Naloxone does not affect cigarette smoking

Abstract

In order to provide information about the hypothesis that endogenous opioids mediate the reinforcing properties of cigarette smoking, the present study examined the effects of naloxone, an opioid antagonist, on cigarette smoking in seven normal volunteers. The study used experimental procedures that had previously been shown sensitive for detecting the effects of other drugs, (including a nicotine antagonist) on smoking. Isolated subjects smoked their regular brand of cigarettes freely in a naturalistic laboratory environment while watching television or reading. Sixty minutes before each 2 h smoking session subjects received an IM injection of naloxone HCl (0.0625, 0.25, 1.0, or 4.0 mg/kg) or placebo. Each subject received each treatment three times in a mixed order across days. Naloxone did not significantly affect any measure of cigarette smoking including number of cigarettes, number of puffs, or expired air carbon monoxide level. Naloxone did, however, produce significant dose-related increases in subject ratings of yawning, stretching, and relaxation. The results of the present study provide no support for the endogenous opioid theory of smoking reinforcement.

Plasma concentrations of beta-endorphin in smokers who consume different numbers of cigarettes per day

“…However, this hypothesis will require further study and confirmation, because the number of cigarettes smoked per day does not reliably predict nicotine levels [10]. Peripheral blood concentrations of b -end do not always correlate highly with central concentrations [6,21], and use of the opioid antagonist naloxone does not appear to modify smoking [15], although some authors have reported positive results [9,19]. Plasma concentrations of cortisol also differed between the groups of smokers we studied; the differences were greater between moderate and heavy smokers than between control subjects and light smokers.…”

Smoking Modulation of μ-Opioid and Dopamine D2 Receptor-Mediated Neurotransmission in Humans

“…Subsequent human clinical trials with naloxone or the longer acting opioid receptor antagonist naltrexone showed inconsistent results both in the degree that these agents diminished tobacco smoking as well as on their behavioral effects (Nemeth-Coslett and Griffiths, 1986;Gorelick et al, 1988;Sutherland et al, 1995;Wewers et al, 1999). Aceto et al (1993) examining the analgesic effects of nicotine in rodents, and Pomerleau (1998) in a review of both human and animal data, postulated that nicotine produced both pro-and antiopioidergic effects.…”

Neural mechanisms underlying nicotine addiction: acute positive reinforcement and withdrawal

“…Thus, the positive reinforcing properties of nicotine could be hypothesized to be modulated by activation of enkephalin neurons along parallel reward systems to the dopamine system (i.e., dopamine-independent systems) (Houdi et al, 1991;Pomerleau & Pomerleau, 1984). Nevertheless, pharmacological studies in humans investigating the effects of naloxone, an opioid receptor antagonist on smoking behavior, have yielded inconsistent results (Karras & Kane, 1980;Nemeth-Coslett & Griffiths, 1986).…”