Epidemiologic Notes and Reports Multistate Outbreak of Poisonings Associated with Illicit Use of Gamma Hydroxy Butyrate

On August 7, 1990, the San Francisco Bay Area Regional Poison Control Center notified the regional office of the Food and Drug Administration (FDA) and the California Department of Health Services of acute poisonings attributed to ingestion of gamma hydroxy butyrate (GHB), which recently has been illicitly marketed nationwide. Manifestations included gastrointestinal symptoms, central nervous system (CNS) and respiratory depression, and uncontrolled movements. Subsequent surveillance, based on contacts among poison-control centers, led to the recognition that similar poisonings had been independently identified in several states. This report summarizes findings from the preliminary investigation of this problem.

From June 4 through November 28, 1990, at least 57 cases of illness attributed to GHB exposure have been reported from California (25 cases, 17 from the San Francisco area); Georgia (15, all from the greater Atlanta area); Florida (seven, six from the greater Tampa area); South Carolina (three); Minnesota (two); Arizona (two); and Ohio, Texas, and Virginia (one each). Patients have presented with histories of ingesting -3 teaspoons of GHB dissolved in water; ingestion is followed within 15-60 minutes by onset of one or more of the following: vomiting, drowsiness, hypnagogic state, hypotonia, and/or vertigo. Loss of consciousness, irregular and depressed respiration, tremors, or myoclonus may follow. Seizure-like activity, bradycardia, hypotension, and/or respiratory arrest have also been reported. Spontaneous resolution occurs in 2-96 hours. The severity and duration of symptoms appear to depend on the dose of GHB and/or the presence of other CNS depressants, most frequently ethanol. In 11 of 12 Georgia patients, four of five Florida patients, and three of four California patients for whom concurrent drug status was known, other psychoactive drugs--including ethanol, benzodiazepines, cannabis, and amphetamines--also had been used.

Although no deaths have been reported, most patients have required emergency room care; at least 11 were hospitalized, and nine required ventilator support or other intensive care. Therapeutic efforts consisted of nonspecific supportive care.

On November 8, FDA issued an advisory warning that GHB use outside of FDA-approved physician-supervised protocols was unsafe and illicit and should stop (1). Persons who have used GHB and have symptoms should consult a physician. Ill persons, physicians, and emergency room staff are encouraged to report suspected cases of GHB-related illness to their regional poison-control centers and state health departments. FDA's investigation into the source(s) of this illicit distribution is ongoing. Sale of GHB was banned by California on November 8 and by Florida on November 9. Reported by: JE Dyer, PharmD, San Francisco Bay Area Regional Poison Control Center; R Kreutzer, MD, A Quattrone, PhD, KW Kizer, MD, California Dept of Health Svcs. RJ Geller, MD, Georgia Poison Control Center; JD Smith, Georgia Dept of Human Resources. SA Normann, PharmD, Florida Poison Information Center; AJ Hill, RA Calder, MD, State Epidemiologist, Florida Dept of Health and Rehabilitative Svcs. T Litovitz, MD, American Association of Poison Control Centers. Food and Drug Administration. Div of Environmental Hazards and Health Effects, Center for Environmental Health and Injury Control, CDC.

Editorial Note

Editorial Note: In the United States, the only legal use of GHB (HOOC-CH 2-CH 2- CH 2OH) has been under specific FDA exemptions for investigational research protocols (e.g., treatment of narcolepsy). In Europe, GHB has also been used as an anesthetic adjunct and experimentally to treat posthypoxic cerebral edema and ethanol withdrawal. During controlled clinical use, the same dose of GHB sometimes caused different responses in different patients and different responses in the same person at different times (M. Mamelak, personal communication, 1990).

GHB has been illegally marketed under a variety of names, including Gamma Hydroxybutyric Acid, Sodium Oxybate, Sodium Oxybutyrate, Gamma Hydroxybutyrate Sodium, Gamma-OH, 4-Hydroxy Butyrate, Gamma Hydrate, and Somatomax PM. It is distributed as the sodium salt in powder or tablet form and is commonly dissolved in water.

GHB has been marketed illicitly to body builders since at least May 1990; it also has been promoted illicitly for weight control and as a sleep aid. In addition, GHB has been illicitly touted as a "replacement" for L-tryptophan, which had been marketed as a food supplement but was recalled in November 1989 when the epidemic of eosinophilia-myalgia syndrome was recognized (2).

GHB allegedly produces a "high," which has led to its further use as an illicit drug. Although the concurrent use of other drugs with similar toxicities may confuse the clinical, toxicologic, and epidemiologic presentation of this problem, the reported symptoms of GHB toxicity are the same as the known pharmacologic effects of the drug. A causal association between use of GHB and these poisonings is also supported by the rapid onset of symptoms after ingestion of GHB, more severe and prolonged symptoms associated with larger doses of GHB, and occurrence of illness in persons who have not used other drugs.

GHB is produced by the body as a normal metabolite and is not a nutritional requirement. In the brain, GHB increases dopamine levels, has effects through the endogenous opioid system, and probably has effects through other independent receptor-dependent mechanisms. GHB is present in many peripheral sites, including the kidney, heart, skeletal muscle, and brown fat. GHB is well absorbed orally, readily crosses the blood-brain barrier, and is subsequently metabolized to carbon dioxide and water without active metabolites (3,4). Effects include amnesia and hypotonia from doses as low as 10 mg/kg, a normal sequence of REM and non-REM sleep from 20-30 mg/kg doses (1-3 g per dose were used in U.S. narcolepsy studies (5)), and anesthesia from doses of approximately 50 mg/kg. In doses greater than 50 mg/kg, GHB decreases cardiac output and subsequently produces increasingly severe respiratory depression, seizure-like activity, and/or coma (4,5). Other effects suggest that, during hypoxia and other energy-limiting conditions, GHB may play a role in reducing energy-substrate demand and consumption and in preventing the production of free radicals (4).

GHB acts synergistically with ethanol to produce CNS and respiratory depression; ethanol also increases the endogenous levels of GHB (4). GHB may potentiate the effects of narcotic analgesics and skeletal muscle relaxants and may be potentiated by the actions of benzodiazepines and neuroleptics (5). Although antagonism may occur with d-amphetamine, naloxone, haloperidol, and drugs used for absence seizures (4), these experimental antagonists have not been assessed as possible treatments for GHB overdose. Anecdotally, naloxone has not been effective in treating a limited number of GHB-related poisonings.

The focus of public education efforts should be that products such as GHB that are promoted for physiologic effects act on the body as drugs. In this context, advertising terms such as "natural," "organic," or "supplement" do not imply safety or legality.

References

1. Food and Drug Administration. Gamma hydroxybutyric acid (Press release). Rockville, Maryland: Food and Drug Administration, November 8, 1990.

2. Swygert LA, Maes EF, Sewell LE, Miller L, Falk H, Kilbourne EM. Eosinophilia-myalgia syndrome: results of national surveillance. JAMA 1990;264:1698-703.

3. Vayer P, Mandel P, Maitre M. Minireview: gamma-hydroxybutyrate, a possible neurotransmitter. Life Sci 1987;41:1547-57.

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

5. United States Pharmaceutical Convention, Inc. USP dispensing information. Vol IB. Drug information for the health care professional, 1990:2914.

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