Psilocybin-Assisted Therapy for the Treatment of... — Clinical Trial Details

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

This Phase II, single-group trial (n=10) will evaluate the safety, acceptability, and efficacy of psilocybin-assisted psychotherapy in patients with non-small cell lung cancer (NSCLC) who also suffer from major depressive disorder. The study aims to determine the impact of psilocybin on depression symptoms, quality of life, cancer-related stress, and existential distress, given the high prevalence of mood disorders in lung cancer patients. Participants will undergo two preparation therapy sessions before receiving oral psilocybin on day 21, followed by an 8-10 hour dosing therapy session. Post-dosing, two additional therapy sessions will occur on days 22 and 28. Throughout the study, blood and urine samples will be collected, and participants will be monitored for adverse events and suicidal ideation at various intervals. The trial will follow participants for 4 and 12 weeks after treatment completion to assess long-term effects.

Detailed Description

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.

Study Arms & Interventions

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.

Interventions

Psilocybin

Participants

Ages

18 – ?

Sexes

All

BMI

Psychosis History

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)

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