Tolerance to and Physical Dependence on Nicotine

Conclusion

This chapter reviews the research pertaining to the accepted notion that animals and humans develop tolerance to and physical dependence on nicotine. There is no empirical evidence for tolerance to any reinforcing properties of nicotine (if such exist). In contrast to heroin and alcohol, humans do not increase their nicotine intake over time. Increased nicotine intake over time in animals has either not been reported, or was confounded with increased nicotine-induced behavioral activation over time. The observations concerning physical dependence in rats, which are highly problematic by themselves, have not been replicated in humans. The smoking withdrawal syndrome in humans is entirely different from the nicotine abstinence syndrome in rats. It cannot be precipitated by opiate antagonists or, more importantly, by the nicotine antagonist mecamylamine. Moreover, it can be abolished by cigarettes that do not contain nicotine, whereas pure nicotine reduces it only partially. Finally, ex-smokers did not show any signs of craving nicotine after 12 weeks of exposure to nicotine at amounts comparable to 35% of the intake of an average smoker. We see the evidence presented in this chapter as adding up to a compelling case against the thesis that nicotine produces either tolerance to euphoric effects (if it has any) or dependence in humans.