Psilocybin Therapy in Advanced Cancer

NCT ID: NCT05398484

Last Updated: 2025-12-04

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE2/PHASE3
• Total Enrollment: 200 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2023-05-24
• Study Completion Date: 2027-01-01

Brief Summary

The purpose of this research is to study the safety and effects of single-dose psilocybin 25mg versus an active placebo (single dose niacin 100mg) 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.

Detailed Description

This trial is designed to evaluate efficacy and psychological mechanisms of single-dose psilocybin-assisted psychotherapy (PAP) to treat psychiatric (anxiety, depression) and existential distress (demoralization, death anxiety), and quality-of-life (QOL), in 200 outpatients with late-stage or advanced cancer. The study will assess the strength and durability of therapeutic effects in a double-blind, parallel-design, placebo-controlled, two-center RCT comparing a single 25mg oral 'high' dose of psilocybin to a single 100mg dose of niacin (active placebo), both delivered in conjunction with a psychotherapy platform.

Conditions

Advanced Cancer

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

Participants receiving Study Drug

Advanced cancer participants will receive experimental medication, psilocybin (25mg). In addition to the pharmacologic intervention, participants will receive a manualized psychotherapy platform. The combination of interventions is referred to as psilocybin-assisted psychotherapy (PAP).

Group Type: EXPERIMENTAL

Psilocybin 25 mgs

Intervention Type: DRUG

One capsule containing 25mg of psilocybin will be administered with water orally. The appearance of psilocybin is Size 2 HPMC opaque.

Psychotherapy

Intervention Type: BEHAVIORAL

The manualized psychotherapy platform will consist of 6 hours of preparatory psychotherapy (prior to the single medication session) and 8 hours of integration psychotherapy following the dosing session.

Participants receiving Placebo

Advanced cancer participants will receive active placebo - single dose of niacin (100mg). In addition to the placebo, participants will receive the same manualized psychotherapy platform as the experimental arm.

Group Type: ACTIVE_COMPARATOR

Niacin 100mg

Intervention Type: DRUG

One capsule contains 100mg of niacin will be administered with water orally. The appearance of the active placebo is Size 2 HPMC opaque.

Psychotherapy

Intervention Type: BEHAVIORAL

The manualized psychotherapy platform will consist of 6 hours of preparatory psychotherapy (prior to the single medication session) and 8 hours of integration psychotherapy following the dosing session.

Interventions

Psilocybin 25 mgs

One capsule containing 25mg of psilocybin will be administered with water orally. The appearance of psilocybin is Size 2 HPMC opaque.

Intervention Type: DRUG

Niacin 100mg

One capsule contains 100mg of niacin will be administered with water orally. The appearance of the active placebo is Size 2 HPMC opaque.

Intervention Type: DRUG

Psychotherapy

The manualized psychotherapy platform will consist of 6 hours of preparatory psychotherapy (prior to the single medication session) and 8 hours of integration psychotherapy following the dosing session.

Intervention Type: BEHAVIORAL

Eligibility Criteria

Inclusion Criteria

• Aged ≥ 21
• Diagnosis of Advanced Cancer defined as:

• Solid tumors to include stage 3 or 4, metastatic illness, or recurrent illness
• Hematologic malignancies to include, but not limited to, Stage 3 or 4 non-Hodgkins lymphoma, late-stage multiple myeloma or second-line therapy for multiple myeloma, and all forms of acute myeloid leukemia
• Functional Status defined as: Eastern Cooperative Oncology Group (ECOG) ≤2 and Palliative Performance Scale (PPS) ≥60%
• Clinically significant Anxiety defined as SIGH-A >17 at Screening
• Have an identified support person: agree to be accompanied home (or to an otherwise safe destination) by the support person, or another responsible party, following dosing
• Participants of childbearing potential must agree to practice an effective means of birth control throughout the duration of the study. A person of childbearing potential is anyone assigned female or intersex at birth who has experienced menarche and who has not undergone surgical sterilization (e.g., hysterectomy, bilateral salpingectomy, bilateral oophorectomy) or has not completed menopause. Menopause is defined clinically as 12 months of amenorrhea in a person over age 45 in the absence of other biological, physiological, or pharmacological causes.

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-5 criteria for:

• Schizophrenia spectrum disorders
• Schizoaffective disorder
• Bipolar I with psychotic features
• Major Depressive Disorder with psychotic features
• Family history of first-degree relative with psychotic or serious bipolar spectrum illness. Examples include first-degree relative with:

• Schizophrenia spectrum disorders
• Schizoaffective disorder
• Bipolar I with psychotic features
• High risk of adverse emotional or behavioral reaction based on investigator's clinical evaluation. Examples include:

• 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 C-SSRS. If C-SSRS items are 4 or 5, participant is ineligible
• History of suicide attempt(s) within the past year
• Have any suicidal ideation or thoughts, in the opinion of the study physician or PI, that presents a serious risk of suicidal or self-injurious behavior
• 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
• Niacin. Note: If taking any supplement containing niacin, agrees to suspend use for at least five days prior to dosing and for the duration of the study
• Have a positive urine drug test including Amphetamines, Barbiturates, Buprenorphine, Benzodiazepines, Cocaine, Cannabis, Methamphetamine, MDMA, Methadone, Opiates (Morphine, Oxycodone), Phencyclidine (PCP), and Tetrahydrocannabinol (THC).

• Note: Prescribed opiate medications (e.g., cancer-related pain) will be allowed to continue through the study period for participants who have been on a stable dose of such medicine for at least 1 month prior to Screening, as determined during review of concomitant medications.
• Note: Prescribed benzodiazepine medications and non-benzodiazepine sleeping medications will be allowed to continue through the study period for participants who have been on a stable dose of such a medicine for at least 6 weeks prior to Screening, as determined during review of concomitant medications.
• Note: Participants using cannabis, including legal cannabis, for any purposes must agree to refrain from use beginning at Screening, as confirmed with a negative Baseline drug test, and through to the end of the study.
• Note: Participants using prescribed psychostimulants (amphetamines and Ritalin), must agree to refrain from use two weeks prior to baseline visit, as confirmed with a negative Baseline drug test, and through to the end of the study.
• Have a psychiatric condition judged to be incompatible with establishment of rapport with the study therapists or safe exposure to psilocybin
• Participants who are pregnant, as indicated by a positive urine pregnancy test at Screening, Baseline, or prior to dosing on medication administration sessions. Participants who intend to become pregnant during the study or who are currently nursing.
• Have any psychological or physical symptom, medication or other relevant finding prior to randomization, based on the clinical judgment of the PI or relevant clinical study staff that would make a participant unsuitable for the study.
• Have an allergy or intolerance to any of the materials contained in either drug product
• Be enrolled in another clinical trial assessing intervention(s) for anxiety, depression, and/or existential distress (e.g., pharmacologic or psychotherapeutic interventions)

• Minimum Eligible Age: 21 Years
• Maximum Eligible Age: 100 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: collaborator

NYU Langone Health

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Stephen Ross, MD

Role: PRINCIPAL_INVESTIGATOR

NYU Langone Medical Center

Locations

University of Colorado Anschutz Medical campus (CU AMC)

Aurora, Colorado, United States

Site Status: RECRUITING

NYU Langone Health

New York, New York, United States

Site Status: RECRUITING

Countries

United States

Central Contacts

Sydney Weiner, MA

Role: CONTACT

sydney.weiner@nyulangone.org

212-263-6283

Stephen Ross, MD

Role: CONTACT

stephen.ross@nyulangone.org

212-263-6289

Facility Contacts

Stacy Fischer, MD

Role: primary

Stacy.Fischer@cuanschutz.edu

303-724-2406

Mary Mancuso

Role: backup

mary.mancuso@cuanschutz.edu

303-724-5729

Sydney Weiner, MA

Role: primary

sydney.weiner@nyulangone.org

212-263-6283

Stephen Ross, MD

Role: backup

stephen.ross@nyulangone.org

212-263-6289

References

Schipper S, Nigam K, Schmid Y, Piechotta V, Ljuslin M, Beaussant Y, Schwarzer G, Boehlke C. Psychedelic-assisted therapy for treating anxiety, depression, and existential distress in people with life-threatening diseases. Cochrane Database Syst Rev. 2024 Sep 12;9(9):CD015383. doi: 10.1002/14651858.CD015383.pub2.

Reference Type: DERIVED

PMID: 39260823 (View on PubMed)

Other Identifiers

22-00498

Identifier Type: -

Identifier Source: org_study_id