Quantitative versus qualitative urinalysis for benzoylecgonine in clinical trials for the assessment of cocaine use.

Urinalysis of benzoylecgonine (BE) concentrations is a primary outcome measure for evaluating medications for treating cocaine addiction. Using simulated BE data from a set of simple clinical models, the advantages of quantitative versus qualitative urinalysis were evaluated, as well as the advantages of once-weekly versus thrice-weekly sampling schedules. A 60 percent reduction in cocaine use, either in daily amount or in weekly frequency, was considered clinically significant. Quantitative urinalysis can detect reductions in both amount and frequency, whereas qualitative urinalysis can detect only a decrease in frequency. For quantitative urinalysis, changes are more easily detected when urine is collected three times a week than when it is collected once a week. For qualitative urinalysis, the majority rule analysis for a thrice-weekly sampling schedule yields an artificially high estimate of the percentage of positive samples, whereas a once-weekly schedule gives a highly variable estimate.

Assessment of laboratory quality in urine drug testing. A proficiency testing pilot study.

As part of a program to develop accreditation guidelines for urine drug testing laboratories, a pilot study for proficiency testing was conducted. Fifty civilian, commercial laboratories were included on a voluntary basis. Drug-free urine specimens were collected and either fortified with commonly abused drugs at concentrations comparable to casual use or submitted unfortified to participating laboratories as blanks. Samples were submitted on both an open and blind basis to the laboratories. Laboratory performance on open proficiency testing was comparable with that reported in existing proficiency testing programs. Blind proficiency testing produced less accurate results in terms of apparent false-negatives, but significant difficulties were evident in carrying out blind testing and in comparing its results with those of open testing. Specific problems have been identified to guide future programs.

Implications of drug levels in body fluids: basic concepts.

Drug concentrations in biological fluids are affected by the dose, route of administration, pattern of drug use, and the dispositional kinetics (distribution, metabolism, and excretion) of the drug. As most drugs are distributed to the site of action by blood, drug concentration measurement in this body fluid provides the best information as to the potential effect on behavior such as driving impairment or on psychological high. Due to wide individual variations in the pharmacokinetics and pharmacodynamics of drugs, however, the use of plasma drug concentrations for the estimation of impairment has not been established for most drugs. As for urinalysis, drug concentrations in the urine are further complicated by other factors such as urine flow and pH. Even if a specific method is used for the quantitation of a specific drug (the active species, not the inactive metabolite), interpretation in forensic samples to predict time of drug use or impairment is not possible, except within broad time periods, because of the variations in urine drug concentration as well as the limited knowledge available about the dose or the route of administration.

Laboratory detection of marijuana use.

Frequent smoking of cannabis (marijuana) has been shown to be associated with a decline in social, mental, and perceptual skills and, during adolescence, with maladaptive emotional development. Urinalysis for the detection of such use can be a useful tool for the physician responsible for treatment and counseling of adolescents who develop habitual use of marijuana. Primary methods for urinalysis detection of cannabis use include the homogeneous enzyme immunoassay (EMIT) and the radioimmunoassay. These and other methods are discussed along with the issues of "false" results (both positive and negative) and the "limits of interpretation" that can be placed on a positive urine result. The pharmacokinetics and metabolism of the active constituents of cannabis are described as well as the interpretation of urinalysis results as they relate to use patterns. Guidelines are presented for the primary care physician for selecting candidates for such testing and for the use of such tests in the treatment or counseling of adolescents for whom marijuana abuse has become a psychological and social problem.

Marijuana: interaction with the estrogen receptor.

Crude marijuana extract competed with estradiol for binding to the estrogen receptor of rat uterine cytosol. Condensed marijuana smoke also competed with estradiol for its receptor. Pure delta 9-tetrahydrocannabinol, however, did not interact with the estrogen receptor. Ten delta 9-tetrahydrocannabinol metabolites also failed to compete with estradiol for its receptor. Of several other common cannabinoids tested, only cannabidiol showed any estrogen receptor binding. This was evident only at very high concentrations of cannabidiol. Apigenin, the aglycone of a flavinoid phytoestrogen found in cannabis, displayed high affinity for the estrogen receptor. To assess the biological significance of these receptor data, estrogen activity was measured in vivo with the uterine growth bioassay, using immature rats. Cannabis extract in large doses exhibited neither estrogenic nor antiestrogenic effects. Thus, although estrogen receptor binding activity was observed in crude marijuana extract, marijuana smoke condensate and several known components of cannabis, direct estrogenic activity of cannabis extract could not be demonstrated in vivo.