Cariprazine for Comorbid Cocaine and Opioid Use Disorder

Eligibility Criteria

• * An informed consent document understood, voluntarily signed and dated by the subject.
• * Males and females, aged 18-65 years old, who meet criteria for cocaine use disorder (CocUD) and moderate or severe opioid use disorder (OUD) (based on DSM-5 criteria), have been on a stable dose of BUP-NX for at least one week, and plan to continue taking BUP-NX for at least 12 weeks.
• * Subject must provide a urine that is cocaine-negative and buprenorphine-positive on the day of enrollment.
• * Females must be non-pregnant, non-lactating, and either be of non-childbearing potential (e.g., sterilized via hysterectomy or bilateral tubal ligation or at least 1 year post-menopausal) or of childbearing potential, but practicing a highly-effective contraception method (failure rate \<1%, guided by CDC reference list).
• * Subject must read at or above eighth grade level, and understand spoken and written English.
• * IQ score of ≥ 80.
• * Subjects must be willing and able to comply with scheduled visits, treatment plan, laboratory tests, and other study procedures, and must have access to a cellphone.
• * Current participation (or participation within 30 days prior to the research study) in clinical trial and receipt of investigational drug(s).
• * Meets DSM-5 criteria for moderate to severe Substance Use Disorder for any substance other than opioids, cocaine, alcohol, marijuana or nicotine as determined by the semi-structured interview. For Alcohol Use Disorder, subjects are excluded if they meet DSM-5 criteria for moderate to severe AUD within the past three months (patients in early or sustained remission are eligible).
• * Meets current or lifetime DSM-5 criteria for schizophrenia or any psychotic disorder, bipolar I or II disorder, or organic mental disorder, including dementia-related psychosis.
• * Meets DSM-5 criteria for Major Depressive Disorder AND is currently taking or clinically requires, antidepressant therapy.
• * Current comorbid GAD, Social Phobia, Specific Phobia are excluded if in current treatment and/or clinically unstable.
• * Current and/or in treatment for Panic Disorder With or Without Agoraphobia, Agoraphobia Without Panic Disorder.
• * Presence of any another psychiatric and/or medical disorder that in the opinion of the PI will interfere with completion of the study or place the patient at heightened risk through participation in the study.
• * Actively suicidal, or present suicidal risk, or who reports a lifetime history of serious or recurrent suicidal behavior, or who has an SBQ-R total score ≥8 at Screening, and/or "yes" answers on items 4 or 5 of the C-SSRS, or in the investigator's clinical judgment present a suicidal risk.
• * Currently homicidal to the extent that immediate attention is required.
• * Has evidence of a history of significant active hepatitis, significant hepatocellular injury as evidenced by elevated bilirubin levels (\>1.3), or, clinically significant levels (over 3x upper limit of normal) of aspartate aminotransferase (AST), or serum alanine aminotransferase (ALT).
• * Has positive serology test results at screening for HIV1/HIV2 antibodies, hepatitis B surface antigen, or hepatitis C antibody. If a subject is hepatitis C antibody positive and RNA negative OR their liver function tests are \<2 times the upper limit of normal (ULN) range, and they have been treated for hepatitis C, the investigator may include the subject with the approval of the Medical Monitor.
• * Anemia more severe than grade 2.
• * Significant renal insufficiency (estimated creatinine clearance less than or equal to 30 ml/min).
• * Current diagnosis of pain requiring opioids.
• * Currently physically dependent on benzodiazepines.
• * Significant medical or psychiatric symptoms or dementia which in the opinion of the investigators would preclude compliance with the protocol, adequate cooperation in the study, or obtaining informed consent.
• * Concurrent medical conditions (such as severe respiratory insufficiency) that may prevent the patient from safely participating in the study.
• * History of seizures (excluding childhood febrile seizure) or uncontrolled seizure disorder.
• * Has received medication that could interact adversely with VRAYLAR or BUP-NX within the time of administration of study agent based on the study physician's guidance.
• * Needs treatment with any psychoactive medications (with the exception of Benadryl used sparingly, if necessary, for sleep).
• * Has demonstrated hypersensitivity or allergy to cariprazine or any ingredients in VRAYLAR capsules or BUP-NX.
• * Currently taking a CYP3A4 inhibitor/inducer or agent metabolized through the CYP3A4 pathway likely to interact with BUP-NX to produce clinically significant and/or unfavorable effects.
• * Any pending legal action that could prohibit participation and/or compliance in study procedures.
• * Living in unstable housing.
• 1. History of serious head trauma or injury causing loss of consciousness that lasted more than 3 minutes and/or associated with skull fracture or intracranial bleeding or abnormal MRI.
• 2. Presence of magnetically active prosthetics, plates, pins, broken needles, permanent retainer, bullets, etc. in patient's body (unless a radiologist confirms that its presence is unproblematic). An x-ray may be obtained to determine eligibility.
• 3. Claustrophobia or other medical condition that disables the participant from lying in the MRI for approximately 60 minutes.
• 4. Non-removable skin patches, at discretion of PI.