Injection heroin use is a chronic problem that fuels the transmission of HIV/AIDS through risky injection behaviors. Methadone and buprenorphine can reduce heroin use and risky injection behavior; however, they have abuse potential, produce physical dependence, can produce lethal overdose, are highly regulated, and some patients simply do not want agonist treatment. Opiate detoxifications can serve as an alternative to agonist treatment, but many injection drug users relapse to heroin use and resume risky injection behaviors after detoxification. Vivitrol(R), an extended release formulation of naltrexone, was recently approved by the FDA for the treatment of opioid dependence, but its clinical utility is uncertain given the reluctance of many opioid- dependent adults to maintain its long-term use, and the fact that some patients continue to use opiates while under naltrexone blockade. Our research in the first period of this grant showed that employment-based reinforcement can be highly effective in promoting long-term adherence to Vivitrol(R). Employment-based reinforcement may be ideally suited to address the limitations of extended release naltrexone by capitalizing on its potential to simultaneously reinforce naltrexone adherence and opiate abstinence. This grant will evaluate the effectiveness of employment-based reinforcement to simultaneously promote high rates of Vivitrol(R) adherence and increase opiate abstinence. In this 5-year study, we propose to evaluate the separate and combined effects of the FDA-approved formulation of extended release naltrexone (Vivitrol(R)) and employment- based reinforcement of opiate abstinence in promoting opiate abstinence and reducing risky injection behavior in recently detoxified, opioid-dependent, injection drug users. After an opioid detoxification and induction onto oral naltrexone, participants will be invited to attend the Therapeutic Workplace for 24 weeks (where they can work and earn wages) and will be randomly assigned to one of four groups that will differ in whether they receive Vivitrol(R), employment-based opiate abstinence reinforcement, both or neither. Participants in Vivitrol(R) conditions will be required take scheduled injections to work and earn wages. Participants exposed to opiate abstinence reinforcement will receive a temporary decrease in their workplace pay if they fail to provide an opiate-free urine sample. The study will assess the effects of the interventions on weekly opiate urinalysis results, and on measures of injection drug use and cocaine use. If this study shows that the combined use of Vivitrol(R) and employment-based reinforcement of adherence and opiate abstinence is effective in maintaining long-term opiate abstinence, this model of employment-based addiction pharmacotherapy could be integrated into community workplaces to disseminate the effective use of Vivitrol(R); it could be used to enhance the utility of other new antagonist-like addiction medications; and it could provide an effective means of reducing injection drug use in individuals who persist in injecting heroin and exposing themselves and others to the risk of acquiring or transmitting HIV infection due to their continued injection drug use and risky injection behaviors. PUBLIC HEALTH RELEVANCE: Injection heroin use is a chronic problem that fuels the transmission of HIV/AIDS through risky injection behaviors. Vivitrol(R), an extended release formulation of naltrexone, was recently approved by the FDA for the treatment of opioid dependence, but its clinical utility is uncertain given the reluctance of many opioid- dependent adults to maintain its long-term use, and the fact that some patients continue to use opiates while under naltrexone blockade. This grant will utilize and evaluate the robust effectiveness and versatility of employment-based reinforcement to simultaneously promote and maintain high rates of Vivitrol(R) adherence and opiate abstinence, and reduce risky injection behaviors in opioid dependent injection drug users.