The relative abuse liability of oral oxycodone, hydrocodone and hydromorphone assessed in prescription opioid abusers

Abstract

Abuse of prescription opioids has risen precipitously in the United States. Few controlled comparisons of the abuse liability of the most commonly abused opioids have been conducted. This outpatient study employed a double-blind, randomized, within-subject, placebo-controlled design to examine the relative abuse potential and potency of oral oxycodone (10, 20 and 40 mg), hydrocodone (15, 30 and 45 mg), hydromorphone (10, 17.5 and 25mg) and placebo. Healthy adult volunteers (n=9) with sporadic prescription opioid abuse participated in 11 experimental sessions (6.5h in duration) conducted in a hospital setting. All three opioids produced a typical mu opioid agonist profile of subjective (increased ratings of liking, good effects, high and opiate symptoms), observer-rated, and physiological effects (miosis, modest respiratory depression, exophoria and decrements in visual threshold discrimination) that were generally dose-related. Valid relative potency assays revealed that oxycodone was roughly equipotent to or slightly more potent than hydrocodone. Hydromorphone was only modestly more potent (less than two-fold) than either hydrocodone or oxycodone, which is inconsistent with prior estimates arising from analgesic studies. These data suggest that the abuse liability profile and relative potency of these three commonly used opioids do not differ substantially from one another and suggest that analgesic potencies may not accurately reflect relative differences in abuse liability of prescription opioids.

Figure 1

Data are shown for mean values (n=9) for pupil diameter (left column) and oxygen saturation (right column) after administration of oxycodone (upper panels), hydrocodone (middle panels) and hydromorphone (lower panels) as a function of time (ordinate) since drug administration during the 6-hr session. Time course analysis revealed significant effects of dose for all three drugs for pupil diameter (F[9,72] = 13.4; p<.001) and oxygen saturation (F[9,72] = 2.3; p = .024). B indicates the baseline time point.

Figure 2

Data are shown for mean values (n=9) for the subject-rated visual analog questionnaires “How High Are You?” (top row), “How Much Do You Like the Drug?” (middle row) and the observer-rated Modified Fraser Scale of opioid agonist signs (bottom row; maximum score 10) after administration of oxycodone (left column), hydrocodone (middle column) and hydromorphone (right column) as a function of time (ordinate) since drug administration during the 6-hr session. Time course analyses revealed significant effects of dose for all three drugs for ratings of “high” (F [9, 72]=2.03; p = .048), “like the drug” (F [9, 72]=3.24; p=.002) and the Fraser scale (F [9,72] = 10.7; p<.0001). B indicates the baseline time point.

Figure 3

The six panels illustrate mean (n=9; ± 1 SEM) values for peak maximum scores (from left to right and top to bottom) on 1) the subject-rated visual analog scale “How High Are You?,” 2) subject ratings of nodding, 3) the subject-rated Agonist Scale, 4) the observer-rated Agonist Scale and for the peak minimum values for 5) pupil diameter (mm) and 6) respiratory rate (breaths/min).