Intravenous oxycodone, hydrocodone, and morphine in recreational opioid users: abuse potential and relative potencies

Abstract

Rationale: Nonmedical use and abuse of prescription opioids is an increasing public health problem. Intravenous (IV) administration of opioid analgesics intended for oral use is not uncommon; yet, little is known about the relative abuse potential of these drugs when administered intravenously to recreational opioid abusers without physical dependence.

Methods: This inpatient study employed a double-blind, randomized, within-subject, placebo-controlled design to examine the relative abuse potential of IV doses of oxycodone, hydrocodone, and morphine. Nine healthy adult participants reporting recreational opioid use and histories of IV opioid use completed 11 experimental sessions, including one active-dose practice session. IV doses were infused over 5 min and included three identical doses of each opioid (5, 10, and 20 mg/10 ml) and saline placebo. Physiological, subjective, and performance effects were collected before and for 6 h after drug administration.

Results: All three opioids produced prototypical mu agonist effects (e.g., miosis; increased ratings of liking) that were generally dose-related. Pharmacodynamic effects were observed within 5 min of IV administration. Physiological effects were more prolonged than subjective effects for all three drugs. While the magnitude of effects was generally comparable across drugs and qualitatively similar, valid potency assays indicated the following potency relationship: oxycodone > morphine > hydrocodone.

Conclusions: There were modest potency differences between oxycodone, hydrocodone, and morphine, but their overall profile of effects was similar, indicating significant abuse potential when administered intravenously.

Figure 1

Data are shown for mean values (n=9) for pupil diameter (top panel) and oxygen saturation (bottom panel) after administration of morphine (left column), oxycodone (middle column) and hydrocodone (right column) as a function of time (X-axis) since drug administration in the 6 h session. Error bars omitted for clarity. Filled symbols indicate a significant difference from the corresponding placebo time point. Time course analysis revealed significant interactions of dose and time condition for pupil diameter and oxygen saturation (F_189,1509 = 2.0, p < 0.0001; F_{189, 1507} = 1.4, p = 0.001, respectively).

Figure 2

Data are shown for mean values (n=9) for responses to “Do you feel any DRUG EFFECT?” (top panel) and “How much do you “LIKE” the drug?” (bottom panel) after administration of morphine (left column), oxycodone (middle column) and hydrocodone (right column) as a function of time (X-axis) since drug administration in the 6 h session. The maximum score is 100. Error bars omitted for clarity. Filled symbols indicate a significant difference from the corresponding placebo time point. Time course analysis revealed significant interactions of dose and time condition for “Do you feel any DRUG EFFECT?” and “How much do you “LIKE” the drug?” (F_333,2661 = 1.4, p < 0.0001; F_333,2662 = 1.3, p = 0.002, respectively).

Figure 3

Data are shown for mean values (n=9) for expired CO₂ (top left panel), Observer-Rated Opioid Agonist Adjectives (top right panel), “Does the drug have any GOOD EFFECTS?” (bottom left panel) and Street Value (bottom right panel) as a function of dose (X-axis). Brackets indicate + 1 SEM. A significant effect of Dose Condition was observed for all four measures (F_{9, 72} values ≥ 7.8, p < 0.0001). Filled symbols are significantly different from placebo (Tukey test; p < 0.05).