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

20 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial is testing psilocybin, a substance from 'magic mushrooms,' on people with PTSD who don't respond to current treatments. Psilocybin helps the brain grow and reduces fear response, which may improve mood and reduce anxiety. Psilocybin has shown promise in treating anxiety and depression in patients with life-threatening cancer, with significant and sustained symptom reduction.

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.

What data supports the effectiveness of this drug for PTSD?

Research shows that psilocybin, the active ingredient in magic mushrooms, has been studied in clinical trials for various mental health conditions like depression and anxiety, with some patients experiencing long-term improvements after just a few sessions. While not directly studied for PTSD, these findings suggest potential benefits for similar psychiatric disorders. ^{1 2 3 4 5}

Is psilocybin generally safe for humans?

Psilocybin can cause challenging experiences, including hallucinations and risky behavior, but when given in controlled settings with support, the risk of lasting psychological distress is very low. In clinical trials, psilocybin has shown promise for treating certain conditions, and its safety profile is being studied with escalating doses in healthy adults. ^{1 5 6 7 8}

How is the drug psilocybin unique in treating PTSD compared to other treatments?

Psilocybin is unique in treating PTSD because it promotes neuroplasticity (the brain's ability to change and adapt) in the hippocampus, which may help with fear extinction, a key process in PTSD therapy. Unlike traditional treatments, psilocybin can lead to long-term improvements after just one or a few sessions, with limited side effects. ^{2 9 10 11 12}

Research Team

Lisa Batten, PhD

Principal Investigator

Halucenex Life Sciences

Paige Stevens, MD

Principal Investigator

Contracted

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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

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, 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]

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]

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]

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 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-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 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]

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 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]

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]

References

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

The pharmacology of psilocybin. [2016]

2. Netherlands pubmed.ncbi.nlm.nih.gov

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

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

Psilocybin in Palliative Care: An Update. [2023]

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

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

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

Survey study of challenging experiences after ingesting psilocybin mushrooms: Acute and enduring positive and negative consequences. [2018]

8. Switzerland pubmed.ncbi.nlm.nih.gov

[Hallucinogenic mushrooms]. [2018]

9. China pubmed.ncbi.nlm.nih.gov

Psilocybin facilitates fear extinction in mice by promoting hippocampal neuroplasticity. [2023]

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

Structure-Activity Relationships for Psilocybin, Baeocystin, Aeruginascin, and Related Analogues to Produce Pharmacological Effects in Mice. [2023]

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

5-MeO-DMT for post-traumatic stress disorder: a real-world longitudinal case study. [2023]

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

Transcriptional regulation in the rat prefrontal cortex and hippocampus after a single administration of psilocybin. [2022]