Psilocybin-assisted Therapy for Post-Traumatic Stress Disorder

(PsiPTSD Trial)

Recruiting at 2 trial locations

Overseen By Chantel T Debert, MD MSc FRCPC

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: University of Calgary

Disqualifiers: Substance use disorder, 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

Compensation: Varies

Number of Visits: 11

76 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

The goal of this randomized controlled trial is to evaluate the efficacy of psilocybin administered with Acceptance and Commitment Therapy (ACT) as an intervention to reduce post-traumatic stress disorder (PTSD) symptom burden in adult (aged 18-65) survivors of intimate partner violence (IPV). This trail will test the following 2 aims: AIM 1 : To compare the efficacy of a therapeutic psilocybin dose at improving outcomes on the PCL-5 and CAPS-5 as compared to an active control psilocybin dose in IPV survivors with chronic PTSD. AIM 2: To evaluate the efficacy of psilocybin on quality of life, cognitive function, motor ability, depression, anxiety, and cognitive flexibility. Participants will be asked to: * Complete a 2 part screening process * Attend a baseline assessment * Complete a psychoeducation preparation session(s) * Attend psilocybin administration session (receive high dose \[25mg\] or low dose psilocybin \[1mg\]) * Complete 5-6 weekly sessions of ACT * Repeat outcome measures at 1-week, 4 weeks, 3 months (online questionnaires only), and 6 months post-psilocybin administration.

Will I have to stop taking my current medications?

The trial information does not specify whether participants need to stop taking their current medications. It's best to discuss this with the trial coordinators or your doctor.

Is psilocybin-assisted therapy safe for humans?

Psilocybin-assisted therapy appears generally safe when administered under supervision, with most side effects being mild and temporary. However, there are rare reports of increased suicidal thoughts and challenging experiences, especially at higher doses or without proper support, so further research is needed to fully understand its safety. ^{1 2 3 4 5}

How is psilocybin-assisted therapy different from other PTSD treatments?

Psilocybin-assisted therapy is unique because it uses a psychedelic drug, psilocybin, in combination with psychotherapy to help patients confront and process traumatic memories, which may lead to long-term improvements after just a few sessions. Unlike traditional PTSD treatments, which can be hard to tolerate and often have limited effectiveness, this approach shows promise in promoting emotional healing and reducing symptoms by enhancing neuroplasticity (the brain's ability to change and adapt). ^{2 3 6 7 8}

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

Research suggests that psilocybin-assisted therapy may help reduce PTSD symptoms by decreasing emotional avoidance and increasing acceptance and self-compassion. Although no direct studies on PTSD exist, psilocybin has shown promise in treating related conditions like depression and anxiety, and early evidence indicates it may help with PTSD symptoms in combat veterans. ^{2 3 6 8 9}

Who Is on the Research Team?

Leah Mayo, PhD

Principal Investigator

Parker Psychedelics Research Chair and Assistant Professor, Department of Psychiatry, University of Calgary, Cumming School of Medicine

Sandy Shultz, PhD

Principal Investigator

Director, Centre for Trauma and Mental Health Research, Vancouver Island University

Pamela Kryskow, MD, CCFP

Principal Investigator

Medical Lead, Psychedelic-assisted Therapy Graduate Program, Vancouver Island University, Medical Director, Roots to Thrive Society

Zachary Walsh, PhD

Principal Investigator

Professor, Department of Psychology, University of British Columbia

Shannon Dammes, RN, MPH

Principal Investigator

Professor, Health Sciences, Vancouver Island University, and Visioning and Development Lead, Roots to Thrive Society

Paul van Donkelaar, PhD

Principal Investigator

Professor, Faculty of Health and Social Development, School of Health and Exercise Sciences

Jodie Gawryluk, PhD

Principal Investigator

Associate Professor, Department of Psychology, University of Victoria

Are You a Good Fit for This Trial?

Adults aged 18-65 who have survived intimate partner violence and suffer from chronic PTSD can join this trial. They must complete a two-part screening, attend assessments, psychoeducation sessions, and ACT therapy post-psilocybin administration. Those with certain health conditions or on conflicting medications may be excluded.

Inclusion Criteria

Minimum PCL-5 score of ≥ 33

At least 6 months since last IPV incident

I have experienced repeated abuse.

Exclusion Criteria

Active suicidal ideation or serious attempt within the past 1 year

Current pregnancy or nursing, trying to become pregnant

Current or recent (within 12 weeks) participation in a clinical trial

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2 parts

2 visits (in-person)

Baseline Assessment

Participants attend a baseline assessment consisting of clinical and behavioral outcome measures

1 day

1 visit (in-person)

Psychoeducation Preparation

Participants complete a psychoeducation preparation session(s) prior to psilocybin administration

1-2 sessions

1-2 visits (in-person)

Psilocybin Administration

Participants receive a single dose of psilocybin (either high dose 25mg or low dose 1mg) administered 24 hours prior to the first ACT session

1 day

1 visit (in-person)

Acceptance and Commitment Therapy (ACT)

Participants complete 5-6 weekly sessions of Acceptance and Commitment Therapy

5-6 weeks

5-6 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment with outcome measures repeated at 1-week, 4 weeks, 3 months (online only), and 6 months post-psilocybin administration

6 months

Online questionnaires at 1-week, 4 weeks, 3 months, and 6 months

What Are the Treatments Tested in This Trial?

Interventions

• Psilocybin

Trial Overview The trial is testing the effectiveness of psilocybin combined with Acceptance and Commitment Therapy (ACT) to alleviate PTSD symptoms in IPV survivors. Participants will receive either a high dose (25mg) or low dose (1mg) of psilocybin and undergo several weeks of ACT.

How Is the Trial Designed?

Group I: High Dose Experimental Treatment 0 Interventions

High Dose (25mg) PEX010 (Oral Psilocybin), 25mg; single dose (38 participants) administered 24hrs prior to first ACT session

Group II: Low Dose Active Control 1 Intervention

Low Dose (1mg) PEX010 (Oral Psilocybin), 1mg; single dose (20 participants) administered 24hrs prior to first ACT session

Who Is Running the Clinical Trial?

University of Calgary

Lead Sponsor

Trials

827

Recruited

902,000+

Vancouver Island University

Collaborator

Trials

2

Recruited

140+

University of British Columbia

Collaborator

Trials

1,506

Recruited

2,528,000+

Published Research Related to This Trial

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]

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]

Citations

1. Germany pubmed.ncbi.nlm.nih.gov

Psilocybin for Trauma-Related Disorders. [2022]

2. 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]

3. Germany pubmed.ncbi.nlm.nih.gov

[Psilocybin-Assisted Treatment of Depression, Anxiety and Substance use Disorders: Neurobiological Basis and Clinical Application]. [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. China pubmed.ncbi.nlm.nih.gov

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

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

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

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

Psilocybin-Assisted Therapy: A Review of a Novel Treatment for Psychiatric Disorders. [2018]

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

Psilocybin history, action and reaction: A narrative clinical review. [2023]

9. Netherlands pubmed.ncbi.nlm.nih.gov

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