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4. PSYCHOPHARMACOLOGY OF DEPENDENCE FOR DIFFERENT DRUG CLASSES

Neurobiological adaptations to prolonged use
Dependence on sedatives and hypnotics may develop with chronic use,
regardless of how often these drugs are used, or their doses. For example,
people may feel an overwhelming urge or craving for the drug only under
specific circumstances, such as social gatherings or times of increased stress
(Jacobs & Fehr, 1987).
It is important to note that many individuals require long-term therapy with
benzodiazepines or barbiturates for epilepsy, brain injuries or other disorders.
This use may lead to tolerance to some of the effects of the drugs, and
withdrawal effects upon cessation of their use. The use of benzodiazepines or
barbiturates for medical purposes may or may not lead to dependence, even if
tolerance and withdrawal are present (see Table 4.1). Problems are more often
related to the non-medical use of benzodiazepines by polydrug users, and their
chronic use by some patients. These include impairment of memory, risk of
accidents, falls and hip fractures in the elderly, a withdrawal syndrome, brain
damage, and oversedation when combined with alcohol or other drugs (which
can lead to coma, overdose and death) (Griffiths & Weerts, 1997). Treatment of
sedative dependence involves slowly tapering off drug use, together with
behavioural therapy (see Chapter 3 for types of behavioural therapies).

Tobacco
Introduction
Although tobacco contains thousands of substances, nicotine is the one most
frequently associated with dependence because it is the component that is
psychoactive and causes observable behavioural effects, such as mood
changes, stress reduction and enhancement of performance. The behavioural
effects associated with nicotine delivered during smoking include arousal,
increased attention and concentration, enhancement of memory, reduction
of anxiety and suppression of appetite.
The average half-life of nicotine is approximately 2 hours but is about 35%
longer in persons with a particular form of a gene (i.e. an allele) for the enzyme
(CYP2A6) that inhibits the primary metabolic pathway of nicotine (Benowitz
et al., 2002). Preliminary studies suggest that the CYP2A6 allele frequency is
more common in Asians than in Africans or Caucasians, and that this
difference partially accounts for the lower daily consumption of cigarettes
and lower risk of lung cancer in Asians as compared to Africans and
Caucasians (Ahijevych, 1999; Tyndale & Sellers, 2001; Benowitz et al., 2002).
This is discussed further in Chapter 5.

Behavioural effects

Nicotine is a potent and powerful agonist of several subpopulations of
nicotinic receptors of the cholinergic nervous system (Henningfield, Keenan

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