Psilocybin-assisted Psychotherapy for Demoralization

Overseen By Gustavo Vazquez, MD, PhD, FRCPC

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Gustavo Vazquez

Must not be taking: MAO inhibitors, Antipsychotics, Mood stabilizers, others

Disqualifiers: Primary brain tumor, Schizophrenia, Bipolar, others

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

Compensation: Varies

Number of Visits: 6

Duration: 6 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether psilocybin-assisted therapy can aid individuals with advanced cancer who feel demoralized—experiencing hopelessness, helplessness, or a lack of purpose. Researchers aim to determine if this approach can enhance mental health and quality of life, given the absence of specific treatments for demoralization. The trial combines therapy sessions with a dose of psilocybin, a compound in psychedelic mushrooms, to assess its safety and effectiveness in reducing demoralization. Individuals with advanced-stage cancer who feel significantly demoralized may be suitable candidates for this study. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this innovative therapy.

Will I have to stop taking my current medications?

The trial requires that you stop taking certain medications that could interact with psilocybin, such as MAO inhibitors, antipsychotics, mood stabilizers, aldehyde dehydrogenase inhibitors, and significant inhibitors of UGT 1A0 or UGT 1A10. If you are on these medications and cannot taper off, you may not be eligible to participate.

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

Research has shown that psilocybin-assisted therapy is generally well-tolerated. For example, a study on psilocybin therapy for AIDS survivors found it reduced feelings of hopelessness, demonstrating both effectiveness and safety, allowing participants to complete the study. Similarly, trials with cancer patients have found psilocybin promising for improving quality of life and reducing anxiety.

In studies with cancer patients and those with major depression, psilocybin therapy proved safe and manageable, with no major side effects reported. While these results are promising, psilocybin is still under investigation and not yet approved for treating feelings of demoralization. Prospective trial participants should discuss any concerns with their healthcare provider. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike traditional treatments for demoralization in advanced cancer patients, which often rely on antidepressants or psychotherapy alone, psilocybin-assisted psychotherapy introduces a novel approach by combining a psychedelic compound with therapeutic guidance. Psilocybin, the active ingredient, is believed to foster profound psychological insights and emotional breakthroughs, potentially offering rapid relief from demoralization. Researchers are excited about this treatment because it targets the root of psychological distress in a unique way, promising not only faster results but also a deeper, more meaningful healing experience for patients.

What evidence suggests that psilocybin-assisted psychotherapy might be an effective treatment for demoralization?

Research has shown that psilocybin-assisted therapy, which participants in this trial will receive, may improve quality of life, manage pain, and reduce anxiety in people with advanced cancer. Studies have found it effective in easing symptoms of anxiety, depression, and deep emotional distress. Although specific studies on demoralization syndrome are lacking, this therapy has shown positive effects on similar mental health issues in cancer patients. These findings suggest that psilocybin-assisted therapy could potentially help those experiencing demoralization, closely related to depression and anxiety. ^{1 3 6 7 8}

Are You a Good Fit for This Trial?

This trial is for adults aged 18-70 with advanced stage cancer who are experiencing demoralization syndrome. Participants will undergo psychotherapy sessions and a psilocybin dosing session. Those showing partial response may receive a second dose.

Inclusion Criteria

English proficiency

Individuals of child-bearing potential who are sexually active must agree to use an acceptable contraceptive method throughout their participation in the study

Moderate-to-severe demoralization as measured by Demoralization Scale≥ 30

Exclusion Criteria

I have been diagnosed with delirium.

Current or past history of schizophrenia, psychotic disorder, bipolar disorder, delusional disorder, paranoid personality disorder, schizoaffective disorder, or borderline personality disorder

Significant suicide risk as defined by suicidal ideation with intent and a plan

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants undergo 6 psychotherapeutic sessions and one psilocybin (25 mg) dosing session

6 weeks

6 psychotherapeutic visits, 1 psilocybin dosing session

Follow-up

Participants are monitored for safety and effectiveness after treatment, with assessments using the Demoralization Scale, Hamilton Depression Rating Scale, Hamilton Anxiety Rating Scale, and Columbia Suicide Severity Rating Scale

10-13 weeks

Optional Second Dosing

Participants with partial response a month after the psilocybin intervention may receive a second psilocybin 25 mg dosing session

What Are the Treatments Tested in This Trial?

Interventions

• Psilocybin-assisted Psychotherapy

Trial Overview The study tests the safety and effectiveness of psilocybin-assisted psychotherapy in reducing feelings of hopelessness (demoralization) in cancer patients. It includes several therapy sessions, one or possibly two doses of psilocybin, and various mental health assessments.

How Is the Trial Designed?

Group I: advanced cancer participants Experimental Treatment 1 Intervention

Who Is Running the Clinical Trial?

Gustavo Vazquez

Lead Sponsor

Trials

2

Recruited

100+

Gustavo Vazquez

Lead Sponsor

Trials

2

Recruited

100+

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 study involving 18 older long-term AIDS survivor men, psilocybin-assisted group therapy was found to be feasible and relatively safe, with no serious adverse reactions reported and only mild expected side effects experienced by some participants.

Participants showed a significant reduction in demoralization levels from baseline to a 3-month follow-up, indicating potential efficacy for psilocybin therapy in addressing psychological distress in this population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Psilocybin-assisted group therapy for demoralized older long-term AIDS survivor men: An open-label safety and feasibility pilot study. Anderson, BT., Danforth, A., Daroff, PR., et al.[2023]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11271737/

Investigating the therapeutic efficacy of psilocybin in advanced ... Psilocybin-assisted therapy shows promising results in improving quality of life, pain control, and anxiety relief for patients with advanced cancer.

2. clinicaltrials.gov clinicaltrials.gov/study/NCT06818994

Safety and Efficacy of Psilocybin-assisted Psychotherapy ... Safety and Efficacy of Psilocybin-assisted Psychotherapy for Demoralization Syndrome in Patients Diagnosed With Advanced Stage Cancer.

3. cancer.gov cancer.gov/research/participate/clinical-trials-search/v?id=NCI-2023-04798

Psilocybin-Assisted Psychotherapy for the Treatment of ... This phase IIb trial studies the safety and effectiveness of psilocybin-assisted psychotherapy in treating anxiety, depression, and existential distress

4. acsjournals.onlinelibrary.wiley.com acsjournals.onlinelibrary.wiley.com/doi/full/10.1002/cncr.35127

Innovations in group‐based psilocybin‐assisted therapy of ... This article relates to: Psilocybin-assisted group therapy in patients with cancer diagnosed with a major depressive disorder

5. 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 ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7599297/

Psilocybin Therapy for AIDS Survivors: Safety & Feasibility We detected a clinically meaningful change in demoralization from baseline to 3-month follow-up (mean difference -5·78 [SD 6·01], ηp2 = 0·47, 90% CI 0·21–0·60).

7. wjgnet.com wjgnet.com/2218-4333/full/v15/i7/908.htm

Investigating the therapeutic efficacy of psilocybin in ... Psilocybin-assisted therapy shows promising results in improving quality of life, pain control, and anxiety relief for patients with advanced cancer.

8. acsjournals.onlinelibrary.wiley.com acsjournals.onlinelibrary.wiley.com/doi/10.1002/cncr.35010

Psilocybin‐assisted group therapy in patients with cancer ... This study explored the safety, feasibility, and efficacy of psilocybin-assisted therapy in patients with cancer and major depressive disorder.