Study of Psilocybin Assisted Psychotherapy to Address Fear of Recurrence

Inclusion Criteria:

1, Aged ≥ 21 2. Diagnosis of:

• early-stage breast cancer at low risk of recurrence

• defined as clinical stage 1 or 2

• completed primary treatment (surgery, chemotherapy [adjuvant, patients maycontinue to be treated with neoadjuvant], and/or radiation) > 6 months ago

• oncologist reported risk of recurrence at 10 years < 20%

• late-stage ovarian cancer at high risk of recurrence

• defined as Clinical stage 3 or 4

• currently in remission

• oncologist reported risk of recurrence at 10 years > 80% 2. Functional Statusdefined as:

• Eastern Cooperative Oncology Group (ECOG) ≤1

• Palliative Performance Scale (PPS) ≥60%

• Ability to tolerate PO medication administration 4. Fear of recurrence at screeningand baseline 5. Have an identified support person

• Agree to be accompanied home (or to an otherwise safe destination) by the supportperson, or another responsible party, following dosing 6. Participants ofchildbearing potential must agree to practice an effective means of birth controlthroughout the duration of the study.

Exclusion Criteria:

1. Unstable medical conditions or serious abnormalities of complete blood count,chemistries, or EKG that in the opinion of the study physician would preclude safeparticipation in the trial. Some examples include:

• Congestive heart failure

• Valvular heart disease

• Clinically significant arrhythmias (e.g., ventricular fibrillation, torsades)or clinically significant EKG abnormality (i.e., QTC interval > 450)

• Recent acute myocardial infarction or evidence of ischemia

• Malignant hypertension

• Congenital long QT syndrome

• Acute renal failure

• Severe hepatic impairment

• Respiratory failure

• eGFR < 50 mL/min/1.73m2

• LFTs > 1.5 x ULN

• WBC < 5 x 10*9/L

• Hemoglobin < 8.0 g/dL

• Platelets < 150 x 10*9/L

2. Risk for hypertensive crisis defined as: Screening, Baseline, Medication session (predose) blood pressure >140/90 mmHg

3. Significant central nervous system (CNS) pathology Examples include:

• Primary or secondary cerebral neoplasm

• Epilepsy

• History of stroke

• Cerebral aneurysm

• Dementia

• Delirium

4. Primary psychotic or affective psychotic disorders Examples include current or pastDSM-5 criteria for:

• Schizophrenia spectrum disorders

• Schizoaffective disorder

• Bipolar I or bipolar II disorder

• Major Depressive Disorder with psychotic features

• Prior history of psychosis due to medical condition or substance use

5. Family history of psychotic or serious bipolar spectrum illnesses. Examples include first-degree relative with:

• Schizophrenia spectrum disorders

• Schizoaffective disorder

• Bipolar I disorder with psychotic features

6. High risk of adverse emotional or behavioral reaction based on investigator'sclinical evaluation and judgement. Examples include:

• Agitation

• Violent behavior

7. Active substance use disorders (SUDs) defined as:

• DSM-5 criteria for moderate or severe alcohol or drug use disorder (excludingcaffeine and nicotine) within the past year

• DAST-10 score of 3 or higher

• Two or more "yes" responses to CAGE screening questionnaire

8. Extensive use of serotonergic hallucinogens (e.g., LSD, psilocybin) defined as:

• Any use in the last 12 months

• >25 lifetime uses

9. Clinically significant suicidality or high risk of completed suicide defined as:

• 'Yes' to C-SSRS Suicidal Ideation items 4 or 5 within the last 2 months atScreening or 'since last visit' at Baseline

• 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 onthe C-SSRS: actual attempt, interrupted attempt, aborted attempt, orpreparatory acts

• Have any suicidal ideation or thoughts, in the opinion of the study physicianor PI, that presents a serious risk of suicidal or self-injurious behavior

10. History of hallucinogen persisting perception disorder (HPPD)

11. Pregnancy/lactation

12. Cognitive impairment as defined by:

• Montreal Cognitive Assessment Test (MoCA) < 23

13. Concurrent Medications

• Antidepressants

• Centrally-acting serotonergic agents (e.g., MAO inhibitors)

• Serotonin-acting dietary supplements (such as 5-hydroxy-tryptophan or St.John's wort)

• Antipsychotics (e.g., first and second generation)

• Mood stabilizers (e.g., lithium, valproic acid)

• Aldehyde dehydrogenase inhibitors (e.g., disulfiram)

• Significant inhibitors of UGT 1A0 or UGT 1A10

• Efavirenz

14. Have a positive urine drug test including Amphetamines, Barbiturates, Buprenorphine,Benzodiazepines, Cocaine, Cannabis, Methamphetamine, MDMA, Methadone, Opiates (Morphine, Oxycodone), and Phencyclidine (PCP).

15. Have a psychiatric condition judged to be incompatible with establishment of rapportwith the study therapists or safe exposure to psilocybin

16. Have any psychological or physical symptom, medication, or other relevant finding ,based on the clinical judgment of the PI or relevant clinical study staff that wouldmake a participant unsuitable for the study.

17. Have an allergy or intolerance to any of the materials contained in the drug product

18. Non-English speaking individual

19. Be enrolled in another clinical trial assessing intervention(s) for anxiety,depression, and/or existential distress (e.g., pharmacologic or psychotherapeuticinterventions)