Psilocybin for PTSD

Overseen By William J Fleming, BA

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Halucenex Life Sciences Inc.

Must be taking: SSRIs, SNRIs

Must not be taking: Methamphetamines, Hallucinogens

Disqualifiers: Uncontrolled hypertension, Substance abuse, Schizophrenia, Bipolar, others

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

Prior Safety Data This treatment has passed at least one previous human trial

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

Compensation: Varies

Number of Visits: 2

Duration: 2 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests psilocybin, a psychedelic medication, to determine its effectiveness for individuals with treatment-resistant PTSD (post-traumatic stress disorder). PTSD can lead to anxiety, flashbacks, and avoidance behaviors, and it remains challenging to treat with only two approved medications available. Participants will receive varying doses of psilocybin to assess its impact on their PTSD symptoms. Suitable candidates for this trial have PTSD that has not improved after trying other treatments, such as medication and therapy. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group of participants.

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. However, it mentions that participants must have treatment-resistant PTSD despite prior SSRI or SNRI treatment, which suggests you may need to continue these medications. It's best to discuss this with the trial staff.

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

Research has shown that psilocybin is usually well-tolerated. In one study, a single 25 mg dose of psilocybin caused no serious side effects. Another study found psilocybin safe when used with psychological support. These studies suggest psilocybin could be a safe option for treating PTSD. However, like any treatment, it may cause side effects, which can vary among individuals. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for PTSD?

Unlike traditional treatments for PTSD, which often include therapy and medications like SSRIs or SNRIs, psilocybin offers a unique approach by targeting serotonin receptors in the brain. Researchers are excited about psilocybin because it has the potential to promote neural plasticity, which may help patients process traumatic memories more effectively. Additionally, psilocybin may produce rapid effects after just a few doses, providing relief much faster than conventional treatments that can take weeks or months to show results.

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

Research has shown that psilocybin, a type of psychedelic drug, might help with PTSD (post-traumatic stress disorder). An earlier study found that a single 25 mg dose of psilocybin was safe for participants and did not cause serious side effects. Participants who took psilocybin showed improvements in PTSD symptoms, quality of life, and daily activities. In this trial, participants will receive psilocybin in varying doses, including a 10 mg low dose and a 25 mg high dose, to evaluate its effectiveness for treatment-resistant PTSD. Psilocybin may help by improving emotional processing, assisting people in facing and dealing with traumatic memories. This evidence suggests that psilocybin could be effective for treating PTSD, especially when other treatments have not worked. ^{1 2 3 5 6}

Who Is on the Research Team?

Lisa Batten, PhD

Principal Investigator

Halucenex Life Sciences

Paige Stevens, MD

Principal Investigator

Contracted

Are You a Good Fit for This Trial?

This trial is for adults aged 18-70 with treatment-resistant PTSD, having moderate to severe symptoms despite at least 3 months of SSRI or SNRI treatment and 4 months of psychotherapy. Participants must understand English. Excluded are those with certain psychiatric disorders, uncontrolled medical conditions, recent substance abuse, high caffeine intake, or who are pregnant without using contraception.

Inclusion Criteria

Subjects must meet the following criteria to be eligible for enrollment into the study.

Subjects must have treatment-resistant PTSD symptoms, defined as a CAPS score of ≥50 (signifying moderate to severe symptoms) following at least 3 months of prior SSRI or SNRI treatment in addition to at least 4 months of psychotherapy.

After signing and dating the informed consent documents, subject eligibility will be assessed. Subjects must meet the following criteria to be eligible for enrollment into the study.

Exclusion Criteria

You have a substance use disorder that could affect the goals of the study, such as drinking more than 5 cups of coffee with caffeine each day, being unable to go without smoking cigarettes or cannabis without feeling uncomfortable, or drinking alcohol within 7 hours before the study.

You are afraid or uncomfortable with having blood drawn or getting injections with needles.

You have been diagnosed with a personality disorder that significantly affects your mental health.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive psilocybin treatment with doses administered on Day 7 and Day 14

2 weeks

2 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

12 months

Optional Extension

Participants may receive an optional low dose of psilocybin at Month 7

Long-term

What Are the Treatments Tested in This Trial?

Interventions

• Psilocybin

Trial Overview The study tests the effects of psilocybin on individuals with PTSD that hasn't improved after standard treatments. It aims to see if psilocybin can alleviate PTSD symptoms when traditional medications like paroxetine and sertraline have failed.

How Is the Trial Designed?

Group I: Psilocybin treatment for treatment-resistant PTSD Experimental Treatment 1 Intervention

Experimental Treatment: Experimental: Psilocybin 10mg (low dose) on Day 7 25mg (high dose) on Day 14 10mg dose (optional top-up low dose) at Month 7 Treatment Description: Drug: Psilocybin drug product suspension Psilocybin is manufactured as a bulk API powder. The psilocybin drug product suspension is prepared by a compounding pharmacist at the clinic site. The psilocybin drug product suspension will be mixed in a glass with water to produce the psilocybin solution for oral consumption. Subjects will be instructed to orally consume the study medication in the glass in its entirety. Psilocybin will be administered in the following doses and at the following time points for this study: * 1 mL of 10mg/mL (low dose) on Day 7 (10 mg) * 2.5 mL of 10 mg/mL (high dose) on Day 14 (25 mg) * \[Optional dose\] 1 mL of 10mg/mL (low dose) on Month 7/Day 210 (10 mg)

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?

Halucenex Life Sciences Inc.

Lead Sponsor

Trials

1

Recruited

20+

Everest Clinical Research

Collaborator

Trials

2

Recruited

300+

KGK Science Inc.

Industry Sponsor

Trials

82

Recruited

6,400+

Najla Guthrie

KGK Science Inc.

Chief Executive Officer since 1997

Research career at the Centre for Human Nutrition, University of Western Ontario

Dr. Bibiane Zakaria

KGK Science Inc.

Chief Medical Officer since 2023

MD from an unspecified institution

Published Research Related to This Trial

A single dose of psilocybin (0.5-20 mg/kg) significantly increases the expression of genes related to neuroplasticity in the prefrontal cortex and hippocampus, suggesting its potential therapeutic effects for mental health disorders.

The study highlights that psilocybin's effects on gene expression are dose-dependent and predominantly observed in the prefrontal cortex, emphasizing the need to assess both gene expression and protein translation to understand its rapid effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Transcriptional regulation in the rat prefrontal cortex and hippocampus after a single administration of psilocybin. Jefsen, OH., Elfving, B., Wegener, G., et al.[2022]

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 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 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]

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]

A single dose of psilocybin significantly reduced fear responses in mice, indicating its potential to facilitate fear extinction, which is crucial for treating PTSD.

Psilocybin promoted hippocampal neuroplasticity by improving dendritic complexity, spine density, and levels of neuroplasticity-related proteins, suggesting it could enhance the effectiveness of exposure-based therapies for PTSD.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Psilocybin facilitates fear extinction in mice by promoting hippocampal neuroplasticity. Du, Y., Li, Y., Zhao, X., et al.[2023]

A single dose of 5-MeO-DMT, derived from the bufotoxin of the Sonoran Desert Toad, resulted in significant and sustained improvements in PTSD symptoms for a 23-year-old female patient, with effects lasting up to 12 months.

The treatment was generally safe, with no serious adverse events reported, although the patient did experience some side effects like nausea and night terrors, highlighting the need for further research to confirm these findings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

5-MeO-DMT for post-traumatic stress disorder: a real-world longitudinal case study. Ragnhildstveit, A., Khan, R., Seli, P., 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]

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]

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]

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]

Citations

1. 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, ...

2. finance.yahoo.com finance.yahoo.com/news/compass-pathways-announces-publication-results-103000296.html

Compass Pathways Announces Publication of Results from ... Open-label Phase 2 study shows a single 25 mg COMP360 psilocybin dose was well tolerated, with no serious adverse events observed, ...

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

Investigating the safety and tolerability of single-dose ... Secondary outcomes (PTSD symptom severity, functional impairment and quality of life) revealed consistent and durable pre-post treatment ...

4. clinicaltrials.gov clinicaltrials.gov/study/NCT05312151

NCT05312151 | The Safety and Tolerability of COMP360 in ... Results Posted Record History. Study Overview. Brief Summary. The Safety and Tolerability of COMP360 in Participants with Post-traumatic Stress Disorder.

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12146596/

Clinical conceptualisation of PTSD in psilocybin treatment Studies have shown that psilocybin can facilitate profound psychological experiences characterised by heightened emotional processing and ...

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/40883964/

A nonrandomized open-label clinical trial Investigating the safety and tolerability of single-dose psilocybin for post-traumatic stress disorder: A nonrandomized open-label clinical ...