Driving Under the Influence of Gamma-hydroxybutyrate (GHB)

Transcription

1 1 Driving Under the Influence of Gamma-hydroxybutyrate (GHB) Alan Wayne Jones*, Anita Holmgren, and Fredrik C. Kugelberg. Department of Forensic Genetics and Forensic Toxicology, National Board of Forensic Medicine, Artillerigatan 12, SE Linköping, Sweden. Abstract With the help of an in-house forensic toxicology database (TXBASE), we searched for all occurrences of gamma-hydroxybutyrate (GHB) in blood samples from impaired drivers apprehended between 1998 and The age and gender of offenders and the concentrations of GHB in blood were evaluated and compared. GHB was determined in blood samples by gas chromatography (GC) with a capillary column (DB-5) and a flame ionization detector after conversion of GHB into gamma-butyrolactone (GBL). The cut-off concentration of GHB in blood for a positive result was 8. The mean and median concentrations of GHB in 473 cases of DUID were 90 and 84, respectively and the highest concentration was 340. The suspects were predominantly men (96%) with an average age of 26 y (range y). GHB was the only drug present in the blood in 185 cases (39%) and the mean and median concentrations were 92 and 85, respectively. The signs of drug influence noted by the arresting police officers included sedation, agitation, unsteady gait, slurred speech, irrational behavior, jerky body movements, dilated pupils and spitting. GHB is a powerful depressant of the central nervous system and recreational use of this substance is incompatible with safe driving. The short elimination half-life of GHB (30-40 min) means that the concentrations reported here are probably a lot less than they were 1-2 hours earlier, such as at the time of driving. Keywords: DUID, GHB, impairment, driving. Introduction Gamma-hydroxybutyrate (GHB) attracted attention as a recreational drug of abuse in Sweden about 10 y ago when a few overdose deaths were documented (1). This led to GHB being classified as a scheduled substance (class II). However, the well-known precursors or prodrugs of GHB, namely gamma-butyrolactone (GBL) and 1,4-butanediol are still not classified as controlled substances and their use and abuse is therefore more difficult to control (1,2). GHB is a water soluble low molecular weight substance that becomes rapidly absorbed from the gut and easily crosses the blood-brain barrier. GHB is eliminated from the blood with a short half-life, which means that in forensic casework the body fluids for toxicological analysis need to be obtained without delay (3). GHB acts as a powerful depressant of the central nervous system and causes a pronounced impairment of cognitive and psychomotor functioning after recreational doses. The mode of action of GHB involves an interaction with brain receptors for the inhibitory neurotransmitter gamma-aminobutyric acid (GABA) (2,3). The structural formulae of GHB and related compounds are shown in figure 1 In this paper, we report age and gender of offenders and the concentrations of GHB in blood samples from motorists apprehended in Sweden for driving under the influence of drugs (DUID). The concentrations of GHB were compared in suspects when this was the only drug present and when GHB occurred together with other recreational drugs.

2 2 H H N H 2 H Gamma-hydroxybutyrate (GHB) Gamma-aminobutyric acid (GABA) H H Gamma-butyrolactone (GBL) 1,4-butanediol (BD) Figure 1. Chemical structures of GHB and its precursors GBL and 1,4-butanediol compared with the inhibitory neurotransmitter GABA. Material and Methods Sweden introduced a zero-tolerance law for driving under the influence of drugs in 1999 and since then the number of blood samples submitted by the police for toxicological analysis has increased more than 12-fold (4). All blood specimens from apprehended drivers are sent to one central laboratory (the National Laboratory of Forensic Toxicology, Linköping) for analysis. The first suspicion of impaired driving usually arises when the police question a motorist in connection with a moving traffic violation, involvement in a crash or when a routine sobriety control is made. If the result of a roadside breath-alcohol screening test is negative (BAC < 0.02 g/100 ml or 20 mg/100 ml) and the driver shows signs and symptoms of drug influence then a specimen of blood is requested for toxicological analysis. The administration of so-called standardized field-sobriety tests prior to arresting a driver is not necessary in Sweden. The main deciding factor is observations made by the arresting police officers, the general appearance and behavior of the individual and any other indications that might suggest use and abuse of drugs other than alcohol. If the analytical results subsequently prove negative there are no negative consequences or reprimands for the police officers concerned. In our laboratory, GHB is determined in blood by gas chromatography (HP 5890 from Hewlett Packard), which was fitted with a flame ionization detector (FID) and gammavalerolactone serves as the internal standard. An aliquot of blood (0.5 g) is first treated with acetone to precipitate proteins and then acidified with sulfuric acid to convert GHB into gamma-butyrolactone (GBL). The GBL is back-extracted into dichlormethane and the volume of solvent is reduced by evaporation under nitrogen and an aliquot injected into the GC instrument with DB-5 (30 m x 0.25 mm and film thickness 0.25 µm) as the stationary phase. The cut-off concentration of GHB in blood for reporting a positive result is 8, which therefore functions as the limit of quantitation (LQ). The detector response was linear up to a GHB concentration of 1000 in blood and the analytical precision (coefficient of variation) was 3.9% at a GHB concentration of 8 and 7.9% at a GHB concentration of 200.

3 3 Results Table 1 gives the age and gender of people apprehended in Sweden for DUID after use of GHB. Besides the vast dominance of men (96%) most individuals were in their mid-twenties although the women were about 5-7 years older than the men. Table 1. Age and gender of people apprehended for DUID after use of GHB. Conditions N Men (%) Women (%) Age of men mean ± SD Age of women mean ± SD GHB alone (97) 5 (3) 25.2 ± ± 6.2 GHB + other drugs (96) 21 (4) 25.7 ± ± 7.2 Table 2 shows the concentrations of GHB in blood from apprehended drivers when this was the only psychoactive substance present and when GHB occurred along with other recreational drugs including ethanol. Table 2. Concentrations of GHB in blood when the only psychoactive substance present and when other recreational drugs, including alcohol, were present. Conditions N Mean Median Highest 2.5 and 97.5 percentiles GHB alone GHB + other drugs Table 3 gives examples of the observations made by the arresting police officers in relation to the age and gender of suspects and the concentration of GHB in their blood. These cases were selected and rank ordered after the highest concentrations of GHB in blood. Note that the samples of blood for the toxicological analysis were taken between 30 and 90 min after driving. The observations of the arresting police officers (Table 3) show that use and abuse of GHB a potent depressant of the central nervous system depressant leads to a wide spectrum of undesirable effects when skilled tasks like driving are performed. There was evidence of sedation, ataxia and decrement in psychomotor performance, which adversely influences driver behavior and increases the risk if a road-traffic crash. Discussion GHB is a fairly recent addition to the growing number of recreational drugs used and abused worldwide (2,3). Indeed, GHB is seemingly more popular with young people in their midtwenties, probably because it is cheap and relatively easy to obtain. GHB acts as a powerful depressant of the central nervous system causing marked changes in a person s actions and behavior (see Table 3), which is not compatible with safe driving. The effects of GHB on the suspects, as noted by arresting police officers (Table 3), were sedation, unsteady gait, and loss of coordination, amongst others. Indeed, a number of overdose deaths have been recorded after use and abuse of GHB (5).

4 4 Table 3. Age, gender and the observations made by the arresting police officers in relation to the concentrations of GHB in blood of DUID suspects. Case Age Gender GHB, bservations made by arresting police officers Male 270 Bloodshot eyes, large pupils, stagger, slurred speech, irrational behavior 2 27 Male 240 Bloodshot and glossy eyes, stagger, slurred speech 3 26 Male 220 Unresponsive, slow breathing, constricted pupils, awakes occasionally Male 200 Slurred speech, jerky movements 5 37 Female 180 Glossy eyes, stagger 6 46 Male 170 Glossy eyes, stagger, slurred speech 7 27 Male 150 Rapid pulse, sweating, small pupils, glossy eyes, staggers and exhibits sedation mixed with aggressiveness 8 26 Male 150 Uncontrollable muscle spasm, stagger, fell asleep in the police car 9 28 Male 150 Confused, large pupils, slow reaction Male 150 Bloodshot and glossy eyes, large pupils, stagger Male 140 Glossy eyes, stagger Male 140 Glossy eyes, large pupils, forced and slurred speech Male 140 Glossy eyes, small pupils, gaze nystagmus, slurred speech, stagger, fell asleep in the police car Male 130 Glossy eyes, small pupils, stagger, fatigue Male 130 Dull, fell asleep in the police car Male 130 Unconscious Male 130 Stagger, jerky movements Male 130 Jerky movements Male 130 Gaze nystagmus, slurred speech Male 130 Large pupils, stagger, forced and slurred speech, dull Female 120 Glossy eyes, dilated pupils, drowsy Male 120 Bloodshot and glossy eyes, large pupils, stagger, slurred and forced speech, jerky movements, nervous Male 72 Glossy eyes, large pupils, slurred speech, jerky movements, spitting, fell asleep in the police car Male 59 Glossy eyes, slurred speech, spitting, irrational behavior Male 36 Dilated pupils, slow reaction, jerky movements, dry mouth 1 Note that the police officers made their observations between 30 and 90 min before the blood sample was obtained for toxicological analysis.

5 5 GHB as its sodium salt (sodium oxybate) has been registered as a drug for the treatment of patients suffering from narcolepsy with cataplexy (XYREM ). However, the recommended doses and the therapeutic concentrations of GHB in blood are much lower than those found impaired drivers reported here. Nevertheless, caution is needed whenever GHB is prescribed owing to the potential for abuse and the risk of impairment of cognitive and psychomotor functioning when skilled tasks such as driving are performed (5). The elimination half-life of GHB from blood is only min (6), which means that the concentrations reported here (table 2 and 3) are probably a lot less than they were at the time of driving or when the police made their observations of the driver s behavior. The time between arrest and blood sampling varies from 30 to 90 min depending on circumstances, such as geographic location of the arrest or availability of a nurse or physician to draw blood. Interpreting the concentrations of GHB in blood in relation to the degree of impairment or the effects produced on the individual is not easy. Nothing is known about the dose of GHB taken nor the time of intake or for that matter whether one of its precursors, GBL or 1,4-butanediol had been used instead. The GHB concentration found in blood of DUID suspects in Sweden (table 2) agree well with the few studies reported from USA (7,8). In conclusion, people use psychoactive drugs for various reasons but primarily to change their behavior, relieve inhibitions, experience euphoria and give them extra confidence. Such alterations in a person s psychic makeup are clearly not advisable when concentration, critical judgments and skilled tasks such as driving a motor vehicle on the highway are concerned. References 1. Eklund A. Gamma-hydroxybutyrate (GHB) endogena koncentrationer, missbruk, trafikolyckor och dödsfall. Nordisk Rettsmed 7;33-35, Gonzales, A, Nutt DJ. Gamma hydroxyl butyrate abuse and dependency. J Psychopharmacol 19; , Drasbek, KR, Christensen JK. Gamma-hydroxybutyrate - a drug of abuse. Acta Neurol Scand 114: , Jones, AW. Driving under the influence of drugs in Sweden with zero concentration limits in blood for controlled substances. Traffic Inj Prev. 6: , Wong, CG, Chan KF,. Gibson KM, Snead, C. Gamma-hydroxybutyric acid: neurobiology and toxicology of a recreational drug. Toxicol Rev. 23: 3-20, Borgen, LA, kerholm, RA, Lai A, Scharf, MB The pharmacokinetics of sodium oxybate oral solution following acute and chronic administration to narcoleptic patients. J Clin Pharmacol. 44: , Couper, FJ, Logan, BK. GHB and driving impairment. J Forensic Sci. 46: , Couper, FJ, Logan, BK. Addicted to driving under the influence a GHB/GBL case report. J Anal Toxicol 28; , 2004.