Self-medication with [gamma]-hydroxybutyrate to reduce alcohol intake.ABSTRACT We describe a 52-year-old man who self-medicated with [gamma]-hydroxybutyrate (GHB GHB abbr. gamma-hydroxybutyrate GHB 1 Gamma-hydroxybutyrate, γ-hydroxy-butyrate See GABA 2 Glycosylated hemoglobin, see there GHb Glycosylated hemoglobin, see there ), a widely available illicit substance, to obtain a decrease in ethanol consumption. He successfully reduced his ethanol intake over a 3-month period, but he was unable to sustain abstinence. Although case reports on the use of GHB to induce euphoria have been published, this is the first report of GHB self-medication to facilitate ethanol abstinence. This report highlights the importance of considering GHB self-medication not only for euphoric and mood altering effects, but also as a potential treatment for ethanol intake reduction. ********** [gamma]-HYDROXYBUTYRATE (GHB) is a proposed neuromodulator that is consumed in a variety of situations among users trying to induce amnesia for the purpose of date rape date rape n. forcible sexual intercourse by a male acquaintance of a woman, during a voluntary social engagement in which the woman did not intend to submit to the sexual advances and resisted the acts by verbal refusals, denials or pleas to stop, and/or physical or euphoria, or trying to increase muscle mass. It is currently being investigated for the pharmacologic management of acute alcohol withdrawal and as an agent to facilitate ethanol abstinence. Physicians should be aware that individuals may use certain illicit drugs, such as GHB, to prevent or diminish symptoms of alcohol withdrawal. The following case is the first published report of self-medication with GHB to prevent symptoms of alcohol withdrawal. CASE REPORT A 52-year-old man with a degree in chemical engineering sought treatment of what he described as panic. He also complained of shaking in his arms. His wife stated he had been difficult to arouse that morning and had been sleepwalking sleepwalking /sleep·walk·ing/ (slep´wawk?ing) somnambulism. sleep·walk·ing n. The act of walking or performing another activity associated with wakefulness while asleep or in a sleeplike state. the night before. The patient reported a 20-year history of ethanol dependence with several previous attempts to discontinue use. His most recent attempt was an inpatient detoxification Detoxification Definition Detoxification is one of the more widely used treatments and concepts in alternative medicine. It is based on the principle that illnesses can be caused by the accumulation of toxic substances (toxins) in the body. program approximately 3 years earlier. He attended Alcoholics Anonymous Alcoholics Anonymous (AA), worldwide organization dedicated to the treatment of alcoholics; founded 1935 by two alcoholics, one a New York broker, the other an Ohio physician. for approximately 6 months after discharge. He stated that his desire to abstain was a final attempt to reconcile with his wife of 26 years. A friend who worked at a health food store helped him obtain GHB via a supplier on the Internet. He purchased GHB in powder form from a distributor in Mexico and prepared a GHB solution with fruit drinks. Three months before presentation, while drinking 250 to 375 mL of whiskey per day, he began taking 30 mL of a 25 mg/mL GHB solution daily. At the time of his visit, he was consuming approximately 30 to 60 mL of whiskey per day with a GHB dose of 30 mL three to four times per day (total daily dose of 2,250 mg or 27 mg/kg/day). He reported that GHB helped suppress his ethanol cravings but did not completely alleviate his desire to drink. Thus, he took diazepam diazepam /di·az·e·pam/ (di-az´e-pam) a benzodiazepine used as an antianxiety agent, sedative, antipanic agent, antitremor agent, skeletal muscle relaxant, anticonvulsant, and in the management of alcohol withdrawal symptoms. without a prescription (unknown dose) once or twice a month to eliminate his cravings. He reported that the one diazepam tablet taken 3 days before presentation had partly alleviated his cravings. He denied a history of other illicit substances, dietary supplements, or herbal medications. His only other medication was valsartan for hypertension. He denie d a history of psychiatric illness. The patient appeared slightly anxious but in no significant distress. Vital signs were blood pressure 165/83 mm Hg, pulse rate pulse rate n. The rate of the pulse as observed in an artery, expressed as beats per minute. 95/min, temperature 98.4[degrees]F, and respiratory rate respiratory rate, n the normal rate of breathing at rest, about 12 to 20 inspirations per minute. systemic inflammatory response syndrome A term that ' 22/min. He weighed 82 kg. Findings on physical examination were normal except for a moderate bilateral upper extremity upper extremity n. The shoulder, arm, forearm, wrist, or hand. Also called superior limb, thoracic limb. tremor both at rest and with movement. His reflexes were brisk, but neurologic examination neurologic examination A battery of clinical tests that evaluates a person's physiologic function and mental status, as well as the presence of any structural–organic lesions that may cause changes in neurologic function. Cf Psychiatric examination. was otherwise within normal limits. Results of mental status examination Mental Status Examination Definition A mental status examination (MSE) is an assessment of a patient's level of cognitive (knowledge-related) ability, appearance, emotional mood, and speech and thought patterns at the time of evaluation. were within normal limits, and he denied any hallucinations Hallucinations Definition Hallucinations are false or distorted sensory experiences that appear to be real perceptions. These sensory impressions are generated by the mind rather than by any external stimuli, and may be seen, heard, felt, and even or difficulties with memory. Complete blood count, urinalysis, and blood chemistry studies all yielded normal values except for a positive test for benzodiazepines Benzodiazepines Definition Benzodiazepines are medicines that help relieve nervousness, tension, and other symptoms by slowing the central nervous system. Purpose Benzodiazepines are a type of antianxiety drugs. in the urine. The blood ethanol level was less than 10 mg/dL. The patient was given normal saline, thiamine, folate folate /fo·late/ (fo´lat) 1. the anionic form of folic acid. 2. more generally, any of a group of substances containing a form of pteroic acid conjugated with l-glutamic acid and having a variety of substitutions. , and lorazepam lorazepam /lor·a·ze·pam/ (lor-az´e-pam) a benzodiazepine used as an antianxiety agent, sedative-hypnotic, preanesthetic medication, and anticonvulsant. lor·az·e·pam n. while in the emergency room. He began feeling better after approximately 6 hours of observation. He was given a prescription for lorazepam and was instructed to return to the emergency department if his symptoms became worse. He was referred to an outpatient chemical dependency program. Despite several attempts to contact him, he was lost to follow-up. DISCUSSION [gamma]-Hydroxybutyrate is considered to be a neuromodulator or neurotransmitter present in the human brain, especially the basal ganglia. [gamma]-Hydroxybutyrate is a metabolite metabolite, organic compound that is a starting material in, an intermediate in, or an end product of metabolism. Starting materials are substances, usually small and of simple structure, absorbed by the organism as food. of [gamma]-aminobutyric acid (GABA GABA ?. GABA abbr. gamma-aminobutyric acid GABA (gamma-aminobutyric acid) A neurotransmitter that slows down the activity of nerve cells in the brain. ) and is a central nervous system depressant depressant, any one of various substances that diminish functional activity, usually by depressing the nervous system. Barbiturates, sedatives, alcohol, and meprobamate are all depressants. Depressants have various modes of action and effects. . It is currently classified as a Schedule I agent in the United States. (1,2) [gamma]-Hydroxybutyrate has been promoted by bodybuilders for its anabolic anabolic pertaining to or arising from anabolism. anabolic steroid steroids with a tissue-building effect. Testosterone is an example of a natural anabolic steroid with the, sometimes undesirable, effect of causing masculinization. effects, and it has also achieved popularity as a recreational drug for its euphoric effects. Users have described the euphoria associated with GHB as being similar to ethanol intoxication without the hangover. Because GHB is not available legally under US law, it is usually produced in underground laboratories or purchased from sources outside the United States. Since GHB production in the United States is unregulated, the purity and concentration of GHB formulations obtained on the street is questionable. The lack of regulation concerning GHB may contribute to some of the cases of overdose ingestion ingestion /in·ges·tion/ (-chun) the taking of food, drugs, etc., into the body by mouth. in·ges·tion n. 1. The act of taking food and drink into the body by the mouth. 2. that have been reported in medical literature. (3) [gamma]-Hydroxybutyrate may be adulterated a·dul·ter·ate tr.v. a·dul·ter·at·ed, a·dul·ter·at·ing, a·dul·ter·ates To make impure by adding extraneous, improper, or inferior ingredients. adj. 1. Spurious; adulterated. 2. Adulterous. or "spiked" with other substances. Currently, the only approved use of GHB in the United States is as an investigational drug for the treatment of narcolepsy narcolepsy, a sleep disorder characterized by excessive daytime sleepiness and recurring unwanted episodes of sleep ("sleep attacks"). People with narcolepsy may abruptly fall asleep at almost any time, including while talking, eating, or even walking. . [gamma]-Hydroxybutyrate has also been suggested as an anesthetic and for the treatment of opiate opiate /opi·ate/ (o´pe-it) 1. any drug derived from opium. 2. hypnotic (2). o·pi·ate n. 1. withdrawal and fibromyalgia fibromyalgia Chronic syndrome that is characterized by musculoskeletal pain, often at multiple sites. The cause is unknown. A significant number of persons with fibromyalgia also have mental disorders, especially depression. . (4) Finally, GHB has been implicated im·pli·cate tr.v. im·pli·cat·ed, im·pli·cat·ing, im·pli·cates 1. To involve or connect intimately or incriminatingly: evidence that implicates others in the plot. 2. as a "date rape" drug because of its rapid hypnotic and amnesic effects at high doses. [gamma]-Hydroxybutyrate products are frequently colorless and odorless; thus, it is easily masked with other beverages. (5,6) [gamma]-Hydroxybutyrate is sold under various names, such as "Nature's Quaalude," "Liquid X," "Easy Lay," and "G-riffick." (4,7) [gamma]-Hydroxybutyrate readily crosses the blood brain barrier. Many of GHB's pharmacologic actions are postulated to be via a GHB receptor in the central nervous system. (8-11) Some hypothesize hy·poth·e·size v. hy·poth·e·sized, hy·poth·e·siz·ing, hy·poth·e·siz·es v.tr. To assert as a hypothesis. v.intr. To form a hypothesis. that the principle method by which GHB reduces alcohol cravings and prevents withdrawal symptoms is a GABAergic mechanism. However, GHB has also been noted to alter concentrations of serotonin, dopamine dopamine (dōp`əmēn), one of the intermediate substances in the biosynthesis of epinephrine and norepinephrine. See catecholamine. dopamine One of the catecholamines, widely distributed in the central nervous system. , acetylcholine acetylcholine (əsēt'əlkō`lēn), a small organic molecule liberated at nerve endings as a neurotransmitter. It is particularly important in the stimulation of muscle tissue. , and endogenous opioids within the central nervous system. (2) In animal studies, GHB has demonstrated both anxiolytic anxiolytic /anx·io·lyt·ic/ (ang?ze-o-lit´ik) 1. antianxiety. 2. an antianxiety agent. anx·i·o·lyt·ic n. A drug that relieves anxiety. and increased dopaminergic dopaminergic /do·pa·min·er·gic/ (do?pah-men-er´jik) activated or transmitted by dopamine; pertaining to tissues or organs affected by dopamine. do·pa·mi·ner·gic adj. activity similar to the "reward" pathway of ethanol. Furthermore, GHB has demonstrated cross-tolerance with ethanol in rodents. (12,13) The half-life of GHB is approximately 30 minutes; thus, it should be dosed on a frequent schedule until a sustained release preparation is available. (2) Although GHB has a wide range of adverse effects, the most frequent have been mild and transient, including dizziness, confusion, nausea, vertigo, and weakness. Most of the serious adverse effects reported were due to (1) nonalcoholic non·al·co·hol·ic adj. A beverage usually containing less than 0.5 percent alcohol by volume. users taking a large dose to achieve a euphoric "high" and/or (2) combining GHB with other drugs, such as amphetamines Amphetamines Sympathomimetic amines; sometimes called speed; synthetic chemicals that stimulate the central nervous system. Mentioned in: Weight Loss Drugs amphetamines , ethanol, or ecstasy. The doses used to obtain euphoria can cause severe aggression, agitation, bradycardia bradycardia: see arrhythmia. , anesthesia, respiratory depression, and coma. (2,7,14,15) Interestingly, alcoholics who use GHB are probably less likely to have dose-related adverse effects than nonalcoholics exposed to the same dose. This phenomenon may partly account for the relatively few instances of toxicity that have occurred during clinical trials of GHB for alcohol withdrawal. Moreover, the same principle would also explain the reports of severe adverse effects that occur in young, nonalcoholic individuals who consume GHB infrequently. Finally, GHB dependence and withdrawal syndrome has been reported in both alcoholics and nonalcoholics after chronic consumption. (2,7,16,17) Additionally, Galloway et al (18) discussed GHB withdrawal syndrome in three chronic users. Much of the research on the use of GHB in acute ethanol withdrawal as well as in long-term abstinence programs has been conducted in Europe (Table). The doses of GHB in these clinical trials were 50 to 150 mg/kg/day, divided. (19-25) In one study by Addolorato et al, (21) GHB and diazepam were noted to be equally efficacious in the treatment of acute alcohol withdrawal. In additional research, Addolorato et al (23) discovered that alcoholics who were unable to maintain abstinence with GHB taken three times per day benefitted from consuming the same dose given six times per day. However, many of the investigations on GHB were open design, lacked placebo control, or involved a small number of patients. The exact dose of GHB required to maintain abstinence and/or to prevent alcohol withdrawal symptoms is yet to be firmly established. The patient we have described had previously consumed a dose significantly smaller than studied in clinical trials to date (27 mg/kg/day vs 50 to 150 mg/kg/day). His failure to achi eve abstinence may be partly due to the low dose consumed. The purity of the purchased product is unknown; thus, the concentration of the prepared solution may have varied. In summary, patients may choose to self-medicate with GHB to abstain from alcohol. Clinicians are encouraged to ask about GHB in screening medication histories in the same way they ask about dietary supplements or other illicit substances. Additionally, GHB should be included in the differential diagnosis when patients present with changes in mood, cognition, or behavior. Although GHB does exhibit promise as pharmacotherapy pharmacotherapy /phar·ma·co·ther·a·py/ (-ther´ah-pe) treatment of disease with medicines. phar·ma·co·ther·a·py n. Treatment of disease through the use of drugs. for alcohol withdrawal, it presently has no Food and Drug Administration indication and is more likely to be used or abused in a recreational setting. Further research will help define the exact role of GHB in both the acute and chronic management of ethanol detoxification.
TABLE
Clinical Trials of [gamma]-Hydroxybutyrate (GHB) in Acute Alcohol
Withdrawal and Abstinence
Trial Enrolled Design *
Gallimberti et al (19) 23 DB, PC, R
GHB vs placebo in acute
withdrawal
Moncini et al (30) 22 OP
GHB for acute withdrawal
Moncini et al (30) 282 OP
GHB for prevention of acute
withdrawal
Moncini et al (20) 17 DB, PC, R
GHB vs placebo for prevention
of relapse
Addolorato et al (21) 60 SB, R
GHB vs diazepam in acute
withdrawal
Addolorato et al (22) 119 OP
GHB use in abstinence
Addolorato et al (23) 154 OP
GHB use in abstinence
Addolorato et al (24) 179 OP
GHB use in abstinence
Gallimberti et al (25) 82 DB, PC, R
GHB vs placebo for
abstinence
Trial Conclusion
Gallimberti et al (19) GHB superior to placebo in
GHB vs placebo in acute decreasing withdrawal symptoms
withdrawal
Moncini et al (30) GHB effective in acute management
GHB for acute withdrawal of acute withdrawal syndrome
Moncini et al (30) GHB prevented the onset of acute
GHB for prevention of acute withdrawal syndrome in 57% of
withdrawal patients
Moncini et al (20) GHB more effective than placebo in
GHB vs placebo for prevention maintaining abstinence at 6 months
of relapse
Addolorato et al (21) GHB and diazapam equally effective
GHB vs diazepam in acute in management of acute withdrawal
withdrawal
Addolorato et al (22) GHB effective in maintaining
GHB use in abstinence abstinence
Addolorato et al (23) GHB effective in maintaining
GHB use in abstinence abstinence
Addolorato et al (24) GHB effective in maintaining
GHB use in abstinence abstinence
Gallimberti et al (25) GHB more effective than placebo
GHB vs placebo for for decreasing alcohol cravings
abstinence
* DB = Double blind
PC = placebo controlled
R = randomized
OP = open
SB = single blind.
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