Psilocybin-Assisted Psychotherapy for Anxiety in People With Stage IV Melanoma

Inclusion Criteria: * Have been diagnosed with Stage IV melanoma with a life expectancy of one year or less * Meet diagnostic criteria for anxiety on the SCID, or a score of 8 or higher on the HADS Anxiety score. * Diagnosis must be a new diagnosis of anxiety subsequent to diagnosis with melanoma. * Are 18 years or older * Live with another adult who is their primary caregiver, who can also provide transportation to and from the cancer center for each experimental session and who also consents to take part in a parallel investigation of anxiety and depression in primary caregivers. The same caregiver may remain overnight with participants after each psilocybin session. * Have a Mini-Mental State Exam score of 27 or higher, an indication of mental functioning. * Are willing to commit to medication dosing, experimental sessions with overnight stay, traveling to follow-up sessions, and to complete the evaluation * Are willing to refrain from taking any anti-depressants during the study period. * Are willing to refrain from taking any benzodiazepines during the 24 hours preceding each scheduled psilocybin, placebo, or open label session. * Are able to communicate in English. Exclusion Criteria: * Meet DSM-IV criteria for bipolar disorder, schizophrenia, or other psychotic disorders. * Meet DSM-IV criteria for abuse of or dependence on any substance (other than caffeine or nicotine) in the past 60 days. * Have first-degree relatives (as parent or full sibling) with past or present psychiatric disorders, including schizophrenia, bipolar affective disorder and other psychoses, but excluding mood disorders. * Cannot have a current diagnosis of anxiety disorder that predates diagnosis with melanoma. * Have used psilocybin or psilocybin-containing mushrooms within the past year. * Require concomitant treatment with anti-psychotic medications, prescribed for the management of either psychiatric symptoms or nausea. The restriction on 5HT2C/5HT3 antagonists is applicable for 24 hours before and including the day of the study. * Are cachectic \[exhibiting signs of wasting\] as indicated by loss of 10% or greater of their total weight. * Have been diagnosed with primary or metastatic cancer of the CNS confirmed by MRI, within 6 weeks of participation in the study. * Have uncontrolled hypertension. * Have baseline laboratory values indicative of severely compromised hepatic function, indicated by unacceptable levels of alkaline phosphatase (ALP) above 750 U/L. Participants must also have laboratory blood screening indicating ALP below 750 U/L immediately prior to administration of psilocybin. * Are women who are pregnant or nursing, or of child bearing potential and are not practicing an effective means of birth control. * Are reasonably judged to present a serious suicide or homicide risk or who are likely to require psychiatric hospitalization during the course of the study. * Are unable to fully understand the potential risks and benefits of the study and give informed consent.