PUBLICATIONS BY TOPIC: PHARMACEUTICAL DRUGS

Wilkinson, C. J. (1998). The abuse potential of zolpidem, administered alone and with alcohol. Pharmacology, Biochemistry and Behavior, 60, 193-202.

The abuse potential of zolpidem, alone and in combination with alcohol, was examined in healthy volunteers with a history of social use of alcohol and drugs. Zolpidem. a short-acting imidazopyridine hypnotic with selectivity for a benzodiazepine receptor subtype (BZ1 or omega1), was administered double blind at 0, 10, or 15 mg with alcohol (0.75 g ethanol/kg b.wt.) or with placebo beverage in a randomized, six-way crossover design. Outcome measures included the Drug Effect Questionnaire (DEQ), the Addiction Research Center Inventory (ARC1-40), and the Profile of Mood States (POMS). Blood alcohol concentrations (BACs) were not significantly modified by zolpidem. Relative to placebo. zolpidem and alcohol significantly (p < 0.05) increased drug strength perception. drug-liking, and drug-disliking scores on the DEQ. On the ARC1-40, zolpidem and alcohol significantly increased sedation/intoxication and dysphoria/fear scores. but did not significantly change euphoria/well-being scores. Zolpidem and alcohol were rated more unfavorably than placebo on the POMS. Alcohol did not have additive effects on the subjective ratings for zolpidem. It is concluded that, for this population and at the doses tested. the abuse potential of zolpidem appears to be modest and not increased by alcohol.

Wilkinson, C. J. (1995). The acute effects of zolpidem, administered alone and with alcohol, on cognitive and psychomotor function. Journal of Clinical Psychiatry, 56, 309-318.

Background : Skills performance impairment after acute doses of zolpidem (a short-acting, nonbenzodiazepine hypnotic), alone and with alcohol, was evaluated in 24 subjects. The study was designed to test whether the effects of zolpidem and alcohol are simply additive or reflect potentiation. Method : Healthy male volunteers participated in a randomized, six-way crossover study of placebo, zolpidem 10 mg, or zolpidem 15 mg in combination with a placebo beverage or an alcohol dose selected to attain a peak blood alcohol concentration of 0.08% (drug administered double-blind; beverages administered single-blind). A laboratory test battery of four tasks measured concurrent information processing ability (divided attention task), information processing rate (visual backward masking task), immediate memory (Sternberg task), and sustained attention (vigilance task). The battery was repeated three times to measure peak (+45 minutes), postpeak (+130 minutes), and residual (+230 minutes) treatment effects after each dosing. Results : Performance on each test-battery task was significantly impaired (p <.05) by both alcohol and zolpidem (combined and each given alone) during the peak-effect assessment. Residual effects were not observed, with the exception of significant alcohol and drug effects on divided attention performance (p <.05). Analysis of variance tests revealed significant main effects of alcohol and zolpidem, but no significant alcohol-by-drug interactions were found for any measure of skills performance. In general, additive effects of alcohol were detected with zolpidem 10 mg but not with zolpidem 15 mg. Conclusion : Although some additive effects of alcohol on performance skills were seen with the lower 10-mg dose of zolpidem, no nonadditive effects were found. That is, alcohol does not appear to potentiate the effects of zolpidem on the various performance skills tested in this population and at the doses and times evaluated. With the exception of persisting deficits (at 4 hours postdose) on the more demanding divided attention task, all other findings were consistent with evidence that zolpidem is a short-acting hypnotic drug.

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