Psilocybin for Psychedelic Experiences

(i2 Trial)

Overseen By Lorenzo Pasquini, PhD

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Robin Carhart-Harris, PhD, MA

Disqualifiers: Pregnancy, Lactation, Mental illness, 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: 6

Duration: 4-8 weeks

12 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to explore the mental and physical effects experienced during a psychedelic trip using psilocybin, a compound found in magic mushrooms. Researchers will observe the brain's reactions with MRI scans while participants are under the influence of psilocybin. This study will lay the groundwork for future research into potential therapeutic uses of psychedelics. Participants should have prior experience with psychedelic substances and be in good mental and physical health. As a Phase 1 trial, the research focuses on understanding how psilocybin works in people, offering participants the opportunity to be among the first to receive this treatment.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the study team to get a clear answer.

Is there any evidence suggesting that this treatment is likely to be safe for humans?

Research shows that psilocybin, the treatment under study, has been safe in other studies. In one study with a 25 mg dose of psilocybin, participants handled it well, and no serious side effects occurred. Another study on psilocybin for depression also revealed no unexpected safety problems. These results suggest that psilocybin is generally safe for people. However, it's important to note that this trial is in the early stages, so the researchers are primarily focused on understanding the treatment's effects and gathering more safety information. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Unlike standard treatments for mental health conditions, which often include medications like SSRIs or therapy, psilocybin is a psychedelic compound that uniquely targets serotonin receptors in the brain to potentially create profound, transformative experiences. Researchers are excited because psilocybin might work faster than traditional treatments, possibly offering relief after just one or a few sessions. Additionally, its novel mechanism of inducing altered states of consciousness could lead to breakthroughs in understanding and alleviating conditions like depression or anxiety in ways that current medications cannot.

What evidence suggests that psilocybin might be an effective treatment for psychedelic experiences?

Research shows that psilocybin, a substance found in certain mushrooms, can significantly change mood and perception. In earlier studies, psilocybin helped with depression and anxiety by creating deep, meaningful experiences that may change thought patterns. These effects likely occur because psilocybin influences serotonin, a brain chemical affecting mood and perception. While more research is needed to fully understand its potential, early results are promising. Participants in past studies reported feeling happier and less anxious after taking psilocybin. In this trial, healthy volunteers will receive up to four doses of psilocybin to further explore its effects. ^{6 7 8 9 10}

Who Is on the Research Team?

Robin Carhart-Harris, PhD

Principal Investigator

University of California, San Francisco

Are You a Good Fit for This Trial?

This trial is for healthy adults aged 21-70 with prior psychedelic experience, but not more than 500 times. They must be able to swallow pills, use technology for data entry, and speak English fluently. Women of childbearing potential must agree to effective contraception; men also need to practice birth control and not donate sperm during the study.

Inclusion Criteria

Have no more than 500 previous experiences with a psychedelic substance

Agree to inform the investigators within 48 hours of any new or changed medical conditions

If able to become pregnant, must be non-lactating, have a negative pregnancy test at study entry and prior to each Experimental Session and must agree to an adequate form of birth control and contraception over the course of the study

Exclusion Criteria

Current chronic cannabis use

Have used alcohol within 24 hours or other psychoactive drugs within 7 days of an Experimental Session (with the exception of the psilocybin used within this study)

I do not have any serious health conditions that would make me unsuitable for the study.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

1 visit

1 visit (in-person)

Treatment

Participants receive four doses of psilocybin with MRI scanning, with breaks of at least seven days between dosing visits

4-8 weeks

4 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment, including a final remote follow-up

4 weeks

1 visit (remote)

What Are the Treatments Tested in This Trial?

Interventions

• Psilocybin

Trial Overview

The study tests how psilocybin affects mental states and physical reactions using MRI scans in participants who have used psychedelics before. It involves four doses of psilocybin over several weeks, with brain imaging sessions after each dose while answering questions about their experiences.

How Is the Trial Designed?

Group I: Psilocybin Experimental Treatment 1 Intervention

Healthy volunteers will receive up to four doses of psilocybin separated from each other by at least one week. The first dosing session will involve 10 mg psilocybin, the remaining three dosing sessions will receive up to 25mg psilocybin.

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?

Robin Carhart-Harris, PhD, MA

Lead Sponsor

Trials

2

Recruited

130+

Published Research Related to This Trial

In a survey of 1993 individuals who experienced challenging psilocybin trips, 39% rated their experience as one of the most difficult of their lives, with 11% reporting risks of physical harm, particularly influenced by dose and lack of support.

Despite the challenges, 84% of respondents felt they benefited from the experience, suggesting that while adverse effects can occur, the overall incidence of serious psychological distress is low, especially in controlled settings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Survey study of challenging experiences after ingesting psilocybin mushrooms: Acute and enduring positive and negative consequences. Carbonaro, TM., Bradstreet, MP., Barrett, FS., et al.[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]

In a study involving eight volunteers, psilocybin was administered, and its metabolite, psilocin, was found to peak in urine concentrations up to 870 microg/L within 2-4 hours after ingestion, indicating a rapid metabolism.

About 3.4% of the psilocybin dose was excreted as free psilocin within 24 hours, and using beta-glucuronidase to treat urine samples significantly increased detectable levels of psilocin, suggesting that enzymatic processes can enhance the detection of this metabolite.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Renal excretion profiles of psilocin following oral administration of psilocybin: a controlled study in man. Hasler, F., Bourquin, D., Brenneisen, R., et al.[2019]

Psilocybin is primarily a pro-drug that converts to the active compound psilocin in the body, which then interacts with serotonin receptors to produce its hallucinogenic effects.

The metabolism of psilocybin and psilocin varies significantly among individuals, affecting their dose-response and potential toxicity, highlighting the need for personalized approaches in therapeutic settings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Metabolism of psilocybin and psilocin: clinical and forensic toxicological relevance. Dinis-Oliveira, RJ.[2018]

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 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]

In a study analyzing the tryptamine content of freshly cultivated Psilocybe cubensis mushrooms, it was found that the caps contained the highest concentration of psilocybin and psilocin, while the mycelium had a lower concentration and no tryptamines were detected in the basidiospores.

Storage conditions significantly affected the stability of tryptamines, with fresh mushrooms stored at -80°C showing the highest degradation, while dried biomass stored in the dark at room temperature maintained the tryptamine levels better.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Stability of psilocybin and its four analogs in the biomass of the psychotropic mushroom Psilocybe cubensis. Gotvaldová, K., Hájková, K., Borovička, J., et al.[2021]

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]

There is a growing trend among young people to consume wild Psilocybin mushrooms for their hallucinogenic effects, but this practice carries risks.

The report highlights seven cases of mushroom overdosage, stressing that while Psilocybin mushrooms are generally considered harmless, there is a significant danger of accidentally consuming toxic mushroom species that can cause serious harm.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The danger of hallucinogenic mushrooms. Mills, PR., Lesinskas, D., Watkinson, G.[2017]

A new liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was developed to quickly and accurately measure the levels of psilocybin and psilocin in magic truffles, with high precision and reliability (r² > 0.99).

The study found that only psilocybin was present in the examined Psilocybe sclerotia, with concentrations ranging from 59.3 to 167.8 µg per 100 mg of fresh truffles, indicating variability in psilocybin content.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Magic truffles or Philosopher's stones: a legal way to sell psilocybin? Pellegrini, M., Rotolo, MC., Marchei, E., et al.[2019]

The study successfully utilized GLC-mass spectrometry to analyze psilocin and psilocybin, two hallucinogenic compounds, by converting them into trimethylsilyl derivatives for better detection.

This method was specifically applied to an extract of the Psilocybe cubensis mushroom, indicating its potential for accurately identifying and quantifying these psychoactive substances in natural samples.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

GLC-mass spectral analysis of psilocin and psilocybin. Repke, DB., Leslie, DT., Mandell, DM., et al.[2019]

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]

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]

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Psilocybin | C12H17N2O4P | CID 10624 - PubChem - NIH

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Psilocybine - the NIST WebBook

Formula · C12H17N2O4P ; Molecular weight · 284.2481 ; Permanent link for this species. Use this link for bookmarking this species for future reference.

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COMP360 Psilocybin for Treatment-Resistant Depression

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News Details

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