Treatment of Heroin and Cocaine With Methadone Maintenance and Contingency Management

Scientific goals. The primary goal is to determine if simultaneous abstinence from heroin and
cocaine can be elicited by combining two approaches: flexible methadone dosing and
voucher-based CM. Secondary goals include: 1) comparing saliva and plasma levels of
methadone, cortisol, and prolactin as predictors of treatment outcome; and 2) evaluating the
impact of methadone maintenance on renal function, lipid profile, and cardiac function.

Methods. During an initial 6-week baseline phase, cocaine-abusing opioid-dependent outpatient
participants (300 enrolled; 180 evaluable) will be stabilized on methadone 70 mg/day. At the
end of baseline, participants who continue to use heroin and cocaine will be randomized to
one of two dosing regimens and one of two CM conditions. In the flexible-dose regimen,
participants will receive individualized dose increases (15 mg/day) to a maximum of 190 mg
/day, based on heroin use and withdrawal. In the fixed-dose regimen, participants methadone
dose will be increased to 100 mg/day and remain fixed there. Dose-group assignment will be
double-blind: investigators will determine participants individualized dose increases, but
only the pharmacists will know which participants actually receive them. The two CM
conditions will be: vouchers contingent on cocaine-negative urine specimens, or noncontingent
vouchers (i.e., vouchers independent of urine cocaine screen results). The main outcome
measure will be the percentage of urines simultaneously negative for both cocaine and illicit
opiates during treatment. For the concurrently run pharmacokinetic-pharmacodynamic portion,
saliva and blood samples will be taken at regular intervals to determine levels of methadone,
cortisol, and prolactin as predictors of treatment outcome. For the concurrently run
medical-outcomes portion, urine (renal function), blood (lipid profile), and ECGs (cardiac
function),will be obtained at set intervals.

Hypothesis. Flexible methadone dosing and voucher-based CM will be safe and result in greater
simultaneous abstinence from heroin and cocaine, higher treatment retention, and higher
health-related QOL when compared to fixed methadone dosing and the absence of CM.

Benefits. Participants will receive methadone, counseling, and some medical care at no
charge. The methadone and voucher interventions are likely to reduce participants' use of
heroin and cocaine. Counseling will include management of HIV risk behaviors. The study
incorporates participant safety monitoring and will provide information relevant to improving
the health and safety of community methadone-maintenance patients. The
pharmacokinetic-pharmacodynamic part of the study does not benefit participants directly, but
may lead to the development of more useful and less invasive drug-monitoring methods.

Risks. Participants may experience side effects from methadone, discomfort during methadone
withdrawal, and discomfort (or, rarely syncope) from blood draws.

- INCLUSION CRITERIA:

1. age between 18 and 65;

2. physical dependence on opioids

3. evidence of cocaine use, by urine screen and self-report

4. able to attend methadone clinic 7 days/week

EXCLUSION CRITERIA:

1. History of schizophrenia or any other DSM-IV psychotic disorder

2. History of bipolar disorder

3. Current Major Depressive Disorder;

4. Current physical dependence on alcohol or sedative-hypnotics, e.g. benzodiazepines

5. Cognitive impairment severe enough to preclude informed consent or valid responses on
questionnaires (Shipley Institute of Living scale-estimated full-scale IQ less than
80)

6. Medical illness that in the view of the investigators would compromise participation
in research

7. Urologic conditions that would inhibit urine collection

8. Previous bowel obstruction.

9. Previous history of the following: major abdominal surgery, major gynecologic / pelvic
surgery, inflammatory bowel disease (Crohn s or ulcerative colitis), Meckel s
diverticulum, congenital atresia or stenosis, diverticulitis, radiation enteropathy or
stricture, bowel neoplasm, endometriosis, inguinal-femoral-umbilical-ventral hernia,
volvulus, or neurogenic megacolon, frequent bezoars.

10. Recent use of medications known to cause severe constipation.

11. History of previous severe respiratory depression or coma due to methadone use.

12. Pregnancy.

13. Personal history of a serious arrhythmia such as ventricular tachycardia, ventricular
fibrillation, or Torsade de pointes; personal history of congenital heart disease or
arrhythmia.

14. Personal history of congenital long QT syndrome (LQT).

15. Family history of a congenital long QT syndrome.

16. Family history of Torsade de pointes.

17. Family history of sudden cardiac death below the age of forty years.

18. Evidence of clinically significant structural heart disease.

19. Personal history of severe electrolyte disorders.

20. Recent use of anti-arrhythmic agents.

21. Poor venous access.

22. Lab values outside the parameters set in Table II. These exclusion values are based
upon the Medical Screening guideline used previously at the NIDA-IRP.

23. CD4 less than 200 or evidence of severely compromised immune system / AIDS

24. Women who are able to get pregnant must agree to use a medically effective form of
contraception while in the study.

Acceptable forms of contraception for this study include:

1. Hormonal contraception (birth control pills, injected hormones, vaginal ring)

2. Intrauterine device

3. Barrier methods with spermicide (diaphragm with spermicide, condom with spermicide)

4. Surgical sterilization (hysterectomy, tubal ligation, or vasectomy in a partner)

Women who do not agree to use these medically effective forms of contraception while in the
study will be excluded.