484 Substance-Related and Addictive Disorders
Pharmacological criteria are the final grouping (Criteria 10 and 11). Tolerance (Crite-
rion 10) is signaled by requiring a markedly in creased dose of the substance to achieve the
desired effect or a markedly reduced effect when the usual dose is consumed. The degree
to which tolerance develops varies greatly across different individuals as well as across
substances and may involve a va riety of central nervous system  effects. For example, tol-
erance to respiratory depression and tolerance to sedating and motor coordination may
develop at different rates, depending on the substance. Tolerance ma y be difficult to de-
termine by history alone, and la boratory tests may be helpful (e .g., high blood levels of the
substance coupled with little evidence of into xication suggest that tolerance is likely). Tol-
erance must also be distinguished from indi vidual variability in the initial sensitivity to
the effects of particular substances. For exam ple, some first-time alcohol drinkers show
very little evidence of intoxication with thre e or four drinks, whereas others of similar
weight and drinking histories have slurred speech and incoordination. 
Withdrawal (Criterion 11) is a syndrome th at occurs when blood or tissue concentra-
tions of a substance decline in an individual who had maintained prolonged heavy use of
the substance. After developi ng withdrawal symptoms, the individual is likely to con-
sume the substance to relieve the symptoms . Withdrawal symptoms vary greatly across
the classes of substances, and separate criter ia sets for withdrawal are provided for the
drug classes. Marked and generally easily me asured physiological signs of withdrawal are
common with alcohol, opioids, and sedatives, hypnotics, and anxiolytics. Withdrawal