Rationale: The subjective, psychomotor, and physiological effects of prescription compounds containing the opioid hydrocodone have not been studied in a population of non-drug-abusing people who might be prescribed these compounds for cough or pain relief.

Objectives: To characterize the effects of a hydrocodone combination product, Hycodan, which contains hydrocodone and a peripherally-acting anticholinergic, homatropine, in non-drug-abusing volunteers.

Methods: Eighteen volunteers participated in a crossover, double-blind study in which they received placebo; 5 mg hydrocodone/1.5 mg homatropine, 10 mg hydrocodone/3 mg homatropine, 20 mg hydrocodone/6 mg homatropine (all PO); 40 mg morphine (PO); and 2 mg lorazepam (PO). Measures were assessed before and for 300 min after drug administration. End-of-session and 24-h measures were taken to assess residual drug effects and overall subjects' assessment of the drug effects. RESULTS. Subjective effects of the hydrocodone/homatropine combination were dose-related, although the majority of statistically significant effects were limited to the highest dose combination tested. A combination of 20 mg hydrocodone/6 mg homatropine and morphine had a similar profile of subjective effects, which included both pleasant and unpleasant effects. Peak liking ratings were increased by 20 mg hydrocodone/6 mg homatropine and morphine, and trough ratings of liking (dislike) were lower in the 20 mg hydrocodone/6 mg homatropine condition, relative to the placebo condition. Post-session ratings of overall liking were not significant, either at the end of the session or 24 h later. Cognitive and psychomotor impairment were more marked with lorazepam than with hydrocodone/homatropine and morphine. Miosis and exophoria were increased in a dose-related manner by hydrocodone/homatropine.

Conclusions: Hycodan at the highest dose tested had effects similar to that of a prototypic mu agonist, morphine. Both drugs produced pleasant (including drug liking) as well as unpleasant subjective effects. Post-session ratings of overall liking and "want to take drug again" were not significant.