Psilocybin Therapy in Advanced Cancer

• Status: Not yet recruiting
• Trial end date: 2027-01-01
• Target enrollment: 0
• Participant gender: All

Summary

The purpose of this research is to study the safety and effects of single-dose psilocybin 25mg versus an active placebo (single dose psilocybin 1mg) in the treatment of anxiety, depression, and existential distress (i.e. loss of meaning and hope; fear of death) in advanced cancer (i.e. stage 3 or 4). Study medications will be administered in conjunction with brief psychotherapy that is designed to treat anxiety, depression and existential distress in advanced cancer.

• Phase: Phase 2/Phase 3
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: NYU Langone Health
• Collaborator: National Cancer Institute (NCI)
• Treatments: Psilocybin

Criteria

Inclusion Criteria:

• Aged ≥ 21

• Diagnosis of Advanced (i.e. stage 3 or 4 solid tumors) Cancer

• Functional Status defined Eastern Cooperative Oncology Group (ECOG) ≤2 and Palliative Performance Scale (PPS) ≥60%

• Clinically significant Depression/Anxiety, with Hospital Anxiety and Depression (HADS) Total score >12 at Screening OR Clinically significant Existential Distress defined as Demoralization Scale Total score >30 and clinically significant Anxiety and Depression defined as HADS total >8

Exclusion Criteria:

• Unstable medical conditions or serious abnormalities of complete blood count, chemistries, or ECG that in the opinion of the study physician would preclude safe participation in the trial. Some examples include

• Congestive heart failure

• Clinically significant arrhythmias (e.g. ventricular fibrillation, torsades) or clinically significant ECG abnormality (i.e. QTC interval > 450)

• Recent acute myocardial infarction or evidence of ischemia

• Malignant hypertension

• Congenital long QT syndrome

• Acute renal failure

• Severe hepatic impairment

• Respiratory failure

• Risk for hypertensive crisis defined as Screening, Baseline, and Medication Session (prior to dosing) Blood Pressure >140/90 mmHg.

• Significant central nervous system (CNS) pathology. Some examples include:

• Primary or secondary cerebral neoplasm

• Epilepsy

• History of stroke

• Cerebral aneurysm

• Dementia

• Delirium

• Primary psychotic or affective psychotic disorders. Some examples include current or past DSM-V criteria for:

• Schizophrenia spectrum disorders

• Schizoaffective disorder

• Bipolar I with psychotic features

• Major Depressive Disorder with psychotic features

• High risk of adverse emotional or behavioral reaction based on investigator's clinical evaluation. Examples include

• Evidence of serious personality disorder (e.g. anti-social personality disorder)

• Agitation

• Violent behavior

• Active substance use disorders (SUDs) defined as: DSM-5 criteria for alcohol or drug use disorder (excluding caffeine and nicotine) within the past year

• Extensive use of serotonergic hallucinogens (e.g. LSD, psilocybin) defined as:

• Any use in the last 12 months

• >25 lifetime uses

• Clinically significant suicidality or high risk of completed suicide defined as

• Active suicidal behavior (interrupted or aborted attempt; preparatory acts) as assessed by Baseline Version of CSSRS. If CSSRS items are 4 or 5, participant is ineligible

• History of suicide attempt(s) within the past year

• History of hallucinogen persisting perception disorder (HPPD)

• Cognitive impairment as defined by: Montreal Cognitive Assessment Test (MoCA) < 23

• Concurrent Medications

• Antidepressants

• Centrally-acting serotonergic agents (e.g. MAO inhibitors)

• Antipsychotics (e.g. first and second generation)

• Mood stabilizers (e.g. lithium, valproic acid)

• Aldehyde dehydrogenase inhibitors (e.g. disulfiram)

• Significant inhibitors of UGT 1A0 or UGT 1A10