Tolerance and Withdrawal

Tolerance is associated with various drugs and involves a number of different body systems; it is particularly noticeable where addictive substances are concerned. It is a phenomenon whereby the body develops an ability to tolerate the effects of a drug. This means that the body has made adjustments to overcome the drug's effects, which then causes the rebound effect referred to above.

With alcohol, there may also be a built-in tolerance in some people who have a family history of alcoholism. This accounts for the low response factor explained in the section on genetics.

Tolerance to alcohol and the depressants involves adaptive changes that up-regulate systems activating the central nervous system. In other words, the brain becomes hyperalert and hypersensitive in order to compensate. Tolerance to the opiates involves a similar process, although different pathways are in use.

Another type of tolerance involves the body's ability to metabolize the drug. Some drugs, such as the barbiturates, stimulate cells in the liver which break down and help eliminate drugs of all types. The rate of elimination of the drug goes up, so the amount needed to produce a clinical effect goes up as well. For this reason, people who are addicted to some types of drugs require higher than normal doses of other drugs to achieve an effect.

Cross-tolerance to similar substances is quite common. For example, if you develop tolerance to one type of depressant drug, you will have increased tolerance to other depressant drugs. Alcohol, barbiturates, and benzodiazepines are all cross-tolerant, so benzodiazepines such as Librium can be used to treat alcohol withdrawal and phenobarbital can be used to treat withdrawal from benzodiazepines. But this can also lead to cross-addiction. For example, an alcoholic might be inappropriately treated by a doctor's prescribing tranquilizers for "nerves" (really chronic withdrawal), which results in a cross-addiction. The person might not need to drink alcohol anymore, but the addiction is still there and active. Exposure to barbiturates or benzodiazepines can also trigger a relapse in a person who has been abstinent from alcohol, or vice versa.

One important system involved with alcohol and the depressants involves the overall electrical stability of the brain.

Seizures, or convulsions, are episodes of unregulated electrical discharge within the brain. In order for a seizure to occur, one of two things has to happen. The first is that there has to be a strong stimulus. The second is that this stimulus has to override the regulatory mechanisms in each cell membrane.

Seizures can be produced in two ways, by the addition of a strong electrical stimulus or by a decrease in the cell membranes' ability to resist the stimulus. When a person develops tolerance to alcohol or to the depressant medications, alterations in the function of a chemical that regulates the movement of calcium in and out of the cells causes these cells to be very sensitive to any kind of stimulation. The cells are unstable, so it takes little provocation to produce a seizure.