Abstract
γ-hydroxybutyric acid (GHB) was synthesized in 1960 by the French physician Henry Labroit (Ropero-Miller and Goldberger, 1998). Because of its then reported low toxicity and lack of side effects, the use of GHB in anesthesia and psychiatry was initially endorsed (Labroit, 1964), but it soon fell out of favor as an anesthetic owing to its unpredictable actions and adverse effects (Ropero-Miller and Goldberger, 1998). GHB has also been studied as a treatment for opioid and ethanol withdrawal; as a treatment for narcolepsy; and in the management of shock. In the 1980s, GHB was promoted in the United States as a growth hormone stimulator (Chin et al., 1998). After the Food and Drug Administration (FDA) banned the over-the-counter sales of l-tryptophan in 1989, GHB was promoted as a replacement sleep aid (Ropero-Miller and Goldberger, 1998). Beginning in 1990, the FDA began an investigation into several reports of GHB-associated vomiting, dizziness, tremors, and seizures resulting in hospitalization and death (FDA, 1997). GHB gained public notoriety with the death of actor River Phoenix, which was purportedly associated with GHB use. At that time, GHB was popular in Los Angeles nightspots, where it was commonly found in powder form. GHB then began appearing on college campuses, first in Florida and Georgia (Minai, 2001). The FDA and the Department of Justice took action against several manufacturers, distributors, and promoters of GHB. Through these actions and the use of embargos and public education campaigns, the distribution and abuse of GHB began to decrease. There was then a resurgence in the use of GHB and accompanying reports of GHB-associated adverse effects and deaths with the creation of clandestine labs (FDA, 1997). Subsequently, the GHB precursors γ-butyrolactone (GBL) and 1,4-butanediol (BD) began to be marketed as natural, nontoxic dietary supplements (FDA 1999a, b).
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
Preview
Unable to display preview. Download preview PDF.
References
Addolorato G, Capristo E, Gessa GL, Caputo F, Stefanni GF, Gasbarrini G. Long-term administration of GHB does not affect muscle mass in alcoholics. Life Sci 1999; 65: 191–6.
Anonymous. IARC Monogr Eval Carcinog Risks Hum 1999; 71: 367–82.
Borgen LA, Cook HN, Hornfeldt CS, Fuller DE. Sodium oxybate (GHB) for treatment of cataphexy. Pharmacotherapy 2002; 22: 798–9.
Cash CD. Gammahydroxybutyrate: an overview of the pros and cons for it being a neurotransmitter and/or a useful therapeuticx agent. Neurosci Behav Rev 1994; 18: 291–304.
CDC. Adverse events associated with ingestion of gamma-butyrolactone—Minnesota, New Mexico, and Texas, 1998–1999. MMWR 1999; 48: 137–40.
CDC. Epidemiologic notes and reports multistate outbreak of poisonings associated with illicit use of gamma hydroxybutyrate. MMWR 1990; 39: 861–3.
CDC. Gamma hydroxy butyrate use—New York and Texas, 1995–1996. MMWR 1997; 46: 281–3.
Chin RL, Sporer KA, Cullison B. Clinical course of γ-hydroxybutyric acid overdose. Ann Emerg Med 1998; 31: 716–22.
Cisek J, Holstege C, Rose R. Seizure associated with butanediol ingestion. J Toxicol Clin Toxicol 1999; 37: 650.
Couper FJ, Logan BK. Determination of y-hydroxybutyrate (GHB) in biological specimens by gas chromatography-mass spectrometry. J Anal Toxicol 2000; 24: 1–7.
Craig K, Gomez HF, McManus JL, Bania TC. Severe gamma-hydroxybutyrate withdrawal: a case report and literature review. J Emerg Med 2000; 18: 65–70.
DEA. Gamma hydroxybutyrate (GHB). Available from: URL: http://www.dea.gov/concern/ ghb.htm. Accessed June 6, 20001.
Detsch O, Erkens U, Schneck H, et al. Cerebral blood flow velocity and carbon dixide vasoreactivity during γ-hydroxybutyrate/fentanyl anaesthesia in non-neurosurgical patients. Eur J Anaesthesiol 1999; 16: 195–200.
Diana M, Mereu G, Mura A, et al. Low doses of γ-hydroxybutyric acid stimulate the firing rate of dopaminergic neurons in unanesthetized rats. Brain Res 1991; 566: 208–11.
Dyer JE. y-Hydroxybutyrate: a health-food product producing coma and seizurelike activity. Am J Emerg Med 1991;9:321–4.
Dyer JE, Andrews KM. Gamma hydroxybutyrate withdrawal. J Toxicol Clin Toxicol 1997; 35: 554.
Dyer JE, Galbo MJ, Andrews KM. 1,4-Butanediol, “pine needle oil”: overdose mimics toxic profile of GHB. J Toxicol Clin Toxicol 1997; 35: 554.
Dyer JE, Reed JH. Alkali burns from illicit manufacture of GHB. J Toxicol Clin Toxicol 1997; 35: 533.
Dyer JE, Roth B, Hyma BA. Gamma-hydroxybutyrate withdrawal syndrome. Ann Emerg Med 2001; 37: 147–53.
Engel P. GHB—what are the implications for states. Presented at the National Association of State Controlled Substances Authorities (NASCSA), 16th Annual Education Conference, Louisville, KY, Nov. 1, 2000.
FDA. FDA re-issues warning on GHB. FDA talk paper T97–10. Rockville, MD: Food and Drug Administration, February 18, 1997.
FDA. FDA warns about GBL-related products. FDA talk paper T99–21. Rockville, MD: Food and Drug Administration, May 11, 1999a.
FDA. FDA warns about products containing y butyrolactone or GBL and asks companies to issue a recall. FDA talk paper T99–5. Rockville, MD: Food and Drug Administration, January 21, 1999b.
FDA. FDA approved Xyrem for cataplexy attacks in patients with narcolepsy. FDA alk Paper T02–31. Rockville, MD: Food and Drug Administration, July 17, 2002.
Ferrara SD, Tedeschi L, Frison G, et al. Therapeutic gamma-hydroxybutyric acid monitoring in plasma and urine by gas chromatography-mass spectrometry. J Pharm Biomed Anal 1993; 11: 483–7.
Ferrara SD, Zotti S, Tedeschi L, et al., Pharmacokinetics of γ-hydroxybutyric acid in alcohol dependent patients after single and repreated oral doses. Br J Clin Pharmacol 1992; 34: 231–5.
Fessenden RJ, Fessenden JS. Organic Chemistry, 3rd ed. Monterey, CA: Brooks/Cole Publishing Company; 1986.
Fieler EL, Coleman DE, Baselt RC. y-Hydroxybutyrate concentrations in pre-and postmortem blood and urine. Clin Chem 1998; 44: 692–3.
Friedman J, Westlake R, Furman M. Grievous bodily harm: y-hydroxybutyrate abuse leading to a Wernicke-Korsakoff syndromes. Neurology 1996; 46: 469–71.
Frison G, Tedeschi L, Maietti S, Ferrara SD. Determination of γ-hydroxybutyric acid (GHB) in plasma and urine by headspace solid-phase microextraction and gas chromatography/positive ion chemical ionization mass spectrometry. Rapid Commun Mass Spectrom 2000; 14: 2401–7.
Gessa GL, Vargiu L, Crabai F, et al. Selective increase of brain dopamine induced by yhydroxybutyrate. Life Sci 1966; 5: 1921–30.
Gorton C. Reply to: butyrolactone-induced central nervous system depression after ingestion of RenewTrient, a “dietary supplement” [letter]. N Engl J Med 1998; 339: 848.
Greene T, Dougherty T, Rodi A. y-Butyrolactone (GBL) withdrawal presenting as acute psychosis. J Toxicol Clin Toxicol 1999; 37: 651.
Harrington RD, Woodward JA, Hooton TM, Horn JR. Life-threatening interactions between HIV-1 protease inhibitors ad the illicit drugs MDMA and γ-hydroxybutyrate. Arch Intern Med 1999; 159: 2221–4.
Hardy LJ, Slifman NR, Klontz KC, et al. Adverse events reported with the use of gamma butyrolactone products marketed as dietary supplements. J Toxicol Clin Toxicol 1999; 37: 649–50.
Helrich M, McAsian TC, Skolnik S, Bessman SP. Correlation of blood levels of 4-hydroxybutyrate with state of consciousness. Anesthesiology 1964; 25: 771–5.
Higgins TF, Borron SW. Coma and respiratory arrest after exposure to butyrolactone. J Emerg Med 1996; 14: 435–7.
Ingels M, Rangan C, Bellezzo J, Clark RF. Coma and respiratory depression following the ingestion of GHB and its precursors: three cases. J Emerg Med 2000; 19: 47–50.
Johansson B, Hardebo J. Cerebrovascular permeability and cerebral blood flow in hypertension induced by y hydroxybutyric acid: an experimental study in the rat. Acta Neurol Scand 1982; 65: 448–57.
Kleinschmidt S, Grundmann U, Janneck U, et al. Total intravenous anaesthesia using propofol, gamma-hydroxybutyrate or midazolam in combination with sufentanil for patients undergoing coronary artery bypass surgery. Eur J Anaesthesiol 1997; 14: 590–9.
Kleinschmidt S, Grundmann U, Knocke T, et al. Total intravenous anaesthesia with gammahydroxybutyrate (GHB) and sufentanil in patients undergoing coronary artery bypass graft surgery: a comparison in patients with unimpaired and impaired left ventricular function. Eur J Anaesthesiol 1998; 15: 559–64.
Kleinschmidt S, Schellhase C, Mertzlufft F. Continuous sedation during spinal anaesthesia: gamma-hydroxybutyrate vs. propofol. Eur J Anaesthesiol 1999; 16: 23–30.
LeBeau MA, Montgomery MA, Miller ML, Burmeister SG. Analysis of biofluids for gammahydroxybutyrate (GHB) and gamma-butyrolactone (GBL) by headspace GC-FID and GC-MS. J Anal Toxicol 2000; 24: 421–8.
Labroit H. Sodium 4-hydroxybutyrate. Int J Neuropharmacol 1964; 3: 433–52.
Lettieri J, Fung H. Absorption and first-pass metabolism of 14C-gamma-hydroxybutyric acid. Res Commun Chem Pathol Pharmacol 1976; 13: 425–37.
Li J. y-Hydroxybutyrate intoxication and overdose [reply]. Ann Emerg Med 1999; 33: 475–6.
Li J, Stokes SA, Woeckener A. A Tale of novel intoxication: a review of the effects of γ-hydroxybutyric acid with recommendations for management. Ann Emerg Med 1998a; 31: 729–36.
Li J, Stokes SA, Woeckener A. A tale of novel intoxication: seven cases of γ-hydroxybutyric acid overdose. Ann Emerg Med 1998b; 31: 723–8.
LoVecchio F, Curry SC, Bagnasco T. Butyrolactone-induced central nervous system depression after ingestion of RenewTrient, a “dietary supplement. ” N Engl J Med 1998; 339: 847–8.
Mamelak M. Gammahydroxybutyrate: an endogenous regulator of energy metabolism. Neurosci Biobehav 1989; 13: 187–98.
McCusker RR, Paget-Wilkes H, Chronister CW, Goldberger BA. Analysis of gammahydroxybutyrate (GHB) in urine by gas chromatography-mass spectrometry. J Anal Toxicol 1999; 23: 301–305.
Minai L. GHB’s ‘stupor effect’ has made it popular. Los Angeles Times, January 29, 2001.
Miguez I, Aldegunde M, Duran R, et al. Effects of low doses of gammahydroxybutyrate on serotonin, noradrenaline, and dopamine concentrations in rat brain areas. Neurochem Res 1988; 13: 531–3.
Palatini P, Tedeschi L, Frison G, et al. Dose-dependent absorption and elimination of gammahydroxybutyric acid in healthy volunteers. Eur J Clin Pharmacol 1993; 45: 353–6.
Ropero-Miller J, Goldberger BA. Recreational drugs. Current trends in the 90s. Clin Lab Med 1998; 18: 727–46.
Ross TM. Gamma hydroxybutyrate overdose: Two cases illustrate the unique aspects of this dangerous drug. J Emerg Nurs 1995; 21: 274–6.
Sapienza, F. Presentation at National Assicoation of State Controlled Substances Authorities (NASCSA) 16th Annual Education Conference, Louisville, KY, Nov. 1, 2000.
Scharf MB, Lai AA, Branigan B, Stover R, Berkowitz DB. Pharmacokinetics of gammahydroxybutyrate (GHB) in narcolepsy patients. Sleep 1998; 21: 507–14.
Sivilotti ML, Burns MJ, Aaron CK, Greenberg MJ. Pentobarbital for severe gammabutyrolactone withdrawal. Ann Emerg Med 2001; 38: 660–5.
Snead OC. Gammahydroxybutyrate. Life Sci 1977; 126: 1935–44.
Thomas G, Bonner S, Gascoigne A. Coma induced by abuse of gammaydroxybutyrate (GHB or liquid ecstasy). BMJ 1997; 314: 35–6.
Wiley J, Dick R, Arnold T. Hematuria from home-manufactured GHB. J Toxicol Clin Toxicol 1998; 36: 502–3.
Vayer P, Mandel P, Maitre M. Gammahydroxybutyrate, a possible neurotransmitter. Life Sci 1987; 1547–57.
Vickers MD. Gammahydroxybutyric acid. Int Anesth Clin 1969; 7: 75–89.
Winters WD, Spooner CE. Various seizure activities following gamma-hydroxybutyrate. Int J Neuropharmacol 1965; 4: 197–200.
Zvosec DL, Smith SW, McCutcheon JR, et al. Adverse events, including death, associated with the use of 1,4-butanediol. N Engl J Med 2001; 344: 87–94.
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2003 Springer Science+Business Media New York
About this chapter
Cite this chapter
Meredith, B., Cupp, M.J., Tracy, T.S. (2003). γ—Hydroxybutyric Acid (GHB), γ-Butyrolactone (GBL), and 1,4-Butanediol (BD). In: Cupp, M.J., Tracy, T.S. (eds) Dietary Supplements. Forensic Science and Medicine. Humana Press, Totowa, NJ. https://doi.org/10.1007/978-1-59259-303-3_11
Download citation
DOI: https://doi.org/10.1007/978-1-59259-303-3_11
Publisher Name: Humana Press, Totowa, NJ
Print ISBN: 978-1-4684-9726-7
Online ISBN: 978-1-59259-303-3
eBook Packages: Springer Book Archive