Relapse Prevention in Stimulant Use Disorder

1. Participants will be recruited from the Clare Foundation (CLARE\|MATRIX), where they will be residing in a residential substance use disorder program. Potential participants recently admitted with stimulant use disorder will be given a flyer/research information sheet describing the study when they are admitted to the study. Interested parties will sign their name on the sheet to indicate their interest, and will meet with a UCLA research associate at Clare to discuss details of the protocol and undergo initial screening following verbal consent. Initial screening involves a one page screening sheet and discussing the information sheet with the research associate at Clare. 2. If participants remain eligible following initial screening, they will enroll in the study and the UCLA research associate will set up an in person screening to sign the informed consent form and undergo additional screening. After completing informed consent and going through the informed consent quiz, a Nurse Practitioner or physician will take a medical history, take a personal and family health profile, perform a physical examination (History \& Physical). Participants who provide written consent will complete questionnaires about their mood, medical, psychiatric and drug use history, personality and life experiences. The screening visit will also include a psychiatric diagnostic interview (MINI International Neuropsychiatric Interview M.I.N.I) completed by a trained diagnostician. Participants will also give a urine sample to determine what drugs they have recently used, a breath sample to determine the carbon monoxide levels in their system. Participants will travel to UCLA to give a blood sample to assess complete blood count, metabolic panel, screening for infectious diseases (Hepatitis B and C, HIV, syphilis) and tests of kidney function and receive an ECG (electrocardiogram). After all screening procedures have been completed, a study physician will collect and review ECG and laboratory tests to determine eligibility. 3. After completing all screening procedures, eligible participants will complete the following baseline assessments: A) Visit 1: i. Prior to completing cognitive tasks behavioral testing, participants will will have their blood drawn by a London laboratory phlebotomist or will visit the Clinical and Translational Research Center (CTRC), where a registered nurse will draw approximately 40mL of blood. Blood samples will be assayed for genetic markers associated with smoking and stimulant use. The purpose of the genetic analysis is to examine the relationship between genetic polymorphisms, treatment outcomes, circulating study drug, and measures of cognitive function. The DNA (deoxyribonucleic acid) samples acquired from this protocol will be added to a larger database of DNA samples collected from participants in London Laboratory protocols. DNA samples will be stored for future use other than the aims and goals of this study. Participants will not receive their results because our laboratory is only qualified for genetic analyses associated with research purposes and is not certified for clinical assessment of genetic information. This blood sample will also be used to determine follicular and luteal phase in female participants. ii. Urine toxicology: Participants will provide urine to assess recent use of drugs. iii. Cognitive/behavioral testing: Participants will complete some of the following tasks to assess inhibitory control and decision-making: Working memory (N-back test), declarative memory (Rey Auditory Verbal Learning Task), sustained attention (Rapid Visual Information Processing), inhibitory control (Stop Signal Test) reward-based decision-making (Monetary Delay Discounting and Reversal Learning, BART \[Balloon Analogue Risk Task\], ART \[Angling Risk Task\]), and impulsive and risk taking behavior (BIS \[Barratt Impulsiveness Scale\], Willingness-to-wait task, Domain-Specific Risk-Taking (DOSPERT) Scale, UPPS-P Impulsive Behavior Scale, TCI \[Temperament Character Inventory\]), Loss Aversion, the Risk and Ambiguity Task, craving (Brief Meth Craving Questionnaire), mindfulness (Multidimensional Assessment of Interoceptive Awareness \[MAIA\], Mindful Attention Awareness Scale \[MAAS\], Body Perception Questionnaire Body Awareness Very Short Form \[BPQ\]), and withdrawal from cigarettes (Shiffman-Jarvik Withdrawal Scale) and amphetamines (Amphetamine Cessation Symptom Assessment \[ASCA\]). 4. Participants in the active medication pool will be assigned to Contrave or Bupropion treatment based on timing of entry into the study (the London laboratory will initially assess Contrave effects). Participants assigned to the convenience control group will complete treatment as usual and will not take medication. The medication conditions will require that participants take capsules as instructed over the course of 8 weeks. Medications for the upcoming week will be dispensed at the beginning of each week. At the end of each week, the participants will meet with the study physician for a check-up to monitor potential adverse events. After the 8-wk regimen, participants will undergo repeat testing cognitive and behavioral tests as described in section 3. Study Intervention and Procedures: All participants will receive inpatient treatment as usual, including cognitive behavioral therapy. Within 10 days of entering treatment, participants in Group 1 (Bupropion Group) will begin receiving daily extended-release oral bupropion (Wellbutrin XL) at a dose of 450 mg, which was well tolerated by individuals with methamphetamine use disorder in a prior study. The dose will be titrated: 150 mg on Days 1 and 2, 300 mg on Days 3 and 4, and 450 mg on Day 5. Dosing will continue for a total of 4 weeks during inpatient treatment, and thereafter for another month, with compliance monitored by smartphone. A reduction to 300 mg will permitted to alleviate medication-related adverse effects if they occur. Participants in Group 2 (Contrave Group) will begin receiving daily oral Contrave at a dose of 360 mg (Naltrexone HCl 32mg, Bupropion HCl 360mg), which was well tolerated by individuals in a prior study The dose will be titrated: 8 mg/90 mg on Week 1, 16 mg/180 mg on Week 2, 24 mg/270 mg on Week 3 and 32 mg/360 mg on Week 4. Dosing will continue for a total of 4 weeks during inpatient treatment, and thereafter for another month, with compliance monitored by smartphone. 5. After completing medication treatment (active) or treatment as usual (control), participants will complete the following assessments: A) Blood draw at UCLA in the final week of drug treatment - a blood sample will be taken to assess plasma levels of drug. B) Visit 2: i. Prior to completing cognitive tasks behavioral testing, participants will will have their blood drawn by a London laboratory phlebotomist or will visit the Clinical and Translational Research Center (CTRC), where a registered nurse will draw approximately 40mL of blood. Blood samples will be assayed for genetic markers associated with smoking and stimulant use. The purpose of the genetic analysis is to examine the relationship between genetic polymorphisms, treatment outcomes, circulating study drug, and measures of cognitive function. The DNA samples acquired from this protocol will be added to a larger database of DNA samples collected from participants in London Laboratory protocols. DNA samples will be stored for future use other than the aims and goals of this study. Participants will not receive their results because our laboratory is only qualified for genetic analyses associated with research purposes and is not certified for clinical assessment of genetic information. This blood sample will also be used to determine follicular and luteal phase in female participants. ii. Urine toxicology: Participants will provide urine to assess recent use of drugs. iii. Cognitive/behavioral testing: Participants will complete some of the following tasks to assess inhibitory control and decision-making: Working memory (N-back test), declarative memory (Rey Auditory Verbal Learning Task), sustained attention (Rapid Visual Information Processing), inhibitory control (Stop Signal Test) reward-based decision-making (Monetary Delay Discounting and Reversal Learning, BART, ART), and impulsive and risk taking behavior (BIS, Willingness-to-wait task, Domain-Specific Risk-Taking (DOSPERT) Scale, UPPS-P Impulsive Behavior Scale, TCI), Loss Aversion, the Risk and Ambiguity Task, craving (Brief Meth Craving Questionnaire), mindfulness (Multidimensional Assessment of Interoceptive Awareness \[MAIA\], Mindful Attention Awareness Scale \[MAAS\], Body Perception Questionnaire Body Awareness Very Short Form \[BPQ\]), and withdrawal from cigarettes (Shiffman-Jarvik Withdrawal Scale) and amphetamines (Amphetamine Cessation Symptom Assessment \[ASCA\]). 6. Follow-up visit - 1 month after exiting inpatient treatment, participants will return to UCLA to complete follow-up procedures assessing cognitive function and stimulant use. A) Visit 3: i. Prior to completing cognitive tasks behavioral testing, participants will will have their blood drawn by a London laboratory phlebotomist or will visit the Clinical and Translational Research Center (CTRC), where a registered nurse will draw approximately 40mL of blood. Blood samples will be assayed for genetic markers associated with smoking and stimulant use. The purpose of the genetic analysis is to examine the relationship between genetic polymorphisms, treatment outcomes, circulating study drug, and measures of cognitive function. The DNA samples acquired from this protocol will be added to a larger database of DNA samples collected from participants in London Laboratory protocols. DNA samples will be stored for future use other than the aims and goals of this study. Participants will not receive their results because our laboratory is only qualified for genetic analyses associated with research purposes and is not certified for clinical assessment of genetic information. This blood sample will also be used to determine follicular and luteal phase in female participants. ii. Urine toxicology: Participants will provide urine to assess recent use of drugs. iii. Cognitive/behavioral testing: Participants will complete some of the following tasks to assess inhibitory control and decision-making: Working memory (N-back test), declarative memory (Rey Auditory Verbal Learning Task), sustained attention (Rapid Visual Information Processing), inhibitory control (Stop Signal Test) reward-based decision-making (Monetary Delay Discounting and Reversal Learning, BART, ART), and impulsive and risk taking behavior (BIS, Willingness-to-wait task, Domain-Specific Risk-Taking (DOSPERT) Scale, UPPS-P Impulsive Behavior Scale, TCI), Loss Aversion, the Risk and Ambiguity Task, craving (Brief Meth Craving Questionnaire), mindfulness (Multidimensional Assessment of Interoceptive Awareness \[MAIA\], Mindful Attention Awareness Scale \[MAAS\], Body Perception Questionnaire Body Awareness Very Short Form \[BPQ\]), and withdrawal from cigarettes (Shiffman-Jarvik Withdrawal Scale) and amphetamines (Amphetamine Cessation Symptom Assessment \[ASCA\]). iv. Stimulant use measurements: Participants will complete timeline followback and self-report assessments of their recent stimulant use.