Psychopharmacology of Psilocybin in Cancer Patients
Condition: Depressive Symptoms; Anxiety; Cancer
MeSH terms: Depression
Intervention: psilocybin
Intervention description: The dose of psilocybin received in the two sessions will range anywhere from low to high.
Intervention MeSH terms: Psilocybin; N,N-Dimethyltryptamine
Phase: Phase 2
Study type: Interventional
Primary purpose: Supportive Care
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 56.0
Sex: All
Minimum age: 21 Years
Maximum age: 80 Years
Healthy volunteers: No

Summary:

      This research is being done to study the psychological effects of psilocybin in cancer
      patients. Psilocybin is a naturally occurring substance found in some mushrooms that some
      cultures have used for centuries in religious practices.
    

Eligibility criteria:

        Inclusion criteria

        Volunteers must:

          -  Have given written informed consent

          -  Have a high school level of education

          -  Be 21 to 80 years old

          -  Has or has had a cancer diagnosis that is potentially life-threatening. Patients with
             an active cancer (e.g. stage III or IV with a poor prognosis) or disease progression
             or recurrence are eligible. Patients who do not have an active cancer or disease
             progression or 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.

          -  Patients receiving chemotherapy, hormonal therapy, radiation therapy, biologic
             therapies may participate while receiving those therapies. Continuing hormonal
             therapy, chemotherapy, or radiation treatment is acceptable if the patient is
             tolerating the therapy or treatment in a sufficient fashion to allow administration of
             oral psilocybin.

          -  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.