ABSTRACT

The extraordinary range of pharmacological effects of γ-hydroxybutyrate (GHB) has attracted scientific attention for more than three decades. Intraperitoneal doses of this simple 4-carbon fatty acid in excess of 200 mg/kg can induce sleep and anaesthetic states in small animals, dramatically raise brain dopamine levels, reduce cerebral deoxyglucose utilization and lower body temperature (Gessa et al. 1966; Roth and Suhr 1970; Lin et al. 1979; Kuschinsky et al. 1985; Mamelak 1989). The behavioural and electroencephalographic changes induced by GHB in small animals also appear to have certain features in common with petit mal epilepsy (Snead 1988). In humans, the unique anaesthetic properties of GHB have been used to advantage during labour and perhaps more widely, following head trauma to reduce cerebral edema (Vickers 1969; Strong 1984; Dabadie et al. 1986). Grace Kelly, the former Princess of Monaco, was treated with GHB soon after her arrival in hospital following her motor vehicle accident (BalabanQuine 1989). Lower oral doses of GHB in man, in the range of 25-35 mg/kg, can stimulate the release of prolactin and growth hormone (Van Cauter et al. 1997). These low doses also can induce both REM sleep and slow wave sleep, and in contrast to hypnotic agents in common use, the effects of GHB on sleep do not change with time (Mamelak et al. 1986). GHB has been shown to inhibit lipid peroxidation and to prevent reperfusion injury and the tissue damage caused by radiation and high oxygen pressure (Laborit 1973; Lavyne et al. 1983; Meerson et al. 1983; Boyd et al. 1990). Indeed, GHB has been found to have tissue protective effects in animals and man in many different organs including brain, liver, lung, heart, kidney, gut and pancreatic beta cells (Dosmagambetova 1983; Lavyne et al. 1983; Boyarinov et al. 1984; Sholokov et al. 1986; Boyd et al. 1990; Pierrefiche et al. 1991 ; Sherman et al. 1994; Bouix et al. 1995; Yamasaki et al. 1999).