We have already demonstrated the effectiveness of behavioral interventions (reinforcement for cocaine-negative urine samples) in large inner-city samples of intravenous polydrug abusers, and we continue to evaluate the best ways to apply the treatment. To examine the effect of reinforcer density in prize-based abstinence reinforcement, heroin/cocaine users (N=116) in methadone maintenance (100 mg/day) were randomly assigned to a noncontingent control group (NonC) or one of three groups that earned prize draws for abstinence: manual drawing with standard prize density (MS), or computerized drawing with standard (CS) or high (CH) density. Probabilities (prizes/draw) were: standard 50%, high 78%; prize density was double blind. Mean prize values were: CH $286; CS $167; MS $139; NonC $171. Outcomes were % opioid/cocaine-negative urines during the 12-week intervention and 8 weeks post-intervention and diagnosis of dependence up to 6 months post study. CH had significantly more negative specimens than NonC during intervention and more than all groups during post-intervention treatment: mean % negative (95% confidence interval) during post-intervention treatment adjusted for baseline drug use and dropout were: CH 55% (14-90%); CS 7% (1-27%); MS 4% (1-12%); NonC: 3% (1-10%). Current cocaine-dependence diagnoses after treatment were significantly lower in contingent compared to noncontingent groups. Computerized drawing with higher-density prizes enhanced reduction of cocaine use; abstinence reinforcement had long-term therapeutic benefits. The major challenge associated with abstinence reinforcement is its likely prohibitive cost and staff/resource intensity, especially when the reinforcement follows an escalating amount schedule. Workflow challenges include varying conditions for meeting inclusion criteria, stratification into various groups, tracking categories of reinforcers chosen, and determination of eligibility for bonus reinforcers based on laboratory results or other protocol-defined criteria. To address these challenges, in collaboration with the Biomedical Informatics Section of the NIDA IRP, we implemented the Automated Contingency Management (ACM) decision support system for abstinence reinforcement. We are continuing to improve the system and to develop mechanisms to make it available to community treatment programs. The availability of such a system would promote technology transfer and increase community use of evidence-based procedures for abstinence reinforcement. In further technology development work, we are exploring the use of handheld electronic devices for treatment delivery in patients daily environment. In individuals who have achieved abstinence, the main concern is the likelihood of relapse. The alpha-agonist lofexidine may help prevent stress-induced relapse to heroin use in patients on methadone maintenance. Both agents, however, exhibit cardiovascular and neurocognitive activities, and the safety of simultaneous administration has never been reported. We examined the hemodynamic and cognitive effects of lofexidine and methadone coadministration. Fourteen patients in methadone maintenance (80 mg/d) received escalating doses of lofexidine (0 to 1.6 mg/d, single blind) for up to 8 weeks. Acute orthostatic vital signs and neuropsychological effects of lofexidine and methadone co-administration were monitored for five hours post-dose on the first day of each new lofexidine dose. Orthostatic vital signs and adverse events (AEs) were assessed daily thereafter to assess effects of repeated dosing. Lofexidine decreased sitting systolic and diastolic blood pressure (BP) (p=0.045 and p=0.033 respectively) compared to placebo (methadone alone); at 0.4 mg lofexidine, the mean decreases in sitting systolic and diastolic BP were 27+17 and 15+16 mm Hg respectively. There was, however, no significant association between changes in orthostatic vitals and lofexidine dose. Decreased cognitive efficiency was also associated with lofexidine administration; higher lofexidine doses adversely affected performance on a mathematical task relative to placebo (p=0.0035). Adverse event incidence was not dose dependent; the majority of events (64.5%) were common side effects of lofexidine. Significant changes in hemodynamic and cognitive efficiency were observed with coadministration of lofexidine and methadone compared to methadone alone. We concluded that methadone and lofexidine should not be administered concomitantly in maintenance treatment until further studies address the safety of combination therapy.