The relationship of addiction, tolerance, and dependence to alcohol and drugs: a neurochemical approach

J Subst Abuse Treat. 1987;4(3-4):197-207. doi: 10.1016/s0740-5472(87)80014-4.


Alcohol and drug addiction are defined in behavioral terms as the preoccupation with, compulsive use of, and relapse to drugs that are descriptive and confirmatory. The basis of addiction may involve neurochemical changes in the brain that distort and redirect the drive states (instincts). Tolerance and dependence may only be incidentally associated with addiction as a result of a nonspecific adaptation by the body to the presence of a drug. The cellular adaptation may be the same in all organs. Addiction to alcohol and drugs may have no specific relationship to tolerance and dependence. Addiction occurs in the absence of observable tolerance and dependence to alcohol and drugs. Alcohol and drug addiction is probably more complex than tolerance and dependence. Addiction is difficult to study because of the variability of behavioral phenomena and the underlying intricacies of the neurosubstrates. Tolerance and dependence are still useful as they are indicators of drug use. It is a misconception that long term chronic use is necessary for tolerance and dependence to develop. Some studies have shown that tolerance can develop within hours and days to a single dose of alcohol or other drugs. Anxiety, depression and insomnia can occur after a single dose of ethanol in humans. These symptoms of withdrawal from the alcohol or drug constitute dependence. Redefining the criteria for addiction tolerance and dependence to alcohol and other drugs may be in order. A neurochemical model may provide a more definitive and uniform basis for considering addiction, tolerance, and dependence to alcohol and drugs.

Publication types

  • Review

MeSH terms

  • Brain Chemistry*
  • Drug Tolerance
  • Ethanol / pharmacology*
  • Humans
  • Substance-Related Disorders / physiopathology*


  • Ethanol