Evaluation of the subjective and reinforcing effects of diphenhydramine, levetiracetam, and valproic acid

Few unscheduled sedating medications have been evaluated for their subjective and reinforcing effects in humans. To increase the information available about unscheduled sedating medications and to evaluate the ability of human laboratory measures to discriminate between scheduled and unscheduled sedating drugs, 24 subjects with a history of experience with several classes of drugs of abuse, including sedatives and/or alcohol, and who reported liking a test dose of pentobarbital 300 mg, were randomized to single doses of diphenhydramine 400 mg, levetiracetam 4000 mg, valproic acid 1500 mg, diazepam 30 mg or placebo in a double-blind, 5-way crossover study. On the Addiction Research Center Inventory-Morphine-Benzedrine Group and the Next Day Questionnaire measures 'Take Again' and 'Willing to Pay', diazepam produced a significantly greater effect than placebo; all three other active drugs did not. Levetiracetam significantly increased the crossover point on the Multiple Choice Procedure, whereas diazepam did not. For the doses studied, the rank order of statistically significant findings suggestive of abuse potential was diazepam (9/10 measures significant) > levetiracetam (6/10) > diphenhydramine (5/10) > valproic acid (2/10).