Psilocybin for Depression

Not currently recruiting at 4 trial locations

Overseen By David Feifel, MD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: COMPASS Pathways

Disqualifiers: Bipolar, Schizophrenia, Personality disorders, 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: 1

Duration: 1 day

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores the use of psilocybin, a compound found in magic mushrooms, to treat major depressive disorder. Researchers aim to assess the safety and effectiveness of a single dose of psilocybin for individuals who haven't responded to other depression treatments. Participants will receive one of three doses to evaluate its impact. This trial suits individuals with major depression who have had the condition for at least three months and have tried other medications without success. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group, offering participants a chance to contribute to groundbreaking research.

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

Yes, you will need to stop taking certain medications, as the trial requires agreement to discontinue all prohibited medications.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that psilocybin is generally safe for treating major depressive disorder. One study found a 25 mg dose of psilocybin to be safe, with most patients tolerating it well. Common side effects included headaches and nausea, which were usually mild and resolved quickly.

Another study found that the antidepressant effects of psilocybin could last up to 12 months, indicating long-lasting benefits with few negative effects. Overall, evidence from multiple studies supports the safety and tolerability of psilocybin, especially at the doses tested in trials. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about psilocybin for treating depression because it offers a novel approach compared to traditional antidepressants like SSRIs and SNRIs. Unlike these standard treatments, psilocybin works by interacting with serotonin receptors in a unique way, potentially leading to quick and profound changes in mood and perception. Moreover, psilocybin may require fewer doses, as its effects can last for weeks after a single administration, which could be a game-changer for those who struggle with daily medication. Additionally, the study explores varying doses (1 mg, 10 mg, and 25 mg) of COMP360 psilocybin, which helps researchers determine the most effective and safe dosage for patients.

What evidence suggests that this trial's treatments could be effective for depression?

Research has shown that psilocybin can help reduce symptoms of depression. In this trial, participants will receive different doses of psilocybin: 25 mg, 10 mg, or 1 mg. Previous studies demonstrated that a single 25 mg dose significantly lowered depression scores more than a smaller 1 mg dose over three weeks. Another study found that the positive effects of the 25 mg dose can last for up to a year. While 10 mg doses are less effective, the 25 mg dose has been linked to bigger, faster, and longer-lasting improvements for people with depression that hasn't responded to other treatments. Overall, psilocybin has shown strong antidepressant effects, with some studies noting its impact is much greater than traditional treatments. ^{6 7 8 9 10}

Are You a Good Fit for This Trial?

Adults with Major Depressive Disorder who haven't improved after one antidepressant treatment, as verified by a specific questionnaire. They must have moderate depression severity and agree to stop taking certain medications. Excluded are those with certain personality disorders, recent psychiatric hospitalization, bipolar or psychotic disorders, ongoing serious mental health issues, or recent use of intensive psychiatric treatments.

Inclusion Criteria

My depression didn't improve after trying a recommended medication.

At Screening, agreement to discontinue all prohibited medications

MADRS total score ≥20 at Screening and Baseline to ensure at least moderate severity of depression

Exclusion Criteria

Psychiatric inpatient within the past 12 months prior to Screening

Lifetime paranoid, schizoid, schizotypal, histrionic, narcissistic personality disorder, or any ongoing serious psychiatric comorbidity based on medical history and clinical judgement

Ongoing post-traumatic stress disorder, obsessive-compulsive disorder, or anorexia nervosa as assessed by medical history and a structured clinical interview (MINI 7.0.2)

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

3-10 weeks

Treatment

Participants receive a single administration of COMP360 with psychological support

1 day

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

6 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Psilocybin

Trial Overview The trial is testing the safety and effectiveness of a single dose of COMP360 psilocybin for people with depression who didn't respond well to their first treatment. It's a controlled study where some participants will receive the actual medication while others may receive a placebo without knowing which one they're getting.

How Is the Trial Designed?

Group I: 25 mg COMP360 Psilocybin Experimental Treatment 1 Intervention

25 mg COMP360 Psilocybin

Group II: 10 mg COMP360 Psilocybin Experimental Treatment 1 Intervention

10 mg COMP360 Psilocybin

Group III: 1 mg COMP360 Psilocybin Active Control 1 Intervention

1 mg COMP360 Psilocybin

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?

COMPASS Pathways

Lead Sponsor

Trials

15

Recruited

1,400+

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12226623/

Psilocybin therapy for treatment resistant depression In summary, recent advances in utilizing psychedelic treatment for participants with depression show promising results (Goodwin et al. 2022; Davis et al. 2021; ...

2. 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 ...

3. ir.compasspathways.com ir.compasspathways.com/News--Events-/news/news-details/2025/Compass-Pathways-Announces-Publication-of-Results-from-COMP004-Study-on-COMP360-Psilocybin-for-Treatment-Resistant-Depression/default.aspx

Compass Pathways Announces Publication of Results from ... The COMP004 study's findings suggest that over a 52-week period, a single administration of 25 mg COMP360 psilocybin demonstrated a longer maintenance of ...

4. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/40736734/

Control Group Outcomes in Trials of Psilocybin, SSRIs, or ... Importance: Psilocybin has demonstrated rapid and sustained antidepressant efficacy, with acute-phase effect sizes often more than double those ...

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

Efficacy of psilocybin for treating symptoms of depression Conclusion Treatment effects of psilocybin were significantly larger among patients with secondary depression, when self-report scales were used ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT06308653

NCT06308653 | Psilocybin for Major Depressive Disorder ... The purpose of this study is to evaluate the efficacy, safety, and tolerability of Psilocybin 25 mg versus placebo in adults with MDD, as assessed by the ...

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

Efficacy and safety of psilocybin in the treatment of Major ... This meta-analysis supports psilocybin's efficacy in treating MDD, particularly at a 25 mg dose, showing a time-dependent therapeutic effect.

8. jamanetwork.com jamanetwork.com/journals/jama/fullarticle/2808950

Single-Dose Psilocybin Treatment for Major Depressive ... This randomized clinical trial examines the timing of onset of action, durability of benefit, and safety profile of single-dose psilocybin ...

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

Efficacy and safety of psilocybin-assisted treatment for ... These findings demonstrate that the substantial antidepressant effects of psilocybin-assisted therapy may be durable at least through 12 months ...

10. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/39754904/

Efficacy and safety of psilocybin in the treatment of Major ... This meta-analysis supports psilocybin's efficacy in treating MDD, particularly at a 25 mg dose, showing a time-dependent therapeutic effect.