Comparing the subjective, psychomotor, and physiological effects of intravenous hydromorphone and morphine in healthy volunteers

Rationale: The psychopharmacological profile of hydromorphone, an opioid th at has been used extensively for many years for post-operative pain managem ent, has not been adequately characterized in non-drug abusers. Objectives: To characterize the subjective, psychomotor, and physiological effects of a range of single doses of hydromorphone in non-drug-abusing volunteers and to compare the effects of hydromorphone with that of morphine, a benchmark mu opioid agonist. Methods: Subjects in a six-session study were injected in an upper extremity vein with 0, 0.33, 0.65, 1.3 mg/70 kg hydromorphone, and 5 and 10 mg/70 kg morphine, using a randomized, double-blind, crossover design. Results: Hydromorphone increased scores on the pentobarbital-chlor promazine-alcohol group and lysergic acid diethylamide scales and decreased scores on the benzedrine group scale of the Addiction Research Center Inve ntory, increased adjective checklist ratings of ("dry mouth", "flushing", a nd "nodding", and increased visual analog scale ratings indicative of both pleasant (e.g., drug liking) and unpleasant (e.g., "feel bad") effects. The subjective effects of morphine at putatively equianalgesic doses to those of hydromorphone were similar to those of hydromorphone, but in some cases of lesser magnitude. Psychomotor impairment was modest with hydromorphone a nd absent with morphine. Both opioids produced dose-dependent decreases in pupil size. A relative potency analysis indicated that hydromorphone was 10 times as potent as morphine (1 mg hydromorphone=10 mg morphine). Conclusio ns: The results of this study demonstrate that 0.33-1.3 mg hydromorphone ha d orderly, dose-related effects on subjective, psychomotor, and physiologic al variables, and similar effects to those of a benchmark mu opioid agonist , morphine.