Coma-Inducing Drug GHB May Be Reclassified
Vol 277, May 21 1997; 1505-1506
JAMA - Medical News & Perspectives
[Erowid Note : GHB became illegal to possess or sell in March 2000]
INCREASING numbers of reports of psychotic illnesses associated with the use of a relatively new recreational drug, gamma-hydroxybutyrate (GHB), have led the Drug Enforcement Agency (DEA) to consider recommending that it be classified as a schedule I drug. If the proposal is accepted by the US Department of Health and Human Services, possession of GHB will become a criminal offense.
To be classified as a schedule I drug, a drug must have no currently accepted medical use, be likely to be abused, and be not proven safe when used under medical supervision.
Speaking at a session devoted to GHB during this year's annual meeting of the American Academy of Forensic Sciences held in New York, NY, DEA scientist Thomas DiBerardino, PhD, suggested that the agency would shortly recommend that GHB be classified as a schedule I controlled substance. "Preliminary findings suggest that GHB does have a high potential for abuse, it has no currently accepted medical applications, and though it is probably safe within certain ranges, there has been 1 death from GHB while the patient was under medical supervision," he said.
Interviewed recently, DiBerardino, who is a chemist in the DEA's Office of Diversion Control in Washington, DC, said, "The DEA is evaluating the data for possible placement of GHB under the Controlled Substances Act." Two states, Georgia and Rhode Island, have classified GHB as a schedule I drug, and others are considering similar action.
Historic Background
The drug GHB was synthesized in 1960 and shown to be capable of crossing the blood-brain barrier. The drug induces a sleeplike state with minor cardiovascular effects. In Europe, this characteristic spurred clinical studies of its potential as an anesthetic. Interest dropped, however, when its use was associated with petit mal and grand mal seizures.
In 1963, GHB was discovered as a naturally occurring substance in the human brain (Nature. 1963;200:1207-1208). Researchers have suggested that it acts as a neurotransmitter, but the mechanism of action producing the clinical effects is unknown. In the 1970s, GHB was used to treat sleep disorders, and some interest in this use continues. It is thought to induce rapid eye movement sleep, decreasing symptoms of narcolepsy, said Jo Ellen Dyer, PharmD, an assistant clinical professor of pharmacy at the University of California, San Francisco.
In 1977, Japanese investigators reported that GHB had steroid-enhancing effects and theorized that it stimulated growth hormone. Although this theory was never proved, the idea "sparked an interest in GHB among bodybuilders, who used it for about 10 years," said Kathleen Andrews, a forensic chemist with the DEA in San Francisco.
The drug is a white hygroscopic powder precipitated from gamma-butyrolactone by the addition of sodium hydroxide. It usually turns up today as a colorless, odorless liquid with a mild salty soapy taste that is easy to mask. In 1990, it appeared on the commercial market as a sedative sold in health food stores and was touted as a replacement for L-tryptophan, which the FDA had taken off the market the previous year.
By November 1990, 9 states had reported 57 instances of such GHB-related illnesses as seizures and comas, and the FDA removed GHB from the market. Despite the ban, GHB continues to be manufactured and sold clandestinely. "An increasing awareness of its psychoactive properties and its euphoric effect created a demand. When the actor River Phoenix collapsed and died outside the Viper Room in Los Angeles, Calif, in October 1993, it was held that he had died of an overdose of GHB. This was never confirmed, but the rumor further stimulated street interest in the agent," said Andrews.
Widespread Use and Ill Effects
Since then, there have been widespread reports of illness caused by GHB. "In at least three quarters of the 50 states, if not the entire United States, GHB is being used in some form or another," said Andrews. A recent report from poison control centers in New York and Texas stated that from August 1995 to September 1996 there were 69 acute poisonings and 1 death caused by GHB (MMWR Morb Mortal Wkly Rep. 1997;46:281-283). "GHB is also being used abroad. Australia and the UK have reported problems with its use," Andrews added.
Use of the drug has increased markedly in the past year. Dyer said that the San Francisco Bay Area Regional Poison Control Center reported 17 to 34 cases of illness associated with GHB annually during the years 1990 to 1995, but in 1996 it reported 89 cases. The life-threatening and acute health effects of GHB are potentiated by other drugs, such as alcohol and marijuana.
Under a variety of names--liquid ecstasy, Gib, Natural Sleep-500, Somatomax, and Georgia Home Boy (from its initials) among them--GHB has become increasingly popular at so-called raves. These young people's dance parties, which began in the 1980s in England, are notorious for being fueled by drugs both legal and illegal (JAMA. 1992;268:1505-1506).
Because of its frequently abrupt coma-inducing effects, ready accessibility, and ease of administration (it is easily poured into a drink), GHB has achieved popularity in some circles as an agent of assault, a "date rape" drug.
"When it was sold in health food stores, the package included a warning that it should not be taken with alcohol and cautions about the dosing interval. To increase exposure, the advice was to take doses more frequently rather than increasing the individual dose," noted Elizabeth Todd, PhD, chief of Drug and Environmental Toxicology, Dallas County Institute of Forensic Sciences, Dallas, Tex. "Since GHB has a very short half-life, from 20 minutes to 1 hour, this may have minimized some of the negative impact that we are now seeing," she said.
Overdose Symptoms and Treatment
Symptoms of GHB overdose include vomiting, bradycardia, coma, clonic muscle movements, induction and emergence delirium, and Cheyne-Stokes respiration. Diagnosis depends on history at the scene, and treatment is aimed at protecting the airway. The high incidence of vomiting carries with it a high risk of aspiration, said Dyer. Benzodiazepines and opiate antagonists are not effective. Lavage or charcoal are of limited benefit because of the small amounts involved (from one fourth of a teaspoon to 4 tablespoons) and the rapid absorption, usually 10 to 15 minutes depending on the size of the dose. The drug is undetectable in the urine after 12 hours. A level teaspoon contains 2.8 g, but since the drug is now made clandestinely it is often far from pure.
Dyer described the case of a 23-year-old female college student who had been taking 3 to 5 "capsfull" of liquid GHB daily for a year for its alleged anabolic effect. For 6 weeks before admission to the detoxification center, she had increased this dose to every 3 hours around the clock. On admission she had increasing symptoms of paranoia with visual and auditory hallucinations; her heart rate was 110, blood pressure 138/98, temperature normal, and urine toxicology negative. During a 9-day withdrawal period she had paranoia, agitation, and delirium. She made an otherwise uneventful recovery. Other withdrawal symptoms include tremor, confusion, increases in heart rate and blood pressure, and hallucination.
One to 6 teaspoons of GHB taken with alcohol will result--within 15 to 30 minutes--in a pronounced coma and substantial respiratory depression possibly necessitating intubation, said Texas toxicologist Todd. But within 1 to 2 hours, spontaneous recovery often occurs. "People have been in deep coma in the emergency room and in the process of intubation will just sit up, spontaneously 'come right back to life,' and wonder why they're there. There is amnesia about the experience," said Todd. She added, "This is a problem both in follow-up and to those who use the drug. It does not provide a deterrent, since they don't really remember their near-death experience."
INCREASING numbers of reports of psychotic illnesses associated with the use of a relatively new recreational drug, gamma-hydroxybutyrate (GHB), have led the Drug Enforcement Agency (DEA) to consider recommending that it be classified as a schedule I drug. If the proposal is accepted by the US Department of Health and Human Services, possession of GHB will become a criminal offense.
To be classified as a schedule I drug, a drug must have no currently accepted medical use, be likely to be abused, and be not proven safe when used under medical supervision.
Speaking at a session devoted to GHB during this year's annual meeting of the American Academy of Forensic Sciences held in New York, NY, DEA scientist Thomas DiBerardino, PhD, suggested that the agency would shortly recommend that GHB be classified as a schedule I controlled substance. "Preliminary findings suggest that GHB does have a high potential for abuse, it has no currently accepted medical applications, and though it is probably safe within certain ranges, there has been 1 death from GHB while the patient was under medical supervision," he said.
Interviewed recently, DiBerardino, who is a chemist in the DEA's Office of Diversion Control in Washington, DC, said, "The DEA is evaluating the data for possible placement of GHB under the Controlled Substances Act." Two states, Georgia and Rhode Island, have classified GHB as a schedule I drug, and others are considering similar action.
Historic Background
The drug GHB was synthesized in 1960 and shown to be capable of crossing the blood-brain barrier. The drug induces a sleeplike state with minor cardiovascular effects. In Europe, this characteristic spurred clinical studies of its potential as an anesthetic. Interest dropped, however, when its use was associated with petit mal and grand mal seizures.
In 1963, GHB was discovered as a naturally occurring substance in the human brain (Nature. 1963;200:1207-1208). Researchers have suggested that it acts as a neurotransmitter, but the mechanism of action producing the clinical effects is unknown. In the 1970s, GHB was used to treat sleep disorders, and some interest in this use continues. It is thought to induce rapid eye movement sleep, decreasing symptoms of narcolepsy, said Jo Ellen Dyer, PharmD, an assistant clinical professor of pharmacy at the University of California, San Francisco.
In 1977, Japanese investigators reported that GHB had steroid-enhancing effects and theorized that it stimulated growth hormone. Although this theory was never proved, the idea "sparked an interest in GHB among bodybuilders, who used it for about 10 years," said Kathleen Andrews, a forensic chemist with the DEA in San Francisco.
The drug is a white hygroscopic powder precipitated from gamma-butyrolactone by the addition of sodium hydroxide. It usually turns up today as a colorless, odorless liquid with a mild salty soapy taste that is easy to mask. In 1990, it appeared on the commercial market as a sedative sold in health food stores and was touted as a replacement for L-tryptophan, which the FDA had taken off the market the previous year.
By November 1990, 9 states had reported 57 instances of such GHB-related illnesses as seizures and comas, and the FDA removed GHB from the market. Despite the ban, GHB continues to be manufactured and sold clandestinely. "An increasing awareness of its psychoactive properties and its euphoric effect created a demand. When the actor River Phoenix collapsed and died outside the Viper Room in Los Angeles, Calif, in October 1993, it was held that he had died of an overdose of GHB. This was never confirmed, but the rumor further stimulated street interest in the agent," said Andrews.
Widespread Use and Ill Effects
Since then, there have been widespread reports of illness caused by GHB. "In at least three quarters of the 50 states, if not the entire United States, GHB is being used in some form or another," said Andrews. A recent report from poison control centers in New York and Texas stated that from August 1995 to September 1996 there were 69 acute poisonings and 1 death caused by GHB (MMWR Morb Mortal Wkly Rep. 1997;46:281-283). "GHB is also being used abroad. Australia and the UK have reported problems with its use," Andrews added.
Use of the drug has increased markedly in the past year. Dyer said that the San Francisco Bay Area Regional Poison Control Center reported 17 to 34 cases of illness associated with GHB annually during the years 1990 to 1995, but in 1996 it reported 89 cases. The life-threatening and acute health effects of GHB are potentiated by other drugs, such as alcohol and marijuana.
Under a variety of names--liquid ecstasy, Gib, Natural Sleep-500, Somatomax, and Georgia Home Boy (from its initials) among them--GHB has become increasingly popular at so-called raves. These young people's dance parties, which began in the 1980s in England, are notorious for being fueled by drugs both legal and illegal (JAMA. 1992;268:1505-1506).
Because of its frequently abrupt coma-inducing effects, ready accessibility, and ease of administration (it is easily poured into a drink), GHB has achieved popularity in some circles as an agent of assault, a "date rape" drug.
"When it was sold in health food stores, the package included a warning that it should not be taken with alcohol and cautions about the dosing interval. To increase exposure, the advice was to take doses more frequently rather than increasing the individual dose," noted Elizabeth Todd, PhD, chief of Drug and Environmental Toxicology, Dallas County Institute of Forensic Sciences, Dallas, Tex. "Since GHB has a very short half-life, from 20 minutes to 1 hour, this may have minimized some of the negative impact that we are now seeing," she said.
Overdose Symptoms and Treatment
Symptoms of GHB overdose include vomiting, bradycardia, coma, clonic muscle movements, induction and emergence delirium, and Cheyne-Stokes respiration. Diagnosis depends on history at the scene, and treatment is aimed at protecting the airway. The high incidence of vomiting carries with it a high risk of aspiration, said Dyer. Benzodiazepines and opiate antagonists are not effective. Lavage or charcoal are of limited benefit because of the small amounts involved (from one fourth of a teaspoon to 4 tablespoons) and the rapid absorption, usually 10 to 15 minutes depending on the size of the dose. The drug is undetectable in the urine after 12 hours. A level teaspoon contains 2.8 g, but since the drug is now made clandestinely it is often far from pure.
Dyer described the case of a 23-year-old female college student who had been taking 3 to 5 "capsfull" of liquid GHB daily for a year for its alleged anabolic effect. For 6 weeks before admission to the detoxification center, she had increased this dose to every 3 hours around the clock. On admission she had increasing symptoms of paranoia with visual and auditory hallucinations; her heart rate was 110, blood pressure 138/98, temperature normal, and urine toxicology negative. During a 9-day withdrawal period she had paranoia, agitation, and delirium. She made an otherwise uneventful recovery. Other withdrawal symptoms include tremor, confusion, increases in heart rate and blood pressure, and hallucination.
One to 6 teaspoons of GHB taken with alcohol will result--within 15 to 30 minutes--in a pronounced coma and substantial respiratory depression possibly necessitating intubation, said Texas toxicologist Todd. But within 1 to 2 hours, spontaneous recovery often occurs. "People have been in deep coma in the emergency room and in the process of intubation will just sit up, spontaneously 'come right back to life,' and wonder why they're there. There is amnesia about the experience," said Todd. She added, "This is a problem both in follow-up and to those who use the drug. It does not provide a deterrent, since they don't really remember their near-death experience."