Subjective, psychomotor, and analgesic effects of oral codeine and morphine in healthy volunteers

Abstract

The subjective, psychomotor, and physiological effects of analgesic doses of oral codeine and morphine were examined in 12 healthy volunteers. Subjects ingested placebo, morphine 20 or 40 mg, or codeine 60 or 120 mg in a randomized, double-blind, crossover design. The smaller and larger doses of each drug were putatively equianalgesic, and the cold-pressor test was included to test this assumption. Codeine and morphine increased ratings of “feel drug effect” but had little effect on other subjective measures, including the Addiction Research Center Inventory, visual analog scales, and adjective checklists. The few subjective effects that were observed were modest and were dose-related for morphine but not for codeine. The drugs did not affect performance on Maddox-Wing, digit-symbol substitution, coordination, auditory reaction, reasoning, and memory tests. Dose-related decreases in pupil size (miosis) were observed following codeine and morphine. Ratings of pain intensity decreased in a dose-related manner for morphine but not for codeine. Plasma codeine and morphine levels varied as an orderly function of dose. These results suggest that oral codeine and morphine are appropriate drugs for outpatient pain relief because they are effective analgesics at doses that have only modest effects on mood, produce few side effects, and do not impair performance. The results also suggest a possible ceiling effect of codeine on analgesia and subjective effects.