Psilocybin-Assisted Therapy for the Treatment of Major Depressive Disorder in Patients With Non-Small Cell Lung Cancer

Not Applicable

Not yet recruiting

• Conditions: Lung Non-Small Cell Carcinoma; Unipolar Depression
• Interventions: Procedure: Biospecimen Collection; Other: Counseling; Other: Interview; Drug: Psilocybin; Other: Survey Administration

• Registration Number: NCT07216404
• Lead Sponsor: Alan Davis

Brief Summary

This phase II trial tests the safety and side effects of psilocybin in combination with therapy for the treatment of major depressive disorder in patients with non-small cell lung cancer. A cancer diagnosis is life-changing, resulting in significant levels of psychological symptoms, including a combination of depression, anxiety, stress, including feelings of existential distress (i.e., loss of meaning, demoralization, despair). Among all cancer patients, those diagnosed with lung cancer have the highest prevalence of mood disorders, such as depression (up to 40%) leading to profound deterioration in quality of life, prolonged hospital stays, poorer treatment adherence, decreased survival rates, and high rates of suicide (5- and 3-times higher than the general population and other cancer patients, respectively). Psilocybin is substance being studied in the treatment of anxiety or depression in patients with advanced cancer. It is taken from the mushroom Psilocybe mexicana. Psilocybin acts on the brain to cause hallucinations (sights, sounds, smells, tastes, or touches that a person believes to be real but are not real). Psilocybin in combination with therapy may be safe and effective in treating major depressive disorder in patients with non-small cell lung cancer.

Detailed Description

PRIMARY OBJECTIVE:

I. To determine the safety and acceptability of psilocybin-assisted psychotherapy with non-small cell lung cancer (NSCLC) patients.

SECONDARY OBJECTIVE:

I. To determine the efficacy of psilocybin-assisted therapy in the reduction of depression and the impact of treatment on quality of life, cancer-related stress, and existential distress.

OUTLINE:

Patients participate in two preparation therapy sessions over 4 hours each on days 7 and 14, then patients receive psilocybin orally (PO) on day 21 and participate in a single dosing therapy session for over 8-10 hours on study. Patients also complete two post-dosing therapy sessions over 2 hours each on days 22 and 28 on study. Patients additionally undergo blood and urine sample collection throughout the study.

After completion of study treatment, patients are followed up at 4 and 12 weeks.

Study Timeline

• Study First Submitted: 2025-09-29
• Status Verified: 2025-10
• Study First Submitted QC: 2025-10-09
• Last Update Submitted: 2025-10-09
• Study First Posted: 2025-10-14
• Last Update Posted: 2025-10-14
• Study Start: 2025-11-20
• Primary Completion: 2026-12-31
• Study Completion: 2026-12-31

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: All
• Target Recruitment: 10

Inclusion Criteria

• Individuals diagnosed with NSCLC, confirmed by pathology report
• Have a Karnofsky performance status >= 60
• Participants receiving chemotherapy, radiation therapy, and biologic therapies may participate while receiving those therapies if they are tolerating the therapy or treatment sufficiently to allow administration of oral psilocybin and if treatments do not result in meeting any of the medical exclusion criteria outlined below
• Moderate to severe symptoms of depression (GRID Hamilton Rating Scale for Depression [GRID-HAMD] > 16)
• English-speaking
• Over the age of 18
• Have given written informed consent
• Able to read
• Be judged by study team clinicians to be at low risk for suicidality, as defined by a score of =< 2 on the Columbia- Suicide Severity rating scale (C-SSRS) ideation subscale, 0 on the behavior subscale, and by overall clinical judgment; and
• Have limited lifetime use of hallucinogens (the following criteria are preferred: no use in the past 5 years; total hallucinogen use less than 10 times)

Exclusion Criteria

• GENERAL MEDICAL EXCLUSION CRITERIA

• Participants who are pregnant (as indicated by a positive urine pregnancy test assessed at intake and before each drug session) or nursing; participants who are of child-bearing potential and sexually active who are not practicing a highly effective means of birth control (i.e., implants, injectables, combined oral contraceptives, progestin containing intrauterine devices [IUDs], or vasectomized partner)

• Participants with partners of child-bearing potential who are sexually active and not practicing a highly effective means of contraception (i.e., condom with spermicidal foam/gel/film/cream/suppository)

• Cardiovascular conditions: Recent history of coronary artery disease or stroke, current uncontrolled angina, uncontrolled hypertension, a clinically significant electrocardiogram (ECG) abnormality as determined by a cardiologist and/or medical monitor (e.g., atrial fibrillation), prolonged corrected QT (QTc) interval (i.e., QTc > 450 msec), artificial heart valve, or transient ischemic attack (TIA) in the past year

• Systolic blood pressure (SBP) > 139 mm HG; diastolic blood pressure (DBP) > 89 mm HG; heart rate (HR) > 90 bpm (mean values of the four or more assessments will not exceed 139 mm Hg systolic, 89 mm Hg diastolic, and/or 90 beats per minute)

• Insulin-dependent diabetes

• Non-insulin dependent diabetes if recent history of symptomatic hypoglycemia

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

  • Unstable primary or secondary (e.g., metastatic) cerebral neoplasm. Stable is defined as treatment within prior 4 weeks or no immediate plans for treatment.
  • Unstable history of seizures
  • Cerebral aneurysm - unstable with plans for intervention or close monitoring
  • Clinical diagnosis of dementia
  • Clinical diagnosis of delirium

• In the investigator's opinion, abnormal and clinically significant results on the physical examination, vital signs, ECG, or laboratory tests at screening may constitute a risk for an individual exposed to psilocybin. This includes platelets below 100,000 platelets per cubic millimeter of blood, liver function tests three times the upper limit of normal, and creatine two times above the normal range. This also includes clinically significant abnormal electrolytes or low hemoglobin (below 10 g/L)

• Any acute condition that would, in the Investigator's judgment, place the subject at significant risk due to safety concerns or compliance with clinical study procedures (e.g., electrolyte imbalance, infection/inflammation, intestinal obstruction, inability to swallow medication, etc.)

• Under active treatment of an investigational agent in a clinical trial

• In the judgement of the clinician, patients currently taking psychoactive medication on a regular (e.g., daily) basis (e.g., cannabis, opiates, Ritalin), other than a daily selective serotonin reuptake inhibitors (SSRI), serotonin-norepinephrine reuptake inhibitors (SNRI), or bupropion (< 300 mg daily) (Patients will not be instructed to hold prescribed psychoactive medications)

• In the judgement of the clinician, patients who self-report or urine test positive for psychoactive medications (e.g., illicit opiates, amphetamines, cocaine) may be excluded, for example recent use by self-report but urine test negative may still be enrolled, while participants with impaired mental status will be excluded

• PSYCHIATRIC EXCLUSION CRITERIA

• Current or past history of meeting Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) criteria for schizophrenia spectrum or other psychotic disorders (except substance/medication-induced or due to another medical condition), or bipolar I or II disorder

• Current or history within one year of meeting DSM-5 criteria for a moderate or severe alcohol or other drug use disorder (excluding caffeine and tobacco)

• Have a first or second-degree relative with schizophrenia spectrum or other psychotic disorders (except substance/medication-induced or due to another medical condition) or bipolar I or II disorder

• Has a psychiatric condition that precludes the establishment of therapeutic rapport, as evidenced by long-term patterns of unstable relationships, a history of significant stress-related paranoia, and identity disturbances

• History of a medically significant suicide attempt as determined by the study team and principal investigator (PI)

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Supportive Care (counseling sessions, psilocybin)	Biospecimen Collection	Patients participate in two preparation therapy sessions over 4 hours each on days 7 and 14, then patients receive psilocybin PO on day 21 and participate in a single dosing therapy session for over 8-10 hours on study. Patients also complete two post-dosing therapy sessions over 2 hours each on days 22 and 28 on study. Patients additionally undergo blood and urine sample collection throughout the study.
Supportive Care (counseling sessions, psilocybin)	Counseling	Patients participate in two preparation therapy sessions over 4 hours each on days 7 and 14, then patients receive psilocybin PO on day 21 and participate in a single dosing therapy session for over 8-10 hours on study. Patients also complete two post-dosing therapy sessions over 2 hours each on days 22 and 28 on study. Patients additionally undergo blood and urine sample collection throughout the study.
Supportive Care (counseling sessions, psilocybin)	Interview	Patients participate in two preparation therapy sessions over 4 hours each on days 7 and 14, then patients receive psilocybin PO on day 21 and participate in a single dosing therapy session for over 8-10 hours on study. Patients also complete two post-dosing therapy sessions over 2 hours each on days 22 and 28 on study. Patients additionally undergo blood and urine sample collection throughout the study.
Supportive Care (counseling sessions, psilocybin)	Psilocybin	Patients participate in two preparation therapy sessions over 4 hours each on days 7 and 14, then patients receive psilocybin PO on day 21 and participate in a single dosing therapy session for over 8-10 hours on study. Patients also complete two post-dosing therapy sessions over 2 hours each on days 22 and 28 on study. Patients additionally undergo blood and urine sample collection throughout the study.
Supportive Care (counseling sessions, psilocybin)	Survey Administration	Patients participate in two preparation therapy sessions over 4 hours each on days 7 and 14, then patients receive psilocybin PO on day 21 and participate in a single dosing therapy session for over 8-10 hours on study. Patients also complete two post-dosing therapy sessions over 2 hours each on days 22 and 28 on study. Patients additionally undergo blood and urine sample collection throughout the study.

Primary Outcome Measures

Name	Time	Method
Ratings of suicidal ideation on the Columbia- Suicide Severity rating scale (C-SSRS)	At baseline, one day post-drug session, and 4 weeks post-drug session	Ratings of suicidal ideation on the C-SSRS will be summarized with means and standard deviations (SD) at baseline, one day post-drug session, and 4 weeks post-drug session. A mixed effects regression model will be fit containing a fixed effect for visit to test for a significant change in ratings of suicidal ideation from baseline to 4 weeks post drug session. Estimated mean differences will be presented with corresponding 95% confidence intervals (CI). An alpha level of 0.05 will be used to determine statistical significance.
Incidence of adverse events	At baseline, one day post-drug session, and 4 weeks post-drug session	Descriptive analysis of adverse event reporting logs will be conducted to determine if any serious adverse events have been reported related to psilocybin administration.
Acceptability of psilocybin-assisted therapy	At end of visit 3 (7 days prior to drug administration) and 4 weeks post-drug session	The mean (SD) change in Participant/Client Satisfaction Questionnaire levels between end of preparatory session 2 (visit 3; 7 days prior to drug administration) and 4 weeks post-drug session will be presented and a paired t-test will be used to test for a significant increase/decrease in acceptability. The estimated mean change will be presented with corresponding 95% confidence interval (CI). An alpha level of 0.05 will be used to determine statistical significance.
Satisfaction of psilocybin-assisted therapy	At end of visit 3 (7 days prior to drug administration) and 4 weeks post-drug session	The mean (SD) change in Participant/Client Satisfaction Questionnaire levels between end of preparatory session 2 (visit 3; 7 days prior to drug administration) and 4 weeks post-drug session will be presented and a paired t-test will be used to test for a significant increase/decrease in satisfaction. The estimated mean change will be presented with corresponding 95% confidence interval (CI). An alpha level of 0.05 will be used to determine statistical significance.

Secondary Outcome Measures

Name	Time	Method
Depression symptom severity	At baseline, end of visit 3 (7 days prior to drug administration), and 4 weeks post-drug session.	Mean (SD) ratings of depression symptom severity will be presented from baseline, end of preparatory session 2 (visit 3; 7 days prior to drug administration), and 4 weeks post-drug session. A mixed effects regression model will be fit containing a fixed effect for visit to test for a significant change in ratings of depressive symptom severity from baseline to 4 weeks post drug session. Estimated mean differences will be presented with corresponding 95% confidence intervals (CI). An alpha level of 0.05 will be used to determine statistical significance.

Trial Locations

Locations (1)

Ohio State University Comprehensive Cancer Center; 🇺🇸 Columbus, Ohio, United States