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Tolerance and physical dependence are common consequences of drug self-administration. For those interested in understanding and modifying alcohol and drug abuse and the problems they cause, the greatest importance of tolerance and physical dependence is in the contribution they make as determinants of drug self-administration. Some alcoholics, for example, can appear normal at BLOOD ALCOHOL CONCENTRATIONS (BAC) that would prostrate most social drinkers. What role, if any, does tolerance play in paving the way to an escalation in drug use and in the medical and psychological problems caused by heavy drug use? In addition to being highly tolerant, alcoholics will also be physically dependent on alcohol. What evidence is there to support the common assumption that physical dependence is a critical factor in maintaining drug self-administration?

Such questions are best answered in the context of a general theory of how drug consumption is regulated. A useful starting point is the proposition that behavior is motivated by its consequences. Where tolerance is concerned, the important consequences of drugs are only those that depend on pharmacological effects. The pharmacological consequences that determine self-administration can be grouped according to whether they promote or restrain drug use. Rewarding consequences are those that increase the likelihood of drug use. Drugs may make a person feel alert, powerful, confident, relaxed, friendly, sexy, or talkative. They may alleviate ANXIETY, DEPRESSION, and physical PAIN. All these consequences and more have been hypothesized and evaluated as promoters of drug use.

People may initiate and maintain an episode of drug use in the pursuit of rewarding consequences, and they may end it because drugs also have aversive pharmacological consequences at higher doses. These effects should also be taken into account as restraints on self-administration. Many restraining consequences of drug use can be suggested, ranging from unwanted dysphoria (a state of unease) to frank physical illness.

In summary, a simple regulatory theory asserts that "reward" drives drug use and "aversion" restrains it. If there is tolerance to the rewarding or aversive effects of drugs, it is clear how tolerance might determine drug use. A reduction in the rewarding effectiveness of a given dose would require an increased dose to obtain the same degree of reward. Similarly, tolerance to aversive effects of a drug might mean a much larger dose could be taken before the restraining aversive effect occurred.

There is remarkably little scientific evidence for the common view that tolerance to the rewarding effects occurs. The common and plausible view that tolerance results in a loss of rewarding effectiveness is based mainly on anecdotal evidence. In contrast, there is ample scientific evidence of substantial tolerance to drug effects that could be viewed as restraints on the motivation to self-administer.

Physical dependence as a promoter of self-administration can be dealt with briefly. The earliest theories of dependence assumed that the avoidance of withdrawal was the most compelling motivation for persistent drug use. The experimental evidence for this view is strongest in the case of opiates, but weak to nonexistent for other drugs, including alcohol.

Tolerance can be characterized as a facilitator of consumption and its consequences, independent of the underlying reasons for drug use. If a person is able to drink a lot more before becoming sleepy or dizzy the capacity to drink is increased regardless of the reason for drinking. If the ability of tissue to resist damage does not increase with the body's capacity to resist the drug effects that regulate consumption, tolerance becomes an important determinant of medical and other problems.

As the twenty-first century begins, concepts of addictive disorders has focussed more on the compulsive and relapsing drug-taking behaviors than on tolerance and physical dependence. To that end, medications have been sought and used in the rehabilitative process. Specific medications have been demonstrated to be helpful for psychiatric disorders coexisting with addiction. Some medications showed promise in controlled studies in helping to rehabilitate patients dependent on nicotine, alcohol, or opiates.