Psilocybin for PTSD

Overseen By Adam Levin, MD

Age: 18 - 65

Sex: Any

Trial Phase: Phase 2

Sponsor: Ohio State University

Must not be taking: Antidepressants, Psychoactive, Serotonergic

Disqualifiers: Pregnancy, Cardiovascular, Epilepsy, Diabetes, 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: 7

15 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial aims to test if using psilocybin along with therapy can safely and effectively treat PTSD in U.S. Military Veterans. Psilocybin helps change brain activity, making it easier for veterans to process their trauma during therapy.

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

Yes, you must stop taking any psychoactive prescription medications and those with a primary centrally-acting serotonergic effect, like Monoamine oxidase inhibitors, to join the trial.

What data supports the idea that Psilocybin for PTSD is an effective drug?

The available research shows that psilocybin has been studied in clinical trials for various psychiatric disorders, including depression and substance use disorders. These studies found that psilocybin is generally well tolerated and can lead to significant, long-lasting improvements even in patients who haven't responded to other treatments. Although the research doesn't specifically mention PTSD, the positive outcomes in similar conditions suggest that psilocybin could be effective for PTSD as well. However, more research is needed to confirm its effectiveness for PTSD specifically. ^{1 2 3 4 5}

What safety data exists for psilocybin treatment?

Psilocybin has been studied for its pharmacology, pharmacodynamics, and clinical effects. It can cause rapid effects on the central nervous system, including ataxia and hallucinations. A survey of 1993 individuals reported that 11% put themselves or others at risk of harm, and 2.7% required medical help. However, in controlled settings with screened and supported participants, the risk of adverse effects is extremely low. An open-label study on healthy adults showed a safety profile for escalating oral doses of psilocybin. Despite some risks, 84% of survey respondents reported benefits from their experiences. ^{1 5 6 7 8}

Is the drug Psilocybin a promising treatment for PTSD?

Yes, Psilocybin is a promising treatment for PTSD. It has shown potential in helping with fear extinction, which is important for PTSD therapy. Studies suggest it can lead to long-term improvements in mental health conditions, including PTSD, by promoting changes in the brain that help reduce fear and anxiety. ^{2 9 10 11 12}

Research Team

Alan K Davis, PhD

Principal Investigator

Ohio State University

Eligibility Criteria

This trial is for US military Veterans aged 21-64 with PTSD, who have a high school education or equivalent and are medically stable. They must not be on antidepressants, have a significant history of drug abuse, severe mental health conditions like schizophrenia or bipolar disorder, cardiovascular issues, diabetes, obesity, or epilepsy.

Inclusion Criteria

US military Veteran

Have at least a high-school level of education or equivalent

I am between 21 and 64 years old.

Exclusion Criteria

I am currently taking medication that affects serotonin in my brain.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Preparatory Therapy

Participants meet with session facilitators for preparatory therapy sessions before the first psilocybin session

1-2 weeks

Up to 4 meetings

Psilocybin Treatment

Participants receive two doses of psilocybin, approximately 2 weeks apart, with post-psilocybin therapy sessions

4 weeks

2 psilocybin sessions, 2 post-therapy sessions

Follow-up

Participants are monitored for safety and effectiveness after treatment

6 months

Visits at 1 and 2 weeks, and 1, 3, and 6 months post-treatment

Treatment Details

Interventions

• Psilocybin

Trial Overview The study is testing the safety and effectiveness of psilocybin-assisted therapy in treating PTSD in veterans. Psilocybin is given under controlled conditions to see if it helps reduce PTSD symptoms more than standard treatments.

Participant Groups

Group I: Psilocybin-assisted therapy Experimental Treatment 1 Intervention

Participants will receive two doses of psilocybin, approximately 2 weeks apart, in conjunction with preparatory and post-psilocybin therapy sessions

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?

Ohio State University

Lead Sponsor

Trials

891

Recruited

2,659,000+

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, 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]

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]

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 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]

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. Switzerland pubmed.ncbi.nlm.nih.gov

[Hallucinogenic mushrooms]. [2018]

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

Intravenous mushroom poisoning. [2019]

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]