Psilocybin Cancer Anxiety Study

Study Overview
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Brief Summary
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The primary objective of this double-blind, placebo-controlled pilot study is to assess the efficacy of psilocybin administration (4-phosphoryloxy-N,N-dimethyltryptamine), a serotonergic psychoactive agent, on psychosocial distress, with the specific primary outcome variable being anxiety associated with cancer. Secondary outcome measures will look at the effect of psilocybin on symptoms of pain perception, depression, existential/psychospiritual distress, attitudes towards disease progression and death, quality of life, and spiritual/mystical states of consciousness. In addition, a secondary objective of the study is to determine the feasibility of administering psilocybin to this patient population, with regards to the following issues: safety, patient recruitment, consent for treatment, and retention. The duration of the proposed investigation will be long enough to administer the drug one time to each of thirty-two patients and to conduct follow-up assessments. This study is separate but similar to a recently completed study at the Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center, run by a psychiatrist, Dr. Charles Grob. Although the outcomes measures would be similar to those used as in the Grob study, the proposed dose of psilocybin is higher at 0.3mg/kg and the total subjects for the study would be 32 instead of 12. The study utilizes a cross-over design at 7 weeks and includes prospective follow-up of 6 months duration. This study has been approved by the Bellevue Psychiatry Research Committee, the NYU Oncology PRMC Committee, the Food and Drug Administration (FDA) through the issuance of an IND (77,138), the New York University School of Medicine Institutional Review Board (NYU IRB), the Health and Hospitals Corporation (HHC)-New York University (NYU) Clinical Translational Science Institute (CTSI), the NYU Bluestone Center for Clinical Research, and the Drug Enforcement Agency (DEA) through the issuance of a schedule I license. It is hypothesized that a one time experience with psilocybin will occasion dramatic shifts in consciousness and awareness that will lead to short-term (ie hours to days) and long-term (up to 6 months in this study, following the administration of the second dosing, either psilocybin or placebo) improvement in anxiety, depression, and pain associated with advanced cancer. The exact mechanism of action is unclear but based on studies done in the 60's using serotonergic hallucinogens in patients with advanced cancer, improvements in anxiety levels, mood and pain were reported. However, a treatment model developed by the famous British psychiatrist Humphrey Osmond, offers one possibility. In this model, serotonergic hallucinogens' therapeutic mechanism lies in their ability to allow the individual to access novel dimensions of consciousness and their efficacy or lack thereof relies on whether a transcendent and mystical state of awareness is attained. Another possible mechanism relates to what Dobkin de Rios and Grob have described as 'managed altered states of consciousness,' where the power of suggestibility, occurring in a safe setting, allows one to transcend a particular state of consciousness (i.e. anxiety and depression associated with advanced illness) as a means to facilitate emotional discharge and to manage irreconcilable conflict.

Official Title
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Effects of Psilocybin on Anxiety and Psychosocial Distress in Cancer Patients

Conditions
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Cancer

Intervention / Treatment
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* Drug: Psilocybin
* Drug: Niacin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age: 18-76 Current or historical diagnosis of cancer Projected life expectancy of at least one year DSM-IV diagnoses: Acute Stress Disorder, Generalized Anxiety Disorder, Anxiety Disorder due to cancer, Adjustment Disorder with anxious features Any stage of cancer diagnosis Exclusion Criteria: Epilepsy Renal disease Diabetes Abnormal liver function Severe cardiovascular disease Malignant Hypertension Baseline blood pressure must be less than or equal to 140/90 Personal history or immediate family members with schizophrenia, bipolar affective disorder, delusional disorder, schizoaffective disorder or other psychotic spectrum illness Current substance use disorder Medication contraindications: anti-seizures medications, insulin, oral hypoglycemics, clonidine, aldomet, cardiovascular medications, anti-psychotics (first and second generation), anti-depressants and mood stabilizers

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 76 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Psilocybin<br>Drug intervention | Drug: Psilocybin<br>* Psilocybin is a serotonergic hallucinogen that will be administered once at a dose of 0.3mg/kg<br>* Other names: 4-phosphoryloxy-N,N-dimethyltryptamine;Drug: Niacin<br>* Psilocybin and niacin will be administered in identically appearing opaque, size 0 gelatin capsules with approximately 180ml of water. The niacin dose will be 250mg<br>|
| Active Comparator: Niacin<br>Active control | Drug: Psilocybin<br>* Psilocybin is a serotonergic hallucinogen that will be administered once at a dose of 0.3mg/kg<br>* Other names: 4-phosphoryloxy-N,N-dimethyltryptamine;Drug: Niacin<br>* Psilocybin and niacin will be administered in identically appearing opaque, size 0 gelatin capsules with approximately 180ml of water. The niacin dose will be 250mg<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| HADS Anxiety | Hospital Anxiety and Depression Scale (HADS) used for measuring anxiety; Scored on a scale of 0-21 (higher score more anxiety) | 2-4 weeks prior to drug administration | 
| HADS Anxiety | Hospital Anxiety and Depression Scale (HADS) used for measuring anxiety; Scored on a scale of 0-21 (higher score more anxiety) | 1 day prior to drug administration 1 | 
| HADS Anxiety | Hospital Anxiety and Depression Scale (HADS) used for measuring anxiety; Scored on a scale of 0-21 (higher score more anxiety) | 1 day post drug administration 1 | 
| HADS Anxiety | Hospital Anxiety and Depression Scale (HADS) used for measuring anxiety; Scored on a scale of 0-21 (higher score more anxiety) | 6 weeks post drug administration 1 | 
| HADS Anxiety | Hospital Anxiety and Depression Scale (HADS) used for measuring anxiety; Scored on a scale of 0-21 (higher score more anxiety) | 1 day prior to drug administration 2 | 
| HADS Anxiety | Hospital Anxiety and Depression Scale (HADS) used for measuring anxiety; Scored on a scale of 0-21 (higher score more anxiety) | 6 weeks post drug administration 2 | 
| HADS Anxiety | Hospital Anxiety and Depression Scale (HADS) used for measuring anxiety; Scored on a scale of 0-21 (higher score more anxiety) | 26 weeks post drug administration 2 | 
| State-Trait Anxiety Inventory (STAI) State | STAI scores 20-80 (higher score more anxiety). Commonly classified as no or low anxiety (20-37), moderate anxiety (38-44), and high anxiety (45-80). | 2-4 weeks prior to drug administration/ Baseline | 
| STAI State | STAI scores 20-80 (higher score more anxiety). Commonly classified as no or low anxiety (20-37), moderate anxiety (38-44), and high anxiety (45-80). | 1 day prior to drug administration 1 | 
| STAI State | STAI scores 20-80 (higher score more anxiety). Commonly classified as no or low anxiety (20-37), moderate anxiety (38-44), and high anxiety (45-80). | 1 day post drug administration 1 | 
| HADS Depression | 0-21 (higher score more depression) | 2-4 weeks prior to drug administration/ Baseline | 
| STAI State | STAI scores 20-80 (higher score more anxiety). Commonly classified as no or low anxiety (20-37), moderate anxiety (38-44), and high anxiety (45-80). | 6 weeks post drug administration 1 | 
| STAI State | STAI scores 20-80 (higher score more anxiety). Commonly classified as no or low anxiety (20-37), moderate anxiety (38-44), and high anxiety (45-80). | 1 day prior to drug administration 2 | 
| STAI State | STAI scores 20-80 (higher score more anxiety). Commonly classified as no or low anxiety (20-37), moderate anxiety (38-44), and high anxiety (45-80). | 1 day post drug administration 2 | 
| STAI State | STAI scores 20-80 (higher score more anxiety). Commonly classified as no or low anxiety (20-37), moderate anxiety (38-44), and high anxiety (45-80). | 6 weeks post drug administration 2 | 
| STAI State | STAI scores 20-80 (higher score more anxiety). Commonly classified as no or low anxiety (20-37), moderate anxiety (38-44), and high anxiety (45-80). | 26 weeks post drug administration 2 | 
| STAI Trait | STAI scores 20-80 (higher score more anxiety). Commonly classified as no or low anxiety (20-37), moderate anxiety (38-44), and high anxiety (45-80). | 2-4 weeks prior to drug administration/ Baseline | 
| STAI Trait | STAI scores 20-80 (higher score more anxiety). Commonly classified as no or low anxiety (20-37), moderate anxiety (38-44), and high anxiety (45-80). | 1 day prior to drug administration 1 | 
| STAI Trait | STAI scores 20-80 (higher score more anxiety). Commonly classified as no or low anxiety (20-37), moderate anxiety (38-44), and high anxiety (45-80). | 1 day post drug administration 1 | 
| STAI Trait | STAI scores 20-80 (higher score more anxiety). Commonly classified as no or low anxiety (20-37), moderate anxiety (38-44), and high anxiety (45-80). | 6 weeks post drug administration 1 | 
| STAI Trait | STAI scores 20-80 (higher score more anxiety). Commonly classified as no or low anxiety (20-37), moderate anxiety (38-44), and high anxiety (45-80). | 1 day prior to drug administration 2 | 
| STAI Trait | STAI scores 20-80 (higher score more anxiety). Commonly classified as no or low anxiety (20-37), moderate anxiety (38-44), and high anxiety (45-80). | 1 day post drug administration 2 | 
| STAI Trait | STAI scores 20-80 (higher score more anxiety). Commonly classified as no or low anxiety (20-37), moderate anxiety (38-44), and high anxiety (45-80). | 6 weeks prior to drug administration 2 | 
| STAI Trait | STAI scores 20-80 (higher score more anxiety). Commonly classified as no or low anxiety (20-37), moderate anxiety (38-44), and high anxiety (45-80). | 6 weeks post drug administration 2 | 
| HADS Depression | 0-21 (higher score more depression) | 1 day prior to drug administration 1 | 
| HADS Depression | Hospital Anxiety and Depression Scale (HADS) used for measuring depression; Scored on a scale of 0-21 (higher score more depression) | 1 day post drug administration 1 | 
| HADS Depression | Hospital Anxiety and Depression Scale (HADS) used for measuring depression; Scored on a scale of 0-21 (higher score more depression) | 6 weeks post drug administration 1 | 
| HADS Anxiety | 0-21 (higher score more anxiety) | 1 day post drug administration 2 | 
| HADS Depression | Hospital Anxiety and Depression Scale (HADS) used for measuring depression; Scored on a scale of 0-21 (higher score more depression) | 1 day post drug administration 2 | 
| HADS Depression | Hospital Anxiety and Depression Scale (HADS) used for measuring depression; Scored on a scale of 0-21 (higher score more depression) | 6 weeks post drug administration 2 | 
| HADS Depression | Hospital Anxiety and Depression Scale (HADS) used for measuring depression; Scored on a scale of 0-21 (higher score more depression) | 26 weeks post drug administration 2 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Death Anxiety Scale | 0-15 (higher score more death anxiety) | 26 weeks post drug administration 2 | 
| Death Anxiety Scale | 0-15 (higher score more death anxiety) | 2 weeks post drug administration 1 | 
| Death Transcendence Scale | 0-60 (higher score more death transcendence) | 2-4 weeks prior to drug administration/ Baseline | 
| Hopelessness | 0-16 (higher score more hopeless) | Baseline | 
| Death Anxiety Scale | 0-15 (higher score more death anxiety) | 2-4 weeks prior to drug administration/ Baseline | 
| Death Transcendence Scale | 0-60 (higher score more death transcendence) | 2 weeks post drug administration 1 | 
| Hopelessness | 0-16 (higher score more hopeless) | 2 weeks post drug administration 1 | 
| Hopelessness | 0-16 (higher score more hopeless) | 26 weeks post drug administration 2 | 
| Demoralization Scale | 0-96 (higher score more demoralized) | 2-4 weeks prior to drug administration/ Baseline | 
| Demoralization Scale | 0-96 (higher score more demoralized) | 2 weeks post drug administration 1 | 
| Demoralization Scale | 0-96 (higher score more demoralized) | 26 weeks post drug administration 2 | 
| QoL Physical Health Scale | 4-20 (higher score improved quality of life domain) | 2-4 weeks prior to drug administration/ Baseline | 
| QoL Physical Health Scale | 4-20 (higher score improved quality of life domain) | 2 weeks post drug administration 1 | 
| QoL Physical Health Scale | 4-20 (higher score improved quality of life domain) | 26 weeks post drug administration 2 | 
| QoL Psychological Scale | 4-20 (higher score improved quality of life domain) | 2-4 weeks prior to drug administration/ Baseline | 
| QoL Psychological Scale | 4-20 (higher score improved quality of life domain) | 2 weeks post drug administration 1 | 
| QoL Psychological Scale | 4-20 (higher score improved quality of life domain) | 26 weeks post drug administration 2 | 
| QoL Social Relationships Scale | 4-20 (higher score improved quality of life domain) | 2-4 weeks prior to drug administration/ Baseline | 
| QoL Social Relationships Scale | 4-20 (higher score improved quality of life domain) | 2 weeks post drug administration 1 | 
| QoL Social Relationships Scale | 4-20 (higher score improved quality of life domain) | 26 weeks post drug administration 2 | 
| QoL Environment Scale | 4-20 (higher score improved quality of life domain) | 2-4 weeks prior to drug administration/ Baseline | 
| QoL Environment Scale | 4-20 (higher score improved quality of life domain) | 2 weeks post drug administration 1 | 
| QoL Environment Scale | 4-20 (higher score improved quality of life domain) | 26 weeks post drug administration 2 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Cancer, Anxiety, Depression, Hallucinogens