Psychopharmacology of Psilocybin in Cancer Patients

Inclusion Criteria

Inclusion criteria

Volunteers must:

- Have given written informed consent

- Have a high school level of education

- Be 21 to 80 years old

- Have had a cancer diagnosis that is potentially life-threatening. Patients with
disease progression are eligible. Patients with no disease progression or no disease
recurrence are only eligible if at least 1 year has elapsed since their diagnosis.

- Have an ECOG performance status of 0, 1, or 2.

- Have a DSM-IV psychiatric diagnosis, as determined by the SCID, of one or more of the
following Axis I psychiatric disorders that is either precipitated by or exacerbated
by the psychological stress of the cancer diagnosis: Generalized Anxiety Disorder;
Acute Stress Disorder; Post traumatic Stress Disorder; Major Depressive Disorder
(mild or moderate severity); 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 will be determined
by BPRU staff.

- Be between cancer therapies or have independently decided to not undergo direct
cancer treatments, such as chemotherapy and radiation, for at least an approximately
1 month duration (2 weeks before the first psilocybin session through the 1 week
follow-up after the second psilocybin session). Continuing hormonal therapy for
breast or prostate cancer is acceptable. If he/she subsequently decides to initiate
or resume treatment for cancer (such as chemotherapy and radiation, but excluding
hormonal therapy for breast or prostrate cancer) at any point before the second
psilocybin session, then the patient will be withdrawn from formal data analysis.
However follow-up data will continue to be collected for the purpose of maximizing
the obtaining of pilot information. After completion of the second psilocybin
session, if a patient decides to resume or initiate treatment, he/she will not be
withdrawn from formal data analysis.

- Agree that for one week preceding each psilocybin session, he/she will refrain from
taking any nonprescription medication, nutritional supplement, or herbal supplement
except when approved by the research team. Exceptions will be evaluated by the
research team and will include acetaminophen, non-steroidal anti-inflammatory drugs,
and common doses of vitamins and minerals.

- Agree not to use nicotine for at least 2 hours before psilocybin administration, and
not again until questionnaires have been completed approximately 7 hours after
psilocybin administration.

- Agree to consume approximately the same amount of caffeine-containing beverage (e.g.,
coffee, tea) that he/she consumes on a usual morning, before arriving at the research
unit on the mornings of psilocybin session days. If the patient does not routinely
consume caffeinated beverages, he or she must agree not to do so on psilocybin
session days.

- Agree not to take any PRN medications on the mornings of psilocybin sessions, with
the exception of daily opioid pain medication. Non-routine PRN medications for
treating breakthrough pain that were taken in the 24 hours before the psilocybin
session may result in rescheduling the treatment session, with the decision at the
discretion of the investigators.

- Agree to refrain from using any psychoactive drugs, including alcoholic beverages,
within 24 hours of each psilocybin administration. As described elsewhere,
exceptions include daily use of caffeine, nicotine, and opioid pain medication.

Exclusion criteria

General Medical Exclusion Criteria

- Cancer with known CNS involvement, or other major CNS disease. In addition to
diagnostic results provided by the referring physician, patients will undergo a
neurological exam performed by our BPRU internist. Any patient with evidence of a
focal deficit will be excluded.

- Hepatic dysfunction as indicated by the following values:

- GGT > 3 x ULN (upper limit of norm)

- AST > 3 x ULN

- ALT > 3 x ULN

- Tot Bili > 3.0 mg/dl

- Known paraneoplastic syndrome or "ectopic" hormone production by the primary tumor
such as the patient could have or be at risk for hypercalcemia, Cushing's syndrome,
hypoglycemia, syndrome of inappropriate antidiuretic hormone secretion, or carcinoid
syndrome

- Cardiovascular conditions: uncontrolled hypertension, angina, a clinically
significant ECG abnormality (e.g. atrial fibrillation), TIA in the last 6 months,
stroke, peripheral or pulmonary vascular disease (no active claudication)

- Blood pressure exceeding screening criteria described below

- Epilepsy with history of seizures

- Renal disease (creatinine clearance < 40 ml/min using the Cockcroft and Gault
equation)

- Insulin-dependent diabetes; if taking oral hypoglycemic agent, then no history of
hypoglycemia

- Females who are pregnant (positive pregnancy test) or nursing, or are not practicing
an effective means of birth control

- Currently taking on a regular (e.g., daily) basis: investigational agents,
psychoactive prescription medications (e.g., benzodiazepines), medications having a
primary pharmacological effect on serotonin neurons (e.g., ondansetron), or
medications that are MAO inhibitors. Long-acting opioid pain medications (e.g.
oxycodone sustained release, morphine sustained release -- which are usually taken at
12 hour intervals) will be allowed if the last dose occurred at least 6 hours before
psilocybin administration; such medication will not be taken again until at least 6
hours after psilocybin administration.

- For individuals who have intermittent or PRN use of investigational agents,
psychoactive prescription medications, medications having a primary pharmacological
effect on serotonin neurons, or medications that are MAO inhibitors, psilocybin
sessions will not be conducted until at least 5 half-lives of the agent have elapsed
after the last dose.

- In addition to the foregoing, patients will be excluded if they are currently using
any the following of potent metabolic inducers or inhibitors: Inducers - Rifamycin
(rifampin, rifabutin, rifapentine), anticonvulsants (carbamazepine, phenytoin,
Phenobarbital), Nevirapine, Efavirenz, Taxol, Dexamethasone), St Johns Wort;
Inhibitors - all HIV protease inhibitors, itraconazole, ketoconazole, erythromycin,
clarithromycin, troleandomycin.

- In addition to the foregoing, patients will be excluded if it is a medical
requirement that they receive any of the following drugs with low therapeutic index
within 12 hours after receiving psilocybin: ergot alkaloids, pimozide, midazolam,
triazolam, lovastatin, simvastatin, fentanyl.

Psychiatric Exclusion Criteria

- Individuals with severity of depression or anxiety symptoms warranting immediate
treatment with antidepressant or daily anxiolytic medication (e.g., due to suicidal
ideation). We will interview patients to determine if referral (e.g., to Community
Psychiatry) is necessary. For all individuals who are consented and screened, we
will notify the referring physician as to: 1) whether the individual enrolled in the
study or not, and 2) if disqualified, why the individual was disqualified. If
disqualification was based on severe depression or anxiety (e.g., suicidal ideation),
this will be included in the information conveyed to the referring physician.
Permission for this contact will be obtained from the participant.

- Current or past history of meeting DSM-IV criteria for Schizophrenia, Psychotic
Disorder (unless substance-induced or due to a medical condition), or Bipolar I or II
Disorder

- Current or past history within the last 5 year of meeting DSM-IV criteria for alcohol
or drug dependence (excluding caffeine and nicotine).

- Have a first or second degree relative with schizophrenia, psychotic disorder (unless
substance induced or due to a medical condition), or bipolar I or II disorder.

- Currently meets DSM-IV criteria for Dissociative Disorder, Anorexia Nervosa, Bulimia
Nervosa, or other psychiatric conditions judged to be incompatible with establishment
of rapport or safe exposure to psilocybin.

Cardiovascular screening:

There will be at least four blood pressure assessment occasions over at least two separate
days. Within a day, assessment occasions will be separated by at least 15 minutes. Each
assessment occasion will involve two or more blood pressure readings. To qualify for the
study, the mean blood pressure (mm Hg) of the four or more assessment occasions will not
exceed 140 systolic and 90 diastolic.

Blood pressure will be taken while subjects are at rest and have been seated or supine for
at least 5 minutes. As recommended by the Joint National Committee on Prevention,
Detection, Evaluation and Treatment of High Blood Pressure, these assessments will involve
the average of 2 or more readings separated by two minutes. If the first 2 readings
differ by more than 5 mm Hg, additional readings will be obtained and averaged. On one or
more of the blood pressure measurement occasions, the volunteer will be acclimated to the
automated blood pressure monitoring equipment by repeatedly taking blood pressure (at
least 3 readings) with the device. Because it has been our experience that time-to-time
blood pressure readings with the automated equipment can be variable due to measurement
artifact, any reading that initially exceeds our threshold value will be reassessed twice
within 4 minutes to assure accuracy.