GHB

GHB has been used both for legitimate clinical and chnical research purposes and for a range of iUicit purposes. It was marketed legally in the United States until 1990, when the U.S. Food and Drug Administration (FDA) banned its sale to consumers. Except for the one indication described later in this section, GHB is a Schedule I controlled substance without other FDA-approved indications. The FDA has also declared y-butyrolactone (GBL) as a List I chemical and 1,4-butanediol (1,4-BD) as a Class I health hazard, practically designating these GHB precursors, which are also industrial solvents, as illicit and unapproved new drugs (National Institute on Drug Abuse 2000). 

Miotto and colleagues (2001) surveyed 42 recreational users of GHB and found that 66% reported episodes of unpredictable loss of consciousness and 26% had overdosed. Forty-five percent of daily users had experienced frequent amnesia during or after use of the drug, suggestive of blackouts typically attributed to severe alcohol abuse. The rate of adverse events was greater... 

Taken for recreational use as an intoxicant, typical acute effects described by misusers are euphoria, relaxation, and increased sexuality (Galloway et al. 1997 Miotto et al. 2001). On the street, GHB is taken in capfuls or teaspoons of a salty/sour liquid, which because of variations in concentration, may range in dose from 0.5 to 5.0 g. Common side effects are nausea, headache, itching, and vomiting (Borgen et al. 2003). Doses of 10—20 mg/kg of GHB typically... 

GHB is an endogenous, water-soluble, four-carbon fatty acid that is found in peripheral organs, including the heart, liver, kidney, and cardiac and skeletal... 

Succinic semialdehyde (SSA) is synthesized in the mitochondria through transamination of y-aminobutyric acid (GABA) by GABA transaminase (GABA-T). Most of the SSA is oxidized by SSA dehydrogenase (SSA-DH) to form succinate, which is used for energy metabolism and results in the end products CO2 + H2O, which are expired. A small portion of SSA (<2%) is converted by SSA reductase (SSA-R) in the cytosol to GHB. GHB may also be oxidized back to SSA by GHB dehydrogenase (GHB-DH). 

GHB has sedative, anxiolytic, and euphoric effects similar to ethanol, likely because of potentiation of cerebral GABAergic and dopaminergic activities. 

Another potential chnical use of GHB is in the treatment of alcohol withdrawal and alcohol dependence. In prechnical studies, GHB inhibited voluntary ethanol consumption in ethanol-preferring rats and suppressed the... 

The development of tolerance for GHB has been repeatedly described in clinical vignettes and demonstrated in animal models. For example, with repeated... 

GHB treatment in mice, tolerance develops to both the hypolocomotion and cataleptic effects of the drug (Itzhak and Ali 2002). There is also preclinical evidence of cross-tolerance and cross-dependence of GHB with alcohol (Colombo et al. 1995 Fadda et al. 1989). As described in the earlier section on clinical pharmacology, GHB and its analogues have been used in humans in the treatment of alcohol withdrawal. Nicholson and Balster (2001) reviewed the evidence for cross-tolerance and cross-dependence of GHB with alcohol. 

The onset of GHB withdrawal symptoms typically begins 1—5 hours after the last dose initial symptoms include anxiety, tremor, tachycardia, nausea, and insomnia (Table 7—1). Untreated, the symptoms may progress within 24 hours to a more severe pattern that is similar to delirium tremens, with dys-... 

Other sedative-hypnotic medications, such as barbiturates, may play a useful role in severe withdrawal from this group of drugs. For example, in a case series of GBL withdrawal, use of intravenous pentobarbital in the range of 1-2 mg/kg/hour lowered the total requirement for intravenous lorazepam (Sivilotti et al. 2001). Antipsychotic medications are often used to reduce psychotic agitation. However, because antipsychotic medications lower the seizure threshold and may contribute to loss of central control of temperature leading to hyperthermia or neuroleptic malignant syndrome (NMS), they are not indicated as first-line medications for GHB withdrawal delirium (Dyer and Roth 2001 McDaniel and Miotto 2001 Sharma et al. 2001). If anti-... 

Although the evidence base for this relatively rare disorder is not well developed, patients who are dependent on GHB appear to benefit from cognitive and motivational psychosocial therapies and from support of recovery in a manner similar to alcohol-dependent patients. However, because of the high likelihood of amnesia and cognitive dysfunction during the acute and subacute phases of GHB withdrawal, psychosocial interventions should, when possible, include significant others who can review and reinforce with the patient the negative consequences of GHB dependence. 

Hall J, Maxwell J Patterns and Trends of GHB, GBL, and 1,4BD Abuse. Austin, TX, Texas Commission on Drug and Alcohol Abuse, 2000. Avalable at http // www.tcada.state.tx.us/research/presentation/Patterns trends GHB/sld001. htm. Accessed March 20, 2003. 

Hernandez M, McDaniel CH, Costanza CD, et al GHB-induced delirium a case report and review of the literature of gamma hydroxybutyric acid. Am J Drug Alcohol Abuse 24 179-183, 1998... 

Itzhak Y, Ali SF Repeated administration of gamma-hydroxybutyric acid (GHB) to mice assessment of the sedative and rewarding effects of GHB. Ann N Y Acad Sci 965 431-60, 2002... 

McDaniel CH, Miotto KA Gamma hydroxybutyrate (GHB) and gamma butyrolac-tone (GBL) withdrawal five case studies. J Psychoactive Drugs 33 143—149,2001... 

McGuire PK, Cope H, Fahy TA Diversity of Psychopathology associated with use of 3,4-methylenedioxymethamphetamine ( Ecstasy ). Br J Psychiatry 165 391—395, 1994 Miotto K, Roth B GHB Withdrawal. Austin, TX, Texas Commission on Alcohol and Drug Abuse, 2001. Available at http //www.tcada.state.tx.us/research/popula-tions/GHB Withdrawal.pdf. Accessed Fehruary 28, 2003. 

National Institute on Drug Abuse All About GBH Report. Rockville, MD, National Institute on Drug Abuse, 2000. Available at http //www.drugabuse.gov/ whatsnew/meetings/GHB/default.html. Accessed March 12, 2003. 

Nelson T, Kaufman E, Kline J, er al The extraneuronal distribution of gamma-hydroxybutyrate. J Neurochem 37 1345—1348, 1981 Nicholson KL, Balster RL GHB a new and novel drug of abuse. Drug Alcohol Depend 63 1-22, 2001... 

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