Markers of Abuse Liability, Neuropsych Testing, and Cue Reactivity

On one of three study dates, subjects received ER morphine tablets, 45 mg (Mallinckrodt Pharmaceuticals, St. Louis, MO). The dose of ER morphine sulfate (45 mg) was selected because of its approximate equianalgesic effect to the dose of hydrocodone-acetaminophen (30/925 mg).

Markers of Abuse Liability, Neuropsych Testing, and Cue Reactivity

On the day of the study session, patients received hydrocodone 30 mg plus N-acetyl-para-aminophenol 975 mg (APAP;Qualitest Pharmaceuticals Inc, Huntsville, AL).

Subjects received a placebo pill if randomized to this arm. Both opioid medications and the placebo were administered in identical capsules.

The first dose of the study medication was taken following collection of baseline measurements, and subsequent measurements were taken hourly thereafter. Respiration, heart rate, arterial oxygen saturation (pulse oximetry), and blood pressure were also monitored at these intervals to insure the safety of subjects.

The subjective effects of the study drug were evaluated with 3 subscales of the Addiction Research Center Inventory (ARCI). The subscales studied included Morphine-Benzedrine Group which measured euphoria (0-16 with higher numbers indicating more euphoria), the Phenobarbital-Chorpromazine-Alcohol Group which measured sedation (-3 to +11 with higher scores indicating more sedation), and the Lysergic Acid Diethylmide Group which measured dysphoria and agitation (-4 to +10 with higher scores indicating more dysphoria). This inventory consists of 49 true/ false questions which survey major domains of drug effects. The ARCI was measured at six timepoints. Of interest were trough sedation, peak euphoria, and trough dysphoria.

The subjective effects of the study drug were evaluated with the short form of the Addiction Research Center Inventory (ARCI. This inventory consists of 49 true/ false questions which survey major domains of drug effects. Participants indicated the pleasurable effects or desirability of the medications on 4 locally developed drug-liking ratings: craving, liking, strong desire, and "want more pain medication." Ratings were made on a 100-mm VAS anchored with 0 at the low end and 10 at the high end. Participants also responded to 11 locally developed drug-effect ratings to assess psychoactive effects. Ratings were again made on a 100-mmVAS anchoredwith 0 at the lowend and 10 at the high end for:"on cloud 9," "high," "good drug effect," "bad drug effect," "impaired,""stoned," "sedated," "confused," "nauseated from," "anxious," and "down". The rating levels over a six hour period were examined to explore the timing of these effects.

The subjective effects of the study drug were evaluated with 3 subscales of the Addiction Research Center Inventory (ARCI). The subscales studied included Morphine-Benzedrine Group which measured euphoria (0-16 with higher numbers indicating more euphoria), the Phenobarbital-Chorpromazine-Alcohol Group which measured sedation (-3 to +11 with higher scores indicating more sedation), and the Lysergic Acid Diethylmide Group which measured dysphoria and agitation (-4 to +10 with higher scores indicating more dysphoria). This inventory consists of 49 true/ false questions which survey major domains of drug effects. The ARCI was measured at six timepoints. Of interest were trough sedation, peak euphoria, and trough dysphoria.

Treatment effects at baseline, 60, 120, 180, 240, and 300 min were assessed with repeated measures ANOVA. A liner mixed-effects model with inclusion of interaction terms (1) treatment and time and (2) random order visit number and time was performed.

The subjective effects of the study drug were evaluated with the short form of the Addiction Research Center Inventory (ARCI. This inventory consists of 49 true/ false questions which survey major domains of drug effects. Participants indicated the pleasurable effects or desirability of the medications on 4 locally developed drug-liking ratings: craving, liking, strong desire, and "want more pain medication." Ratings were made on a 100-mm VAS anchored with 0 at the low end and 10 at the high end. Participants also responded to 11 locally developed drug-effect ratings to assess psychoactive effects. Ratings were again made on a 100-mmVAS anchoredwith 0 at the lowend and 10 at the high end for:"on cloud 9," "high," "good drug effect," "bad drug effect," "impaired,""stoned," "sedated," "confused," "nauseated from," "anxious," and "down". The rating levels over a six hour period were examined to explore the timing of these effects.