This paper reflects the research and thoughts of a student at the time the paper was written for a course at Bryn Mawr College. Like other materials on Serendip, it is not intended to be "authoritative" but rather to help others further develop their own explorations. Web links were active as of the time the paper was posted but are not updated.
2001 Second Web Report
The potential advancements in our understanding of the functioning of the nervous system through this "hands-on" research strategy is confounded by the politics that surrounds recreational drug use in the US. Inevitably, the sub-culture of drug experimenters that pops-up as a result of stringent anti-drug enforcement, is not a random sample of the human population. While the DEA and FDA impose upon the research attempts of today's youth, shared information technology has created a space for future scientists to compare their methods and results. Looking up designer drugs on the Internet, I came to a greater understanding of the physiology of the brain as well as the preferences and behavioral patterns of today's youth. Easily manufactured, ubiquitously used, and derived from substances already occurring in the body, GHB is a model drug for addressing these issues.
GHB, or gamma-hydroxybutric acid, was first synthesized in 1960 (1). Laborit, a French researcher interested in the effects of GABA on the brain used GHB, a GABA metabolite that can more readily cross the blood brain barrier, in his investigation (2). Laborit serendipitously discovered that GHB was capable of producing rapid, deep sleep. This substance was initially embraced by the medical community for its anesthetic and non-toxic properties (1,2). Subsequent to Laborit's discovery, numerous other studies reported the beneficial physiological effects of GHB including its ability to treat sleep disorders such as narcolepsy and insomnia, as well as alcoholism and alcohol related withdrawal symptoms (1,2). GHB is also a potent facilitator of childbirth. GHB is prescribed to women in labor in many European countries because the drug helps to increase the strength of contractions and increase the dilation of the cervix (2).
People who use GHB recreationally report a state of tranquility, mild euphoria and pleasant drowsiness (2). As mentioned, multiple studies have supported the clinical value of GHB as an anesthetic and a treatment for anxiety or arousal-related symptoms, such as withdrawal and sleep disorders (2,4). There is little evidence supporting a dependency potential, or long-term negative physiological effects of GHB use. In fact, users report feeling refreshed after taking GHB. What is more, GHB appears to interact with certain brain chemicals to promote bone growth, cell division, and the mobilization of stored energy. Before being banned in the US, this drug became popular among the health conscious for its purported ability to stimulate growth hormone release and in doing so, aid in muscle building and fat reduction (1). Growth hormone works to supply energy for physical development by breaking-down stored fats and directing the nutrients toward growing tissue (9).
GHB has also been used in a clinical setting to protect from cell death in the brain. Because GHB acts through decreasing the metabolic demand of the central nervous system, researchers postulate that the drug may actually protect cells. When the body is in a state of increased metabolic demand, GHB may prevent damage due to decreased glucose availability. GHB has also been shown to protect cells from hypoxic damage, which results when there is a deficit of oxygen (2,6).
GHB was eventually rejected as an anesthetic drug because of its inability to produce analgesia, or pain inhibition (1,2,6). The selectivity of this sleep-mimicking agent provides a case for why GHB may, in fact, be a "clean" and safe treatment for non-pain related conditions. Moreover, the elimination half-life of GHB is only 27 minutes for a 10-12.5 mg/kg dose. The substance is completely eliminated via the expiration of carbon dioxide (3). The metabolism is so efficient that within four to five hours GHB can no longer be detected in the urine of rodents administered the drug through injection (2). It is perhaps easiest to appreciate the "clean" effects of GHB by looking at how it acts on the brain. GHB exists naturally in the brain, with highest concentrations of the chemical found in the basal ganglia (3). It is a metabolite and precursor of GABA, an inhibitory neurotransmitter (2,8), and is therefore considered a brain nutrient. Researchers believe that GHB may operate as a neurotransmitter (2,4) and may induce its physiological effects through binding at various sites of the brain, namely the hypothalamus and the limbic system (3). However, there is currently little empirical evidence to support this claim.
Laborit established that GHB facilitates inhibition pathways. Although the obvious explanation would be that GHB is increasing the availability and activity of GABA, research has established that GHB acts on dopaminergic, or dopamine producing pathways. GHB achieves its effects by interfering with the production and the release of dopamine in the mesolimbic and nigrostriatal pathways (8). Dopamine, and the structures of the mesolimbic pathway in particular, are implicated with the reward pathway in the brain (3). The eventual release of stored dopamine after GHB administration could help to explain the feelings of well-being and alertness experienced after taking GHB. It is conceivable that a body-high is sustained even after the drug has left the system through the activation of reward pathways by the release of the excess dopamine. The mechanism of hypotonia, or muscle relaxation, may be partially explained by the inhibitory effect of GHB on dopamine, as dopamine pathways are implicated in motor responses. Likewise, the reports of feeling alert after doing the drug may be attributed to an enhancement of motor control through increased levels of dopamine following the active period of GHB.
Before endorsing the use of this drug for healthful or clinical purposes, it should be noted that it remains unclear how GHB achieves its many, specific effects on the brain and on the physical state of our body. However, the lack of long-term negative effects of GHB makes it difficult to understand why the FDA prohibited the sale and manufacture of GHB in 1990 (1) and why the DEA issued a congressional testimony against the use of GHB in 1997 (2). The negative sentiment surrounding the distribution and use of this drug is connected to the use of GHB to manipulate the conscious state of another person. Although the neuropsychological effects of this drug do not appear especially harmful, GHB, and most drugs, affect humans in several ways. GHB use is accompanied by changes in perception, affect, and levels of behavioral inhibition. The use of GHB as a "date-rape-drug" indicates that harm and health are not only connected to the physical effects of drug use, but also the environmental circumstances that make the output/behavioral effects of drug use dangerous. In the case of GHB, the situational risk is mode of administration. Based on the innocuous physiological profile of GHB, it appears that the dangers of this drug are social in nature. This distinction is important because it clarifies how strategies to prevent the abuse of drugs and promote health (2) are connected to physiological as well as behavioral states.
Please refer to the following resources for further explanation of the chemical composition of this drug and commentary on the physiological and social risks associated with the use and availability of GHB.
2) The Vaults of Erowid Website , a report from the Cognitive Enhancement Research Institute
3) Biopsychiatry Website , an article entitled: Neuropharmacological mechanisms of drug reward: beyond dopamine in the nucleus accumbens
4) Biopsychiatry Website , an article entitled: Evaluation of the discriminative stimulus and reinforcing effects of gammahydroxybutrate
5) The US department of Health and Human Services Website , a report on the use of GHB in New York and Texas
6) The Quackwatch Homepage , a report entitled: Gamma-Hydroxybutyric Acid A Growing Danger
7) US department of Justice Website , DEA Congressional Testimony from March 11, 1997
8) The Vaults of Erowid Website , a report on GHB Neuropharmacolgy
9) Sapolsky, Robert (1998). Why Zebras Don't Get Ulcers. W.H. Freeman and Co.: New York, NY. (non-WEB reference)
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