Physiological dependence on a drug occurs when nerve cells have adapted so well to the drug that they require the drug for normal functioning. A person is physiologically dependent on a drug when sudden drug abstinence is followed by withdrawal signs. These may be thought of as "rebound" effects. For example, if heart rate is increased by taking a drug, then abstinence may result in a decreased heart rate for a few days. Similarly, feelings of contentment that accompany cigarette smoking may be replaced by irritability, and weight loss may be replaced with weight gain. Many other drugs that are abused produce rebound effects.

For example, the constipation that normally accompanies narcotic use is replaced by diarrhea; the muscular relaxation produced by alcohol and sedative drugs is replaced by tremors and even convulsions. When drugs produce extensive and possibly life-threatening rebound syndromes, as is the case with opiates and sedatives, the drug is said to be capable of producing physiologic dependence.

It has not been scientifically proven that nicotine produces a significant withdrawal syndrome. Only about one-third of the people who stop smoking experience physical discomfort and this are not usually as severe as that associated with drugs such as morphine or alcohol. On the other hand, as with morphine and alcohol, physical dependence on nicotine may only occur in extremely heavy users.

At this time, it appears that addiction to nicotine is more like cocaine dependence than morphine dependence. With all three drugs, behavior becomes compulsive because of the physical effects of the drug on the brain. The only difference is that abstinence from morphine causes withdrawal symptoms, whereas abstinence from cocaine and nicotine may not. These facts have tended to blur the long held separation of physical and psychological dependence.

A common misconception is that drug abuse is the same as physical dependence; it is not. Physical dependence need not occur to produce drug abuse and, if it does occur, it does not ensure that drug abuse will occur. For instance, many people periodically abuse alcohol or narcotics without ever becoming physically dependent. Also, there are drugs with an enormously high potential for abuse, such as cocaine and amphetamine, which do not produce a clear-cut syndrome of withdrawal.

On the other side of the coin, a person may become physically dependent on a drug and yet never seek that drug or learn to abuse that drug. This happens frequently when people are given narcotics for pain relief. Only a very small portion of these people abuse the drug or continue to take it when it is no longer medically required. Tobacco Tolerance

As cigarettes are smoked throughout the day, the effects become smaller and smaller. Often smokers assert that their first cigarettes of the day are the "best tasting", with the rest being smoked out of habit or need. When repeated use of drug results in smaller and smaller responses, the phenomenon is called "tolerance". In other words, it takes more of the drug to produce the same effect. This explains why the first few cigarettes of the day cause the greatest increase in heart rate and blood pressure, the greatest decrease in the knee reflex, and the strongest psychological effect. Repeated injections of nicotine produced progressively smaller psychological effects on the subject.

Tolerance develops when the body becomes more efficient at detoxifying and eliminating the drug (metabolic tolerance). People who have smoked for many years eliminate nicotine from their systems much more quickly than nonsmokers. Tolerance also occurs when the nerve cells become less responsive to nicotine doses. With nicotine, much of this tolerance is lost overnight and quickly regained when smoking resumes the next day. Finally, tolerance can also occur by means of behavioural adjustments as the person learns to compensate for any disruptive effects of the drug. All of these forms of tolerance occur with nicotine, and all appear to be critical in allowing people to learn quickly to enjoy smoking and to get over sickness that often occurs when it is first tried.