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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests whether psilocybin, a psychedelic compound, combined with psychological support, is a safe treatment for individuals with both post-traumatic stress disorder (PTSD) and alcohol use disorder (AUD). The researchers aim to determine if this combination can reduce symptoms and improve well-being. The study seeks military veterans or first responders who wish to reduce their drinking and have been coping with PTSD. 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?

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.

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

Research has shown that psilocybin, a substance found in certain mushrooms, is being studied for its safety and potential benefits in treating PTSD and alcohol use disorder. In an earlier study, participants with PTSD received single doses of psilocybin. The study found that psilocybin was generally well-tolerated, with most participants not experiencing severe side effects.

Some reports suggest that psilocybin can help reduce PTSD symptoms when used alongside therapy. Another review found that psychedelics, like psilocybin, might improve mood and could be effective for mental health issues such as substance use disorders and PTSD.

Overall, while researchers continue to study psilocybin, current evidence suggests it could be safe to use under medical supervision. ^{1 2 3 4 5}

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

Researchers are excited about psilocybin for treating PTSD and alcoholism because it offers a novel approach compared to traditional therapies. Unlike standard treatments such as antidepressants or cognitive behavioral therapy, psilocybin, a psychedelic compound, works by potentially rewiring the brain’s neural pathways, which can lead to profound changes in perception and mood. This unique mechanism of action may allow for deep psychological insights and emotional breakthroughs, which are not typically achieved with conventional medications. Furthermore, psilocybin treatment can potentially yield results after just one or two sessions, offering a faster path to relief than many current options that require long-term use.

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

Research has shown that psilocybin, one of the treatments in this trial, may help reduce PTSD symptoms when used with psychological support. Early data suggests that just one dose can lessen these symptoms, especially when combined with therapy. Studies also indicate that psilocybin might help with substance-use issues, such as alcohol use disorder. This suggests potential benefits for individuals dealing with both PTSD and alcohol problems. Although more research is needed, early results are promising for psilocybin as a treatment option. Participants in this trial will receive either psilocybin or a placebo, both with nondirective psychological support, to further evaluate its effectiveness. ^{2 4 6 7 8}

Who Is on the Research Team?

Nathan B Sackett, MD

Principal Investigator

University of Washington

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

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]

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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10845102/

The Psychedelic Future of Post-Traumatic Stress Disorder ... Though they did not specifically measure trauma history or PTSD symptoms, outcome data indicate improvements in psychological well-being using this measure ...

2. ptsd.va.gov ptsd.va.gov/professional/treat/txessentials/psychedelics_assisted_therapy.asp

Psychedelic-Assisted Therapy for PTSD Finally, preliminary data suggests that a single administration of psilocybin along with group psychotherapy can decrease symptoms of PTSD in older long-term ...

3. hopkinsmedicine.org hopkinsmedicine.org/psychiatry/research/psychedelics-research

Psychedelics Research and Psilocybin Therapy Upcoming studies will determine the effectiveness of psilocybin as a new therapy for opioid addiction, Alzheimer's disease, post-traumatic stress disorder (PTSD) ...

4. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0165178124001719

Efficacy and safety of psychedelics for the treatment ... Our analyses suggest that psychedelics reduce negative mood, and have potential efficacy in other mental disorders, such as substance-use disorders and PTSD.

5. clinicaltrials.gov clinicaltrials.gov/study/NCT05876481

Evaluation of Psilocybin-assisted Psychotherapy (PaP) for ... PaP may similarly benefit the treatment of posttraumatic stress disorder (PTSD). Research indicates high treatment drop-out rates (approximately 30%) among PTSD ...

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 ...

7. clinicaltrials.gov clinicaltrials.gov/study/NCT05243329

Investigating the Therapeutic Effects of Psilocybin in ... The present study aims to investigate the effect of psilocybin on treatment-resistant PTSD. Official Title. Investigating the Therapeutic Effects of Psilocybin ...

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

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