Please select the eligibility criteria that correspond to the clinical trial below.
Title: Effects of Psilocybin on Anxiety and Psychosocial Distress in Cancer Patients
Brief Summary: The primary objective of this double-blind, placebo-controlled pilot study is to assess the efficacy of psilocybin administration (4-phosphoryloxy-N,N-dimethyltryptamine), a serotonergic psychoactive agent, on psychosocial distress, with the specific primary outcome variable being anxiety associated with cancer. Secondary outcome measures will look at the effect of psilocybin on symptoms of pain perception, depression, existential/psychospiritual distress, attitudes towards disease progression and death, quality of life, and spiritual/mystical states of consciousness. In addition, a secondary objective of the study is to determine the feasibility of administering psilocybin to this patient population, with regards to the following issues: safety, patient recruitment, consent for treatment, and retention. The duration of the proposed investigation will be long enough to administer the drug one time to each of thirty-two patients and to conduct follow-up assessments. This study is separate but similar to a recently completed study at the Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center, run by a psychiatrist, Dr. Charles Grob. Although the outcomes measures would be similar to those used as in the Grob study, the proposed dose of psilocybin is higher at 0.3mg/kg and the total subjects for the study would be 32 instead of 12. The study utilizes a cross-over design at 7 weeks and includes prospective follow-up of 6 months duration. This study has been approved by the Bellevue Psychiatry Research Committee, the NYU Oncology PRMC Committee, the Food and Drug Administration (FDA) through the issuance of an IND (77,138), the New York University School of Medicine Institutional Review Board (NYU IRB), the Health and Hospitals Corporation (HHC)-New York University (NYU) Clinical Translational Science Institute (CTSI), the NYU Bluestone Center for Clinical Research, and the Drug Enforcement Agency (DEA) through the issuance of a schedule I license.

It is hypothesized that a one time experience with psilocybin will occasion dramatic shifts in consciousness and awareness that will lead to short-term (ie hours to days) and long-term (up to 6 months in this study, following the administration of the second dosing, either psilocybin or placebo) improvement in anxiety, depression, and pain associated with advanced cancer. The exact mechanism of action is unclear but based on studies done in the 60's using serotonergic hallucinogens in patients with advanced cancer, improvements in anxiety levels, mood and pain were reported. However, a treatment model developed by the famous British psychiatrist Humphrey Osmond, offers one possibility. In this model, serotonergic hallucinogens' therapeutic mechanism lies in their ability to allow the individual to access novel dimensions of consciousness and their efficacy or lack thereof relies on whether a transcendent and mystical state of awareness is attained. Another possible mechanism relates to what Dobkin de Rios and Grob have described as 'managed altered states of consciousness,' where the power of suggestibility, occurring in a safe setting, allows one to transcend a particular state of consciousness (i.e. anxiety and depression associated with advanced illness) as a means to facilitate emotional discharge and to manage irreconcilable conflict.


Options:
A: Inclusion Criteria:

1. Male or female, aged \>18 years.
2. Current DSM IV diagnosis of Major Depressive Disorder.
3. Under palliative care.
4. Confirmed diagnosis of cancer.
5. Not on any antidepressants

Exclusion Criteria:

1. Clinical significant abnormal laboratory values.
2. Clinically significant abnormal ECG.
3. Documented history of other psychiatric diagnosis (schizophrenia, bipolar disorder, organic brain disorder, dementia etc.)
B: Inclusion Criteria:

* Age: 18-76
* Current or historical diagnosis of cancer
* Projected life expectancy of at least one year
* DSM-IV diagnoses: Acute Stress Disorder, Generalized Anxiety Disorder, Anxiety Disorder due to cancer, Adjustment Disorder with anxious features
* Any stage of cancer diagnosis

Exclusion Criteria:

* Epilepsy
* Renal disease
* Diabetes
* Abnormal liver function
* Severe cardiovascular disease
* Malignant Hypertension
* Baseline blood pressure must be less than or equal to 140/90
* Personal history or immediate family members with schizophrenia, bipolar affective disorder, delusional disorder, schizoaffective disorder or other psychotic spectrum illness
* Current substance use disorder
* Medication contraindications: anti-seizures medications, insulin, oral hypoglycemics, clonidine, aldomet, cardiovascular medications, anti-psychotics (first and second generation), anti-depressants and mood stabilizers
C: Inclusion Criteria:

* Scheduled to receive FOLFOX chemotherapy with individual oxaliplatin doses of 85 mg/m\^2 per cycle given in 2 week cycles (e.g. modified \[m\] FOLFOX6 or FOLFOX4) Adequate complete blood count (CBC) and creatinine values (per attending physician) obtained =\< 28 days prior to registration Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) of 0, 1 or 2 Negative pregnancy test done =\< 7 days prior to registration, for women of childbearing potential Ability to complete questionnaire(s) by themselves or with assistance Life expectancy \>= 4 months Strong inhibitors of CYP3A4: \> 5-fold increase in the plasma area under the curve (AUC) values or more than 80 % decrease in clearance

  * Indinavir (Crixivan®)
  * Nelfinavir (Viracept®)
  * Atazanavir (Reyataz®)
  * Ritonavir (Norvir®)
  * Clarithromycin (Biaxin®, Biaxin XL®)
  * Itraconazole (Sporanox®)
  * Ketoconazole (Nizoral®)
  * Nefazodone (Serzone®)
  * Saquinavir (Fortovase®, Invirase®)
  * Telithromycin (Ketek®) Inducers of CYP3A4
  * Efavirenz (Sustiva®)
  * Nevirapine (Viramune®)
  * Carbamazepine (Carbatrol®, Epitol®, Equetro™, Tegretol®, Tegretol-XR®)
  * Modafinil (Provigil®)
  * Phenobarbital (Luminal®)
  * Phenytoin (Dilantin®, Phenytek®)
  * Pioglitazone (Actos®)
  * Rifabutin (Mycobutin®)
  * Rifampin (Rifadin®)
  * St. John's wort

Exclusion Criteria:

Any of the following:

* Pregnant women
* Nursing women History of an allergic reaction to, or intolerance of, venlafaxine Treatment =\< 7 days with other antidepressants, anticonvulsants, monoamine oxidase (MAO) inhibitors, or other neuropathic pain medication agents such as carbamazepine, phenytoin, valproic acid, gabapentin, lamotrigine, topical lidocaine patch or gel, capsaicin cream, or amifostine; in addition, they may not be taking other agents for the treatment of neuropathy, nor other known moderate or strong CYP 2D6 (which consist of Cinacalcet \[Sensipar™\], quinidine, and Terbinafine \[Lamisil®, Lamisil AT®\]), nor the strong inducer of CYP 2D6 terbinafine (Lamisil®, Lamisil AT®), nor the following drugs that substantially effect CYP 3A4 Moderate inhibitors of CYP3A4: \> 2-fold increase in the plasma AUC values or 50-80% decrease in clearance
* Aprepitant (Emend®)
* Erythromycin (Erythrocin®, E.E.S. ®, Ery-Tab®, Eryc®, EryPed®, PCE®
* Fluconazole (Diflucan®)
* Grapefruit juice
* Verapamil (Calan®, Calan SR®, Covera-HS®, Isoptin SR®, Verelan®, Verelan PM®)
* Diltiazem (Cardizem®, Cardizem CD®, Cardizem LA®, Cardizem SR®, Cartia XT™, Dilacor XR®, Diltia XT®, Taztia XT™, Tiazac®) Other medical conditions which, in the opinion of the treating physician/allied health professional, would make this protocol unreasonably hazardous for the patient Prior neurotoxic chemotherapy Concurrent radiotherapy Current (within the last month) pre-existing peripheral neuropathy of any grade Uncontrolled hypertension (defined as 3 consecutive readings over the past year of over 160 systolic, and over 100 diastolic)
D: 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.

Answer: B