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NEUROSCIENCE OF PSYCHOACTIVE SUBSTANCE USE AND DEPENDENCE

effects of amphetamines on behaviour in children with ADHD and in people
with narcolepsy do not show signs of tolerance. It is important to note that
even though methamphetamine is used to treat ADHD in children, the
therapeutic doses for ADHD and other disorders such as narcolepsy are much
lower than the daily amounts taken for non-medical use.
Although tolerance develops to some aspects of psychostimulant use,
sensitization, or an increase in the hyperactivity or stereotypy induced by
amphetamine also occurs, even if the doses are spread out over days or weeks.
Cross-sensitization with cocaine occurs, and is thought to be the result of
increased dopamine in the striatum (Kalivas & Weber, 1988). Sensitization is
thought to play a critical role in dependence (see Chapter 3).

Neurobiological adaptations to prolonged use
Long-term use of amphetamine may result in sleeping problems, anxiety,
suppression of appetite, and high blood pressure. People who use
amphetamine often take sedative/hypnotic drugs to counteract these effects,
and thus the incidence of polydrug use is high (Jacobs & Fehr, 1987).
Amphetamine users sometimes ingest increasing quantities of
amphetamine in “runs” that last 3–6 days. This continuous use has been
modelled in animals, and changes in behaviour are observed consistent with
hallucinatory-like effects. This pattern of use is neurotoxic and produces brain
damage. Continuous infusion of low doses of amphetamine into rats produces
a depletion of nigrostriatal dopamine, its precursors and metabolites, and
receptors (Robinson & Becker 1986).
With long-term use of methamphetamine there is a decrease in dopa-
mine D receptor availability in the caudate and putamen, and a decrease in
2
metabolic rate in the orbitofrontal cortex (Volkow et al., 2001a) (see Fig. 4.3),
and loss of dopamine transporters that is associated with motor and cognitive
impairment (Volkow et al., 2001b).
There are limited data available on the proportion of current amphetamine
users who are dependent (see Box 4.7). A review of the medical literature
indicates that some antidepressant drugs may decrease craving for
amphetamines (Srisurapanont, Jarusuraisin & Kittirattanapaiboon, 2001).
However, this may also be related to the comorbidity of psychostimulant
dependence and depression (see Chapter 6).

Ecstasy

Introduction
Ecstasy or 3,4-methylenedioxymethamphetamine (MDMA) is a synthetic
amphetamine, also known as XTC, E, Adam, MDM or “love drug” (Shaper,
1996). Ecstasy can be classified as a psychostimulant, belonging to the same
group as cocaine and the amphetamines, since many of its acute effects are

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