Modulating effects of a cold water stimulus on opioid effects in volunteers

Abstract

The purpose of this study was to characterize the effect of a painful stimulus on morphine and butorphanol effects in healthy non-drug abusing volunteers. Thirteen subjects with no history of opiate dependence participated in a randomized, placebo-controlled, double-blind, crossover trial in which each subject received saline, 2 mg/70 kg butorphanol, and 10 mg/70 kg morphine, IV, in each of two conditions, periodic forearm immersions into either ice-cold water (2 degrees C) or into warm water (37 degrees C). Both opioids reduced self-reported ratings of pain intensity, indicative of analgesia. Several of the subjective effects of morphine were attenuated either during or in between cold-water immersions, including visual analog scale ratings of "coasting (spaced out)," "high (drug "high")," "sleepy (drowsy, tired)," and "lightheaded". In contrast, some of butorphanol's subjective effects were increased by the cold-water manipulation. Morphine impaired psychomotor performance during one of the warm-water immersions, but not during the cold-water immersions. Psychomotor impairment induced by butorphanol was not affected by water temperature. This study provides evidence that opioid effects can be modulated by a painful stimulus in humans.

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

“…These results suggest that patients taking these drugs may be able to function e¤ectively outside the medical setting. Although this extrapolation must be made cautiously because the e¤ects of opioids in patients may be a¤ected by illness or the presence of pain, studies have shown that pain tends to attenuate, rather than enhance, the subjective and psychomotor e¤ects of opioids (Wol¤ et al 1940;Zacny et al 1996;Conley et al 1997). The present results are also consistent with the notion that opioids as a class of drugs generally tend not to impair cognitive / psychomotor performance signiÞcantly (Ja¤e and Martin 1990;Bigelow 1991;Roache 1991;Zacny 1995Zacny , 1996.…”

Effects of stress on responses to methamphetamine in humans

“…Söderpalm and de Wit (2002) found that social stress reduced the stimulant-like effects of alcohol and increased self-reports of sedation. Zacny et al (1996) and Conley et al (1997 reported that brief exposure to a coldwater stressor dampened or abolished the subjective (including euphorigenic) effects of opioids fentanyl and morphine. The range of conditions under which stress dampens or enhances subjective drug effects remains to be determined.…”

Effects of the triple monoamine uptake inhibitor amitifadine on pain-related depression of behavior and mesolimbic dopamine release in rats

“…Morphine is a mu opioid receptor agonist that produces strong analgesia and also has abuse liability [21]. However, the abuse potential of morphine depends in part on a history of prior opioid exposure [2], and in opioid-naïve humans, morphine can produce analgesia without prominent abuse-related effects [17,55]. Similarly, in opioid-naïve rats, morphine can block acid-induced depression of both ICSS and NAc DA without producing an abuse-related increase in either ICSS or NAc DA in the absence of the noxious stimulus [25,38].…”