up
Awe Experience (AWE-S)
Time frame: Baseline (Visit 3 - Treatment Visit) to 6-month Follow-up
Challenging Experiences (CEQ)
Time frame: Baseline (Visit 3 - Treatment Visit) to 6-month Follow-up
Psychological Flexibility (AAQ-II)
Time frame: Baseline (Visit 2 - Preparation for Treatment) to 6-month Follow-up
Closeness to Others (IOS)
Time frame: Baseline (Visit 0 - Screening) to 6-month Follow-up
Meaning in Life (MIL)
Time frame: Baseline (Visit 2 - Preparation for Treatment) to 6-month Follow-up
Psychological Insight (PIQ)
Time frame: Baseline (Visit 3 - Treatment Visit) to 6-month Follow-up
Personality Traits (NEO-FFI)
Time frame: Baseline (Visit 2 - Preparation for Treatment) to 6-month Follow-up
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 23 Jun 2026.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Madison Focht contact
Jennifer K Penberthy, PhD principal investigator
University of Virginia
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Early Phase 1 study testing Psilocybin 25 mg and Functional Magnetic Resonance Imaging (fMRI) in people with Prolonged Grief Disorder, run by University of Virginia at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 19 inclusion and 28 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 23 Jun 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Early Phase 1 (sometimes called Phase 0) studies give a very small amount of a treatment to a few people, mainly to see how the body handles it.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Fatma Wise, PhD ((434) 243-0568, uvagrieftrial@uvahealth.org), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Recruitment Rate (time frame: Through end of enrollment period). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 23 Jun 2026.