Psilocybin-assisted therapy for major depression in people with non-small cell lung cancer

Exploring the Safety, Acceptability, and Efficacy of Psilocybin Among Non-Small Cell Lung Cancer Patients With Major Depressive Disorder: A Proof-of-Concept Trial (DREAM LUNG STUDY)

This phase II trial tests whether a single oral dose of psilocybin combined with psychotherapy can reduce moderate-to-severe depression in adults with non-small cell lung cancer.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 10 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Ohio State University Comprehensive Cancer Center (Academic / other)
• Drugs / interventions: chemotherapy, radiation
• Locations: 1 site (Columbus, Ohio)
• Trial ID: NCT07216404 on ClinicalTrials.gov

What this trial studies

This phase II interventional trial gives adults with non-small cell lung cancer and moderate-to-severe depression preparatory psychotherapy sessions, a single supervised oral dose of psilocybin with an extended dosing therapy session, and post-dose integration sessions, with follow-up at 4 and 12 weeks. The protocol includes two preparatory therapy sessions, an 8–10 hour supervised dosing session on day 21, two shorter post-dosing therapy sessions, and repeated clinical ratings and biospecimen collection. Primary outcomes focus on safety and acceptability, while secondary outcomes measure changes in depressive symptoms, quality of life, cancer-related stress, and existential distress. Participants must meet performance status and suicidality criteria and be able to tolerate oral medication and attend in-person English-language sessions.

Who should consider this trial

Good fit: Adults (≥18) with pathologically confirmed non-small cell lung cancer, Karnofsky performance status ≥60, moderate-to-severe depression (GRID-HAMD >16), low suicidality, limited lifetime hallucinogen use, and ability to attend in-person English-language therapy sessions are ideal candidates.

Not a fit: Patients with high suicide risk, unstable medical conditions or concurrent treatments that prevent safe oral dosing, severe psychiatric comorbidity, extensive prior hallucinogen use, poor performance status, or inability to travel to Columbus, Ohio are unlikely to benefit or be eligible.

Why it matters

Potential benefit: If successful, this approach could rapidly reduce depressive symptoms and existential distress and improve quality of life and potentially cancer-treatment adherence for patients with NSCLC.

How similar studies have performed: Small randomized and open-label trials of psilocybin-assisted psychotherapy in advanced cancer and major depression have reported rapid and sometimes durable reductions in depression and anxiety, though larger confirmatory trials are still limited.

Eligibility criteria

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)

Where this trial is running

Columbus, Ohio

• Ohio State University Comprehensive Cancer Center — Columbus, Ohio, United States (Recruiting)

Study contacts

• Principal investigator: Alan K Davis, PhD — Ohio State University Comprehensive Cancer Center
• Study coordinator: Ohio State University Comprehensive Cancer Center

Conditions Lung Non-Small Cell Carcinoma; Unipolar Depression