Psilocybin for Prolonged Grief Disorder

Overseen By Tamika Braveheart, Registered Nurse

Age: 18+

Sex: Any

Trial Phase: Phase < 1

Sponsor: University of Virginia

Must be taking: Antidepressants

Must not be taking: Benzodiazepines, Opioids, MAOIs, others

Disqualifiers: Cardiovascular conditions, Type 1 diabetes, Severe psychiatric disorder, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 7

Duration: 1 day

12 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

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).

Do I need to stop taking my current medications for the trial?

You may need to stop taking certain medications for this trial. Participants must refrain from taking nonprescription medications, nutritional supplements, or herbal supplements for one week before each drug session, unless approved by the study investigators. Additionally, you cannot take muscle relaxers, antihistamines, or medications that cause lethargy or impair cognitive ability within one day prior to the psilocybin session.

Is psilocybin generally safe for human use?

Psilocybin, found in certain mushrooms, can cause rapid effects on the brain, leading to hallucinations and other symptoms like ataxia (loss of control of body movements) and hyperkinesis (increased movement). While some adverse reactions have been reported, such as vomiting and increased heart rate, these are often manageable with supportive care. ^{1 2 3 4 5}

How is the drug psilocybin unique in treating prolonged grief disorder?

Psilocybin is unique because it works by affecting serotonin receptors in the brain, which can lead to psychedelic experiences that may help with emotional processing. Unlike traditional treatments, psilocybin can show long-term improvements after just one or a few sessions, and it is being explored for its potential to treat various psychiatric disorders with limited side effects. ^{3 4 6 7 8}

What data supports the effectiveness of the drug psilocybin for treating prolonged grief disorder?

Research shows that psilocybin has been studied in clinical trials for various psychiatric disorders, including depression and anxiety, with patients often experiencing significant improvements after treatment. Although more research is needed, these findings suggest potential benefits for other conditions like prolonged grief disorder. ^{6 8 9 10 11}

Who Is on the Research Team?

Jennifer K Penberthy, PhD

Principal Investigator

University of Virginia

Are You a Good Fit for This Trial?

Adults aged 21-65 with Prolonged Grief Disorder, who speak English, can avoid psychoactive drugs and caffeine before sessions, use effective birth control if applicable, have low suicide risk, are stable on certain antidepressants for two months prior to the trial, and have limited hallucinogen use. Excludes pregnant or nursing individuals, those with significant medical conditions or psychiatric disorders like schizophrenia or bipolar I disorder.

Inclusion Criteria

I am between 21 and 65 years old.

Participant must agree to taper or not consume caffeine on the day of intervention

Fluent in English

Exclusion Criteria

Person who is pregnant, nursing, or planning to get pregnant determined at screening and before drug session by urine test or self-report

BMI <18

History of claustrophobia

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Preparation

Participants undergo a preparation session before receiving psilocybin

1 week

Treatment

Participants receive a single dose of 25 mg psilocybin

1 day

1 visit (in-person)

Integration

Two semi-structured integration sessions to process the psilocybin experience

2 weeks

2 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

6 months

4 visits (in-person)

What Are the Treatments Tested in This Trial?

Interventions

• Psilocybin

Trial Overview The study is testing a single dose of Psilocybin (25 mg) to see if it's feasible as a treatment for Prolonged Grief Disorder. Participants will be observed in a controlled setting during the drug session which lasts up to 10 hours.

How Is the Trial Designed?

Group I: Open-label, single arm trial Experimental Treatment 1 Intervention

25 mg psilocybin administered to each participant

Psilocybin is already approved in United States, European Union for the following indications:

Approved in United States as Psilocybin for:

• Treatment-resistant depression (TRD) under Breakthrough Therapy designation

Approved in European Union as Psilocybin for:

• Treatment-resistant depression (TRD) under PRIME designation

Who Is Running the Clinical Trial?

University of Virginia

Lead Sponsor

Trials

802

Recruited

1,342,000+

Published Research Related to This Trial

Psilocybin shows promising effects in alleviating anxiety, depression, and emotional distress in palliative care patients, with a favorable safety profile, based on recent studies and reports.

Despite its potential benefits, psilocybin is not yet approved for therapeutic use in the U.S., and significant barriers exist for access, particularly for vulnerable populations like the elderly and those in palliative care.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Psilocybin in Palliative Care: An Update. Whinkin, E., Opalka, M., Watters, C., et al.[2023]

Psilocybin, a serotonergic psychedelic, has shown promise in treating various psychiatric disorders, including depression and substance use disorders, with 9 clinical trials conducted between 2000 and 2020.

The treatment is generally well tolerated with limited side effects, and some patients with treatment-resistant conditions have experienced significant long-term improvements after just a few sessions, indicating its potential efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Treatment with psilocybin: applications for patients with psychiatric disorders]. Breeksema, JJ., Koolen, MHB., Somers, M., et al.[2021]

A meta-analysis of psilocybin studies found that higher doses of psilocybin are associated with stronger subjective experiences, particularly in areas like perceptual alterations and ego dissolution, based on data from standardized questionnaires.

Challenging experiences were less affected by dose, suggesting that individual and environmental factors also play a significant role in the psilocybin experience, indicating that these findings are most relevant in controlled settings rather than recreational use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dose-response relationships of psilocybin-induced subjective experiences in humans. Hirschfeld, T., Schmidt, TT.[2022]

This study found that the binding of serotonin 2A receptors (5-HT2AR) in the brain can predict how long the peak effects of psilocybin last and how quickly individuals return to normal consciousness after its effects wear off.

Higher levels of 5-HT2AR binding were associated with lower scores on the Mystical Experience Questionnaire, suggesting that individual differences in receptor availability may influence the subjective experience of psilocybin, which could have implications for its therapeutic use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Brain serotonin 2A receptor binding predicts subjective temporal and mystical effects of psilocybin in healthy humans. Stenbæk, DS., Madsen, MK., Ozenne, B., et al.[2022]

Psilocybin-containing mushrooms, commonly known as hallucinogenic or 'magic' mushrooms, rapidly affect the central nervous system within 0.5-1 hour of ingestion, leading to effects such as ataxia, hyperkinesis, and hallucinations.

The review discusses the significant toxicity associated with these mushrooms, highlighting the need for awareness and understanding of their pharmacology, clinical effects, and potential treatment for adverse reactions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Hallucinogenic mushrooms]. Reingardiene, D., Vilcinskaite, J., Lazauskas, R.[2018]

A 30-year-old man experienced severe symptoms, including vomiting and muscle pain, after receiving an intravenous injection of Psilocybe mushroom extract, highlighting the potential dangers of using hallucinogenic substances in non-traditional ways.

The patient showed rapid improvement with supportive care, suggesting that while the effects of Psilocybe mushrooms can be serious, timely medical intervention can effectively manage the symptoms.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intravenous mushroom poisoning. Curry, SC., Rose, MC.[2019]

Psilocybin, a prodrug for psilocin, shows strong agonist activity at the serotonin 5-HT2A receptor, which is responsible for its psychedelic effects, and has been shown to have nanomolar affinity for various serotonin receptor subtypes in both in vitro and in vivo studies.

In mouse experiments, psilocybin and related compounds induced head twitch responses, a sign of psychedelic activity, which were blocked by a 5-HT2A antagonist, confirming the involvement of this receptor in their effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Structure-Activity Relationships for Psilocybin, Baeocystin, Aeruginascin, and Related Analogues to Produce Pharmacological Effects in Mice. Glatfelter, GC., Pottie, E., Partilla, JS., et al.[2023]

Psilocybin, a hallucinogenic compound found in certain mushrooms, has been associated with increasing rates of drug abuse, highlighting the need for comprehensive pharmacological understanding.

Despite its historical use in the 1960s for experimental medical purposes, recent research has only begun to uncover the pharmacological properties of psilocybin, indicating a gap in knowledge that needs to be addressed.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The pharmacology of psilocybin. Passie, T., Seifert, J., Schneider, U., et al.[2016]

This study identified phenylethylamine in Psilocybe semilanceata mushrooms, which may contribute to adverse reactions during psilocybin intoxication, as evidenced by a case involving three young men who experienced severe symptoms.

The levels of phenylethylamine in these mushrooms can vary significantly, with the highest concentration found in the case of hospitalization, suggesting that this compound could play a role in the tachycardia and other symptoms not directly linked to psilocybin.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Presence of phenylethylamine in hallucinogenic Psilocybe mushroom: possible role in adverse reactions. Beck, O., Helander, A., Karlson-Stiber, C., et al.[2019]

The study developed highly sensitive and accurate methods using liquid chromatography-mass spectrometry (LC-MS) and tandem mass spectrometry (LC-MS-MS) to effectively distinguish between psilocin and psilocybin, two active compounds in magic mushrooms.

Detection limits for these compounds were extremely low, ranging from 1 to 25 picograms, and the methods demonstrated high precision with low variability, making them suitable for analyzing psilocin and psilocybin content in various samples.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Liquid chromatography-mass spectrometric and liquid chromatography-tandem mass spectrometric determination of hallucinogenic indoles psilocin and psilocybin in "magic mushroom" samples. Kamata, T., Nishikawa, M., Katagi, M., et al.[2016]

Citations

1. United States pubmed.ncbi.nlm.nih.gov

Psilocybin in Palliative Care: An Update. [2023]

2. Netherlands pubmed.ncbi.nlm.nih.gov

[Treatment with psilocybin: applications for patients with psychiatric disorders]. [2021]

3. United States pubmed.ncbi.nlm.nih.gov

Dose-response relationships of psilocybin-induced subjective experiences in humans. [2022]

4. United States pubmed.ncbi.nlm.nih.gov

Brain serotonin 2A receptor binding predicts subjective temporal and mystical effects of psilocybin in healthy humans. [2022]

5. United States pubmed.ncbi.nlm.nih.gov

Systematized Review of Psychotherapeutic Components of Psilocybin-Assisted Psychotherapy. [2022]

6. Switzerland pubmed.ncbi.nlm.nih.gov

[Hallucinogenic mushrooms]. [2018]

7. United States pubmed.ncbi.nlm.nih.gov

Intravenous mushroom poisoning. [2019]

8. United States pubmed.ncbi.nlm.nih.gov

Structure-Activity Relationships for Psilocybin, Baeocystin, Aeruginascin, and Related Analogues to Produce Pharmacological Effects in Mice. [2023]

9. United States pubmed.ncbi.nlm.nih.gov

The pharmacology of psilocybin. [2016]

10. England pubmed.ncbi.nlm.nih.gov

Presence of phenylethylamine in hallucinogenic Psilocybe mushroom: possible role in adverse reactions. [2019]

11. United States pubmed.ncbi.nlm.nih.gov

Liquid chromatography-mass spectrometric and liquid chromatography-tandem mass spectrometric determination of hallucinogenic indoles psilocin and psilocybin in "magic mushroom" samples. [2016]