Within-subject comparison of the psychopharmacological profiles of oral oxycodone and oral morphine in non-drug-abusing volunteers

Abstract

Rationale: Nonmedical use and abuse of prescription opioids is a significant problem in the USA. Little attention has been paid to assessing the relative psychopharmacological profile (including abuse liability-related effects) of specific prescription opioids.

Objectives: The aim of this study is to directly compare the psychopharmacological profile of two oral opioids within the same subject.

Methods: A randomized, placebo-controlled, crossover study was done in which 20 non-drug-abusing volunteers ingested 10 and 20 mg of oxycodone, 30 and 60 mg of morphine, and placebo in separate sessions. Drug doses were equated on an objective measure of opiate effects: miosis. Subjective, psychomotor, reinforcing, and physiological effects of the opioids were assessed.

Results: In general, the two opioids at equimiotic doses produced similar prototypic opiate-like effects and psychomotor impairment of similar magnitude. However, several effects were found only with 20 mg oxycodone. Both drugs produced abuse liability-related subjective effects but also dysphoric effects, particularly with 60 mg morphine. Neither drug at either dose functioned as a reinforcer, as measured by the Multiple Choice Procedure. Relative potency ratios indicated an average oxycodone/morphine [corrected] ratio of 1:3 [corrected]

Conclusions: The psychopharmacological profile of oxycodone and morphine at equimiotic doses had many similarities; however, differences were found in producing abuse liability-related and dysphoric effects. In the medical community, it is commonly accepted that oral oxycodone is 1.5 to 2 times as potent as oral morphine in producing analgesia; using this ratio, although patients may experience similar degrees of pain relief, those receiving oxycodone may be experiencing stronger and potentially different psychopharmacological effects.

Fig 1

Time course of the effects of oxycodone 10 mg (circle) and 20 mg (inverted triangle), morphine 30 mg (square) and 60 mg (diamond), and placebo (triangle) on “feel drug effect” ratings from the DEL/TA (a) and pupil size (b). Each point represents 20 subjects (a) or 19 subjects (b; subject 7 excluded because two pictures could not be scored). Solid symbols on the graph indicate that an active dose of the drug is significantly different from placebo at a given time point (Tukey post hoc test; p<0.05)