GHB - Gamma Hydroxy Butyrate

CONTENTS

Overview

Excerpt from Morbidity and Mortality Weekly Report

Common questions about GHB and GBL

Links

Link to an abstract in the Annals of Emergency Medicine:
Gamma-hydroxybutyrate overdose and physostigmine: Teaching new tricks to an old drug?

OVERVIEW

Slang or Street Names: Grievous Bodily Harm, G, Liquid Ecstasy, Georgia Home Boy.

GHB can be produced in clear liquid, white powder, tablet, and capsule forms, and it is often used in combination with alcohol, making it even more dangerous. GHB has been increasingly involved in poisonings, overdoses, “date rapes,” and fatalities. The drug is used predominantly by adolescents and young adults, often when they attend nightclubs and raves. GHB is often manufactured in homes with recipes and ingredients found and purchased on the Internet.

GHB is usually abused either for its intoxicating/sedative/euphoriant properties or for its growth hormone-releasing effects, which can build muscles.

Some individuals are synthesizing GHB in home laboratories. Ingredients in GHB, gamma-butyrolactone (GBL) and 1,4-butanediol, can also be converted by the body into GHB. These ingredients are found in a number of dietary supplements available in health food stores and gymnasiums to induce sleep, build muscles, and enhance sexual performance.

GHB is a central nervous system depressant that can relax or sedate the body. At higher doses it can slow breathing and heart rate to dangerous levels which can cause death.

GHB’s intoxicating effects begin 10 to 20 minutes after the drug is taken. The effects typically last up to 4 hours, depending on the dose. At lower doses, GHB can relieve anxiety and produce relaxation; however, as the dose increases, the sedative effects may result in sleep and eventual coma or death.

Overdose of GHB can occur quickly, and the signs are similar to those of other sedatives: drowsiness, nausea, vomiting, headache, loss of consciousness, loss of reflexes, impaired breathing, and ultimately death.

GHB is cleared from the body relatively quickly, so it is sometimes difficult to detect in emergency rooms and other treatment facilities.

EXCERPTED FROM:

Morbidity and Mortality Weekly Report

 
Adverse Events Associated With Ingestion of Gamma-Butyrolactone-Minnesota, New Mexico, and Texas, 1998-1999
 

 
MMWR. 1999;48:137-140

Products containing gamma-butyrolactone (GBL)* are marketed for many claimed purposes, including to induce sleep, release growth hormone, enhance sexual activity and athletic performance, relieve depression, and prolong life. GBL is converted by the body into gamma-hydroxybutyrate (GHB), a drug banned outside of clinical trials approved by the Food and Drug Administration (FDA). Recognized manifestations of GHB toxicity include bradycardia, hypothermia, central nervous system depression, and uncontrolled movements. This report describes seven cases of GBL toxicity involving the product "Revivarant," which is labeled as containing 1.82 g of GBL per fluid ounce, reported from two hospital emergency departments (EDs) in Minnesota during October-December 1998 and summarizes an additional 34 cases of GBL toxicity reported to poison centers in New Mexico and Texas during October 1998-January 1999.

Minnesota

Patient 1.
 
On November 26, 1998, a 24-year-old man vomited and had seizures shortly after drinking 3-4 oz of Revivarant. His behavior became unusual, and he alternated between extreme agitation and profound calm. Paramedics noted that his skin was warm, flushed, and profusely diaphoretic, and he had bradycardia (pulse as low as 45 beats per minute [bpm]). Systolic blood pressure was 110 mm Hg. Transcutaneous oxygen saturations (SpO2) were 96% on room air, and blood glucose by fingerstick was 90 mg/dL. During transport to an ED, he had periods of combativeness lasting 30 to 60 seconds followed by coma lasting 1-3 minutes. In the ED, he was unconscious with spontaneous eye opening, a positive withdrawal reflex, and no speech (Glasgow Coma Scale of 7); rectal temperature was 94.8 F (34.9 C). A urine toxicology screen and blood ethanol test were negative. He was intubated and admitted to the intensive-care unit (ICU) with a diagnosis of toxic encephalopathy. During the next 7 hours, his heart rate increased from 42 to 116 bpm and he became more alert. He had no recollection of events except for having ingested Revivarant. He was discharged with normal mental status.

Patient 2.
 
On December 12, 1998, a 46-year-old woman had a seizure and lost consciousness after drinking approximately 2.7 oz of Revivarant in conjunction with ethanol. Paramedics found her unconscious and in severe respiratory depression with a pulse of 54 bpm. Oxygen was administered by mask; she had an SpO₂ of 87%. On arrival in the ED, physical examination identified sinus bradycardia (54 bpm); temperature of 96.1 F (35.6 C); and miotic pupils. A serum ethanol level was 0.11%. She was admitted to the ICU, mechanically ventilated through the night, and awoke in improved condition the next morning; she was discharged with no memory of the events.

Patient 3.
 
On November 8, 1998, a 31-year-old man drank approximately 1 oz of Revivarant, four beers, and a large sip of wine. Shortly thereafter, he gradually lost consciousness and subsequently fell. He regained consciousness but had involuntary muscle movements and episodes of confusion. Paramedics noted that he was ambulatory but confused. On physical examination in the ED, he was agitated, anxious, and unable to recall the preceding events. His shoulders twitched, and he had a small abrasion below his left eye. He had a pulse of 64 bpm and hypothermia (oral temperature of 95.2 F [35.1 C]). Breath ethanol level was 0.08%. He denied previous GBL use or illicit drug use. He recovered completely and was discharged.

Patients 4 and 5.
 
On October 31, 1998, a 24-year-old man (patient 4) and a 26-year-old man (patient 5) each drank 10-13 oz of Revivarant while drinking alcohol at a bar. On leaving the bar, witnesses observed them fall and become unresponsive. On arrival at the ED, they alternated between somnolence and confusion. When awake, neither patient could consistently follow commands. Patient 4 had fecal incontinence. Vital signs for both patients were within normal limits. Breath ethanol levels were 0.09% (patient 4) and 0.15% (patient 5). Neither patient had a history of using medications or illicit drugs. After 2 hours of observation, the patients recovered but were unable to recall most of the evening's events.

Patients 6 and 7.
 
On December 12, 1998, a 19-year-old woman (patient 6) and a 22-year-old woman (patient 7) were brought to an ED by friends because of vomiting and decreased levels of consciousness. These symptoms followed ingestion of Revivarant (2 oz by patient 6 and an unknown amount by patient 7). Patient 6 had drunk one beer; patient 7 had had no ethanol. Vital signs were normal except for respiratory depression. On physical examination, patient 6 was lethargic and disoriented. Patient 7 exhibited intermittent periods of extreme agitation, necessitating chemical treatment and physical restraint, punctuated by moments of calm during which her attention focused on minor details. Mental changes for both patients resolved, and they were discharged approximately 4 hours after arrival.

New Mexico

Texas

From October 2, 1998, through January 24, 1999, Texas poison-control centers identified 20 adverse events resulting in ED visits among persons who had ingested GBL-containing products. Twelve (60%) of the cases were reported in January. Patients' ages ranged from 11 to 41 years; 13 were male. Products known to have been used included "RenewTrient" (six cases), "Revivarant" (four), "Revivarant-G" (two), and "Blue Nitro Vitality" (two). Ten persons also ingested ethanol and/or other drugs. Ten patients were admitted to the hospital from the ED. The most common symptoms and signs were obtundation (13 [65%]), prolonged unconsciousness (nine [45%]), respiratory depression (nine [45%]), anxiety/nervousness (seven [35%]), nausea/vomiting (six [30%]), confusion (six [30%]), tremors/twitching (four [20%]), tachycardia (three [15%]), and combativeness (three [15%]). One person had respiratory arrest; no deaths were reported.

EDITORIAL COMMENTS:

GBL is metabolized to GHB in the body, but because of better absorption GBL has greater bioavailability than GHB on an equimolar basis. Clinical effects of GHB appear to be dose-related and include reports of vomiting, hypotonia, tremors, seizures, aggression, impairment of judgment, coma, respiratory depression, hypothermia, and bradycardia. GHB mixed with ethanol acts synergistically to produce central nervous system and respiratory depression. Symptoms usually resolve with supportive care within 2-96 hours. Death occurring when GHB was the sole intoxicant also has been reported. Toxic effects of GBL would be expected to be similar or identical to those of GHB, but previous clinical experience is limited. There is no antidote for GHB; treatment consists of supportive therapy until symptoms of toxicity subside. A withdrawal syndrome, which can include insomnia, tremor, and anxiety, has been reported following discontinuance of GHB in chronic, high-dose users.

GBL is an industrial and household solvent of acrylate polymers, and unintentional poisonings have been reported. It also is marketed as a dietary supplement at health food stores and on the World-Wide Web under several trade names. Although labeled as dietary supplements, GBL-containing products are illegally marketed, unapproved new drugs that have been involved in at least 55 reports of adverse events, including one death. On January 21, 1999, FDA asked manufacturers to recall their GBL-containing products and warned consumers through press releases to avoid taking these products.Public education efforts should inform consumers that FDA review procedures for drugs are different than those used for dietary supplements. Consumers should be alert to the potential dangers of these products and understand that terms such as "natural" do not necessarily imply safety. Physicians should counsel patients about these products and be prepared to recognize and treat the toxic reactions that some might produce. Chronic GBL users should be monitored for withdrawal symptoms when discontinuing use of the product. Depending on the severity of the withdrawal symptoms, medical intervention may be required. Physicians are encouraged to report serious adverse events associated with these products to FDA's MEDWATCH program, telephone (800) 332-1088.

*Also is known as dihydro-2(3H)-furanone; 4-butanolide; 2(3H)-furanone, dihydro; tetrahydro-2-furanone; and butyrolactone gamma. 

REFERENCES

Li J, Stokes SA, Woeckener A. A tale of novel intoxication: a review of the effects of gamma-hydroxybutyric acid with recommendations for management. Ann Emerg Med. 1998;31:729-36. MEDLINE

Lettieri J, Fung HL. Improved pharmacological activity via pro-drug modification: comparative pharmacokinetics of sodium gamma-hydroxybutyrate and gamma-butyrolactone. Res Commun Chem Pathol Pharmacol. 1978;22:107-18. MEDLINE

Mamelak M. Gammahydroxybutyrate: an endogenous regulator of energy metabolism. Neurosci Biobehav Rev. 1989;13:187-98. MEDLINE

CDC. Multistate outbreak of poisonings associated with illicit use of gamma hydroxy butyrate. MMWR. 1990;39:861-3.

CDC. Gamma hydroxy butyrate useNew York and Texas 1995-1996. MMWR. 1997;46:281-3.

Rambourg-Schepens MO, Buffet M, Durak C, Mathieu-Nolf M. Gamma butyrolactone poisoning and its similarities to gamma hydroxybutyric acid: two case reports. Vet Hum Toxicol. 1997;39:234-5. MEDLINE

LoVecchio F, Curry SC, Bagnasco T. Butyrolactone-induced central nervous system depression after ingestion of RenewTrient, a "dietary supplement" [Letter]. N Engl J Med. 1998;339:847-8. MEDLINE

Galloway GP, Frederick SL, Staggers FE, Gonzales M, Stalcup SA, Smith DE. Gamma-hydroxybutyrate: an emerging drug of abuse that causes physical dependence. Addiction. 1997;92:89-96. MEDLINE

Higgins TF, Borron SW. Coma and respiratory arrest after exposure to butyrolactone. J Emerg Med. 1996;14:435-7. MEDLINE

Food and Drug Administration. FDA warns about products containing gamma butyrolactone or GBL and asks companies to issue a recall. Rockville, Maryland: US Department of Health and Human Services, Public Health Service, Food and Drug Administration, 1999. (Talk paper T99-5). Available at: http://www.fda.gov/bbs/topics/ANSWERS/ANS00937.html. Accessed February 24, 1999.

Common questions about GHB and GBL

Q: What are GHB and GBL?

A: GHB and its legal cousin, GBL, were initially sold in health food stores and used by body builders, who thought the chemicals would stimulate muscle growth. Both drugs slow down the central nervous system. Once GBL is ingested, it metabolizes into GHB.

Q: What are the street names for GHB?

A: G, Scoop, Liquid Ecstasy, Georgia Home Boy, Grievous Bodily Harm, Liquid X, Easy Lay.

Q: What are some products that contain GHB or GBL and are available on the Internet?

A: Blue Nitro, Revivarant, Renewtrient, Revitalize Plus, Serenity, Enliven, SomatoPro, Invigorate, Midnight Blue and Zen.

Q: Who is using GHB and GBL?

A: It is usually taken at parties, clubs or raves. It is found at gyms, and it has been used as a date-rape drug because it is odorless, colorless and virtually tasteless. It does have a salty taste, however.

Q: What are the effects of GHB and GBL use?

A: It is said to mimic alcohol consumption, producing euphoria in the user. In larger doses, it can put someone to sleep. In dangerously high doses, it can induce nausea, vomiting, seizures and coma.

Q: Is GHB legal?

A: In Michigan, GHB is a Schedule I drug, in the same category as heroin or cocaine. Convictions for making the drug can bring up to seven years in prison. Possessing the drug can bring a two-year prison sentence. Use can result in one year in jail.

There is no federal penalty for the drug, but the U.S. House and Senate recently passed legislation that would put it in the Schedule I category, making use and manufacture of it illegal except for medical testing. The bill awaits approval by President Clinton.

The FDA banned over-the-counter sales in 1990.

Sources: The Maryland Drug Early Warning System and http://www.ashesonthesea.com/ghb

LINKS

In the Grip of GHB

GHB: The Stone Cold Truth

Health.org

Quackwatch

Partnership for a Drug Free America

Federal Drug Administration

ClubDrugs.org

Link to an abstract in Pediatric Emergency Care
Gamma-hydroxybutyrate, gamma-butyrolactone, and 1,4-butanediol: a case report and review of the literature.

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