Gamma hydroxybutyrate (GHB)

Gamma hydroxybutyrate (GHB) is a powerful, rapidly acting central nervous system depressant. It was first synthesized in the 1920s and was under development as an anesthetic agent in the 1960s. GHB is produced naturally by the body in small amounts but its physiological function is unclear.

GHB was sold in health food stores as a performance enhancing additive in bodybuilding formulas until the Food and Drug Administration (FDA) banned it in 1990. It is currently marketed in some European countries as an adjunct to anesthesia. GHB is abused for its ability to produce euphoric and hallucinogenic states and for its alleged function as a growth hormone that releases agents to stimulate muscle growth. GHB became a Schedule I Controlled Substance in March 2000.

In the United States, GHB is produced in clandestine laboratories with no guarantee of quality or purity, making its effects less predictable and more difficult to diagnose. GHB can be manufactured with inexpensive ingredients and using recipes on the Internet. Gamma butyrolactone (GBL) and 1,4-butanediol are analogs of GHB that can be substituted for it. Once ingested, these analogs convert to GHB and produce identical effects. GBL, an industrial solvent, is used as an immediate precursor in the clandestine production of GHB. The FDA has issued warnings for both GBL and 1,4-butanediol, stating that the drugs have a potential for abuse and are a public health danger.

What are the dangers of GHB use?

GHB can cause many problems, including the following:

Drowsiness
Dizziness
Nausea
Vomiting
Changes in blood pressure
Trouble breathing
Aggressive behavior
Impaired judgment
Hallucinations
Seizures
Coma
Death

These effects usually appear 10 to 20 minutes after a person takes the drug.

Gamma hydroxybutyrate - Physicochemical

The sodium salt of GHB has a molecular formula of C4H7NaO3 and a molecular weight of 126.09. The Chemical Abstract Society (CAS) Number for the sodium salt of GHB is 502-85-2.

GHB appears to have no legitimate use as an industrial chemical. Interestingly, 1,4-butanediol (1,4-BD) and gamma-butyrolactone (GBL), 2 GHB precursor molecules, are used extensively in chemical manufacturing. In the year 2001, it is estimated that the United States' industrial consumption of 1,4-BD will be an astonishing 387,000 metric tons. Major uses of 1,4-BD are the synthesis of tetrahydrofuran, polybutylene terephthalate resins, GBL, and polyurethanes.

Gamma-hydroxybutyrate Range of Toxicity

Early work on GHB as an anesthetic demonstrated altered levels of consciousness associated with the following serum concentrations:

greater than 260 mg/L, patients were unresponsive to painful stimuli (comatose)
156-260 mg/L, patients were asleep but responsive
52-156 mg/L, patients exhibited spontaneous movement with occasional eye opening
less than 52 mg/L, patients awakened (Helrich et al. 1964)

In agreement with these findings, 6 narcolepsy patients receiving therapeutic doses of GHB (3 g at bedtime repeated 4 hours later; total dose 26.4 - 52.4 mg/kg) achieved mean peak serum concentrations of 62.8 and 91.2 mg/L (Scharf et al. 1998B). In animals, the lethal doses ranged from 5-15 times the coma-inducing dose. Ethanol has been shown to have a significant synergistic effect on the sedative action of GHB in rats.

Scheduling and Legislation for Gamma-hydroxybutyrate

In response to the use of drugs in sexual assaults, Congress passed the Drug-Induced Rape Prevention and Punishment Act of 1996 to combat drug-facilitated crimes of violence, including sexual assaults. The act imposes harsh penalties for distribution of a controlled substance to an individual without the individual's knowledge and consent with intent to commit a crime of violence, including rape.

On February 18, 2000, the Hillory J. Farias and Samantha Reid Date-Rape Prevention Act of 2000 (Public Law 106-72) became law. It made GBL a List I chemical subject to the criminal, civil, and administrative sanctions of the Federal Controlled Substances Act of 1970. As a result of the law, GHB became a Schedule I Controlled Substance. A Schedule I drug has a high potential for abuse, is not currently accepted for medical use in treatment in the United States, and lacks accepted safety for use under medical supervision.

On March 20, 2001, the Commission on Narcotic Drugs placed GHB in Schedule IV of the 1971 Convention of Psychotropic Substances. This placement affects international drug control laws with which countries that are a part of the convention must comply. Schedule IV mandates international requirements on licensing for manufacture, trade, and distribution of the drug. It also requires parties to comply with prohibition of and restrictions on export and import of the drug and to adopt measures for the repression of acts contrary to these laws and regulations.

On July 17, 2002, Xyrem, a drug with an active ingredient of sodium oxybate or GHB, was approved by the FDA to treat cataplexy attacks in patients with narcolepsy. Cataplexy is a condition characterized by weak or paralyzed muscles. Xyrem, when used as medically prescribed, is a Schedule III Controlled Substance. A Schedule III Controlled Substance has less potential for abuse than Schedule I and II categories, is currently accepted for medical use in treatment in the United States, and may lead to moderate or low physical dependence. Illicit use of Xyrem is subject to Schedule I penalties.