Psilocybin for Post-Concussion Syndrome

(PatACT Trial)

Overseen By Chantel T Debert, MD MSc FRCPC

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: University of Calgary

Disqualifiers: Substance use disorder, Schizophrenia, Bipolar, Epilepsy, 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: 12

40 Participants Needed

Trial Summary

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

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

What data supports the effectiveness of the drug psilocybin for treating post-concussion syndrome?

Psilocybin has shown promise in recent clinical trials for treating depression and substance use disorders, suggesting potential benefits for other conditions. However, specific data on its effectiveness for post-concussion syndrome is not available in the provided research. ^{1 2 3 4 5}

Is psilocybin generally safe for human use?

Psilocybin has been studied in healthy adults with escalating doses, showing a safety profile that is generally well-tolerated. However, adverse reactions such as hallucinations, ataxia (loss of control of body movements), and tachycardia (fast heart rate) have been reported, especially when mushrooms are used recreationally. Supportive care can help manage these symptoms if they occur. ^{1 2 5 6 7}

How is the drug psilocybin unique in treating post-concussion syndrome?

Psilocybin is unique because it is a psychedelic compound that has shown promise in treating various psychiatric disorders by potentially altering brain function and perception, which is different from traditional treatments for post-concussion syndrome that typically focus on symptom management. It is being explored for its ability to provide long-term improvements after just one or a few sessions, unlike many standard treatments that require ongoing use. ^{1 3 5 8 9}

What is the purpose of this trial?

The goal of this randomized controlled trial is to evaluate the safety, feasibility, and efficacy of psilocybin assisted therapy as an intervention to reduce symptom burden in adult patients (aged 18-65) with persistent post-concussion symptoms (PPCS). This trail will test the following 2 aims: AIM 1 : To test the safety and feasibility of an active psilocybin-assisted psychotherapy to an active control for patients with PPCS AIM 2: To evaluate the efficacy of an active psilocybin-assisted psychotherapy compared to an active control as a treatment for PPCS Participants will be asked to: * Complete a 2 part screening process * Attend a baseline assessment * Complete a psychoeducation preparation session(s) * Attend psilocybin administration session (receive high dose \[25mg\] or low dose psilocybin \[1mg\]) * Complete 5-6 weekly sessions of Acceptance and commitment therapy (ACT) * Repeat outcome measures at 1-week, 4 weeks, 3 months, and 6 months post-psilocybin administration (online only at 6 months).

Research Team

Chantel T Debert, MD MSc FRCPC CSCN

Principal Investigator

University of Calgary

Eligibility Criteria

Adults aged 18-65 with persistent post-concussion symptoms can join this trial. They must complete a two-part screening, attend assessments and therapy sessions, and be available for follow-ups up to six months after treatment. Those with certain health conditions or who cannot commit to the study schedule are excluded.

Inclusion Criteria

I have rarely used drugs like LSD or magic mushrooms.

Ability to read/write English

My symptom severity score is 13 or higher with at least 3 symptoms rated 3 or more.

Exclusion Criteria

I or a close family member have been diagnosed with schizophrenia or bipolar disorder.

Active suicidal ideation or serious attempt within the past 1 year

Current or recent (within 12 weeks) participation in a clinical trial

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

2 visits (in-person)

Baseline Assessment

Participants attend a baseline assessment and complete a psychoeducation preparation session

1 week

1 visit (in-person)

Psilocybin Administration

Participants receive a single dose of psilocybin (high dose 25mg or low dose 1mg) followed by Acceptance and Commitment Therapy (ACT) sessions

5-6 weeks

5-6 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment with outcome measures repeated at 1-week, 4 weeks, 3 months, and 6 months post-dosing

6 months

4 visits (virtual)

Treatment Details

Interventions

• Psilocybin

Trial Overview The trial is testing psilocybin-assisted therapy's safety and effectiveness in treating long-lasting symptoms after a concussion. Participants will receive either a high dose (25mg) or low dose (1mg) of psilocybin during one session, followed by weekly psychotherapy sessions.

Participant Groups

Group I: High dose (25mg) Experimental Treatment 1 Intervention

High Dose (25mg) PEX010 (Oral Psilocybin), 25mg; single dose (20 participants) administered 24hrs prior to first ACT session

Group II: Low dose (1mg) Active Control 1 Intervention

Low Dose (1mg) PEX010 (Oral Psilocybin), 1mg; single dose (20 participants)administered 24hrs prior to first ACT session

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 Calgary

Lead Sponsor

Trials

827

Recruited

902,000+

University of British Columbia

Collaborator

Trials

1,506

Recruited

2,528,000+

Findings from Research

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]

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 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]

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]

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 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]

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]

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]

References

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

The pharmacology of psilocybin. [2016]

2. Switzerland pubmed.ncbi.nlm.nih.gov

[Hallucinogenic mushrooms]. [2018]

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

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

4. England pubmed.ncbi.nlm.nih.gov

Renal excretion profiles of psilocin following oral administration of psilocybin: a controlled study in man. [2019]

5. Switzerland pubmed.ncbi.nlm.nih.gov

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

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

Intravenous mushroom poisoning. [2019]

7. England pubmed.ncbi.nlm.nih.gov

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

8. England pubmed.ncbi.nlm.nih.gov

Magic truffles or Philosopher's stones: a legal way to sell psilocybin? [2019]

9. Netherlands pubmed.ncbi.nlm.nih.gov

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