Gamma-Hydroxybutyrate (GHB) for Bodybuilding
December 2000; Volume 3; 140-142
By Dónal P. O’Mathúna, PhD
Gamma-hydroxybutyrate (ghb) is better known in the gym and on the street as "liquid ecstasy," "Georgia home boy," "grievous bodily harm," "salty water," "somatomax," "easy lay," "cherry menth," and a host of other deceptive names.1 Compounds converted into GHB in the body are found in Revivarant, Revitalizer, Blue Nitro, and Weight Belt Cleaner. Bodybuilders claim GHB improves their performances by releasing growth hormone, inducing restful sleep, and stimulating fat metabolism. Others use GHB to lose weight, induce sleep, or produce euphoria. The latter effect allegedly is accompanied by aphrodisiac and disinhibitory effects, giving GHB notoriety at rave dances and as a "date rape" drug.
GHB has another sinister side, exemplified by a growing list of athletes and party-goers who have died or had serious adverse effects from GHB and related substances.2 In December 1999, NBA basketball player Tom Gugliotta of the Phoenix Suns took an herbal remedy containing gamma-butyrolactone (GBL), which rapidly forms GHB in the body. He almost died from respiratory failure.3 Like Gugliotta, the lucky ones end up in emergency departments where recovery often is rapid and complete, leading casual observers to believe that medical attention is unnecessary if someone passes out after taking GHB.4 Given the serious consequences of using GHB casually, and the importance of rapidly responding to its adverse effects, clinicians should be aware of this dangerous supplement.
Background and Nomenclature
An endogenous substance, GHB also is easily synthesized from readily available chemicals. During the 1980s, it became popular among bodybuilders after studies showed it stimulated the release of human growth hormone.5 However, its sale was banned by the U.S. Food and Drug Administration (FDA) in 1990 after numerous adverse effects were reported.2 In spite of this, products containing GHB were marketed as dietary supplements, and home manufacturing kits were developed.1 These kits remain a popular source of GHB.
Other products containing closely related compounds, including GBL (also called furanone di-hydro) and 1,4-butanediol (BD), have been promoted to bodybuilders. Both of these are converted rapidly into GHB in the body with the same range of effects. Some products now claim to have all the same effects as GHB, but none of the banned substances. Some people have suffered GHB poisoning after using these products.4
GHB has been used as a "date rape" drug because it rapidly causes muscle relaxation and reduced inhibitions. Some victims not only were sexually assaulted, but also had serious adverse effects, and several died. This led to passage of the Hillory J. Farias and Samantha Reid Date-Rape Drug Prohibition Act of 2000.6 This Congressional legislation modified the Controlled Substances Act, and included GHB as a Schedule 1 Controlled Substance, like opium and cocaine.
Pharmacology
GHB is found in most tissues of the body, and
probably is a neurotransmitter. GHB is formed endogenously by the breakdown of gamma-aminobutyric acid, which is one of the principal inhibitory neurotransmitters and a CNS depressant.7 Orally, GHB is rapidly absorbed and eliminated, with its serum concentration peaking after about 40 minutes and heavily vanishing after four hours.8
Mechanism of Action
GHB’s mechanism of action has not been elucidated.9 It crosses the blood-brain barrier where it interferes with dopamine levels in a complex, dose-dependent way.10 GHB’s relief of the symptoms of narcolepsy is believed to be mediated via these dopaminergic effects.11 GHB facilitates deep slow-wave sleep, during which growth hormone release naturally increases.11 This may explain why higher levels of growth hormone have been detected after GHB administration. However, this effect is short-lasting, and its effect on athletic performance and muscle mass have not been investigated.
Clinical Studies
A search of MEDLINE, International Pharmaceutical Abstracts, and TOXLINE (using GHB, GBL, gamma hydroxybutyrate, and gamma hydroxybutyric acid) revealed no clinical studies of their effects on muscle mass or athletic performance. Clinical studies over the past 20 years have shown that GHB substantially reduces the signs and symptoms of narcolepsy.8 Narcolepsy is characterized by sudden sleep attacks, temporary loss of muscle tone while awake (cataplexy), and hypnagogic hallucinations, all of which are relieved by GHB.12 GHB initially was used as an anesthetic agent, particularly with children, but was replaced by more effective agents.13 GHB also has been used during alcohol withdrawal, although its effectiveness here remains under investigation.10
Adverse Effects
The U.S. Drug Enforcement Agency connects GHB to more than 45 deaths and 5,500 emergency department visits since 1990.2 Side effects range from nausea, vomiting, dizziness, and drowsiness to delusions, depression, vertigo, hallucinations, amnesia, seizures, depressed respiration, bradycardia, low blood pressure, coma, and death.
Milder symptoms are elicited with 10 mg/kg orally, with unconsciousness and coma occurring with 50 mg/kg.14 People vary unpredictably in their responses, and the same person may react differently to the same dose on different occasions. Responses usually occur within 15 minutes of ingesting GHB.7
Although even serious effects usually resolve within a few hours, one report of GHB-induced delirium lasted nine days.15 Some believe taking two or more capfuls (30-50 mg/kg) daily can lead to addiction.7 No readily available serum test for GHB exists. Detection requires gas chromatographic-mass spectrometer urinalysis, which is not widely available in U.S. hospitals and does not differentiate between GHB and GBL.15
Drug Interactions
GHB potentiates the effects of endogenous opiates and exogenous narcotics.11 Alcohol, benzodiazepines, and other neuroleptics potentiate the effects of GHB. No effective GHB antagonist has been identified.
Formulation
GHB is available as a clear, colorless, odorless liquid, or in salt form as a white powder. Proponents usually recommend that bodybuilders take one capful (2.5-5 g) of liquid or powder daily before going to bed. Many also recommend experimenting with the dose until users get the desired effects. This recognizes people’s variability in their sensitivity to GHB, but also is a recipe for adverse effects.
Regulation
The FDA considers GHB, GBL, and BD unapproved and dangerous drugs and has confiscated products from retailers.16 The Date-Rape Drug Prohibition Act of 2000 reclassified GHB and its analogues as Schedule 1 drugs and resulted in the establishment of a nationwide surveillance and reporting system.6 However, the law recognized that GHB may have a legitimate use in the treatment of narcolepsy and made allowance for alternative scheduling of particular drug products containing GHB, provided they obtain the usual FDA approval. On October 2, 2000, Orphan Medical Inc. filed a new drug application with the FDA, and hopes to begin marketing GHB for narcolepsy symptoms as Xyrem® (sodium oxybate) in mid-2001.17 In spite of these regulations, GBL was available in November 2000 on Internet bodybuilding pages "as a solvent only."18
Conclusion
While GHB leads to the release of growth hormone, no clinical studies support its effectiveness in increasing muscle mass or athletic performance. In contrast, significant evidence demonstrates that its use as a "dietary supplement" causes adverse effects. This contrasts with the lack of adverse effects when GHB is used in clinical trials for the treatment of narcolepsy, where 25 mg/kg usually is taken at bedtime, followed by the same dose three to four hours later. While bodybuilders may start at this dose, they often take much more hoping for increased effects. Additionally, the questionable quality of GHB synthesized "on the street" and the potentiation of its effects by alcohol may contribute to the growing incidence of adverse effects.
Recommendation
Bodybuilders and athletes should be actively discouraged from using GHB and related products. Products available on the Internet or in health food stores cannot be trusted. The only current legitimate use for GHB is in trials of its effectiveness for treating narcolepsy. Unfortunately, illegitimate use of GHB appears to be increasing. If bodybuilders present at emergency departments in an unconscious state, GHB overdose should be considered. Gastric lavage and charcoal are of little use since GHB is absorbed rapidly.9 Naloxone has been ineffective as an antidote.7 Protection of the airway, and close observation while the body eliminates GHB often is sufficient for safe recovery. Patients who survive the acute crisis usually can be discharged after six to eight hours.
Dr. O’Mathúna is Professor of Bioethics and Chemistry at Mount Carmel College of Nursing in Columbus, OH.
References
1. From the Centers for Disease Control and Prevention. Gamma hydroxy butyrate use—New York and Texas, 1995-1996. JAMA 1997;277:1511.
2. Nordenberg T. The death of the party. All the rave, GHB’s hazards go unheeded. FDA Consum 2000;34:
14-19.
3. D’Alessandro D. Your attention, please. The Sporting News. January 10, 2000: 44.
4. Ingels M, et al. Coma and respiratory depression following the ingestion of GHB and its precursors: Three cases. J Emerg Med 2000;19:47-50.
5. Takahara J, et al. Stimulatory effects of gamma-hydroxybutyric acid on growth hormone and prolactin release in humans. J Clin Endocrinol Metab 1977;44:
1014-1017.
6. Hillory J. Farias and Samantha Reid Date-Rape Drug Prohibition Act of 2000. Available at: www.ghbkills.com/samlaw.htm. Accessed Oct. 6, 2000.
7. Schwartz RH Gamma-hydroxy butyrate. Am Fam Physician 1998;57:2078, 2081.
8. Scharf MB, et al. Pharmacokinetics of gammahydroxybutyrate (GHB) in narcoleptic patients. Sleep 1998;21:
507-514.
9. Smith KM. Drugs used in acquaintance rape. J Am Pharm Assoc 1999;39:519-525.
10. Tunnicliff G. Sites of action of gamma-hydroxybutyrate (GHB)—A neuroactive drug with abuse potential. J Toxicol Clin Toxicol 1997;35:581-590.
11. Chin MY, et al. Acute poisoning from gamma-hydroxybutyrate in California. West J Med 1992;156:380-384.
12. Kalra MA, Hart LL. Gammahydroxybutyrate in narcolepsy. Ann Pharmacother 1992;26:647-648.
13. Lane RB. Gamma hydroxy butyrate (GHB). JAMA 1991;265:2959.
14. Bernasconi R, et al. Gamma-hydroxybutyric acid: An endogenous neuromodulator with abuse potential? Trends Pharmacol Sci 1999;20:135-141.
15. Hernandez M, et al. GHB-induced delirium: A case report and review of the literature of gamma hydroxybutyric acid. Am J Drug Alcohol Abuse 1998;24:
179-183.
16. Report serious adverse events associated with dietary supplements containing GBL, GHB, or BD. Available at: www.fda.gov/medwatch/safety/1999/gblghb.htm. Accessed Oct. 6, 2000.
17. Orphan Medical Inc. Xyrem® NDA for narcolepsy symptoms submitted by Orphan Medical. Available at: www.orphan.com/press_release_detail.cfm?ID=117. Accessed Nov. 14, 2000.
18. Revivarant. Available at: www.musclesoft.com/revivarant.htm. Accessed Nov. 14, 2000.
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December 2000; Volume 3; 140-142
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