GHB precursors

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). 

GHB precursors, or analogs (similar chemical compounds also known as chemical cousins ), were the legal way for users to achieve effects physiologically equivalent to GHB. Then, in February 2000, federal legislation made the GHB precursors controlled substances. 

On February 18, 2000, the Hillary Farias and Samantha Reed Date-Rape Prohibition Act (Public Law 106-172) made the GHB precursor GBL a List I chemical, subject to the criminal, civil, and administrative sanctions of the Controlled Substances Act. On March 13, 2000, GHB became a Schedule I controlled substance (65 FR 13235-13238), subject to the regulatory controls and the criminal, civil, and administrative sanctions of the Controlled Substances Act. Schedule I, which is the same as for heroin, LSD, and marijuana, states that the drug has no medical use and cannot be prescribed, and that the drug has a high potential for abuse. 

Aside from GBL, another GHB precursor chemical, known as 1,4-butanediol, is used extensively in chemical manufacturing. In 2001, it was estimated that the industrial consumption of 1,4-butanediol in the United States would be 387,000 metric tons.30 Though its major legitimate uses are in the synthesis of other chemicals, it is also an abused recreational drug. Consumption of both GBL and 1,4-BD can cause the same effects as those of GHB, since they are converted in the body into the active drug.31 For this reason, both GBL and 1,4-BD sales are regulated. 

This class includes drugs with sedating or amnesic effects. GHB (gamma hydroxybutyric acid), the GHB precursor, 1,4-butanediol (1,4-BD), and Rohypnol or flunitrazepam are sometimes used for sexual assault or for the central nervous system (CNS) effects. Both GHB and Rohypnol have been referred to as date... 

Kraner, J.C., Plassard, J.W., McCoy, D.J., Rorabeck, J.A., Witeck, M.J., Smith, K.B. and Evans, M.A. (2000). A death from ingestion of 1,4-butanediol, a GHB precursor. In Program and Abstracts of the Society of Forensic Toxicologists Annual Meeting, Milwaukee, WI, Poster 39. 

GHB is readily manufactured from its precursor, gamma-butyrolactone (also known as 2(3h)-furanone dihydro, or GBL). GHB is relatively easy to synthesize in household laboratories, mixing ingredients such as floor cleaning products, nail polish, and super glue removers with sodium hydroxide in the form of lye. Unintentional poisonings from bad homemade batches are not uncommon. 

Two of the most potentially deadly precursors of GHB, both of which are converted into GHB in the body, have been identified by the FDA. One is gamma butyrolactone (GBL), which is marketed under brand... 

Additionally, GHB and its precursors are used by body builders as an alternative to anabolic steroids. The drug has been marketed for its alleged ability to release large amounts of natural human growth hormone during sleep, build muscle, and reduce fat. 

Since these initial cases, laws against GHB have been tightened and the government has increased efforts to prosecute illegal distributors and users of GHB and its precursors. 

In 1963, GHB was found to occur naturally in many mammalian cells, including those in the brain. Since that time, it has been purported to act as a neurotransmitter. GHB is both a precursor and metabolite of GABA, although it does not act directly on GABA receptor sites. Recently, a putative GHB receptor has been cloned. This means it may be possible that... 

Ingels, M., C. Rangan, J. Bellezzo, and R. F. Clark. Coma and Respiratory Depression Following the Ingestion of GHB and Its Precursors Three Cases. The Journal of Emergency Medicine 19 (1) (2000) 47-50. 

Ingels M, Rangan C, Bellezzo J, and Clark R (2000) Coma and respiratory depression following the ingestion of GHB and its precursors Three cases. Journal of Emergency Medicine 19(1) 47-50. 

Toxic manifestations of GHB or its precursors include nausea and vomiting, bradycardia, hypotension, coma, seizures, and severe but not prolonged respiratory depression. Periods of agitation may be interspersed... 

Figure 34-32 Metabolism of y-hydroxybutyrate and its precursors. /, alcohol dehydrogenase 2, aldehyde dehydrogenase 3, lactonase 4, GHB dehydrogenase J, SSA reductase 6, GABA transaminase 7, glutamate decarboxylase 8, SSA dehydrogenase.

The decreased Internet availability of kits to make GHB has been accompanied by an increased availability of chemical precursors to GHB as well as GHB analogs. Also available in gyms and health food stores, these substances include y-butyrolactone (GBL) and 1,4-butanediol. GBL is converted in the body to GHB. Labels of marketed products may use unfamiliar synonyms to disguise the actual content. GBL is also known by the chemical names 2(3H)-furanone dihydro, butyrolactone, 4-butyrolactone, dihydro-2(3H)-furanone, 4-butanolide, 2(3H)-furanone, dihydro, tetrahydro-2-fura-none, and butyrolactone-y. 

The studies of the origin of GHB in A. bisporus demonstrated the involvement of the shikimate-chorismate pathway (Scheme 102). Labeling experiments showed an efficient incorporation of H- and C-labeled shikimic acid 439,440) and C-labeled chorismic acid 441) into the 4-hydroxyaniline moiety of GHB. It was also demonstrated that in the biochemical shikimate-4-hydroxyaniline conversion in the mushroom, amination occurred at the 4 position of one of the carboxylic acid intermediates [initially assumed to be shikimic acid 439)]. Additionally, the p-aminobenzoic acid, which proved to be 441) the precursor of 4-hydroxyaniline, underwent a decarboxylative hydroxylation catalyzed by a FAD-dependent monooxygenase 4-aminobenzoate hydroxylase in the presence of NAD(P)H and O2. This enzyme from A. bisporus was recently purified to homogeneity by Tsuji et al. 442). 

Hartvigsen, K., Ravandi, A., Harkewicz, R., Kamido, H., Bukhave, K., Holmer, G., and Kuksis, A. (2006) l-0-alkyl-2-(to-oxo)acyl-su-glycerols from shark oil and human milk fat are potential precursors of PAF mimics and GHB. Lipids, 41, 679-693. 

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