Attention-deficit/hyperactivity disorder, medication treatment, and substance use patterns among adolescents and young adults.

OBJECTIVE: The aim of this study was to examine the relationship between current active attention-deficit/hyperactivity disorder (ADHD) symptoms, medication treatment, and substance use patterns among college students. METHOD: Three hundred and thirty-four students at a local college were surveyed for current ADHD symptoms and psychopharmacological treatment. The survey was conducted in conjunction with an annual national survey that probes students about their substance use patterns and attitudes. RESULTS: Participants with ADHD as ascertained by medication treatment of ADHD had greater past-year tobacco and marijuana use. Among those with ADHD, participants with active ADHD symptoms were more likely to have past-year tobacco and other drug (besides tobacco, alcohol, and marijuana) use as compared to those without active ADHD symptoms. In addition, participants with active ADHD symptoms were more likely to have past-month "other" drug use as compared to those without active ADHD symptoms. Among those prescribed medications for ADHD, 25% reported ever using their medication to "get high" and almost 29% reported ever giving or selling their medication to someone else. CONCLUSIONS: Results of our preliminary study indicated that ADHD symptom control may be important to protect against increased risk of substance use (particularly tobacco and drugs other than alcohol and marijuana) among college-age students with ADHD. Further studies of misuse/diversion of prescription stimulant medication among college students are needed.

Evaluation of hepatotoxic potential of drugs by inhibition of bile-acid transport in cultured primary human hepatocytes and intact rats.

Inhibition of canalicular bile acid efflux by medications is associated with clinical liver toxicity, sometimes in the absence of major liver effects in experimental species. To predict the hepatotoxic potential of compounds in vitro and in vivo, we investigated the effect of clinical cholestatic agents on [3H]taurocholic acid transport in regular and collagen-sandwich cultured human hepatocytes. Hepatocytes established a well-developed canalicular network with bile acid accumulating in the canalicular lumen within 15 min of addition to cells. Removing Ca2+ and Mg2+ from the incubation buffer destroyed canalicular junctions, resulting in bile acid efflux into the incubation buffer. Canalicular transport was calculated based on the difference between the amount of bile acid effluxed into the Ca/Mg2+-free and regular buffers with linear efflux up to 10 min. Hepatocytes cultured in the nonsandwich configuration also transported taurocholic acid, but at 50% the rate in sandwiched cultures. Cyclosporin A, bosentan, CI-1034, glyburide, erythromycin estolate, and troleandomycin inhibited efflux in a concentration-dependent manner. In contrast, new generation macrolide antibiotics with lower incidence of clinical hepatotoxicity were much less potent inhibitors of efflux. An in vivo study was conducted whereby glyburide or CI-1034, administered iv to male rats, produced a 2.4-fold increase in rat total serum bile acids. A synergistic 6.8-fold increase in serum total bile acids was found when both drugs were delivered together. These results provide methods to evaluate inhibitory effects of potentially cholestatic compounds on bile-acid transport, and to rank compounds according to their hepatotoxic potential.