Psilocybin-Induced Psychedelic Experiences During Sleep

(CoPE Pilot Trial)

Overseen By Project Manager

Age: 18 - 65

Sex: Any

Trial Phase: Phase 1

Sponsor: University of Wisconsin, Madison

Must not be taking: Psilocybin interactors

Disqualifiers: Sleep disorders, Pregnancy, Cardiac valve disease, 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: 2

Duration: Up to 9 days

6 Participants Needed

Trial Summary

What is the purpose of this trial?

This study is being done to identify a dosing strategy that will allow IV psilocybin to be administered to sleeping participants without awakening them.

Will I have to stop taking my current medications?

The trial excludes people who are currently using medications that may interact with psilocybin, so you might need to stop taking certain medications to participate.

What data supports the effectiveness of the drug psilocybin?

Research shows that psilocybin may help reduce symptoms of depression and anxiety, especially in people with cancer-related psychological distress, and has shown promise in treating addiction to alcohol and cigarettes. ^{1 2 3 4 5}

Is psilocybin generally safe for humans?

Psilocybin has been studied for its effects on the brain and body, and while it can cause hallucinations and other effects like increased heart rate, it has shown promise in treating conditions like depression. In a study with healthy adults, different doses were tested, and the safety profile was described, indicating it can be used safely under controlled conditions. ^{1 6 7 8 9}

How does the drug psilocybin differ from other treatments for sleep-related conditions?

Psilocybin is unique because it alters sleep patterns by delaying REM sleep onset and reducing NREM sleep maintenance, which may contribute to its potential antidepressant effects. Unlike traditional sleep medications, psilocybin's effects on sleep are linked to its ability to change consciousness and promote neuroplasticity (the brain's ability to reorganize itself). ^{1 4 10 11 12}

Research Team

Charles Raison, MD

Principal Investigator

University of Wisconsin, Madison

Eligibility Criteria

This trial is for medically healthy, English-speaking individuals. It's not suitable for those on medications that interact with psilocybin, have sleep disorders like insomnia or apnea, are pregnant women at any point during the study, or have a history of heart transplant or stroke.

Inclusion Criteria

English-speaking

Live within 150 miles of Madison, WI for duration of study

Medically healthy

Exclusion Criteria

I am not pregnant.

I have a heart valve problem.

I have a sleep disorder such as insomnia, sleep apnea, restless legs syndrome, or narcolepsy.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive IV psilocybin with or without clonidine, with dosing protocols tested in both asleep and awake states

Up to 9 days

Multiple visits with at least 2 weeks between dosing sessions

Follow-up

Participants are monitored for safety and effectiveness after treatment, including psychosocial support through integration sessions

Up to 19 days

Treatment Details

Interventions

• Psilocybin
• Saline

Trial Overview The study tests intravenous (IV) psilocybin administration in sleeping participants to find a dose that doesn't wake them and to see if it induces psychedelic experiences. A saline solution is used as a comparison.

Participant Groups

Group I: Initial Groups 1A and 2A Experimental Treatment 2 Interventions

Participants will receive 2mg of IV psilocybin over 2 minutes or 10 minutes while asleep during an overnight visit and 10 mL of placebo (saline) over 2 minutes or 10 minutes while asleep during another overnight visit. The order of administration will be determined by the study protocol.

Group II: Group 2B: 10-minute IV Psilocybin+Clonidine in Awake Participants Experimental Treatment 2 Interventions

If Group 2A participants can sleep 1 hour post-dosing and/or have no memory of dosing, Group 2B moves forward and participants will receive 0.2 mg clonidine and 2 mg of IV psilocybin over 10 minutes while awake.

Group III: Group 2A: 2-minute IV Psilocybin+Clonidine / Saline in Asleep Participants Experimental Treatment 3 Interventions

If Group 1A participants fail to sleep 1 hour post-dose, Group 2A moves forward. Participants will receive 10 mL of placebo (saline) over 10 minutes while asleep during their first overnight visit. Participants will receive 0.2 mg oral clonidine and either 2 mg of IV psilocybin or saline over 10 minutes while asleep during their second overnight visit.

Group IV: Group 1B: 2-minute IV Psilocybin+Clonidine Infusion in Awake Participants Experimental Treatment 2 Interventions

If Group 1A participants can sleep 1 hour post-dosing and/or have no memory of dosing, Group 1B moves forward and participants will receive 0.2 mg clonidine and 2 mg of IV psilocybin over 2 minutes while awake.

Group V: Group 1A: 2-minute IV Psilocybin+Clonidine / Saline in Asleep Participants Experimental Treatment 3 Interventions

Participants will receive 10 mL of placebo (saline) over 2 minutes while asleep during their first overnight visit. Participants will receive 0.2 mg oral clonidine and either 2 mg of IV psilocybin or saline over 2 minutes while asleep during their second overnight visit.

Group VI: Group 2C: 10-minute IV Psilocybin Alone in Awake Participants Active Control 1 Intervention

If Group 2A allows for sleep 1 hour post dose, Group 2C will move forward and participants will receive 2mg of IV psilocybin over 10 minutes while awake for comparison.

Group VII: Group 1C: 2-minute IV Psilocybin Alone in Awake Participants Active Control 1 Intervention

If Group 1A allows for sleep 1 hour post dose, Group 1C will move forward and participants will receive 2mg of IV psilocybin over 2 minutes while awake for comparison.

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 Wisconsin, Madison

Lead Sponsor

Trials

1,249

Recruited

3,255,000+

Tiny Blue Dot Foundation

Collaborator

Trials

10

Recruited

660+

Usona Institute

Collaborator

Trials

18

Recruited

1,100+

Tiny Blue Dot Foundation

Collaborator

Trials

9

Recruited

640+

Findings from Research

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]

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 has shown promise in reducing symptoms of depression and anxiety, particularly in cancer patients, with effects lasting for at least six months after a single treatment, based on three controlled studies.

In small pilot studies, psilocybin has also demonstrated potential effectiveness in treating addiction to alcohol and cigarettes, suggesting its versatility as a therapeutic agent.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Potential Therapeutic Effects of Psilocybin: A Systematic Review. Goel, DB., Zilate, S.[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]

In a study of 27 patients with moderate to severe major depressive disorder, psilocybin-assisted treatment showed significant and lasting antidepressant effects, with 75% of participants experiencing a treatment response and 58% achieving remission after 12 months.

There were no serious adverse events related to psilocybin, indicating a favorable safety profile, and participants reported meaningful personal and spiritual experiences that correlated with increased well-being, although these did not directly predict improvements in depression.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of psilocybin-assisted treatment for major depressive disorder: Prospective 12-month follow-up. Gukasyan, N., Davis, AK., Barrett, FS., et al.[2022]

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]

In a study involving 12 healthy adults, escalating doses of psilocybin (0.3, 0.45, and 0.6 mg/kg) were administered safely, with no serious adverse events reported, indicating a favorable safety profile for this psychedelic compound.

The pharmacokinetics of psilocin, the active metabolite of psilocybin, were linear across the tested doses, with an elimination half-life of about 3 hours, suggesting that no dose adjustments are necessary for individuals with mild to moderate renal impairment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacokinetics of Escalating Doses of Oral Psilocybin in Healthy Adults. Brown, RT., Nicholas, CR., Cozzi, NV., et al.[2022]

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]

In a case study involving 'magic mushroom' intake, psilocin was detected in urine, primarily in its glucuronide form, indicating that enzymatic hydrolysis is essential for accurate analysis.

The study established a reliable GC-MS method for detecting psilocin, revealing that most of the psilocin in serum was also conjugated, with very low concentrations of free psilocin found in both urine and serum.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Detection of psilocin in body fluids. Sticht, G., Käferstein, H.[2019]

References

1. Switzerland pubmed.ncbi.nlm.nih.gov

[Hallucinogenic mushrooms]. [2018]

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

Psilocybin in Palliative Care: An Update. [2023]

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

Potential Therapeutic Effects of Psilocybin: A Systematic Review. [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

Efficacy and safety of psilocybin-assisted treatment for major depressive disorder: Prospective 12-month follow-up. [2022]

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

Intravenous mushroom poisoning. [2019]

7. Switzerland pubmed.ncbi.nlm.nih.gov

Pharmacokinetics of Escalating Doses of Oral Psilocybin in Healthy Adults. [2022]

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

The pharmacology of psilocybin. [2016]

9. England pubmed.ncbi.nlm.nih.gov

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

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

Psilocin acutely alters sleep-wake architecture and cortical brain activity in laboratory mice. [2022]

11. Switzerland pubmed.ncbi.nlm.nih.gov

The Effects of Daytime Psilocybin Administration on Sleep: Implications for Antidepressant Action. [2021]

12. Ireland pubmed.ncbi.nlm.nih.gov

Detection of psilocin in body fluids. [2019]