Psilocybin-Assisted Psychotherapy in Patients With Advanced Cancer on Maintenance Therapy

Eligibility Criteria

• 1. Participants must have one of the following histology documented tumor types: non-small cell lung carcinoma, renal cell carcinoma, urothelial carcinoma, prostate cancer, head and neck squamous cell carcinoma, ovarian cancer, breast cancer, gastric/GEJ cancer, cervical, anal, or MSI-high
• 2. Documentation of locally advanced, recurrent, or metastatic incurable malignancy that has partially responded or progressed after at least 1 available standard therapy and disease is stable (no progression of disease for 3 months or more on current treatment regimen)
• 3. No prior grade 3 AEs on current standard of care cancer treatment regimen;
• 4. Age ≥ 25 years; as by the age of 25 brain is fully developed.
• 5. Have a DSM-V psychiatric diagnosis, as determined by the SCID (Structured Clinical Interview for DSM, by a board certified psychiatrist), of one or more of the following Axis I psychiatric disorders that is judged to have been precipitated by the psychological stress of the cancer diagnosis: Generalized Anxiety Disorder; Acute Stress Disorder; Posttraumatic Stress Disorder; Major Depressive Disorder; Dysthymic Disorder; Adjustment Disorder with Anxiety; Adjustment Disorder with Depressed Mood; Adjustment Disorder with Mixed Anxiety and Depressed Mood; Adjustment Disorder with Disturbance of Conduct; Adjustment Disorder with Disturbance of Emotions and Conduct. Psychiatric diagnosis are determined by a MD Anderson board certified psychiatrist.
• 6. At least 6 months life expectancy as per primary medical oncologist.
• 7. Have an ECOG performance status of 0, 1, or 2.
• 8. Must have no major cognitive impairment and be oriented to person, place, and time (e.g. mini mental exam).
• 9. Must demonstrate willingness to travel to MD Anderson Cancer center for all treatment and follow-up sessions, as well as consent to complete all evaluation instruments and assessments.
• 10. Agree to abstain from any nicotine products for at least 12 hours prior to psilocybin administration until approximately 12 hours after (or when all post-session questionnaires have been completed) as well as on days of salivary sample collection.
• 11. Refrain from any psychoactive drugs (including alcohol) for 48 hours prior to psilocybin sessions (except as described above for nicotine and caffeine) and must refrain from psychoactive drugs 12 hours after psilocybin sessions. Must consent to urine drug screen (UDS) which will be given before receiving psilocybin. Participants with positive drug test will be retested (UDS) after 6 weeks and included if the repeated UDS is negative. Participant tested positive for a prescribed substance are eligible. Participant failing on the 2nd test (UDS) will be excluded.
• 12. Must be free from any regularly scheduled psychotropic (antidepressant/anxiolytic class) medications and those with primary MOA on serotonergic neurons (e.g., ondansetron) for a minimum of 2 weeks prior to study or 4 weeks for SSRI. Intermittent or PRN use of short-acting anxiolytics may be permitted as defined below in exclusionary criteria).
• 13. Inhibitors of monoamine oxidase, UGT1A9, 1A10, and aldehyde or alcohol dehydrogenase should be discontinued 5 half-lives prior to active dose of psilocybin.
• 14. Eligible participants will have a responsible individual that will provide transportation home after the psilocybin session is complete.
• 15. Fluent in English
• 1. History of depression prior to cancer diagnosis.
• 2. Clinically significant suicidality or high risk of completed suicide defined as:
• 3. History of bipolar disorder, psychosis (of any nature), and seizures.
• 4. Functionally limiting comorbid conditions such as second primary malignancies in CNS or chest, and history of total laryngectomy or total .glossectomy.
• 5. ECG with QTc \> 450.
• 6. Patients with metal implants.
• 7. Asymptomatic ALT or AST elevations \>/= 5X upper limit of normal, symptomatic ALT or AST elevations \>/= 2X upper limit of normal, or total bilirubin \>/= 2X upper limit of normal.
• 8. The effects of psilocybin on the developing human fetus are unknown. For this reason, pregnant women will be excluded (Urine test for screening), women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation. This includes all female participants, between the onset of menses (as early as 8 years of age) and 55 years unless the participant presents with an applicable exclusionary factor which may be one of the following:
• 9. persons with first- or second-degree relatives who have schizophrenia or other psychotic disorders, or bipolar I or II disorder.
• 10. Actively progressing disease as defined by the primary oncologist.
• 11. Vulnerable populations, including children and cognitively impaired patients, will not be enrolled in this study.
• 12. Participants with brain metastases.
• 13. Risk for hypertensive crisis defined as Screening, Baseline, and Medication Session (prior to dosing) Blood Pressure \>140/90 mmHg and HR\> 90 bpm.
• 14. 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:
• 15. Significant central nervous system (CNS) pathology. Some examples include:
• 16. a. High risk of adverse emotional or behavioral reaction based on investigator's clinical evaluation. Examples include: i. Agitation ii. Violent behavior b. Active substance use disorders (SUDs) defined as: DSM-5 criteria for moderate or severe alcohol or drug use disorder (excluding caffeine and nicotine) within the past year c. Extensive use of serotonergic hallucinogens (e.g., LSD, psilocybin) defined as: i. Any use in the last 12 months ii. \>25 lifetime uses d. History of hallucinogen persisting perception disorder (HPPD) e. Concurrent Medications i. Antidepressants ii. Centrally-acting serotonergic agents (e.g., MAO inhibitors) iii. Antipsychotics (e.g., first and second generation) iv. Mood stabilizers (e.g., lithium, valproic acid) v. Aldehyde dehydrogenase inhibitors (e.g., disulfiram) vi. Significant inhibitors of UGT 1A0 or UGT 1A10 vii. 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 f. Have a positive urine drug test including Amphetamines, Barbiturates, Buprenorphine, Benzodiazepines, Cocaine, Cannabis, Methamphetamine, MDMA, Methadone, Opiates (Morphine, Oxycodone), Phencyclidine (PCP), and Tetrahydrocannabinol (THC).
• 17. Participants who have any of the below niacin contraindications:
• 1. Active liver disease or unexplained persistent elevations in hepatic transaminases
• 2. active peptic ulcer disease
• 3. arterial bleeding
• 4. Hypersensitivity to niacin or any component of this medication
• 18. BP\> 200/110 (or malignant hypertension defined as 200/120) would prevent a patient from receiving psilocybin dosing and would prompt calling a physician during blood pressure monitoring for cardiac risk evaluation.