Gamma-Hydroxybutyrate (GHB) With-Drawal

T h e California Journal of Emergency Medicine 11:1 April 2001 Parr 2 ~ f t l l eGHB rei,ie~t. article sel-ries p a g e 16 phoric and purported anabolic effects, a clinical GHB withdrawal syndrome has emerged among habitual users. The habit-forming nature of GHB and a description of clinical features associated with abruptly stopping or decreasing use was first noted in 1994.' A withdrawal syndrome is characterized by various expectant psychological andlor physical signs and symptoms caused by the abrupt cessation of a drug that is used habitually. Given the ~nultiple independent descriptions of similar signs and symptoms associated with the cessation of chronic GUB use. GUB is now considered to possess a true withdrawal syndrome. Based on these case series and reports, the signs and symptoms of GHB withdrawal include varying degrees of anxiety. agitation. and in- somnia. Ophthalrnoplegia with sixth cranial nerve palsies has been reported in association with GHB withdrawal, although this niay represent concomitant thiamine deficiency. Autonomic hy- peractivity manifesting as diaphoresis, tremors. tachycardia or elevated blood pressure is commonly reported. Behavioral and psychiatric features include paranoia, hallucinations (auditory and/ or visual) and delirium. Syn~ptoms may manifest as soon as 12 hours after last use and may last LIPto 12 days. It is believed that more severe symptoms occur in individuals with longer habits and in those taking larger amounts of CHB. Many patients will also have a history of prior GHB cessation failure^.^ The largest report of cases implicating a physical de- pendence to GHB came from Italian researchers using GHB for treatment of alcohol dependence.' Eleven patients (10% of sub- jects completing a 24 week protocol of t.i.d. dosing of 50rngIkg CHB) developed cravings for the drug and voluntarily increased their doses to achieve ailxiolytic and hypnotic effects. The au- thors noted that anxiety and insomnia were reported after decreas- ing the GHB doses. which likely represented mild GHB with- drawal. Sii?zilarih to O f h e r Withcirawal Syflch-ortles GHB withdrawal appears to be very similar to ethanol, benzodiazepine (BZD) and barbiturate withdrawal. This similar- ity is likely related to GHB's chemical structural similarity with GABA. the principle inhibitory CNS neurotransmitter. GHE exhibits a marked affinity for the GABA, receptor. compared to the GABA, receptor, as well as an affinity for a recently discov- ered CHB-specific receptor. An extensive review of the neurop- harmacology of GHB by TunnicliH reveals that low doses of CHB tend to inhibit CNS dopamine release, whereas in higher and sustained doses. analogous to a habitual user, CNS dopamine lev- els increase. A decrease or total cessation of the dependent drug is all that is needed to precipitate the clinical withdrawal, a feature common to many sedative-hypnotic agents. Table 1 shows the time course of symptoms for the withdrawal syndromes from GHB and some other substances of abuse. Autoi~omic hyperactivity is common in CNS depressant withdrawals, with symptoms ranging from mild tachycardia and tremor to extreme diaphoresis and elevated blood pressure. Sei- zures have not been reported to occur in GHB withdrawal, how- ever, the number of case reports is relatively small. Aside froin seizures, no other clinical feature reliably distinguishes GHB with- drawal froin the other sedative-hypnotic withdrawal syndromes. Thus, obtaining a truthful history from the patient, a close friend or relatives is crucial. For patients who openly adinit to habitual CHB use, GAMMA-HYBWQXYBUPVRATE (GHB) WITH- DRAWL Worth Everett, MD Department o f Emergency Medicine University o f Pennsylvania M e d i c a l Center Philadelphia, PA Case A 35-year-old man with no significant medical history presented to a university ED complaining of anxiety. tremors and insomnia. The patient denied use of common street drugs or tobacco. He admitted to social weekend alcohol consumption, but had not been drinking during the preceding 2 weeks. His vital signs were: temperature 37.2OC, pi~lse 105/min. respirations 161 min. blood pressure 148188 mmHg. Physical examination re- vealed a muscular young man with a resting tremor and obvious anxiety. but was otherwise unremarkable. The patient's girlfriend took the physician aside and revealed the actual reason for seeking E D treatment was that he was trying to quit using GHB. She also confirmed he had nor been drinking alcohol and was not a habitual alcohol user. The patient subsequently admitted to using increas- ing amounts of GHB for the previous 2.5 years, and was consum- ing 1 to 2 capfuls of liquid GHB 4 to 6 times daily (exact dose unknown). His last dose was 20 hours prior to presentation. The patient first started using GHB at the urging of weight-lifting friends. He had attempted to quit multiple times without suc- cess. A presumptive diagnosis of GHB withdrawal was made. The patient was treated with 20 mg of oral diazepam in the ED, which relieved the tremors. After a 3-hour observation period. he was discharged with a 3-day prescription for lorazepam. referred to a local primary care clinic and given substance abuse counseling information. Although laboratory confirmation of GHB use was not obtained. this case illustrates the features of GHB withdrawel that will be discussed in this article: the clinical manifestations of the GHB withdrawal syndrome, the similarities to withdrawal from other sedative-hypnotic agents. and the treatment options. Recognizing and treating GHB withdrawal will be of increasing importance to emergency physicians as its popularity continues to grow. Clirlical Marl(festc~tions GHB is a naturally occurring substance. found in high- est concentrations in the basal ganglia and hypothalamus of brain tissue.' Although commercial sale of GHB is illegal in the United States. it is still easy to obtain, as evidenced by its abundance at rave parties. GHB recipes and various precursor formulations containing gamma-butyrolactone, 1.4-butanediol, dihydro-2(3H)- furanone and 4-butanolide are also available via the internet.? The precursors are converted in vivo to GHB after ingestion. GHB is popular among rave crowds and body-builders. and has been im- plicated as a date-rape drug. Investigational narcolepsy treat- ment is the only FDA approved use for GHB in the United States. As GHB use has increased because of its sedative. eu-