Within the context of clinical trials, the section evaluates methodological issues relevant to both research and treatment, such as monitoring drug use. In an earlier study, we showed that chronic cocaine use by active illicit users produced a longer plasma half-life than expected based on acute low-dose cocaine studies. In further analyses we examined urinary excretion patterns of cocaine metabolites as benzoylecgonine (BE) equivalents from 18 of the same individuals, housed for up to 14 days on a closed research unit, and evaluated whether creatinine normalization of BE equivalents increased mean detection time and reduced mean within-subject variability. Mean time to first negative specimen (BE equivalents <300 ng/mL) was 43.6 + 17.1 (SD) hours. BE equivalents fluctuated across successive specimens; 69% of participants tested positive at least once after testing negative, and the mean time to last positive specimen was 57.5 + 31.6 hours after the first specimen. Thus, mean cocaine metabolite detection times were consistent with prolonged elimination, with 63% of participants testing positive longer than the expected 48-hour window of detection after admission to the unit. Mean total time to last positive was even longer when self-reported time of last use of cocaine was considered: 81 + 34 hours. Creatinine normalization, with the cutoff of 300 ng BE equivalents/mg creatinine, increased detection time: mean time to first negative specimen was 54.8 + 20.7 hours, and mean time to last positive specimen was 88.4 + 51.0 hours. Creatinine normalization did not reduce the fluctuation of BE equivalents across successive specimens. Thus, creatinine normalized values may be useful when the goal is to maximize the probability or duration of cocaine metabolite detection. In another study we determined concentrations of methadone in 1093 urine specimens collected thrice weekly in 27 outpatients during up to 17 weeks of observed methadone ingestion (35 to 80 mg/day) using a semiquantitative homogeneous enzyme immunoassay (CEDIA). We used a separate CEDIA assay to measure methadone's main metabolite, 2-ethylidene-3,3-diphenylpyrrolidine (EDDP), which may help detect compliance in fast metabolizers or patients who adulterate samples to simulate compliance. Methadone concentrations were more variable than those of EDDP. Concentrations of methadone were <100 ng/mL in one specimen, between 100 and 300 ng/mL in 27, and >300 ng/mL in all others. EDPP concentrations were >100 ng/mL in all specimens, suggesting that EDDP should be detectable in urine from compliant patients. Methadone and EDDP concentrations significantly increased with methadone dose and (in one participant with poor clinic attendance) significantly decreased following missed methadone doses. Nevertheless, variability was too great to permit estimation of methadone dose (or detect a single missed administrations) from any single specimen. In a third project we determined whether cannabinoid-positive urine specimens in heroin-dependent outpatients predict other drug use or impairments in psychosocial functioning, and whether such outcomes are better predicted by cannabis-use disorders than by cannabis use itself. Retrospective analyses were conducted on data collected from 408 polydrug abusers participating in one of three clinical trials evaluating a behavioral intervention for cocaine or heroin use during methadone maintenance. Trials lasted 25-29 weeks with follow-up evaluations out to one year posttreatment. Participants were categorized as nonusers, occasional users, or frequent users of cannabis based on thrice-weekly qualitative urinalyses. Cannabis use was not associated with retention, use of cocaine or heroin, or any other outcome measure during or after treatment. Cannabis-use disorders were weakly associated with psychosocial problems at posttreatment follow-up. Cannabinoid-positive urines need not be a major focus of clinical attention during treatment for opiate dependence, unless patients report symptoms of cannabis-use disorders.