A dose-response analysis of the subjective, psychomotor and physiological effects of intravenous morphine in healthy volunteers

Abstract

The purpose of this study was to characterize the subjective, psychomotor and physiological effects of morphine in healthy volunteers. Subjects (10 males and 2 females) without histories of opiate dependence were injected in an antecubetal vein with 0, 2.5, 5.0 or 10 mg/70 kg of morphine, by using a randomized, double-blind, cross-over design. Subjective effects, psychomotor performance and physiological measures were assessed immediately before the injection and for up to 5 hr afterward. Morphine increased the Pentobarbital-Chlorpromazine-Alcohol Group, Amphetamine, the Lysergic Acid Diethylamide and the Morphine-Benzedrine Group scores and decreased Benzedrine Group scores on the Addiction Research Center Inventory. Increased visual analog scale ratings of "stimulated," "high," "sedated," "coasting or spaced out" and "drunken" were also obtained. On an opiate adjective checklist, subjects reported increased ratings of "flushing," "dry mouth" and "tingling." Drug liking was not significantly altered by morphine, but there was substantial intersubject variability with this measure. Some aspects of psychomotor performance (reaction time, Digit Symbol Substitution Test and Maddox Wing) were impaired by morphine; however, eye-hand coordination was not. Miosis was induced by morphine. Most effects of morphine were dose-related, some effects peaked soon after morphine injection (e.g., increased stimulated and high ratings) and dissipated gradually, whereas other effects did not peak until later into the session (sedation or exophoria). Our results are fairly consistent with other studies examining morphine effects in healthy volunteers, and also indicate that the profile of morphine effects differ between healthy volunteers and those with a history of opiate dependence.