Recruiting
Phase 2
Phase 3

Psilocybin Therapy

Sponsor:

NYU Langone Health

Code:

NCT05398484

Conditions

Advanced Cancer

Eligibility Criteria

Sex: All

Age: 21 - 70+

Healthy Volunteers: Not accepted

Interventions

Psilocybin 25 mgs

Niacin 100mg

Psychotherapy

Study Details

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.

Conditions

Advanced Cancer

Study ID

NCT05398484

Start date

May 24, 2023

Status verified date

Dec, 2025

Completion date

Jan 1, 2027

Anticipated

Primary completion date

Jan 1, 2027

Anticipated

Eligibility Criteria

Eligibility Criteria

Sex: All

Age: 21 - 70+

Healthy Volunteers: Not accepted

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)

Study Design

Enrollment

200 participants

Anticipated

Allocation

Randomized

Intervention Model

Parallel Assignment

Primary purpose

Treatment

Interventions and Outcome Measures

Arms

experimental: 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).

active comparator: 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.

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.

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.

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.

Primary outcome measure

  • Change in Structured Interview Guide for the Hamilton Anxiety Scale (HAM-A): SIGH-A Score [ Time Frame: Baseline, Week 8 ]

Central Contacts and Locations

Central contacts

Sydney Weiner, MA

212-263-6283sydney.weiner@nyulangone.org

Stephen Ross, MD

212-263-6289stephen.ross@nyulangone.org

Locations

University of Colorado Anschutz Medical campus (CU AMC)

Recruiting

Aurora, Colorado, United States, 80045

Contacts

Stacy Fischer, MD

303-724-2406Stacy.Fischer@cuanschutz.edu

Mary Mancuso

303-724-5729mary.mancuso@cuanschutz.edu

Principal Investigator:

Stacy Fischer, MD

NYU Langone Health

Recruiting

New York, New York, United States, 10016

Contacts

Sydney Weiner, MA

212-263-6283sydney.weiner@nyulangone.org

Stephen Ross, MD

212-263-6289stephen.ross@nyulangone.org

Principal Investigator:

Stephen Ross, MD

More Information

Sponsor

NYU Langone Health

Last update posted

Dec 4, 2025

Last verified

Dec, 2025

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-10. This information was provided to ClinicalTrials.gov by NYU Langone Health on 2025-12-04.