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`GHB: An Important Pharmacologic and Clinical Update
`
`Michael S. Okun
`Emory University, Department of Neurology, Atlanta, Georgia, USA and University of Florida, Department of Neurology,
`The Brain Institute, Gainesville, Florida, USA
`
`Lisa A. Boothby
`Columbus Regional Healthcare System: The Medical Center, Columbus, Georgia, USA
`
`Richard B. Bartfield, Paul L. Doering
`University of Florida, Department of Pharmacy, Drug Information Center, Gainesville, Florida, USA
`
`Received January 2nd, 2001, Revised July 12th, 2001, Accepted July 13th, 2001
`
`Abstract Gamma-hydroxybutyrate
`intoxica-
`(GHB)
`tion is a significant cause of morbidity and mortality in
`patients taking the drug for recreational purposes. Due
`to the recent increase in emergency room visits, hospi-
`tal admissions, and deaths, it has become necessary to
`re-examine the pharmacology, pharmacokinetics, phar-
`macodynamics, clinical manifestations, and potential
`adverse effects associated with GHB use. We present an
`important pharmacologic and clinical update on GHB.
`
`INTRODUCTION
`There has been a recent resurgence in the recreational
`use of gamma-hydroxybutyrate (GHB) in the United
`States. Historically, GHB was sold in health food stores
`until it was removed from the retail market by the
`in 1991.1
`Food and Drug Administration
`(FDA)
`However, the Dietary Supplement Health and Educa-
`tion Act of 1994 (DSHEA) made possible the legal sale
`of GHB precursors, gamma-butyrolactone (GBL) and
`1,4-butanediol.2 Once
`ingested, both GBL and 1,4
`butanediol are converted enzymatically to GHB which
`can then exert its pharmacologic effects. Some of the
`medicinal uses of GHB include narcolepsy, depression,
`alcohol withdrawal, epilepsy, and anesthesia.2 GHB
`has become a popular drug of abuse when used alone
`or in combination with other substances. Bodybuild-
`ers have used it for its alleged anabolic effect on mus-
`cles. Pre-clinical trials with GHB have been performed
`looking specifically at the interactions of brain neu-
`rotransmitters.
`
`Corresponding Author: Michael S. Okun, Emory University,
`Department of Neurology, Wesley Woods Health Center Building,
`3rd Floor, 1841 Clifton Road NE, Atlanta, Georgia, USA.
`msokun@dnamail.com
`
`
`
`Many of the problems in the United States arise from
`those who make GHB from recipes obtained over the
`Internet. GHB or its precursors are especially toxic
`when mixed with alcohol and other drugs to increase
`its euphoric effects.3-5 This combination has led to sig-
`nificant morbidity and mortality.1-8 When GHB and
`alcohol are consumed together the risk of respiratory
`depression increases substantially, exacerbating the tox-
`icity of either drug alone.2 This paper will review what
`is known about GHB and suggest appropriate emer-
`gency room management.
`
`WHAT IS GHB?
`GHB is a chemical compound structurally similar to
`the inhibitory brain neurotransmitter GABA. Its pro-
`posed function
`is as an
`inhibitory neuromodulator
`within the central nervous system, affecting the func-
`tion of other neurotransmitters in the dopaminergic
`and gabaergic systems.2 Physiologic and pharmacolog-
`ical actions are thought to be mediated through specific
`GHB receptors, GABA B receptors, or a combination.9
`Pre-clinical studies conducted
`in monkeys
`illustrate
`that GHB induces a trance-like stupor accompanied by
`electroencephalographic changes and hypothermia.10
`In hepatic failure and during alcohol intoxication, the
`rates of GHB synthesis and degradation are decreased,
`resulting in increased GHB serum levels and subse-
`quent increased toxicity.2, 11
`
`Many people abusing GHB frequent nightclubs and
`raves, while others compound GHB using recipes
`obtained through the Internet. Many users ingest GHB
`for its purported anabolic effect of enhancing body
`mass. Some utilize GHB to self-medicate conditions
`such as depression and alcoholism, although there
`remains a paucity of literature to support its use for
`
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`these diagnoses. Because the vehicle is often disguised
`as a clear, salty tasting liquid that is easily masked in
`alcoholic beverages, it has earned a reputation as a date
`rape drug.3, 4 From August of 1995 through Septem-
`ber of 1996, poison control centers in New York and
`Texas reported 69 acute poisonings and one death
`attributed to GHB.12 In Minnesota during October
`through September 1998, an additional 34 cases of GBL
`toxicity were reported.13 At Shands Hospital at the
`University of Florida, there were five MICU admis-
`sions requiring intubations related to GHB toxicity in
`a span of less than 2 years. Due to the recent resurgence
`of this substance as a drug of abuse, every case of unex-
`plained sudden coma without evidence of head injury,
`known intake of other coma inducing drugs, or signs
`and
`symptoms of
`increased
`intracranial pressure
`should be considered a possible GHB overdose and
`treated appropriately. GHB is not included in routine
`toxicology screens.14
`
`GABA AND PROPOSED MECHANISMS OF ACTION
`The precise pharmacological mechanism of action for
`GHB remains to be elucidated. However, many studies
`suggest the probable presence of specific GHB binding
`sites apart from the GABA receptor binding sites.15, 16
`It is also postulated that GHB may mimic the action of
`GABA acting as a neurotransmitter or neuromodula-
`tor.17 There is compelling evidence that GHB forma-
`tion may
`occur
`via
`a GABA
`independent
`mechanism.15, 16
`
` The clinically relevant question
`remains: How does GHB work within the GABA
`inhibitory neurotransmitter system?17
`
`GHB is behaviorally and biochemically distinct from
`GABA. Studies suggest that GHB does not consis-
`tently
`affect GABA A or GABA B
`induced
`responses.18 However, the data is conflicting.2, 15-19
`GHB does not appear to be a GABA prodrug or a
`GABA agonist. Yet the GHB precursor, Gamma-buty-
`rolactone (GBL), may have
`limited GABA agonist
`activity.18 One theory suggests the GABA B receptors
`may be stimulated by the GABA formed through GHB
`metabolism.19 Another theory suggests GHB induces a
`G-protein-mediated decease
`in adenyl cyclase via a
`GHB-specific G protein coupled presynaptic receptor
`that is different from GABA B.2, 16 Based on the data
`available from animal models, an
`indirect receptor
`pathway mechanism is suspected.
`
`GHB meets many of the criteria of a neuromodulator
`or neurotransmitter, since it is a metabolite of GABA,
`and it is synthesized and stored in cerebral neurons.20
`Neuronal depolarization releases GHB into the extra-
`cellular space in a calcium dependent manner. Stimula-
`tion of
`receptors produces hyperpolarization
`in
`dopaminergic structures. This hyperpolarization causes
`a decrease in dopamine release. However, in the hip-
`pocampus and frontal cortex GHB induces a depolar-
`ization secondary to cGMP and inositol phosphate
`turnover.11 After GHB is metabolized, it is not recon-
`verted back into GABA.
`
`DOPAMINE AND PROPOSED MECHANISMS OF ACTION
`GHB has a profound effect as an inhibitory neurotrans-
`mitter in the dopaminergic system. The concentration
`of GHB normally found in the human brain is two to
`three times higher in the basal ganglia than in the cere-
`bral cortices.21 GHB is utilized often in neurological
`research since it is one of only a few substances that
`acts primarily on dopamine release, and it acts as an
`inhibitor in vivo.22, 24, 25 However, a paradoxical reac-
`tion occurs in rats anesthetized with urethane23 or in
`patients with high
`serum concentrations of cal-
`cium.24 In these instances, GHB stimulates dopamine
`rather than having the expected inhibitory response.23
`
`OPIATE RECEPTORS AND PROPOSED MECHANISMS
`OF ACTION
`GHB and morphine have similar clinical effects,
`including euphoria, respiratory depression, and poten-
`tial for dependence with prolonged use.2, 26 GHB
`activity is reversed in part upon naloxone administra-
`tion.27, 28 The mechanism for naloxone reversing
`GHB effects is unknown. While it has been theorized
`that GHB may have central effects by acting as a direct
`opiate agonist, studies have shown that GHB does not
`bind to mu, delta, and kappa opioid receptors.26 GHB
`may be an indirect agonist acting on enkephalin or
`dynorphin receptors, but this is not clear.28 There-
`fore, reversal of GHB by naloxone probably does not
`involve an opioid mechanism, but may result from the
`reversal of GHB induced inhibition of central dopam-
`ine release.26, 27
`
`OTHER INTRACEREBRAL EFFECTS IN ANIMAL MODELS
`Intraperitoneal GHB infusion causes increased dopam-
`ine in the cerebral hemispheres as well as in the hypo-
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`in
`subsequent decrease
`a
`is
`thalamus. There
`norepinephrine secretion in the hypothalamus with no
`change in serotonin concentrations. Low doses of GHB
`may
`selectively
`affect
`catecholaminergic neuronal
`activity.29 Currently it is unclear whether this data is
`applicable to humans.
`
`GHB is found in high concentrations in some periph-
`eral tissues. It is thought that GHB may play a role in
`decreasing energy substrate consumption, protect tis-
`sues from anoxia, and protect tissues from excessive
`metabolic demand since GHB serum concentrations
`are known to rise under stressful circumstances. There-
`fore, it may be an endogenous protective agent when
`tissue energy supplies are low.30, 31
`
`SLEEP AND GROWTH HORMONE EFFECTS
`The effects of GHB on sleep have been well docu-
`mented.31-40 During the first two hours after sleep
`onset, there is an increase in growth hormone secre-
`tion, as well as an increase in stage IV sleep time.32 This
`effect has led to the unsubstantiated use of GHB by
`bodybuilders. Abrupt but transient elevations in pro-
`lactin and cortisol have also been observed. Yet, thy-
`rotropin and melatonin concentrations do not appear
`to be altered.32 GHB pharmacokinetics were exam-
`ined in a small cohort of adult narcoleptic patients at
`steady-state concentrations. Results confirmed nonlin-
`ear pharmacokinetics, and capacity-limited elimination
`when patients received fixed doses of 3 grams twice
`nightly.33
`
`A small, double-blind crossover study examined the
`effect of GHB in patients with narcolepsy.37 A thera-
`peutic effect with decreased cataplexy, as well as
`improved nocturnal
`sleep
`quality was
`demon-
`strated.37 GHB rapidly induced sleep without sup-
`pressing REM sleep in both normal and narcoleptic
`patients.37 Another study demonstrated that cata-
`plexy was decreased by GHB with fewer attacks and
`decreased subjective arousals.38 In a placebo-con-
`trolled, double-blind, cohort study examining the effi-
`cacy of GHB on nocturnal or diurnal sleep, stage III
`and IV sleep was increased, whereas stage I sleep was
`diminished. GHB improved the REM efficiency and
`decreased the wake time after sleep onset.39 GHB pro-
`moted cataplexy when administered during the day.
`However, it decreased daytime cataplexy when given
`
`
`
`at night.40 Based on these studies, GHB has clearly
`shown benefit in treatment of narcolepsy. However,
`GHB is currently a schedule 1 controlled drug, and its
`only permitted therapeutic use is within clinical tri-
`als.41 A new pharmaceutical formulation of GHB,
`known by
`its USAN name sodium oxybate, may
`become a schedule III pharmaceutical used for the
`treatment of narcolepsy.41-45 GHB currently is desig-
`nated as orphan drug status for the treatment of narco-
`lepsy, and is only permitted within the scope of clinical
`trials.44 The FDA will consider the safety and efficacy
`of NDA 21-196, Xyrem® (sodium oxybate, Orphan
`Medical, Inc.) in meetings scheduled for 2001.45
`
`TREATMENT OF SUBSTANCE ABUSE
`GHB use in the treatment of substance abuse is com-
`monplace in European countries.45-50 A randomized,
`single-blind, controlled cohort study was conducted in
`Italy to compare the efficacy and safety of diazepam
`versus GHB in the treatment of alcohol withdrawal
`symptoms (AWS).46 GHB was faster to decrease anxi-
`ety, agitation, and depression scores. The statistical sig-
`nificance of the differences between groups was not
`evaluated. Both treatment arms were determined safe
`and both were well tolerated in AWS management.46
`
`An open label, multicenter study was conducted with
`GHB in the treatment of alcohol withdrawal symp-
`toms in one hundred seventy-nine patients. The study
`group was treated for six months with a 50-mg/kg dose
`of GHB daily. The drug was well tolerated with no
`serious adverse effects. Complete abstinence was
`attained in 78% of treated patients during the study
`period. This was accompanied by a reduction in alco-
`hol craving when measured by the standardized Alco-
`hol Craving Scale. Forty-three patients
`remained
`abstinent at six months. Thirty subjects remained
`abstinent at one year.47 Another study examined
`GHB potential to decrease alcohol withdrawal symp-
`toms and demonstrated efficacy in reducing tremors,
`sweating, nausea, depression, anxiety, and restlessness.
`There was a noted common side effect of dizziness.48
`GHB may be useful in the treatment of alcohol depen-
`dence and accompanying withdrawal symptoms.46-50
`Larger, well controlled, long term studies need to be
`conducted to substantiate these observations.
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`GHB has also been studied for its effects on opiate
`withdrawal.51-54 It had no consistent effects when
`used as pre-treatment for naloxone precipitated opiate
`withdrawal.51, 52 Small, non-controlled studies sug-
`gested there may be a benefit in this population,53, 54
`but true efficacy has yet to be established.
`
`ADVERSE EFFECTS
`Adverse effects associated with GHB are dose-depen-
`dent. An oral dose of 10 mg/kg has been reported to
`cause amnesia and hypotonia. Doses of 20 to 30 mg/kg
`have
`resulted
`in somnolence within 15 minutes,
`whereas doses of greater than 50 mg/kg result in
`unconsciousness and coma. Small doses less than 10
`mg/kg have resulted in nausea, vomiting, dizziness,
`confusion, drowsiness, decreased respirations and sei-
`zure-like phenomenon.55 In addition to respiratory
`depression, hypotension and bradycardia may result.
`Dizziness may occur acutely or for several weeks after
`taking the last GHB dose. The synergy of GHB and
`alcohol or other recreational drugs is of greatest clini-
`cal concern.2-5 The combination seems to worsen res-
`piratory symptoms and exacerbate central nervous
`system effects.2-5, 55 GHB has also been associated
`with a withdrawal syndrome of insomnia, anxiety, and
`tremor that usually resolves within three to twelve
`days.20 GHB use has been correlated with hypother-
`mia and EEG findings of spike and wave discharges
`that may explain the described seizure-like phenome-
`non
`in users. Studies have shown no correlation
`between GHB-induced absence seizures and hypother-
`mia. They seem to occur by separate, independent
`mechanisms.56 Clinicians should keep in mind that
`serum levels may fluctuate with circadian rhythm. One
`study demonstrated that daytime levels of GHB are
`only 61% of nighttime levels. This fact may be clini-
`cally important since most overdoses present to the
`emergency room at night.57
`
`TREATMENT OF GHB TOXICITY
`Treatment of GHB toxicity involves supportive care
`measures since the majority of GHB effects, even when
`mixed with other drugs, will wear off within hours.
`The most serious of these effects is the respiratory
`depression that can lead to hypoxia and death. The
`challenge in treating patients who have acquired GHB
`on the street is that there is no way to ascertain the
`dose they have consumed. Further, users often believe
`
`that they have taken a low dose but have unknowingly
`consumed a higher concentration contained in a small
`volume.
`
`Naloxone administration in the treatment of GHB is
`controversial. As mentioned earlier, naloxone is an opi-
`ate antagonist that has been shown to reverse many of
`the central effects of GHB. It has been our experience
`that many patients who are using GHB also concomi-
`tantly use opiate drugs that appear
`in
`toxicology
`screens. It is the high association with opiate use as well
`as a favorable response in treated animals that we rec-
`ommend use of the drug.
`
`Because GHB has been used in the study of epilepsy,
`there is a question regarding the necessity, benefits, and
`risks associated with the use of anticonvulsants in the
`treatment of GHB-induced seizures. EEG changes
`induced by GHB were normalized with Phenobarbital
`administration.58 In addition, myoclonic jerking was
`abolished with ethosuximide, decreased with diaz-
`epam, and increased with clonazepam.58 Anticonvul-
`sants
`experimentally decreased
`the
`frequency of
`myoclonic jerking when administered prior to GHB.58
`Stupor was decreased with ethosuximide.58 Valproate
`and ethosuximide are thought to decrease the GABA-
`like effect at the GABA B receptor by inhibition of
`GHB dehydrogenase.59 The question for the clinician
`to ponder is whether the use of anticonvulsants will
`alter the respiratory depression and CNS side effects of
`GHB in humans. There is no clear answer at this time.
`Theoretically, benzodiazepines may worsen
`respira-
`tory depression, whereas,
`intravenous valproic acid
`merits further study in humans and consideration as a
`potential treatment for GHB induced seizures. Diaz-
`epam has been used in humans to treat GHB and GBL
`withdrawal syndrome with success. Reported regimens
`have utilized diazepam for 6 to 11 days.60-62
`
`Another therapeutic option for the treatment of GHB
`toxicity is physostigmine.1, 63-65 Historically, GHB
`was used in Europe for anaesthesia. Its use was cur-
`tailed because of side effects including long recovery
`times due to difficulty in arousal after surgical proce-
`dures. Henderson and Holmes demonstrated that 2mg
`of intravenous physostigmine provided a rapid, safe,
`and sustained awakening in GHB anesthetized-patients
`within a 2 to 10 minute window.64 The mechanism of
`GHB reversal
`involves the cholinergic system with
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`direct or indirect effects on dopamine and GABA.
`Physostigmine can cause cholinergic crisis and caution
`should be exercised when administering the drug. Side
`effects of physostigmine include nausea, vomiting, sali-
`vation and bradycardia. Atropine should be at the bed-
`side, especially since GHB also causes bradycardia.63
`Despite its proven benefit, the side effects of physostig-
`mine may present more of a risk than a benefit in treat-
`ing GHB overdose.65 At our hospital, routine use is
`not recommended. Physostigmine is considered if there
`is an acute need to wake the patient for neurological or
`physical examination in cases of emergent surgery after
`a traumatic accident.
`
`The final note on treatment is that many patients with
`GHB overdose awaken from a comatose state suddenly
`and may display
`aggressive behavior. Therefore,
`patients with suspected overdose should be restrained
`with soft wrist and ankle restraints as well as a posey-
`vest. This precaution will eliminate difficulty in secur-
`ing the patient’s airway during a sudden awakening
`and decrease the risk for aspiration pneumonia and
`self-extubation. Patients may awaken and attempt to
`self-extubate before they are adequately exchanging
`oxygen. Extubate patients who are aggressive and vio-
`lent with caution. Patients may not oxygenate well
`without ventilation despite normal movement of all
`extremities and the ability to communicate with staff.
`
`MECHANISM FOR THE SUDDEN AWAKENING IN GHB
`The one truly distinguishing feature of GHB toxicity is
`the sudden awakening of the patient from a comatose
`state to a normal or hyperactivated state of arousal. A
`similar awakening is seen in patients who have strokes
`involving the paramedian vessels that supply medial
`thalamus and areas of the reticular activating system.
`Similarly, patients with paramedian infarctions arouse
`suddenly from a comatose state and have continuous
`fluctuations in their level of consciousness. Clinically
`these arousal syndromes can be treated by dopamine
`agonists or amphetamines. It is known that extrastri-
`atal sources66,67 of dopamine exist and they are cur-
`rently being mapped. The dopamine pathways
`involving medial thalamic areas remain unpublished at
`this time. One potential mechanism for coma followed
`by sudden awakening in GHB toxicity may involve
`transient
`inhibition of medial
`thalamic dopamine
`release by GHB that may have a strong inhibitory
`
`effect on the dopamine neurotransmitter system. The
`paramedian infarction of the thalamus may provide a
`useful model for the study of the sudden awakening
`phenomenon. This mechanism remains to be eluci-
`dated.
`
`CLINICAL PRESENTATION
`Eight cases of GHB overdose presented to the Univer-
`sity of Florida for acute management between August
`1997 and April 1998. Previously we described the six
`common presentations of GHB toxicity1 (Table 1).
`
`Table 1: Clinical Presentations of GHB Toxicity
`
`1. Abrupt Awakening
`2. Self Extubation with the Possibility of
`Aspiration Pneumonia
`3. Mixed with Other Drugs
`4. Bradycardia or Atrial Fibrillation
`5. Mixed with Ecstasy
`6. Observation of a patient without intubation
`
`
`Since most cases present post-ingestion of multiple
`drugs of abuse, it is important to understand the poten-
`tial central nervous system (Table 2), cardiovascular
`(Table 3), respiratory (Table 4), and other adverse
`effects of GHB and popular drugs of abuse (Table 5).
`
`Patients often arrive in the emergency room with low
`Glasgow Coma Scale (GCS) scores and respiratory
`depression. They are often hypothermic with no focal
`neurological deficits aside from their severely depressed
`level of consciousness. A warming blanket should be
`employed if needed. Alcohol levels may be low despite
`their comatose state. They are often taking other recre-
`ational drugs including opiates, warranting the use of
`naloxone. Coma is typically self-limiting whether intu-
`bated or not they will wake up in a few hours. As
`stated above, sudden awakening is often accompanied
`by agitation and violence and warrants prophylactic
`use of restraints to prevent self-extubation, aspiration
`pneumonia, and injury to the patient or staff. Patients
`may be awake and intubated, but still not adequately
`breathing on their own. Patients should be monitored
`prior to extubation to ensure the return of normal res-
`pirations. GHB- induced bradycardia may be masked
`by concomitant use of amphetamines, cocaine, or by
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`Table 3: Cardiovascular Effects of GHB Toxicity
`Compared to Other Drugs of Abuse*
`
`GHB
`
`Cocaine(70)
`
`Ecstasy (M DM A a,b)*,(71)
`
`Ethanola,(72)
`
`Heroin/Opiate(73)
`
`M ethamphetam ine*,(74)
`
`Bradycardia,
`hypotension
`Paroxysm al atrial
`tachycardia,
`hypertension,
`Im m ediate death due to
`direct cardiotoxicity
`without the appearance
`of CNS effects
`Hypertension followed
`by hypotension,
`spontaneous bleeding,
`tachycardia, ventricular
`arrhthmias
`Cardiac dysfunction
`(profound bradycardia)
`Sinus bradycardia,
`sinus tachycardia,
`hypertension,
`hypotension,
`palpitations, syncope
`Atrial & ventricular
`arrhythmias, chest pain,
`hypertension,
`m yocardial ischem ia,
`palpitations
`*Features may be variable. M DM A = 3,4-
`methylenedioxymethylamphetamine
`a. Also known as “E”, “XTC”, “X”, and “ADAM ”
`b. Presentation may vary
`c. Also known as “Speed”, “Crank”, “Go”, “Crystal”,
`and “Crystal-meth”
`
`
`dehydration. It is unclear at this time whether or not
`GHB can precipitate abnormal heart rhythms, but
`atrial fibrillation has been reported.1,68, 69
`
`The implementation of an effective emergency depart-
`ment protocol can prevent morbidity and mortality as
`well as decrease hospital admissions associated with
`this drug of abuse.1 Due to the resurgence of GHB as
`a drug of abuse, health care providers must take an
`active role
`in
`the
`identification and
`treatment of
`patients with GHB associated toxicity.
`
`Table 2: CNS Effects of GHB Toxicity Compared to Other
`Drugs of Abuse*
`
`GHB
`
`Cocaine(70)
`
`Amnesia, coma, seizure-
`like phenomenon,
`unconsciousness
`Confusion, anxiety,
`dizziness, delerium,
`headache, mydriasis,
`exopthalmus,
`hyperresponsive
`reflexes, convulsions,
`unconciousness
`Agitation, coma,
`convulsions, mydriasis,
`panic, paranoia
`CNS depression,
`decreased or absent deep
`tendon reflexes, coma
`Glasgow Coma Scale
`Score of <12, miotic
`pupils
`Methamphetamine*,c, (74) Agitation, anxiety,
`hallucinations, delerium,
`toxic psychosis, siezures
`
`Ecstasy (MDMAa) *,(71)
`
`Ethanolb,(72)
`
`Heroin/Opiate(73)
`
`*Features may be variable. MDMA = 3,4-
`methylenedioxymethylamphetamine
`a. Also known as “E”, “XTC”, “X”, and “ADAM”
`b. Presentation may vary
`c. Also known as “Speed”, “Crank”, “Go”, “Crystal”,
`and “Crystal-meth”
`
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`Table 4: Respiratory Effects of GHB Toxicity Compared to
`Other Drugs of Abuse*
`
`GHB
`Cocaine(70)
`
`Respiratory depression
`Death from respiratory
`arrest, irregular (Cheyne-
`Stokes) respiration
`Ecstasy (MDMAa,b) *,(71) Respiratory depression
`Respiratory depression
`Ethanola,(72)
`Heroin/Opiate(73)
`Respiratory depression
`<12 breaths/min
`Dyspnea
`Methamphetamine*, (74)
`*Features may be variable. MDMA = 3,4-
`methylenedioxymethylamphetamine
`a. Also known as “E”, “XTC”, “X”, and “ADAM”
`b. Presentation may vary
`c. Also known as “Speed”, “Crank”, “Go”, “Crystal”,
`and “Crystal-meth”
`
`Table 5: Miscellaneous Effects of GHB Toxicity Compared
`to Other Drugs of Abuse*
`
`GHB
`Cocaine(70)
`
`Ecstasy (MDMAa)
`*,(71)
`
`Ethanola,(72)
`
`Heroin/Opiate(73)
`
`Hypotonia
`Chills, diaphoresis,
`hyperthermia, nausea,
`pallor, vomiting
`Diaphoresis, elevated
`serum creatinine, creatine
`phosphokinase, & LFTs,
`hypoglycemia,
`hyperthermia, metabolic
`acidosis, muscle rigidity
`BAL 150 to >300 mg%,
`flushed skin progressing to
`cyanosis, hypoglycemia,
`hypothermia, peripheral
`vasodilation, shock
`Circumstantial evidence or
`history of heroin, response
`to naloxone
`Methamphetaminec,(74) Hyperthermia,
`rhabdomyolosis
`*Features may be variable. MDMA = 3,4-
`methylenedioxymethamphetamine
`a. Also known as “E”, “XTC”, “X”, and “ADAM”
`b. Presentation may vary
`c. Also known as “speed”, “crank”, “go”, “crystal”, and
`“crystal-meth”
`
`
`[2]
`
`[3]
`
`[4]
`
`[5]
`
`[6]
`
`[7]
`
`[8]
`
`[9]
`
`[10]
`
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