Inclusion Criteria:
1. >18 years of age.
2. Ability to speak and read English (patient to provide written informed consent and
participate in PEARL intervention, as determined by study personnel).
3. Resident of Ontario.
4. No cognitive impairment indicated in medical record or by attending oncologist or
palliative care physician.
5. Confirmed diagnosis of stage IV solid tumour cancers, sarcoma, endocrine, melanoma
cancers, or stage 4 lymphoma with expected survival of greater than 6 months as
determined by their oncologist or palliative care physician.
6. At least mild depressive symptoms, defined as >8 on the Patient Health
Questionnaire-9 (PHQ-9) (Kroenke et la., 2001).
7. Interest in and ability to participate in and complete the PEARL intervention and
protocol as outlined.
8. Participants who are sexually active and could become pregnant must be using
effective birth control (per their physician), prior to study entry, during study
participation, and for the duration of the study. Participants who are sexually
active and could inseminate a partner must agree to use effective birth control
after psilocybin administration until the end of study. For participants of
child-bearing potential, a negative serum pregnancy test result is required at
screening. A urine pregnancy test will be administered on the morning of psilocybin
administration for applicable participants. Participants cannot be pregnant or
nursing through the duration of the study.
9. If using prescribed medications or other substances, participants must agree to
refrain from taking them if instructed by study investigators. These include:
- - not using any non-prescription medication, nutritional supplement, or herbal
supplement except when approved by the treatment team (exceptions will be
evaluated by the Investigator and will include acetaminophen, non-steroidal
anti-inflammatory drugs, and common doses of vitamins and minerals),
- not using nicotine for at least 2 hours before psilocybin administration, and
not again until approximately 7 hours after psilocybin administration,
- consuming approximately the same amount of caffeine-containing beverages (e.g.,
coffee, tea) that they consume on a usual morning before arriving at the
treatment centre for the psilocybin session day,
- not taking any as needed medications on the mornings of psilocybin sessions
(with the exception of daily and as needed opioid pain medication),
- refraining from using any psychoactive drugs, including alcoholic beverages,
within 24 hours of the psilocybin administration.
10. Participants must have someone drive them after the session to where they are
staying (home, hotel or another location), because psilocybin may affect their
alertness and concentration on the evening of the dosing session.
Exclusion Criteria:
1. Primary cancer of the brain, or metastasis to the brain associated with clinically
significant symptoms (e.g., affective, cognitive, personality-related, psychotic, or
other symptoms, including seizures).
2. Symptoms consistent with delirium, psychosis, or other symptoms judged to be
incompatible with establishment of rapport or safe exposure to psilocybin.
3. A history of past intolerability of psilocybin or other psychedelics.
4. Past/present psychiatric diagnoses including bipolar disorder, psychotic disorders,
active substance use disorders or suicidality (as distinguished from desire for
hastened death or readiness for death, per the discretion of the study team).
5. If participant is under 30 years of age and has first degree relative with a primary
psychotic disorder.
6. Severe hypertension (defined as systolic blood pressure >150/or diastolic pressure
>95) based on two readings on the same day. If the second reading remains over
150/95, the patient can be brought in for another reading on a different day.
Patients can be re-screened for participation once blood pressure is adequately
controlled.
7. Moderate or severe hepatic impairment, as defined by Child-Pugh class B or C, or
elevations in AST or ALT greater than 3 times the upper limit of normal.
8. Severe renal impairment (defined as eGFR < 30).
9. Known paraneoplastic syndrome or "ectopic" hormone production by the primary tumor
if incompatible with psilocybin, determined in consultation with the study
palliative care physician. Patients could be enrolled if it is determined that the
patient's condition is compatible with psilocybin administration.
10. Cardiovascular conditions including uncontrolled hypertension, angina, a clinically
significant ECG abnormality (e.g., atrial fibrillation without rate control),
transient ischemic attack in the last six months, stroke, peripheral or pulmonary
vascular disease (no active claudication).
11. Uncontrolled epilepsy or history of seizures in past 6 months.
12. Participants with diabetes who are unable to skip a meal (lunch), or whose diabetes
requires administration of medication more than twice daily, or who have had
symptomatic hypoglycemia within the prior 30 days.
13. GI bleed in last 6 months.
14. Use of other agents that would be inappropriate to take with psilocybin in the
judgement of the investigator. These agents may include psychoactive prescription
medications (e.g., benzodiazepines, lithium, Selective serotonin reuptake
inhibitors), medications having a primary pharmacological effect on serotonin-2a
(5-HT2A) receptors (e.g., olanzapine), or medications that are monoamine oxidase
(MAO) inhibitors, any potent metabolic inducers (e.g. rifamycin, rifampin,
rifabutin, rifapentine, carbamazepine, phenytoin, phenobarbital, nevirapine,
efavirenz, taxol, dexamethasone, St John's wort) or inhibitors (e.g. HIV protease
inhibitors, itraconazole, ketoconazole, erythromycin, clarithromycin,
troleandomycin).
Of note, in suitable patients, these medications may be paused or tapered between study
enrolment and prior to the start of the intervention when it is deemed safe to do so. A
safe and appropriate tapering regimen will then be developed based on the particular
medication, on a case-by-case basis. If taking an MAO inhibitor, the psilocybin session
will not be conducted until at least 5 half-lives of the agent have elapsed after the
last dose. Patients prescribed opioids will be allowed to take their usual dose regimen
for analgesia, including the use of as needed analgesic medications on psilocybin session
days.
