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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to test whether psilocybin-assisted therapy, using a psychedelic compound, can safely and effectively reduce symptoms in people with persistent post-concussion symptoms (PPCS). Participants will receive either a high or low dose of psilocybin, followed by therapy sessions. The trial targets individuals who have experienced ongoing symptoms for at least three months after a concussion. It may suit those who have struggled with these symptoms for a while and have not used many hallucinogens before. As a Phase 1 trial, this research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this innovative therapy.

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.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that psilocybin is generally safe for study participants. In one study, participants took a single 25 mg dose of psilocybin without experiencing any serious side effects. Another study found that a single psilocybin session with support was well-tolerated. Some mild or moderate effects, such as nausea or headaches, have been noted, but these are not serious.

Psilocybin has been tested for conditions like treatment-resistant depression, and safety reviews did not find any unexpected problems. This suggests that while some side effects might occur, psilocybin is considered safe enough for further testing in humans. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Researchers are excited about using psilocybin for post-concussion syndrome because it offers a novel approach compared to standard treatments like rest, physical therapy, and medications for symptom management. Psilocybin is unique because it acts on serotonin receptors in the brain, potentially promoting neural plasticity and healing. While traditional treatments often focus on alleviating symptoms, psilocybin may address underlying neurological changes, offering a more comprehensive recovery pathway. Additionally, the use of a single dose could mean quicker, more efficient results, making it a promising option for those seeking relief from persistent post-concussion symptoms.

What evidence suggests that psilocybin might be an effective treatment for post-concussion syndrome?

This trial will compare the effects of different doses of psilocybin on post-concussion syndrome. Research suggests that psilocybin might alleviate symptoms of this condition. Studies have shown that psilocybin can reduce brain swelling and enhance brain function. One case study highlighted its potential to aid athletes with persistent concussion symptoms. Psilocybin could restore normal brain activity and improve both mental and physical well-being. Although more research is necessary, these early findings suggest that psilocybin could be a promising treatment option. ^{6 7 8 9 10}

Who Is on the Research Team?

Chantel T Debert, MD MSc FRCPC CSCN

Principal Investigator

University of Calgary

Are You a Good Fit for This Trial?

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

Ability to read/write English

I have rarely used drugs like LSD or magic mushrooms.

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

Exclusion Criteria

Active suicidal ideation or serious attempt within the past 1 year

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

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

Timeline for a Trial Participant

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)

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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 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-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 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]

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 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]

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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11838531/

Psilocybin as a Treatment for Repetitive Mild Head Injury We provide unprecedented data that psilocybin can reduce vasogenic edema, restore normal vascular reactivity and functional connectivity.

2. mdpi.com mdpi.com/2813-1851/4/3/22

Psilocybin Use in an Intercollegiate Athlete with Persisting ... This case highlights the potential role of classic psychedelics as adjuvant agents in treating persisting symptoms after concussion.

3. concussionalliance.org concussionalliance.org/newsletter/2021/7/15/psilocybin-for-tbi-researchers-hope-to-improve-lives

Psilocybin for TBI–researchers hope to improve lives (7/15/ ... This study aims to produce measurable outcomes regarding both the psychological and physiological effects of psilocybin in TBI treatment.

4. withpower.com withpower.com/trial/phase-1-post-concussion-syndrome-9-2024-40032

Psilocybin for Post-Concussion Syndrome (PatACT Trial) 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.

5. clinicaltrials.gov clinicaltrials.gov/ct2/show/NCT03806985?term=psilocybin+va&draw=2&rank=3

Effects of Psilocybin in Concussion Headache The purpose of this study is to investigate the effects of oral psilocybin in post-traumatic headache. Subjects will be randomized to receive placebo, ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT05312151

NCT05312151 | The Safety and Tolerability of COMP360 in ... Study Details | NCT05312151 | The Safety and Tolerability of COMP360 in Participants With Post-traumatic Stress Disorder | ClinicalTrials.gov.

7. ir.compasspathways.com ir.compasspathways.com/News--Events-/news/news-details/2025/Compass-Pathways-Announces-Publication-of-Results-from-Phase-2-Study-of-COMP360-Psilocybin-for-Post-Traumatic-Stress-Disorder/default.aspx

News Details Open-label Phase 2 study shows a single 25 mg COMP360 psilocybin dose was well tolerated, with no serious adverse events observed, ...

8. journals.sagepub.com journals.sagepub.com/doi/10.1177/02698811251362390

Investigating the safety and tolerability of single-dose ... In this trial, COMP360 psilocybin administered in a single session with psychological support was found to be generally well-tolerated and ...

9. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12030455/

The Emergence of Psilocybin in Psychiatry and Neuroscience These findings suggest a general openness within the sports community toward exploring psilocybin as a treatment for persistent post-concussion symptoms (PPCS) ...

10. psychiatrictimes.com psychiatrictimes.com/view/comp360-psilocybin-for-treatment-resistant-depression-positive-phase-3-efficacy-data

COMP360 Psilocybin for Treatment-Resistant Depression Additionally, according to the Independent Data Safety Monitoring Board, who reviewed safety data for COMP360, there were no unexpected safety ...