Psilocybin for Depression in Adults with Cancer

(2Dose Trial)

Overseen By Study Contact

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Sunstone Medical

Must not be taking: Antidepressants, Antipsychotics, Cannabis, others

Disqualifiers: Schizophrenia, Bipolar, Substance use, others

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: 3

56 Participants Needed

Trial Summary

What is the purpose of this trial?

This is a Phase 2, single-center study to explore the efficacy, safety, and tolerability of up to two 25-mg doses of psilocybin administered at an interval of 9 to 10 weeks in patients with MDD and cancer. This two-part study will administer a fixed dose (25 mg) of psilocybin in a double-blind, randomized, placebo-controlled portion (Dosing Session 1) and subsequently allow rollover into an open-label portion (Dosing Session 2; fixed dose of psilocybin, 25 mg) for patients who do not achieve remission of MDD symptoms after the first dose. In Dosing Session 1, groups of two to four patients will be randomized, as a cohort, to receive either psilocybin 25 mg or niacin 100 mg (active placebo) in a group session, with each patient supported by their dedicated study therapist and monitored by a second therapist via video feed. In Dosing Session 2, all eligible participants (i.e., patients who have not achieved remission defined as MADRS \< 10 at V7) will receive psilocybin 25 mg in an open-label fashion using the group session model. The study population will include adult men and women who are 18 years of age or older and have diagnoses of both MDD and a malignant neoplasm. MDD is defined as the Diagnostic and Statistical Manual of Mental Disorders, 5th edition (DSM-5) diagnostic criteria for a single or recurrent episode of MDD without psychotic features. A diagnosis of a malignant neoplasm is defined as having a diagnostic code from C00 to C97 according to the International Classification of Diseases, 10th edition (ICD-10). Participants will be recruited through referrals from specialized psychiatric and oncology services as well as through patient self-referrals. The majority of participants will have no prior exposure to psilocybin or so-called "magic mushrooms"; however, participants with prior recreational experience with psilocybin or "magic mushrooms" are eligible.

Will I have to stop taking my current medications?

The trial requires that participants are not currently taking any antidepressant, antipsychotic medications, or medical cannabis at the start of the study. If you are on these medications, you would need to stop them before participating.

What data supports the effectiveness of the drug psilocybin for depression in adults with cancer?

Research shows that psilocybin can reduce symptoms of depression, including in cancer patients, and has been effective in treating major depressive disorder. Studies also suggest that psilocybin-assisted therapy can provide rapid and substantial antidepressant effects. ^{1 2 3 4 5}

Is psilocybin safe for humans?

Psilocybin has been studied in clinical trials and is generally considered safe for humans when used in controlled settings, although it can cause temporary effects like hallucinations and changes in perception. A pilot study in cancer patients with depression found it to be safe, and a systematic review highlighted its safety in treating depression and anxiety in life-threatening diseases. ^{5 6 7 8 9}

How is the drug psilocybin unique in treating depression in adults with cancer?

Psilocybin is unique because it can rapidly reduce symptoms of depression with just one or two doses, unlike many traditional antidepressants that require daily use. It works by altering brain activity and perception, which may help patients with cancer experience relief from depression and anxiety more quickly. ^{1 2 7 10 11}

Eligibility Criteria

Adults with both Major Depressive Disorder (MDD) and cancer, who are not on antidepressants or antipsychotics, can join this trial. They must have a depression score of ≥20 and be able to consent. Pregnant women, those with recent drug abuse or certain medical conditions like heart issues or uncontrolled diabetes cannot participate.

Inclusion Criteria

Signed informed consent form (ICF)

I am 18 years old or older.

I have been diagnosed with major depression for at least 3 months.

Exclusion Criteria

I am not taking any medications that affect my heart's rhythm.

Current (within the past year) alcohol or drug use disorder as defined by the DSM-5 (MINI 7.0.2) at Screening (V1)

A marked prolongation of QT/QTc interval (e.g., repeated demonstration of a QTc interval > 450 ms at screening

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Dosing Session 1

Participants receive either psilocybin 25 mg or niacin 100 mg (active placebo) in a group session

1 day

1 visit (in-person)

Dosing Session 2

Eligible participants receive psilocybin 25 mg in an open-label group session

1 day

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

8 weeks

Multiple visits (in-person and virtual)

Treatment Details

Interventions

• Psilocybin

Trial Overview The study tests if two doses of psilocybin (25 mg each) help adults with MDD and cancer feel better compared to a placebo. The first dose is given in a controlled setting; patients who don't improve may receive another dose openly later.

Participant Groups

Group I: Psilocybin Experimental Treatment 1 Intervention

Group II: Placebo Placebo Group 1 Intervention

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?

Sunstone Medical

Lead Sponsor

Trials

3

Recruited

110+

Findings from Research

Psilocybin has shown promise in clinical trials for reducing symptoms of depression, indicating its potential as a novel treatment option.

Patients with treatment-resistant depression (TRD) may benefit the most from psilocybin therapy, although the risks associated with its use are still not fully understood.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Assessing potential of psilocybin for depressive disorders. Kozak, Z., Johnson, MW., Aaronson, ST.[2023]

A systematic review of 7 studies involving 136 participants found that psilocybin has a significant antidepressant effect, particularly at higher doses (30-35 mg/70 kg), with a Hedges' g of 3.059 indicating strong efficacy.

The study suggests that psilocybin can effectively reduce depressive symptoms in both major depression and depressed cancer patients, but further clinical trials are needed to confirm these findings and optimize dosing.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dose effect of psilocybin on primary and secondary depression: a preliminary systematic review and meta-analysis. Li, NX., Hu, YR., Chen, WN., et al.[2022]

Medicinal mushrooms like Shiitake, Turkey Tail, and Scaly Wood show promise in cancer treatment by potentially preventing lymph node metastasis, prolonging survival, and reducing side effects from chemotherapy, based on a review of nine studies.

The review highlights the need for more rigorous research, including randomized controlled trials with larger sample sizes, to confirm these benefits and determine the most effective dosages for patients with high-mortality cancers such as gastric, breast, and colorectal cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Therapeutic Effects of Medicinal Mushrooms on Gastric, Breast, and Colorectal Cancer: A Scoping Review. Dan, A., Swain, R., Belonce, S., et al.[2023]

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]

The HOPE trial, involving 12 cancer patients, showed that psilocybin-assisted group therapy is safe, with no serious adverse events reported, and resulted in significant reductions in depression symptoms over six months.

Participants experienced substantial decreases in depression scores, with six out of twelve achieving remission at two weeks, indicating that this group therapy model could be an effective treatment for depression in cancer patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

HOPE: A Pilot Study of Psilocybin Enhanced Group Psychotherapy in Patients With Cancer. Lewis, BR., Garland, EL., Byrne, K., et al.[2023]

In a study involving 12 healthy adults, escalating doses of psilocybin (0.3, 0.45, and 0.6 mg/kg) were administered safely, with no serious adverse events reported, indicating a favorable safety profile for this psychedelic compound.

The pharmacokinetics of psilocin, the active metabolite of psilocybin, were linear across the tested doses, with an elimination half-life of about 3 hours, suggesting that no dose adjustments are necessary for individuals with mild to moderate renal impairment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacokinetics of Escalating Doses of Oral Psilocybin in Healthy Adults. Brown, RT., Nicholas, CR., Cozzi, NV., et al.[2022]

Psilocybin, a hallucinogenic compound found in certain mushrooms, has been associated with increasing rates of drug abuse, highlighting the need for comprehensive pharmacological understanding.

Despite its historical use in the 1960s for experimental medical purposes, recent research has only begun to uncover the pharmacological properties of psilocybin, indicating a gap in knowledge that needs to be addressed.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The pharmacology of psilocybin. Passie, T., Seifert, J., Schneider, U., et al.[2016]

Psilocybin-containing mushrooms, commonly known as hallucinogenic or 'magic' mushrooms, rapidly affect the central nervous system within 0.5-1 hour of ingestion, leading to effects such as ataxia, hyperkinesis, and hallucinations.

The review discusses the significant toxicity associated with these mushrooms, highlighting the need for awareness and understanding of their pharmacology, clinical effects, and potential treatment for adverse reactions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Hallucinogenic mushrooms]. Reingardiene, D., Vilcinskaite, J., Lazauskas, R.[2018]

Psilocybin has shown significant therapeutic effects in reducing symptoms of depression and anxiety in patients with life-threatening diseases, based on a systematic review and meta-analysis of clinical trials involving 92 patients.

The results indicate that psilocybin may be a safe and effective treatment option, particularly for cases resistant to conventional therapies, with significant improvements measured by the Beck Depression Inventory and State-Trait Anxiety Inventory.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Psilocybin as a New Approach to Treat Depression and Anxiety in the Context of Life-Threatening Diseases-A Systematic Review and Meta-Analysis of Clinical Trials. Vargas, AS., Luís, Â., Barroso, M., et al.[2020]

In a double-blind, placebo-controlled trial with 29 cancer patients, a single dose of psilocybin (0.3 mg/kg) combined with psychotherapy led to significant and lasting reductions in anxiety and depression, with 60-80% of participants showing sustained improvements at a 6.5-month follow-up.

The positive effects of psilocybin were linked to the mystical experiences it induced, which helped improve patients' quality of life, reduce existential distress, and foster better attitudes towards death.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Rapid and sustained symptom reduction following psilocybin treatment for anxiety and depression in patients with life-threatening cancer: a randomized controlled trial. Ross, S., Bossis, A., Guss, J., et al.[2022]

In a randomized clinical trial involving 27 adults with major depressive disorder (MDD), psilocybin therapy combined with psychological support led to significant reductions in depression severity, with large effect sizes observed at weeks 1 and 4 after treatment.

71% of participants showed a clinically significant response to psilocybin therapy within a week, and over half achieved remission, indicating that psilocybin could be an effective treatment option for MDD.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of Psilocybin-Assisted Therapy on Major Depressive Disorder: A Randomized Clinical Trial. Davis, AK., Barrett, FS., May, DG., et al.[2022]

References

1. England pubmed.ncbi.nlm.nih.gov

Assessing potential of psilocybin for depressive disorders. [2023]

2. Netherlands pubmed.ncbi.nlm.nih.gov

Dose effect of psilocybin on primary and secondary depression: a preliminary systematic review and meta-analysis. [2022]

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

Therapeutic Effects of Medicinal Mushrooms on Gastric, Breast, and Colorectal Cancer: A Scoping Review. [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. United States pubmed.ncbi.nlm.nih.gov

HOPE: A Pilot Study of Psilocybin Enhanced Group Psychotherapy in Patients With Cancer. [2023]

6. Switzerland pubmed.ncbi.nlm.nih.gov

Pharmacokinetics of Escalating Doses of Oral Psilocybin in Healthy Adults. [2022]

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

The pharmacology of psilocybin. [2016]

8. Switzerland pubmed.ncbi.nlm.nih.gov

[Hallucinogenic mushrooms]. [2018]

9. Switzerland pubmed.ncbi.nlm.nih.gov

Psilocybin as a New Approach to Treat Depression and Anxiety in the Context of Life-Threatening Diseases-A Systematic Review and Meta-Analysis of Clinical Trials. [2020]

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

Rapid and sustained symptom reduction following psilocybin treatment for anxiety and depression in patients with life-threatening cancer: a randomized controlled trial. [2022]

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

Effects of Psilocybin-Assisted Therapy on Major Depressive Disorder: A Randomized Clinical Trial. [2022]