Experts have agreed that nonbenzodiazepine hypnotics have a reduced risk of abuse/dependence compared with benzodiazepines. However, this may not be the case when these drugs are taken for a prolonged period and in higher doses than recommended (1). To our knowledge, the present case is the first to describe intranasal zaleplon abuse for its stimulant and rewarding effect, which lends support to the concern of some investigators who maintain that individuals with a history of substance abuse may be at increased risk of abuse of these agents. Some studies showing that the physical dependence and reinforcing effects for zaleplon may be similar to those of benzodiazepines corroborate this reservation (2–4). The underlying mechanism of zaleplon abuse and stimulating effect is unknown. However, following chronic exposure to benzodiazepines or benzodiazepine-like agents, alterations in GABAA receptor sensitivity occur, which contribute to the development of tolerance, dependence, and withdrawal. Moreover, a complex interaction (mostly a tonic inhibitory control) between the dopaminergic reward brain structures (ventral tegmental area, nucleus accumbens, ventral pallidum) and GABA function exists. It can be speculated that chronic and/or high exposure to GABAA receptor agonists could lead to a receptor inhibitory-excitatory switch in these reward-related areas that could contribute to addiction (5). Consequently, clinicians should be warned of the abuse potential of zaleplon, especially in multisubstance abusing individuals.
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