Effect of naloxone on cigarette smoking

Several recent studies have tried to link endogenous opioid peptides (endorphins) with smoking reinforcement. Karras and Kane (1980) showed a one-third decrease in smoking after administration of the opiate antagonist naloxone. However, Nemeth-Coslett and Griffiths (1986) failed to replicate this result with use of a wide range of doses. The current study was an attempt to replicate Karras and Kane's results using 10 male chronic smokers. Each subject received naloxone (10 mg sc) or placebo in a double-blind, cross-over design (cross-over interval 6-14 days) after overnight abstinence from tobacco use. Naloxone reduced the number of cigarettes smoked by 16% in the first 1/2 hour smoking period, with a 10% reduction in carbon monoxide level 1 hour later. Naloxone had no effect on subjective and physiological variables and did not cause any signs of a tobacco withdrawal syndrome. These results are consistent with those of Karras and Kane, and suggest a role for endorphins in smoking reinforcement. Inconsistent results across studies may be due to methodological factors, such as differences in smoking deprivation time and postnaloxone administration testing intervals because naloxone has a short half-life.