Psilocybin for Post-Traumatic Stress Disorder and Alcoholism

(Psi-PS Trial)

Overseen By Christina Sargent

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Nathan Brashares Sackett

Must not be taking: Antidepressants, Antipsychotics, Stimulants, Psychedelics

Disqualifiers: Seizure disorder, Schizophrenia, Bipolar, others

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

Compensation: Varies

Number of Visits: 6

40 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

Yes, you will need to stop taking certain medications, such as SSRIs, SNRIs, MAOIs, TCAs, antipsychotics, lithium, stimulants, or other psychedelics, as they are listed in the exclusion criteria.

What data supports the effectiveness of the drug psilocybin for treating PTSD and alcoholism?

Research shows that psilocybin, a compound found in 'magic mushrooms', has shown promise in treating various mental health disorders, including depression and addiction, with some patients experiencing long-term improvements. Although specific studies on PTSD and alcoholism are limited, early evidence suggests psilocybin may help reduce symptoms related to trauma and addiction. ^{1 2 3 4 5}

Is psilocybin generally safe for humans?

Psilocybin has been studied for its safety in humans, showing promise in treating conditions like PTSD and alcohol dependence. While some people report challenging experiences, the risk of lasting harm is low when psilocybin is used in controlled, supportive settings. Most participants in studies report benefits despite any difficulties. ^{1 2 3 6 7}

How is the drug psilocybin unique in treating PTSD and alcoholism?

Psilocybin is unique because it is a psychedelic drug that may help treat PTSD and alcoholism by promoting neuroplasticity (the brain's ability to change and adapt) and facilitating fear extinction, which are not typical mechanisms of action for standard treatments. Unlike traditional therapies, psilocybin is administered in a few supervised sessions combined with psychotherapy, potentially offering long-term improvements even for treatment-resistant cases. ^{2 3 5 6 8}

What is the purpose of this trial?

This study is a phase 2 single-site, double-blind, placebo-controlled, randomized clinical trial with an open-label extension phase to examine the safety, efficacy, and durability of psilocybin (25 mg) combined with psychological support (Psi-PS) for treatment of approximately 40 military veterans and first responders (ages 18-65) with co-occurring alcohol use disorder (AUD) and posttraumatic stress disorder (PTSD). Psychological support is defined as providing safety, reassurance, active listening, and empathetic presence during the drug administration session in a nondirective manner. We hypothesize that Psi-PS may provide a safe and effective treatment for participants.

Research Team

Nathan B Sackett, MD

Principal Investigator

University of Washington

Eligibility Criteria

This trial is for military veterans and first responders aged 18-65 who are struggling with both PTSD and alcohol use disorder. Participants must not have other health conditions that could interfere with the study or be at risk of harming themselves.

Inclusion Criteria

Have a primary care provider

I am between 18-65 years old with both alcohol use and PTSD diagnoses.

I have someone to stay with me overnight after the DAS procedure.

Exclusion Criteria

A reported history of a personality disorder at time of screening

Reported history or findings on SCID-CT of known exclusionary psychiatric conditions, including schizophrenia, schizoaffective disorder, bipolar disorder type I or type II

A reported history of a serious suicide attempt (SSA) in previous 12-months

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Preparation

Two 60-minute telehealth preparation sessions with two facilitators

1-2 weeks

2 visits (virtual)

Drug Administration Session (DAS)

One 6-8-hour session where 25 mg of oral psilocybin or placebo is administered in a clinical setting with two facilitators present

1 day

1 visit (in-person)

Integration

Three 60-minute telehealth integration sessions with two facilitators

3-4 weeks

3 visits (virtual)

Follow-up

Participants are monitored for safety and effectiveness after treatment

24 weeks

Multiple visits (in-person and virtual)

Open-label Extension

Participants who received placebo are offered Psi-PS following the same procedures

6 weeks

Treatment Details

Interventions

• Psilocybin

Trial Overview The study tests if psilocybin (25 mg) combined with psychological support can help treat PTSD and AUD in participants. It's a phase 2 trial, where half get psilocybin plus support, while the other half receive a placebo (maltodextrin) with support.

Participant Groups

Group I: Psilocybin + Nondirective Psychological Support Experimental Treatment 1 Intervention

The intervention is composed of two 60-minute telehealth preparation sessions (Prep 1 and Prep 2) with two facilitators; one 6-8-hour drug administration session (25 mg of oral psilocybin) in a clinical setting with the same two facilitators present; and three 60-minute telehealth integration sessions (Integration 1-3) with the same two facilitators. Ideally the entire intervention will be delivered over 6 weeks allowing for some flexibility based on schedules and logistics.

Group II: Placebo + Nondirective Psychological Support Placebo Group 1 Intervention

The arm is composed of two 60-minute telehealth preparation sessions (Prep 1 and Prep 2) with two facilitators; inert placebo (25 mg of Maltodextrin) administered in a clinical setting with the same two facilitators present; and three 60-minute telehealth integration sessions (Integration 1-3) with the same two facilitators. Ideally the entire intervention will be delivered over 6 weeks allowing for some flexibility based on schedules and logistics.

Who Is Running the Clinical Trial?

Nathan Brashares Sackett

Lead Sponsor

Trials

1

Recruited

40+

Washington State Legislation

Collaborator

Trials

1

Recruited

40+

Findings from Research

Psilocybin, found in 'magic mushrooms', shows promise as a non-addictive alternative for treating mental health disorders like major depressive disorder and addiction, potentially addressing the urgent need for new therapies amid rising addiction and suicide rates.

Current research indicates that psilocybin may offer therapeutic benefits without the overdose risks associated with traditional mind-altering substances, suggesting a safer option for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Psilocybin Therapeutic Research: The Present and Future Paradigm. Kargbo, RB.[2021]

In a study of 27 patients with moderate to severe major depressive disorder, psilocybin-assisted treatment showed significant and lasting antidepressant effects, with 75% of participants experiencing a treatment response and 58% achieving remission after 12 months.

There were no serious adverse events related to psilocybin, indicating a favorable safety profile, and participants reported meaningful personal and spiritual experiences that correlated with increased well-being, although these did not directly predict improvements in depression.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of psilocybin-assisted treatment for major depressive disorder: Prospective 12-month follow-up. Gukasyan, N., Davis, AK., Barrett, FS., 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 proof-of-concept study involving 10 alcohol-dependent participants, psilocybin administration led to a significant increase in abstinence rates after treatment, with effects maintained for up to 36 weeks.

Participants experienced no significant adverse events, suggesting that psilocybin is safe for use in this context, and the intensity of the psilocybin effects predicted positive changes in drinking behavior and cravings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Psilocybin-assisted treatment for alcohol dependence: a proof-of-concept study. Bogenschutz, MP., Forcehimes, AA., Pommy, JA., et al.[2022]

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]

References

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

Psilocybin Therapeutic Research: The Present and Future Paradigm. [2021]

2. Germany pubmed.ncbi.nlm.nih.gov

Psilocybin for Trauma-Related Disorders. [2022]

3. England pubmed.ncbi.nlm.nih.gov

Study protocol of an open-label proof-of-concept trial examining the safety and clinical efficacy of psilocybin-assisted therapy for veterans with PTSD. [2023]

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

Efficacy and safety of psilocybin-assisted treatment for major depressive disorder: Prospective 12-month follow-up. [2022]

5. Netherlands pubmed.ncbi.nlm.nih.gov

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

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

Psilocybin-assisted treatment for alcohol dependence: a proof-of-concept study. [2022]

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. China pubmed.ncbi.nlm.nih.gov

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