CNS Stimulant Physical Dependence Potential a. Tolerance to Drug Effects

The assessment of tolerance to the effects of the CNS stimulants has
been directed mainly at two of their pharmacologic effects:
anorexia and mood elevation. Tolerance to the appetite-suppressant
effects has been demonstrated to occur in numerous studies. It
appears; however, that obesity has many complex components, at least
one of which, the 'craving" for food, may interact with the
evaluation of tolerance effects (Wooley and Wooley 1981).
The currently accepted criterion for the appetite suppressant effect
is that weight is lost and not recovered. The fact that the rate of
weight loss rapidly decreases over the course of treatment is taken
as evidence of tolerance. Stunkard (1979) has suggested that these
criteria are not valid for assessing tolerance, since a deceleration
in weight loss is common even in more drastic treatments of obesity
such as jejunoileal bypass surgery. Additionally, the metabolic
characteristics of the body change as a result of weight loss, and
these changes should be taken into account when assessing tolerance.
Food that has been ingested during a period of weight loss is more
efficiently metabolized than when the caloric balance is in steady
state (Keesey et al. 1976). A more appropriate determinant of
whether tolerance has developed or not may be the degree of weight
gain following cessation of drug treatment. Tolerance would be
shown by a return to normal weight despite continued administration
of the drug. Rebound hyperphagia and weight gain, upon withdrawal
of the drug, would constitute a withdrawal reaction.
Tolerance to the mood elevating effects of CNS stimulants has been
assessed and, in addition,
effects (Gunne 1977).
is distinct, from the appetite-suppressant
Tolerance to the euphoric effects of
amphetamine (as measured by a subjective questionnaire) was found to
develop rather quickly over 14 days of daily treatment (Rosenberg et
al. 1963). In addition, these authors demonstrated that there was
no cross-tolerance to LSD. To date, no studies have been conducted
to directly compare the degree of tolerance development to the
subjective effects of CNS stimulants.