Psilocybin for Depression

(PIVOT Trial)

Not yet recruiting at 4 trial locations

Overseen By Anchal Ghera, MS

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: VA Office of Research and Development

Must be taking: Antidepressants

Must not be taking: Psychedelics, Sedatives

Disqualifiers: Bipolar, Schizophrenia, Severe substance use, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

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

Compensation: Varies

Number of Visits: 2

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether psilocybin, a compound in certain mushrooms, can help treat depression in U.S. military Veterans, including those with posttraumatic stress disorder (PTSD). The researchers aim to determine the effectiveness and safety of psilocybin for these conditions. Participants will receive different doses of psilocybin in groups to compare results. Veterans experiencing depression despite trying at least two different antidepressants might be suitable for this study. As a Phase 3 trial, this study represents the final step before potential FDA approval, offering participants a chance to contribute to groundbreaking treatment advancements.

Do I need to stop my current medications to join the trial?

The trial requires that any antidepressants you are taking must be at stable doses for at least 4 weeks before starting the study. Some medications are prohibited, so you may need to stop those at least 2 weeks before the trial begins. Check the allowed and prohibited medication list for details.

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

Research has shown that psilocybin is generally safe for treating depression. Past studies reported no serious side effects linked to psilocybin, and participants did not experience major problems during long-term follow-ups. Some studies found that a single dose could cause mild side effects, but these were not serious. Overall, previous research indicates that patients have tolerated psilocybin well. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for depression?

Unlike the standard treatments for depression, which often include medications like SSRIs and SNRIs, psilocybin offers a novel approach by acting on the brain's serotonin receptors in a unique way. Researchers are excited about psilocybin because it may lead to rapid improvements in mood and emotional processing, potentially showing results in just a few sessions. Additionally, psilocybin is derived from mushrooms, offering a natural alternative to synthetic drugs, and it may have lasting effects after just a few doses, unlike daily medications. This has the potential to transform how we approach treatment for depression, offering hope for more effective and faster-acting solutions.

What evidence suggests that psilocybin might be an effective treatment for depression?

Research has shown that psilocybin can greatly reduce symptoms of depression. In studies, participants who took psilocybin experienced a significant decrease in depression levels compared to those who took a placebo. Johns Hopkins Medicine found that psilocybin helps ease symptoms of major depression in adults, with positive effects lasting up to six months after treatment in some cases. This provides strong evidence that psilocybin is effective in treating depression. Participants in this trial will receive either an intervention dose or a comparator dose of psilocybin to further evaluate its effectiveness. ^{4 6 7 8 9}

Who Is on the Research Team?

Lori Lynne Davis, MD AB

Principal Investigator

Birmingham VA Medical Center, Birmingham, AL

Are You a Good Fit for This Trial?

This trial is for U.S. military Veterans who are struggling with depression that hasn't improved with standard treatments, including those who may also have PTSD. Participants must meet specific health and psychological criteria to ensure safety.

Inclusion Criteria

MADRS ≥ 20 at baseline

Signed informed consent and HIPAA

Participants of child-bearing potential must have negative pregnancy test & agree to adhere to a medically acceptable method of birth control during the study

Exclusion Criteria

Lifetime bipolar, schizophrenia spectrum, or other psychotic disorders

History of severe traumatic brain injury (TBI)

Suicidal ideation/behavior Type 4 or Type 5 intensity on C-SSRS within past 6 months of baseline

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Preparation and Dosing

Participants undergo preparation, administration, and integration psychological support with two psilocybin dosing sessions

1 month

2 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after each dosing session

6 months

Multiple visits (in-person and virtual)

What Are the Treatments Tested in This Trial?

Interventions

• Psilocybin

Trial Overview The study is testing the effectiveness of psilocybin, a psychedelic compound, in treating depression among veterans. It's a controlled trial where some participants will receive psilocybin while others may receive a placebo or alternative treatment.

How Is the Trial Designed?

Group I: Intervention Experimental Treatment 1 Intervention

Psilocybin intervention dose

Group II: Control Active Control 1 Intervention

Psilocybin comparator dose

Who Is Running the Clinical Trial?

VA Office of Research and Development

Lead Sponsor

Trials

1,691

Recruited

3,759,000+

Citations

1. bmj.com bmj.com/content/385/bmj-2023-078084

Efficacy of psilocybin for treating symptoms of depression In our meta-analysis we found that psilocybin use showed a significant benefit on change in depression scores compared with placebo. This is ...

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

Psychedelics Research and Psilocybin Therapy Previous studies by Johns Hopkins Medicine researchers showed that psychedelic treatment with psilocybin relieved major depressive disorder symptoms in adults ...

3. jamanetwork.com jamanetwork.com/journals/jamanetworkopen/fullarticle/2836921

Control Group Outcomes in Trials of Psilocybin, SSRIs, or ... This meta-analysis found that participants receiving control treatment in psilocybin trials had significantly less improvement in depression ...

4. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/37844352/

Psilocybin-assisted therapy for depression: A systematic ... A review of open-label trials showed robust decreases in depressive symptoms following psilocybin administration. These findings provide preliminary evidence ...

5. akjournals.com akjournals.com/view/journals/2054/aop/article-10.1556-2054.2025.00461/article-10.1556-2054.2025.00461.xml

Five-year outcomes of psilocybin-assisted therapy for ... Two recent studies found that depression was significantly reduced for up to six months post-treatment in participants with TRD and MDD, ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8864328/

Efficacy and safety of psilocybin-assisted treatment for major ... There were no serious adverse events judged to be related to psilocybin in the long-term follow-up period, and no participants reported ...

7. jamanetwork.com jamanetwork.com/journals/jamapsychiatry/fullarticle/2772630

Effects of Psilocybin-Assisted Therapy on Major ... This randomized clinical trial found that psilocybin-assisted therapy was efficacious in producing large, rapid, and sustained antidepressant effects in ...

8. nejm.org nejm.org/doi/full/10.1056/NEJMoa2206443

Single-Dose Psilocybin for a Treatment-Resistant Episode ... Psilocybin at a single dose of 25 mg, but not 10 mg, reduced depression scores significantly more than a 1-mg dose over a period of 3 weeks but was associated ...

9. sciencedirect.com sciencedirect.com/science/article/abs/pii/S016517812400622X

Efficacy and safety of psilocybin in the treatment of Major ... Psilocybin demonstrates a rapid-onset of action, with significant antidepressant effects within the first week. · Antidepressant benefits of psilocybin are ...