Naltrexone, smoking behaviour and cigarette withdrawal.

In order to examine the role of endogenous opioids in the reinforcing effects of nicotine, a double-blind, placebo-controlled, cross-over design was used to study the effects of the opiate antagonist, naltrexone, on smoking behaviour and cigarette withdrawal in 12 heavy smokers. Although naltrexone (50 mg) appeared to reduce the perceived difficulty of abstaining during 24-h cigarette withdrawal, other withdrawal symptoms were unaffected. Naltrexone also had no effect on a variety of biochemical and behavioural measures of nicotine intake or on subjective satisfaction and enjoyment from the first cigarette smoked after 24-h abstinence. Similarly naltrexone (100 mg) had no effect on smoking behaviour, nicotine intake or satisfaction from smoking during a 48-h period of ad libitum smoking. However, during the ad libitum smoking period naltrexone caused mood changes of the kind that occur during tobacco withdrawal. Since nicotine intake and smoking behaviour were unaffected, the mood changes are unlikely to have been mediated by blockade or any other form of opioid interaction with nicotinic mechanisms. These findings provide evidence against the notion that the endogenous opioids are involved in mediating the reinforcing properties of nicotine in smokers under normal conditions.