Academic journal article Forensic Science Communications

Forensic Science Update: Gamma-Gydroxybutyrate (GHB)

Academic journal article Forensic Science Communications

Forensic Science Update: Gamma-Gydroxybutyrate (GHB)

Article excerpt

Introduction

The past decade has seen a dramatic increase in the use of gamma-hydroxybutyrate (GHB) and related substances. Because of their current popularity as recreational compounds of abuse and their unfortunate effectiveness as "drug-facilitated sexual assault" agents, forensic scientists are being called upon to determine the role of these compounds in overdose and sexual assault cases with increasing frequency. The objective of this paper is to provide an update on the history, mechanism, clinical effects, legal status, legitimate use, and laboratory analysis of these compounds.

History

The compound gamma-hydroxybutyrate (GHB) originated about 40 years ago when it was synthesized as a peripherally administered agonist of the inhibitory neurotransmitter, gamma-aminobutyric acid (GABA). In 1963, GHB was reported to be an endogenous compound in the mammalian brain (Bessman and Fishbein 1963). Since that time, several researchers have claimed GHB to be a putative neurotransmitter because it appears to fulfill the necessary requirements (reviewed in Mandel et al. 1987; Tunnicliff 1992; Vayer et al. 1987).

* GHB is synthesized in brain tissue from GABA by way of a succinic semialdehyde intermediate.

* Prior to release into the synaptic cleft, the synthesized GHB is located within discrete storage vesicles.

* The stimulated release of GHB from neural tissue occurs in a calcium-dependent manner.

* A sodium-dependent, high-affinity membrane transport system has been demonstrated.

* Both high- and low-affinity receptors have been described specifically in neural tissue that have high specificity for GHB.

* Within the central nervous system, the administration of GHB is associated with dose-dependent increases in dopamine concentrations suggesting a physiologic role in the regulation of central dopaminergic activity. It also increases serotonin turnover. Electrophysiology studies reveal an inhibitory effect of GHB in the substantia nigra and neocortex.

* When radiolabeled GHB is injected into rats, most of the labeled carbon is recovered as carbon dioxide, suggesting an endogenous metabolic fate through the Kreb's Cycle. In addition, the metabolism of GHB appears to involve conversion to GABA by way of a nonsuccinic semialdehyde intermediate and/or beta-oxidation to carbon dioxide.

That GHB is an endogenous compound has been made even more evident by the recent description of an apparent inborn error of GHB metabolism due to a deficiency in succinic semialdehyde dehydrogenase (SSADH). This deficiency causes an accumulation of endogenous GHB, GABA, and products of gamma-oxidation, leading to motor problems including ataxia, hyporeflexia, and seizures as well as mental retardation, hyperkinesis, psychosis, and numerous other neurologic manifestations (Gibson et al. 1998). Accumulated GHB has been shown to reach plasma concentrations as high as 100 mg/L in affected individuals (Jakobs et al. 1984) which are not normally detected in healthy individuals (Fieler et al. 1998).

Because GHB can be administered peripherally to induce sleep, it has been employed clinically in Europe in the field of anesthesia. As it has no analgesic properties, GHB must be used in combination with an opiate analgesic. Its long half-life, compared with newer agents, and its association with myoclonus have substantially reduced its use in anesthesia, although it has been shown to protect tissues from the damaging effects of hypoxia and ischemia (reviewed in Li et al. 1998).

Recent Use

During the 1980s, GHB was marketed in health food stores, training gyms, fitness centers, and on the Internet. Allegedly providing anabolic benefits by stimulating growth hormone release, it was used by body builders and for strength training. In addition, it was promoted as a natural treatment for insomnia and to induce weight loss. Apparently, the purported euphoric effects of GHB were also discovered at this time. …

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