Please cite this article in press as: Høiseth, G., et al., Impairment due to amphetamines and benzodiazepines, alone and in combination. Drug Alcohol Depend. (2014), http://dx.doi.org/10.1016/j.drugalcdep.2014.10.013 ARTICLE IN PRESS G Model DAD-5331; No. of Pages 6 Drug and Alcohol Dependence xxx (2014) xxx–xxx Contents lists available at ScienceDirect Drug and Alcohol Dependence j ourna l h o me pa ge: www.elsevier.com/locate/drugalcdep Impairment due to amphetamines and benzodiazepines, alone and in combination Gudrun Høiseth a,b,* , Hilde Andås a , Liliana Bachs a , Jørg Mørland a a Norwegian Institute of Public Health, Division of Forensic Sciences, Oslo, Norway b Center for Psychopharmacology, Diakonhjemmet Hospital, Oslo, Norway a r t i c l e i n f o Article history: Received 23 May 2014 Received in revised form 8 October 2014 Accepted 15 October 2014 Available online xxx Keywords: Drug use Amphetamines Benzodiazepines Impairment Motor vehicle a b s t r a c t Introduction: The impairing effects of combined use of amphetamines and benzodiazepines among recre- ational drug users are not well described, but knowledge about this is important in the risk assessment of such combined drug use. The aim of this study was to compare the impairment, among apprehended drivers, as judged by a clinical test of impairment (CTI), in cases where a combination of amphetamines and benzodiazepines was detected, in blood, with cases where only one of the two drug groups was detected. Methods: The results of CTI judgments were compared to toxicological drug tests of blood samples that were obtained at the time of CTI screening in cases containing amphetamines only, cases containing dif- ferent benzodiazepines only, and cases containing a combination of amphetamines and benzodiazepines. Results: There were significantly more drivers being judged as impaired in the combined group (n = 777), compared both with amphetamines alone (n = 267,  2 = 47.8, p < 0.001) and benzodiazepines alone (n = 153,  2 = 7.0, p = 0.008). This was also seen when only including the lowest concentrations of ben- zodiazepines ( 2 = 4.3, p = 0.038). The concentrations of the drugs were higher in the single drug groups, compared with the combined group. Conclusion: This study indicates that during real-life driving, those influenced by both amphetamines and benzodiazepines are more impaired, as judged by the CTI, compared with those influenced by either drug alone, although the combined group showed lower drug concentrations. © 2014 Elsevier Ireland Ltd. All rights reserved. 1. Introduction Amphetamines and benzodiazepines are popular among recre- ational drug users. These two drug classes are also frequently combined, and this is verified by the frequent detection of benzo- diazepines and amphetamines together (seen in about 15% of some categories of forensic blood samples; Bogstrand and Gjerde, 2014; Gjerde et al., 2013; Ojaniemi et al., 2009; Verschraagen et al., 2007). Although the prevalence of amphetamines and benzodiazepine use among drivers vary by country, these drugs are frequently found in both impaired and fatally injured drivers (Gjerde et al., 2011a,b), and both benzodiazepines and amphetamines are doc- umented to cause driving impairment (Bosanquet et al., 2013; Verster et al., 2006). The reason for the combined use is often to * Corresponding author at: Norwegian Institute of Public Health, Division of Foren- sic Sciences, PO Box 4404 Nydalen, N-0403 Oslo, Norway. Tel.: +47 21 07 78 99; fax: +47 22 38 32 33. E-mail address: gudrun.hoiseth@fhi.no (G. Høiseth). add stimulating or sedating effects to the drug experience, but the effects of this combination on drug related impairment are not well known. Debate exists as to whether a combination of the stimulant amphetamines and the depressant benzodiazepines will actually attenuate some of their individual impairing effects as indicated in some studies (Marks et al., 2014; Mintzer and Griffiths, 2003; Rush et al., 2004). Studies attempting to answer this question are, however, not necessarily transferable to real-life situations, where higher drug doses most often are ingested. Such studies are difficult to conduct with a controlled experimental design, due to ethical and safety restrictions in combing high doses of the respective drugs. Blood samples collected in real-life from suspected impaired drivers often contain drugs of abuse. In studies investigating blood samples collected from fatally injured drivers, alcohol and/or drugs have been found in 30–50% of the cases, with alcohol being the most prevalent drug, detected in 20–40% (Ahlm et al., 2009; Brady and Li, 2014; Carmen del Rio et al., 2002; Drummer et al., 2004; Gjerde et al., 2011a,b). These drivers are often experienced drug users and represent a population using benzodiazepines for non- therapeutic purposes (Bogstrand and Gjerde, 2014). In cases of http://dx.doi.org/10.1016/j.drugalcdep.2014.10.013 0376-8716/© 2014 Elsevier Ireland Ltd. All rights reserved.