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To the Editor: Nonbenzodiazepine hypnotic agents were developed to minimize the adverse effects of benzodiazepines. These hypnotics bind to the α1, α2, and α3 subunits of the gamma-aminobutyric acid type A (GABAA) receptor complex. Zaleplon preferentially binds to the α1 subunit. These compounds offer less abuse liability relative to benzodiazepines, although this is debatable under certain circumstances (1). We present the case of a patient who abused intranasal zaleplon in order to experience a “high” feeling.
“Mr. A” was a 28-year-old man with a 13-year history of polysubstance abuse (cannabis, cocaine, and heroin). He had been abusing mainly cocaine over the past 5 years and had unsuccessfully tried several treatments to achieve abstinence 1 year prior, following a prolonged stay in a monastery. As a result of sleep difficulties, he was prescribed zaleplon (10 mg/night) as needed. Over the next 3 months, the dose was gradually increased to 70–80 mg/day. Subsequently, he noticed that zaleplon had a mood uplifting effect. To boost this effect, he started taking the drug intranasally by snorting seven to eight pulverized capsules. The patient mentioned that intranasal zaleplon produced a euphoric feeling resembling that of cocaine, although less intense and of a shorter duration. This pattern of abuse persisted for almost 1 year, and withdrawal symptoms (anxiety, nervousness) emerged whenever he tried to reduce its use. He was offered inpatient detoxification treatment, which he declined.
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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