TRIPS - Treatment to Improve Depression and/or Anxiety Using Psilocybin-assisted Psychotherapy in Cancer Survivors

Inclusion Criteria: 1. Subjects must have solid or hematological malignancy that does not involve the brain. 2. Documentation of current malignancy that was treated and the patient has no evidence of disease in the previous 6 months 3. Age ≥ 18 years. 4. Have a DSM-V psychiatric diagnosis, as determined by the SCID (Structured Clinical Interview for DSM), of one or more of the following Axis I psychiatric disorders that is judged to have been precipitated by the psychological stress of the cancer diagnosis: Generalized Anxiety Disorder; Acute Stress Disorder; Posttraumatic Stress Disorder; Major Depressive Disorder, 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 diagnoses are determined by. an MD Anderson licensed healthcare provider with graduate-level profession training and clinical experience in psychotherapy, licensed to practice independently. 5. Have an ECOG performance status of 0, 1, or 2. 6. Must have no major cognitive impairment and be oriented to person, place, and time (e.g. mini mental exam). 7. Must demonstrate willingness to travel to MD Anderson Cancer center for all treatment and follow-up sessions, as well as consent to complete all evaluation instruments and assessments. 8. Agree to abstain from any nicotine products for at least 8 hours prior to fMRI performance. 9. Refrain from any psychoactive drugs (including alcohol) for 48 hours prior to psilocybin sessions and must refrain from psychoactive drugs 12 hours after psilocybin sessions. Must consent to urine drug screen (UDS) which will be given before receiving psilocybin. Participants with positive drug test will be retested (UDS) after 6 weeks and included if the repeated UDS is negative. Patient tested positive for a prescribed substance are eligible. Patient failing on the 2nd test (UDS) will be excluded. 10. Must be free from any regularly scheduled psychotropic (antidepressant/anxiolytic class) medications for a minimum of 2 weeks prior to study. Intermittent or PRN use of short-acting anxiolytics or and anti-nausea medications (e.g., ondansetron) may be permitted as defined below in exclusionary criteria). Ondansetron could be taken but must be stopped at least 24 hours before psilocybin administration. 11. Inhibitors of monoamine oxidase, UGT1A9, 1A10, and aldehyde or alcohol dehydrogenase should be discontinued 5 half-lives prior to active dose of psilocybin. 12. Eligible subjects will have a third-party transportation by a licenses driver (e.g. friend, family or a driver) after the psilocybin session is complete. If a driver is used, a friend or family member must accompany them in the vehicle home 13. Fluent in Englishria). Ondansetron could be taken but must be stopped at least 24 hours before psilocybin administration. Exclusion Criteria: 1. Clinically significant suicidality or high risk of completed suicide defined as: i. Answer 'Yes' to C-SSRS Suicidal Ideation items 4 or 5 within the last 2 months at Screening or 'since last visit' at Baseline ii. Report having had any C-SSRS Suicidal Behavior item within the past 12 months at Screening or 'since last visit' at Baseline, as defined by 'Yes' to any of the following on the C-SSRS: actual attempt, interrupted attempt, aborted attempt, or preparatory acts iii. Have any suicidal ideation or thoughts, in the opinion of the study physician or PI, that presents a serious risk of suicidal or self injurious behavior 2. History of bipolar disorder, psychosis (including a history of schizophrenia). 3. Functionally limiting comorbid conditions such as second primary malignancies in CNS or chest, and history of total laryngectomy or total glossectomy precluding them from communicating. 4. The effects of psilocybin on the developing human fetus are unknown. For this reason, pregnant women will be excluded (Urine test for screening), women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstaining from intercourse with the opposite sex) prior to study entry and for the duration of study participation. This includes all female patients, between the onset of menses (as early as 8 years of age) and 55 years unless the patient presents with an applicable exclusionary factor which may be one of the following: * Postmenopausal (no menses in greater than or equal to 12 consecutive months). * History of hysterectomy or bilateral salpingo-oophorectomy. * Ovarian failure (Follicle Stimulating Hormone and Estradiol in menopausal range, who have received Whole Pelvic Radiation Therapy). * History of bilateral tubal ligation or another surgical sterilization procedure. Approved methods of birth control are as follows: Hormonal contraception (i.e. birth control pills, injection, implant, transdermal patch, vaginal ring), Intrauterine device (IUD), Tubal Ligation or hysterectomy, Subject/Partner post vasectomy, Implantable or injectable contraceptives, and condoms plus spermicide. Not engaging in sexual activity for the total duration of the trial and the drug washout period is an acceptable practice; however periodic abstinence, the rhythm method, and the withdrawal method are not acceptable methods of birth control. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately. 5. Persons with first-degree relatives who have schizophrenia or other psychotic disorders, or bipolar I or II disorder diagnosed by a qualified mental health professional. 6. Documentation of current malignancy that is being treated with palliative intent. 7. Vulnerable populations, including children and cognitively impaired patients, will not be enrolled in this study. 8. Patie