Psilocybin-Assisted Therapy for Improving Pain in Patients with Advanced Cancer

Inclusion Criteria

• Participants must be 18 years old or older
• Participants must have advanced cancer, defined as a cancer that is unlikely to be cured or controlled with treatment
• Participants must evaluate their average pain on Brief Pain Inventory (BPI) Severity Scale >= 4/10 over the past week
• Participants must receive chronic opioid pharmacotherapy for pain with an oral morphine equivalent (OME) >= 120mg/day or patients must not tolerate side effects caused by systemic opioids despite a rigorous trial of a combination of evidence-based therapies
• Participants must have been seen by a palliative care clinician either at Dana-Farber Cancer Institute (DFCI), Massachusetts General Hospital (MGH) or associated satellites in the last three months
• Participants must have an Eastern Cooperative Oncology Group (ECOG) performance status =< 2
• Platelets >= 50,000/mcL (on last available bloodwork)
• Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 5 x institutional upper limit of normal (ULN) (on last available bloodwork)
• Participants must be able to understand and willing to sign a written informed consent document
• Participants must be able to swallow pills
• Participants must agree to have study visits audio and video recorded, including the experimental sessions and non-drug therapy sessions
• Participants must provide a contact (relative, spouse, close friend or other support person) who is willing and able to be reached by the investigators in the event of a participant becoming suicidal or unreachable
• Participants must agree to inform the investigators within 48 hours of any new medical conditions and procedures
• Participants must agree to the following lifestyle modifications: * Comply with requirements for diet, * Refrain from certain medications prior to experimental sessions, * Be driven home after each experimental session, * Commit to medication dosing, therapy, and study procedures

Exclusion Criteria

• Patients deemed to be poor candidates for the study in the judgement of the treating oncologist or palliative care clinician
• Participants with a condition impairing oral intake or digestive absorption
• Participants who are not able to give adequate informed consent
• Participants who have a significant suicide risk as defined by suicidal ideation with intent and with or without a plan as endorsed on items 4 and/or 5 on the C-SSRS within the past 6 months or at visit 0 (V0)
• Participants who have a history of, or a current diagnostic of primary psychotic disorder, major depressive disorder with psychotic features, bipolar affective disorder type 1 or history of or current dissociative identity disorder; and participants who have an ongoing substance use disorder (defined as active in the past year). * Participants with first-degree relatives with schizophrenia or bipolar disorder may be eligible depending on their age and personal and family psychiatric history. The decision will be made by the principal investigator and study psychiatrist based on risk assessment
• Participants for whom there is a potential for adverse drug-drug interactions. Concomitant medications with significant potential to interact with study medications will be exclusionary if they cannot be tapered. These include the following: * Tricyclic antidepressants (TCAs) * Efavirenz * Serotonin-acting dietary supplements (i.e. 5-hydroxy-tryptophan or St. John’s wort) * Centrally-acting serotonergic agents (e.g. monoamine oxidase [MAO] inhibitors) * Antipsychotics (e.g. first and second generation) * Mood stabilizers (e.g. lithium, valproic acid) * Aldehyde dehydrogenase inhibitors (e.g. disulfiram) * Significant inhibitors of UGT 1A0 or UGT 1A10 Any contra-indicated psychiatric medication will be tapered if possible in an appropriate fashion to avoid withdrawal effects. They will be discontinued long enough before the psilocybin session to avoid the possibility of any drug-drug interaction (the interval will be at least five times the particular drug and active metabolites’ half-life + one week for stabilization). Patients may continue using serotonergic antidepressants, including selective serotonin reuptake inhibitors (SSRIs) and/or serotonin and norepinephrine reuptake inhibitors (SNRIs) if they have been using the same regimen for at least 6 weeks prior to enrollment
• Participants who have evidence or history of significant (controlled or uncontrolled) hematological, endocrine, cerebrovascular, cardiovascular, coronary, pulmonary, renal, gastrointestinal, immunocompromising, or neurological disease, including seizure disorder, or any other medical disorder judged by the investigator to significantly increase the risk of psilocybin administration (participants with hypothyroidism who are on adequate and stable thyroid replacement will not be excluded)
• Participants with brain tumors or brain metastases that haven’t been successfully treated
• Participants with lab abnormalities that may contribute to somnolence, confusion or delayed metabolism of psilocybin and/or with severe lab abnormalities (grade 3 or more per Common Terminology Criteria for Adverse Events [CTCAE] scale)
• Participants with a diagnosis of cirrhosis or liver failure
• Participants who have uncontrolled hypertension using the standard criteria of the American Heart Association (values of 140/90 milligrams of Mercury [mmHg] or higher assessed on three separate occasions)
• Participants who have a heart rate > 100 beats per minute (bpm) on three separate occasions
• Participants who have a history of ventricular arrhythmia at any time, other than occasional premature ventricular contractions (PVCs) in the absence of ischemic heart disease
• Participants who have Wolff-Parkinson-White syndrome or any other accessory pathway that has not been successfully eliminated by ablation
• Participants who have a history of arrhythmia, other than premature atrial contractions (PACs) or occasional PVCs in the absence of ischemic heart disease, within 12 months of screening. Participants with a history of atrial fibrillation, atrial tachycardia, atrial flutter or paroxysmal supraventricular tachycardia or any other arrhythmia associated with a bypass tract may be enrolled if they have been successfully treated
• Participants who have a history of additional risk factors for Torsade de pointes (e.g., heart failure, hypokalemia, family history of long QT syndrome)
• Participants who a recent history of myocardial infarction in the past year or symptomatic coronary artery disease or symptoms of heart failure. Participants with a remote history of coronary artery disease (CAD) or heart failure may be eligible pending medical clearance.
• Participants who have a marked baseline prolongation of QT/corrected QT (QTc) interval. For purposes of eligibility, this is defined as repeated demonstration of a QT interval corrected on the electrocardiogram (EKG) performed at screening, using Fridericia’s formula (QTcF) > 450 milliseconds (ms) in males and > 460 ms in females
• For transgender or non binary participants, QTc interval will be evaluated based on sex assigned at birth, unless the participant has been on hormonal treatment for five or more years
• Women who are pregnant, nursing, or able to become pregnant and are not practicing an effective means of birth control * Acceptable methods of contraception are the following: intrauterine device, injected/implanted/intravaginal/transdermal hormonal method, oral hormones plus a barrier contraception, abstinence, vasectomized sole partner, or double barrier contraception
• Participants who have hypersensitivity to any ingredient of the IMP (investigational medicinal product)