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

NCT07216404 | Recruiting Phase 2 DMC FDA Drug

• 2 other identifiers: OSU-24170NCI-2025-06353
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 1

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.

Conditions

Lung Non-Small Cell Carcinoma; Unipolar Depression

Outcome Measures

Primary Outcomes (4)

• Ratings of suicidal ideation on the Columbia- Suicide Severity rating scale (C-SSRS)

  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.

  At baseline, one day post-drug session, and 4 weeks post-drug session

• Incidence of adverse events

  Descriptive analysis of adverse event reporting logs will be conducted to determine if any serious adverse events have been reported related to psilocybin administration.

  At baseline, one day post-drug session, and 4 weeks post-drug session

• Acceptability of psilocybin-assisted therapy

  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.

  At end of visit 3 (7 days prior to drug administration) and 4 weeks post-drug session

• Satisfaction of psilocybin-assisted therapy

  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.

  At end of visit 3 (7 days prior to drug administration) and 4 weeks post-drug session

Secondary Outcomes (6)

• Depression symptom severity

  At baseline, end of visit 3 (7 days prior to drug administration), and 4 weeks post-drug session.

• Quality of life (Medical Outcomes Study-Short Form-12)

  AT baseline, preparatory session 2, and 4 weeks post-drug session

• Quality of Life (European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Lung Cancer 13)

  At baseline, preparatory session 2, and 4 weeks post-drug session

• Quality of Life (Impact of Events Scale-Revised)

  At baseline, preparatory session 2, and 4 weeks post-drug session

• Quality of Life (Demoralization Scale)

  At baseline, preparatory session 2, and 4 weeks post-drug session

Study Arms (1)

Supportive Care (counseling sessions, psilocybin)

EXPERIMENTAL

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.

Procedure: Biospecimen Collection; Other: Counseling; Other: Interview; Drug: Psilocybin; Other: Survey Administration

Interventions

Biospecimen Collection PROCEDURE

Undergo blood and urine sample collection

Also known as: Biological Sample Collection, Biospecimen Collected, Specimen Collection

Supportive Care (counseling sessions, psilocybin)

Counseling OTHER

Participate in therapy sessions

Also known as: Counseling Intervention

Supportive Care (counseling sessions, psilocybin)

Interview OTHER

Ancillary studies

Supportive Care (counseling sessions, psilocybin)

Psilocybin DRUG

Given PO

Also known as: [3-[2-(dimethylamino)ethyl]-1H-indol-4-yl] dihydrogen phosphate

Supportive Care (counseling sessions, psilocybin)

Survey Administration OTHER

Ancillary studies

Supportive Care (counseling sessions, psilocybin)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Individuals diagnosed with NSCLC, confirmed by pathology report
• Have a Karnofsky performance status \>= 60

You may not qualify if:

• 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)
• 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.

Sponsors & Collaborators

• Alan Davis: lead

Study Sites (1)

Ohio State University Comprehensive Cancer Center

Columbus, Ohio, 43210, United States

RECRUITING

Related Links

• The Jamesline

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung; Depressive Disorder

Interventions

Specimen Handling; Counseling; Interviews as Topic; Psilocybin

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases; Mood Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Investigative Techniques; Mental Health Services; Behavioral Disciplines and Activities; Community Health Services; Health Services; Health Care Facilities Workforce and Services; Data Collection; Epidemiologic Methods; Health Care Evaluation Mechanisms; Quality of Health Care; Health Care Quality, Access, and Evaluation; Public Health; Environment and Public Health; Indole Alkaloids; Alkaloids; Heterocyclic Compounds; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Tryptamines; Indolizidines; Indolizines

Study Officials

• Alan K Davis, PhD

  Ohio State University Comprehensive Cancer Center

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Ohio State University Comprehensive Cancer Center

CONTACT

18002935066; osucccclincaltrials@osumc.edu

Michelle Pham, M.S.

CONTACT

pham.303@osu.edu

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: SUPPORTIVE CARE
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: September 29, 2025
• First Posted: October 14, 2025
• Study Start: January 1, 2026
• Primary Completion (Estimated): October 31, 2027
• Study Completion (Estimated): October 31, 2027
• Last Updated: May 14, 2026

Record last verified: 2026-05

Locations

US (1)