Chemical structure of GHBGamma-hydroxybutyrate powder
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Gamma-hydroxybutyrate

Gamma-hydroxybutyrate (4-hydroxybutanoic acid, C4H8O3) is both a drug and a naturally occurring compound found in the central nervous system as well as in other organs such as the liver, kidneys, heart and bones. GHB is structurally similar to the ketone body beta-hydroxybutyrate. As a drug it is used most commonly in the form of a chemical salt (Na-GHB or K-GHB). The sodium salt is commercially known as sodium oxybate. more...

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Uses

Endogenous

The precise function of GHB in the body is not clear. It is an immediate precursor to GABA, a neurotransmitter which regulates awakeness, physical activity and sleep. As GABA cannot cross the blood-brain barrier, GHB obtained from food may be used for converting to GABA. GHB prevents cells from oxygen starvation, which might explain presence of the compound in vital organs. GHB was also found to have neuroprotective capabilities.

Medical

It has been used as a general anesthetic, and a hypnotic in the treatment of insomnia. GHB has also been used to treat clinical depression, and improve athletic performance. In the United States, the Food and Drug Administration permits the use of GHB under the trade name Xyrem to reduce the number of cataplexy attacks in patients with narcolepsy. In Italy, under the trade name Alcover, GHB is used in the treatment of alcoholism (50 to 100 milligrams per kilogram per day, in 3 or more divided doses), both for acute alcohol withdrawal and medium to long term detoxification.

Recreational

GHB is an intoxicant. It may be known as G, Liquid X, Liquid E. It is less commonly known as GHB, Gamma-oh, Georgia Homeboy, Georgia Hillbilly, Blue Verve, Gamma-G, Qi, scoop, or goop.

Its potential for use as a date rape drug in the 1990s led to it being placed in the US on Schedule I of the Controlled Substances Act in March, 2000. On March 20, 2001, the Commission on Narcotic Drugs placed GHB in Schedule IV of the 1971 Convention on Psychotropic Substances. In the UK it was made a class C drug in June 2003.

The sodium salt of GHB has a thin, very salty, chemical taste. At low doses, GHB can cause a state of euphoria, increased sociality and intoxication. This kind of use is particularly common at rave parties. At higher doses, GHB may induce nausea, dizziness, drowsiness, visual disturbances, depressed breathing, amnesia and unconsciousness. The effects of GHB can last from 1.5 to 3 hours.

Some chemicals convert to GHB in the stomach and blood. GBL, or gamma-butyrolactone, is one such precursor. It is 1,6 times less potent than GHB, so 1ml of GBL is equivalent to 0,4g of GHB. GBL has also a shorter onset and is longer acting than GHB. GBL has an extremely bad taste and is also known to irritate innards and skin.

Other precursors include 1,4-butanediol. There may be additional toxicity concerns with these precursors.

Mode of action

The action of GHB has yet to be fully elucidated. GHB clearly has at least two sites of action, stimulating the newly characterized and aptly named "GHB receptor" as well as the GABAB. GHB, if it is indeed a neurotransmitter, will only reach concentrations high enough to act at the GHB receptor, as it only has weak affinity fo the GABAB. However, during recreational usage, GHB can reach very high concentrations in the brain, relative to basal levels, and can act at the GABAB receptor . GHBs action at the GABAB is probably responsible for its sedative effects. GHB-mediated GABAB receptor stimulation inhibits dopamine release as well as causes the release of natural sedative neurosteroids (like all other GABAB agonists e.g. Baclofen). In animals GHBs sedative effects can be stopped by GABAB antagonists (blockers).

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Use of GHB compounds among college students
From American Journal of Drug and Alcohol Abuse, 11/1/05 by Alvaro Camacho

INTRODUCTION

Gamma hydroxybutyric acid (GHB) is a naturally occurring small chain fatty acid (1) that has been described as a possible neurotransmitter (2-4). Since about 1990, GHB has been abused on the street; names include "Liquid Ecstasy," "Soap," "Easy Lay," and "Georgia Home Boy." GHB and its precursors, gamma butyrolactone and 1,4 butanediol, have been involved in poisonings, overdoses, date rapes, and deaths (5, 6). GHB emergency room visits increased from 55 in 1994 to 2.973 in 1999 (7, 8). In 1999, GHB accounted for 32% of illicit drug-related poison center calls in Boston (7, 9). These products, obtainable over the Internet and sometimes still sold in health food stores, are also available at some gyms, raves, nightclubs, college campuses, and are particularly popular among gay men. The products are commonly mixed with alcohol, have a short duration of action, and are not easily detectable on routine hospital toxicology screens (7).

GHB is a popular recreational drug used by young adults (10-12). It appears to have a high abuse potential because it produces euphoria, hallucinogenic effects, relaxation, tolerance, and severe withdrawal symptoms (14, 15). In the United States, GHB compounds have been marketed illicitly to body builders as a growth hormone stimulant to build muscular mass. They have also been promoted as a replacement for L-tryptophan to improve sleep (16, 17). Two GHB precursors, gamma-butyrolactone and 1,4 butenadiol also have been marketed to improve athletic performance, enhance sexual activity, and release growth hormone (18). Dietary supplements containing these precursors are widely available through the Internet under different names such as Serenity, Growth Hormone Release Extract (GHRE), Thunder Nectar, and Revitalize Plus among others (19, 20). This article describes the pattern of use and knowledge about GHB compounds among college students, who are frequently the "cutting edge" of new patterns of drug abuse.

METHODS

A survey was distributed in the student health clinic of a large university from July 2002 until January 2003. Anonymous surveys were placed for distribution at patient registration areas. Students were asked to complete only one questionnaire, even if they made multiple visits to the student health clinic during the period of study. Students who answered the survey placed them in a secured box. The investigators collected the surveys from the boxes on a weekly basis. During that period, a total of 18,744 students attended the clinic; 37% were male and 63% were female. Their age distribution was as follows: 13,339 patients between ages of ages 18-25, 4,812 patients between ages of 26-35, and 988 patients older than 35.

The participants were asked about the use of the following compounds: Serenity, Revitalize-Plus. Growth Hormone Release Extract (GHRE), Somato-Pro, Enliven, NRG-3, Thunder Nectar, White Belt Cleaner, GBL, Butenadiol, and GHB. They were also asked about their amount of use over the last 6 months, as well as their knowledge of GHB compounds' addictive potential, GHB legal status, and effects experienced when using any of these compounds. The study was approved by the University of California, San Diego Human Subjects Protection Program.

RESULTS

A total of 215 students answered the survey. The mean age of the participants was 22.8 (S.D. 3.5) years and their average level of education was 16.5 (S.D. 2.5) years. Among the respondents, 90 were male (41.9%) and 125 (58.1%) were female. There was no difference between men and women in terms of age or years of education. The participants described their sexual orientation as follows: 163 (75.8%) heterosexual, 32 (14.9%) homosexual, l0 (4.7%) bisexual; 10 students (4.7%) did not indicate their sexual orientation. Respondents were asked if they recognized the previously mentioned GHB-related compounds. The most commonly recognized compound was GHB (53%), followed by GHRE (46%). The most commonly used compounds were GHRE (28.8%) and GHB (19%). GHRE users reported consumption 23 times per month, while GHB users reported use 1-2 times per month.

The respondents reported frequent effects from using GHB-compounds, including euphoria (n = 41), increased energy (n = 51), weight loss (n = 59), and dizziness (n = 13). Other reported effects were irritability (n = 3), a decreased need for sleep (n = 3), and social problems associated with the use of GHB (n = 1).

Regarding the use of GHRE, there was a significant difference between males and females (chi square] = 49.0 df = 1 p<0.001). A total of 59 women reported using GHRE, compared to only 3 men. Fifty-seven of the GHRE users reported their sexual orientation as heterosexual, 3 as bisexual, and 2 as homosexual. Ninety-six percent of GHRE users (57/62) reported weight loss as an effect--and among the 59 women, 55 reported weight loss as a reason for using GHRE. Increased energy was reported by 23 out of the 59 women who used GHRE and the 3 men. Figure 1A summarizes the results.

[FIGURE 1 OMITTED]

Consistent with previous reports (21), GHB tended to be used preferentially by gay and bisexual individuals ([chi square] = 7.2 df= 1 p = 0.07). Eighty-eight percent of GHB users (36/41) reported euphoria as a common effect from the compound. Only 2 GHB users reported weight loss. Twenty-three men and 2 women reported increased energy associated with the use of GHB. Increased energy was reported more often by gay/bisexual participants than heterosexuals ([chi square] = 79.9 df = 3 p < 0.01). Figure 1B summarizes these results.

Participants answered questions about their general knowledge of GHB-compounds. Among the 215 participants, 43 thought GHB was addictive, 18 thought that Serenity was addictive, and 11 thought that Thunder-Nectar was addictive. Only 40 of the 215 participants knew that GHB was illegal and only 6 knew that GHB has addictive potential (Table 1).

DISCUSSION

College students frequently experiment with addictive substances (22). Our results showed that college students are using GHB compounds for a variety of reasons. Interestingly, the reported effects varied according to gender and sexual orientation. Female participants reported ease in losing weight and increased energy when using GHRE. On the other hand, homosexual participants reported increased euphoria but not weight loss when using GHB.

GHB is a known substance of abuse and continues to pose serious risks for users (23). Our data show that college students have limited knowledge about the wide variety of GHB compounds and their illegal and addictive nature. Future studies are needed to specifically address the possible misuse of GHB among a representative sample of college students.

Our preliminary study has several limitations. The sample of participants is small considering the number of people who attended the clinic during the period of the study, although the gender and age demographics of the sample reflect that of the clinic. Distribution of the survey was limited to the student health clinic, and as the clinic saw approximately 35% of the student body during the time of the survey, this sample would not appear too nonrepresentative of the population as a whole. The same patient may have responded to more than one survey, although participants were requested to complete the form only once. There may have been selection bias by respondents who completed the survey. Based on our results, it is important to conduct larger epidemiological studies to clarify the patterns of use of GHB and its compounds on college campuses.

Clinicians and health workers should educate patients about this new compound as it appears that the general knowledge about GHB is quite limited. It will be important to foster open communication and continued education on college campuses to prevent serious consequences associated with the misuse of GHB. Given the different reasons that different groups use these drugs, targeted education programs may be more appropriate than blanket ones.

REFERENCES

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(4.) Maitre M, Rumigny JF, Cash CD, Mandel P. Subcellular distribution of gamma hydroxybutyrate binding sites in rat brain: principal localization in the synaptosomal fraction. Biochem Biophys Res Commun 1983; 110:262-265.

(5.) National Institute on Drug Abuse. Conference highlights increasing GHB abuse. NIDA Notes 2001:16.

(6.) National Institute on Drug Abuse. Club Drugs. NIDA InfoFacts. 2000. Available at: http:///www.drugabuse.gov/Infofax/Clubdrugs.html. Last accessed March 2004.

(7.) Substance Abuse and Mental Health Service Administration. The DAWN Report. 2000. Available at: www.samhsa.gov. Last accessed March 2004.

(8.) Drug Abuse Warning Network. The DAWN Report. Club Drugs 2001 Update. Available at: http://www.samhsa.gov/oas/dawn.htm. Last accessed March 2004.

(9.) National Institute on Drug Abuse. Some facts about club drugs. NIDA Notes 2001. Available at: http://www.nida.nih.gov/ClubAlert/ ClubDrugAlert.html. Last accessed March 2004.

(10.) Galloway GP, Frederick SL, Staggers FE, Gonzales M, Stalcup A, Smith DE. Gamma-hydroxybutarate: an emerging drug of abuse that causes physical dependence. Addiction 1997: 92:89-96.

(11.) Freese TE, Miotto KA, Reback CJ. The effects and consequences of selected club drugs. J Subst Abuse Treat 2002: 23:151-156.

(12.) McDaniel CH, Miotto KA. Gamma hydroxybutyrate (GHB) and gamma butyrolactone (GBL) withdrawal: five case studies. J Psychoact Drugs 2001; 33:143-149.

(13.) Nimmerrichter AA, Walter H, Gutierrez-Lobos KE, Lesch OM. Double-blind controlled trial of gamma-hydroxybutyrate and clomethiazole in the treatment of alcohol withdrawal. Alcohol Alcohol 2002; 37:67-73.

(14.) Centers for Disease Control. Multistate outbreak of poisonings associated with the illicit use of gamma hydroxybutyrate. JAMA 1991; 265:447-448.

(15.) Degenhardt L, Darke S, Dillon P. The prevalence and correlates of gamma-hydroxybutyrate (GHB) overdose among Australian users. Addiction 2003: 98:199-204.

(16.) Morbidity and Mortality Report. Multistate outbreak of poisonings associated with illicit use of gamma hydroxybutyrate. MMWR 1990; 39:861-862.

(17.) Mamelak M, Scharf MB, Woods M. Treatment of narcolepsy with gamma hydroxybutyrate: a review of clinical and sleep laboratory findings. Sleep 1986; 9:285-289.

(18.) Centers for Disease Control. Adverse events associated with ingestion of gamma-butyrolactone. Minnesota, New Mexico, Texas, 1998-1999. MMWR 1999: 48:137-140.

(19.) Ingels M, Rangan C, Bellezo J, Clark RF. Coma and respiratory depression following the ingestion of GHB and its precursors: three cases. J Emerg Med 2000: 19:47-50.

(20.) Schneir AB, Ly BT, Clark RF. A case of withdrawal from the GHB precursors gamma butyrolactone and 1,4 butenadiol. J Emerg Med 2001; 21:31-33.

(21.) Camacho A, Matthews SC, Dimsdale JE. Use of GHB compounds by HIV positive individuals. Am J Addict 2004; 13:120-127.

(22.) Pedersen W, Skrondal A. Ecstasy and new patterns of drug use: a normal population study. Addiction 1999; 94:1695-1706.

(23.) Community Epidemiology Work Group. Epidemiologic trends in drug abuse. In Proceedings of the Community Epidemiology Work Group. Bethesda, MD: NIH Publication, National Institute on Drug Abuse, 2002.

Alvaro Camacho, M.D., (1) Scott C. Matthews, M.D., (1) Brian Murray, M.D., (2) and Joel E. Dimsdale, M.D. (1)

(1) Department of Psychiatry, University of California, San Diego, California, USA

(2) Student Health and Wellness Center, University of California, San Diego, California, USA

The authors thank Ronalee Mizoguchi, R.Ph. for her assistance in preparing this manuscript.

Address correspondence to Joel E. Dimsdale, M.D., Department of Psychiatry, UCSD, 9500 Gilman Dr., La Jolla, CA 92093-0804, USA; Fax: (619) 543-5462; E-mail: jdimsdale@ucsd.edu

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