The effect of d,l-methamphetamine on simulated driving performance
- First Online:
- Cite this article as:
- Silber, B.Y., Croft, R.J., Downey, L.A. et al. Psychopharmacology (2012) 219: 1081. doi:10.1007/s00213-011-2437-7
- 111 Views
Illicit drugs such as methamphetamine are commonly abused drugs that have also been observed to be prevalent in drivers injured in road accidents. The exact effect of methamphetamine or its specific isomers on driving and driving behaviour have yet to be thoroughly investigated.
Twenty healthy recreational illicit stimulant users (ten males, ten females), aged between 21 and 34 years (mean = 24.3 years, SD = 3.4 years), attended two testing sessions involving oral consumption of 0.42 mg/kg d,l-methamphetamine or a matching placebo. The drug administration was counterbalanced, double-blind, and medically supervised. At each session, driving performance was assessed 2.5 h post-drug administration.
Mean blood and saliva d,l-methamphetamine concentrations of approximately 90 and 400 ng/ml, respectively, at 2 h and 95 and 475 ng/ml at 3 h were observed. These levels of d,l-methamphetamine were found not to significantly impair, or improve, driving performance at the 2.5-h post-drug administration time point.
The findings of this study illustrate that d,l-methamphetamine has no significant effect on simulated driving performance.
The effect of d,l-methamphetamine on simulated driving performance
Methamphetamine is considered to be one of the most popular abused stimulants amongst drivers. Within the transport industry, particularly long-distance drivers, methamphetamine has long been used for its functional use of allowing longer and more sustained work performance. Methamphetamine exists in two isomeric forms (Logan 2002), dextro (d-) and levo (l-), with the d isomer having greater central nervous system (CNS) potency than the l isomer (Hardman and Limbird 1996). A racemic mixture of methamphetamine (d,l-) is less potent than the d-isomeric form and more potent than the l-isomeric form (Logan 2002). There is limited evidence that delineates the possibly variable effects of different forms of amphetamines, let alone the available preparations of methamphetamine on driving-related skills and behaviours.
It is important to assess amphetamines that are commonly used by drivers to allow for comparison to in situ driving. Research in the USA, Europe, and Australia has indicated an increasing use of amphetamines in the population and an increasing prevalence in drivers suspected of driving under the influence of drugs, those injured in car accidents, and in road fatalities. Switzerland introduced a two-tier system based on impairment by any psychoactive substances which affect the capacity to drive safely and sanctions drivers who have ≥1.5 ng/ml of THC; amphetamine; methamphetamine; 3,4-methylenedioxymethamphetamine (MDMA); 3,4-methylenedioxyethylamphetamine; cocaine; or free morphine. In the first year, 4,794 driving under the influence of drugs (DUID) offenders (4,243 males, 543 females) had their blood sample assessed as part of the first nationwide survey concerning DUID (Senna et al. 2010); 89% of drivers suspected of DUID were found to return a positive blood sample, and the most common drugs observed in the blood were: cannabinoids (48% of total number of cases), ethanol (35%), cocaine (25%), opiates (10%), amphetamines (7%), benzodiazepines (6%), and methadone (5%).
In Washington State, USA, two studies separated by 9 years have illustrated the changing patterns of drug use with respect to fatally injured drivers (Logon and Schwilke 1996; Schwilke et al. 2006). Blood samples were collected from 370 fatally injured drivers between February 1, 2001, and January 31, 2002, with alcohol being detected in 41% of cases, cannabinoids in 12.7%, and CNS stimulants (cocaine and amphetamines) in 9.7%. Methamphetamine was detected in 4.9% of cases, reflecting an increase of 200% from the authors' previous study 9 years earlier. This increase in fatalities returning a positive methamphetamine sample coincides with the increased popularity of the drug and a remarkable increase of 1,500% in DUID cases involving methamphetamine between 1993 and 2001 in Washington State (Schwilke et al. 2006). Similarly, the US 2007 National Road Safety survey (Lacey et al. 2009) reported that the incidence of fatalities involving drugs was around 25%, while the number of drug drivers on the road was around 14%—evidence for double the risk of an accident.
In Australia, the prevalence of drugs in injured and deceased drivers involved in road accidents is increasing (Drummer et al. 2003). Between 1990 and 1999, 3,398 driver fatalities were investigated with alcohol being present in 29.1% of drivers (Drummer et al. 2003), and drugs were present in the blood of 26.7% of cases (cannabis 13.5%, opioids 4.9%, stimulants 4.1%, benzodiazepines 4.1%). More recently, Victoria introduced mandatory drug testing for all injured drivers taken to hospital after a road accident (Drummer et al. 2011), with penalties being issued for drivers testing positive to methamphetamine, MDMA, and THC. Of the 1,714 drivers assessed, 29% of the sample tested positive to alcohol, and 12.5% returned positive samples for the three illicit drugs, with THC being present in 9.8%, methamphetamine in 3.1%, and MDMA in 0.8% of cases. Whilst alcohol and THC remain the most frequently encountered drugs used by drivers and remain a serious issue for countries attempting to police DUID, the increasing prevalence of amphetamine use by both young adults and professional drivers and its observed role in traffic accidents warrants further investigation.
Whilst methamphetamine is considered to be one of the most popularly abused drugs by drivers (Drummer et al. 2007), surprisingly, little research into driving under the influence of methamphetamine has been conducted. The one published study (Mitler et al. 1993) observed a dose-dependent improvement for both narcolepsy patients and matched controls on a simple driving task with the patients receiving 0, 20, or 40–60 mg of methamphetamine and controls receiving 0, 5, or 10 mg of methamphetamine. In contrast, epidemiological evidence suggests that drivers affected by methamphetamine are inattentive, drive erratically, drift in-between lanes, exhibit impatience, do not drive appropriately to the speed limit, and generally display increased risk taking (Lemos 2009; Logan 2001; Ogden and Moskowitz 2004; Silber et al. 2006; Walsh et al. 2004).
Other amphetamine-type preparations have been found to differentially affect driving performance. MDMA administration has been found to improve tracking performance but reduce car-following performance (Kuypers et al. 2006; Ramaekers et al. 2006) in controlled on-road driving. In an earlier study (Brookhuis et al. 2004), MDMA and multiple drug users completed a driving simulation prior to and after going to a ‘rave’, with MDMA users exhibiting a decreased sense in risk taking and being involved in four times as many crashes in comparison to controls (Brookhuis et al. 2004). Dexamphetamine consumption has also been observed to impair simulated driving performance, with a 0.42-mg/kg dose producing decrements in signalling, stopping at red lights, and reaction time (Silber et al. 2005). Findings from studies that have examined the effects of amphetamine analogues such as dexamphetamine and MDMA (which have similar psychoactive properties to methamphetamine) indicate that dexamphetamine impairs driving ability (Silber et al. 2006) on simulated driving tasks, and MDMA reduces car weaving but impairs car following in on-road driving tests during acute intoxication (Ramaekers et al. 2006).
No study has yet examined the effect of the racemic mix of d,l-methamphetamine on driving ability. Given the rising prevalence of methamphetamine usage and its purported role in driving accidents, controlled studies examining driving performance whilst under the effect of methamphetamine are of critical importance. The aim of the present study was to assess the acute effects (2–3 h post-administration) of d,l-methamphetamine on simulated driving performance, using a repeated-measures, counterbalanced, double-blind, placebo-controlled design. In light of the limited experimental and epidemiological data reviewed, it was expected that following d,l-methamphetamine consumption, participants would exhibit performance deficits on a range of driving variables when compared to placebo and exhibit driving behaviour that was less safe.
Twenty healthy recreational illicit stimulant users (ten males, ten females), aged between 21 and 34 years (mean = 24.3 years, SD = 3.4 years), with an average male weight of 81.2 kg (SD = 12.6) and an average female weight of 59.7 kg (SD = 6.9) were recruited. All participants had a minimum of 11 years of education, and a valid, full driver's licence. All participants were consumers of caffeine, with an average daily intake of 1.0 cup of coffee (range 0–2 cups). Of the 20 participants, 11 were self-assessed smokers, averaging 3.5 cigarettes a day (range 0–22). Participants were informed that they were free to withdraw from the study at any time. The Institutional Research Ethics Committee approved the research.
d,l-Methamphetamine (Lipomed, Arlesheim, Switzerland) was prepared by mixing d,l-methamphetamine with magnesium carbonate, which was encapsulated in soft gelatine capsules to render them visually indistinguishable from the placebo capsules, which contained only magnesium carbonate. Capsules contained either 2, 5, or 10 mg d,l-methamphetamine. Each participant was administered an oral dose of 0.42 mg/kg d,l-methamphetamine.
A repeated-measures, counterbalanced, double-blind, placebo-controlled design was employed. Participants completed two treatment conditions, placebo and 0.42 mg/kg d,l-methamphetamine, separated by a 2-week wash-out period, to reduce residual effects of the drug from the first session. All participants consented to refrain from consuming alcohol for at least 24 h prior to each testing session and illicit drugs for at least 7 days prior to each testing session.
The driving simulator was the CyberCAR™ LITE driver training and evaluation simulator (Thoroughbred Technologies Pty. Ltd.). The steering wheel, a ‘force feedback’ with integrated horn, indicators, headlights, ignition, automatic gears, and hand brake, was affixed to a bench. Brake and accelerator pedals were placed underneath the bench. Participants could adjust the pedal and seat position to suit their height. The simulator task was projected onto a 175 × 120-cm white screen (distance from steering wheel was 280 cm). Participants observed a two-dimensional computer-generated driving scene, as they would through a vehicle windscreen. The simulated dashboard, which was also projected onto the white screen, included a speedometer, rear-view mirror, and side mirrors. The tasks administered employed a simulated conventional on-road light motor vehicle with automatic transmission. The CyberCAR™ LITE simulator is predominantly used in industry, government, and educational agencies for training of both novice and experienced drivers (Papafotiou et al. 2005). Previous studies that have employed the CyberCAR™ LITE simulator have demonstrated that this driving simulator is sensitive to the effects of drugs on driving ability (Papafotiou et al. 2005). Following previous research in our laboratory (Papafotiou et al. 2005), a subset of 33 relevant variables were analysed, with each variable reflecting an error that can typically occur during driving. In accordance with the CyberCAR™ LITE driving simulator manual (Thoroughbred Technologies Pty. Ltd.), each variable score was multiplied by that variable's ‘loading factor’, a number which represents the severity of the error, and subsequently, all adjusted variable scores were summed to give an overall driving performance score. Driving simulator variable scores were summed separately for the day- and night-time driving conditions.
Blood and saliva samples
Three blood and three saliva samples were taken from each participant by a registered nurse during each experimental session. As d-amphetamine has a peak blood concentration between 2 and 4 h (Kupietz et al. 1985; Angrist et al. 1987; Brauer et al. 1996), the first blood and saliva samples were obtained 120 min after administration of the drug, the second samples 170 min after administration of the drug, and the third samples 240 min after administration of the drug. Ten-millilitre samples of blood were obtained using a syringe by venipuncture from the antecubital vein. One-millilitre samples of saliva were obtained using Cozart Rapiscan (Biomediq DPC Pty. Ltd.) saliva collection kits. The saliva collection method involved placing a cotton swab collector into the mouth. An indicator colour (blue) appears at the end of the swab once the swab absorbs 1 ml of saliva. The swab containing saliva is then placed into a test tube containing 2 ml of assay buffer. The swab is then compressed using a small plunger (to separate the saliva from the swab). Blood and saliva samples were immediately stored in a −20°C freezer and subsequently transported to a −70°C freezer after 5–7 days. Blood samples were screened for the seven major drug classes (opiates, amphetamines, benzodiazepines, cannabinoid, barbiturates, cocaine, and methadone) using ELISA/EMIT screens. Subsequently, blood and saliva samples were analysed for specific amphetamine levels using the gas chromatography mass spectroscopy method (Moeller and Kraemer 2002).
Driving simulator variable results for placebo and d,l-methamphetamine conditions
Driving simulator variables
Dangerous action skid
No signal cancel when entering freeway
No signal when entering freeway
Incorrect signalling at intersection
No signal cancel at intersection
Wheels not straight on approaching intersection
No signal when changing lane
No signal cancel when changing lane
No signal when moving off
No signal cancel when moving off
Waited too long before moving off
No signal cancel when overtaking (left)
No signal cancel when overtaking (right)
No signal when overtaking (left)
No signal when overtaking (right)
Speed control brake inappropriate
Driving too fast
No safe following distance
Driving too slow
Straddled barrier line
Released brake inappropriately when stopping
Not sufficient clear space when stopping
Did not stop at red traffic light
Straddled the solid line
Exceeded speed limit
Advanced situation collision
Speed of vehicle when emergency situation occurred (freeway)
Speed of vehicle when emergency situation occurred (city)
Reaction time (emergency stop)
Stopping distance from vehicle/object at emergency stop (freeway)
Stopping distance from vehicle/object at emergency stop (city)
As can be seen in Table 1, there was a trend towards decreased braking ability observed during the d,l-methamphetamine condition, with drivers releasing the brakes inappropriately when stopping more often than during the placebo condition (T = 0, p = 0.10). Additionally, during the d,l-methamphetamine condition, participants drove too fast for the traffic conditions more often than during the placebo condition (trend level) (T = 3.50, p = 0.10). Finally, drivers in the d,l-methamphetamine condition were also found to travel slower on the freeway, at a trend level, at the time that an emergency situation occurred relative to the placebo condition (T = 51, p = 0.08).
In summary, the present experiment found that 0.42 mg/kg of d,l-methamphetamine did not significantly impair simulated driving performance, in recreational stimulant users, 2–3 h post-drug administration. At the individual driving variable level, participants in the d,l-methamphetamine condition were observed to release the brakes inappropriately when stopping, drive too fast for the traffic conditions, and travel slower on the freeway at the time that an emergency situation occurred relative to the placebo condition, although these differences were only evident at a trend level. Overall, the results of the present study suggest that a single acute therapeutic dose of d,l-methamphetamine does not significantly impair driving performance. As the driving simulator task was completed within 2–3 h post-drug administration period, and as d,l-methamphetamine blood concentrations are relatively constant during this period, it is reasonable to conclude that mean blood and saliva d,l-methamphetamine concentrations of approximately 90 and 400 ng/ml, respectively, at 2 h and 95 and 475 ng/ml at 3 h do not significantly impair, or improve, driving performance.
Given that the only published study examining the effect of methamphetamine consumption on driving identified a dose-dependent improvement in performance (Mitler et al. 1993) and, in contrast, epidemiological evidence suggests drivers under the influence of methamphetamine drive erratically and engage in more risk-taking behaviour on the road, the lack of a significant improvement or decrement in driving performance following d,l-methamphetamine consumption is vexing. A number of possible contributors to the findings of the current study and the implication of the role of methamphetamines in driving-related injuries and deaths exist. The concentration of methamphetamine at the respective blood-taking time points of between 0.90 and 0.95 ng/ml may not have produced sufficient subjective effects to impair driving performance in a manner consistent with epidemiological evidence despite the measured levels exceeding those detected in the Drummer and colleagues (Drummer et al. 2011) study of injured Australian drivers. The inference of impairment attributable to methamphetamine in the case of hospital admissions is difficult to compare with controlled drug administration, with the inevitable and inconsistent delays in taking blood samples from injured drivers at hospital, patterns of previous drug use and alcohol, effects of fatigue, dosage differences, and acute and chronic tolerance differences being impossible to control for outside of the laboratory.
Relatively low doses of amphetamines have previously been associated with improved aspects of cognitive performance ostensibly related to driving (Silber et al. 2006) in controlled studies. Recreational users or ‘abusers’ of methamphetamine consume higher and repeated doses of methamphetamine, but it is not possible to assess the effects of these higher ‘abuse’ levels of amphetamines on driving performance in controlled laboratory conditions due to ethical limitations. This discrepancy may further account for inconsistency between our results and the incidence of injuries and deaths of drivers with methamphetamine in their blood and the descriptions of their real-life driving where they reportedly drift out of their lanes of travel or cross divided lines, are involved in high speed collisions, and general weaving (Lemos 2009; Logan 2001). Our relatively small (N = 20) sample of recreational users of illicit substances were only marginally affected by the dose of d,l-methamphetamine, with only trend levels of deficits being observed for driving speeds and braking appropriately. More cognitively demanding, longer, or repeated assessments of driving performance may be necessary to further elucidate the modulatory effects of amphetamine consumption upon driving. Repeated driving and blood assessments may also contribute to reducing any possible variance in the peak subjective effects and metabolism of methamphetamine that may have mitigated any driving improvements or decrements apparent in the current study.
Whilst methamphetamine has been reported to induce transient cognitive improvement and mood enhancement, its consumption has also been linked to deterioration in driving ability, whether through increased risk-taking behaviour (Dastrup et al. 2010) or cognitive disruption. This is of particular concern given the documented use of methamphetamine by professional drivers to facilitate completion of long-haul drives on time. The driving behaviours that were found to be impaired in the current study, inappropriate braking and speed control, somewhat reflect the typical driving behaviours that are most commonly compromised in real-life amphetamine-impaired drivers. The magnitude of these deficits, however, was not statistically significant or indicative of particularly compromised driving ability. Having said this, driving requires the simultaneous execution of several tasks involving a range of cognitive processes, such as attention, motor coordination, decision making, and working memory, across the entire course of a journey. Minor lapses in the ability to operate a motor vehicle or transient risky behaviour on the road as a result of methamphetamine consumption could account for the incidence of methamphetamine detection in injured and deceased drivers. As such, the findings presented herein suggest that d,l-methamphetamine administered at the levels supplied did not impair driving performance in a manner consistent with epidemiological evidence or improve performance consistent with suggesting short-term cognitive enhancement on simple measures. Given the growing prevalence of illicit drugs being found in the blood of deceased (amphetamines 4.1%, Drummer et al. 2004) and injured drivers (methamphetamine 3.1%, MDMA 0.8%, Drummer et al. 2011) in Australia, the short-term consequences of the use of methamphetamine and other amphetamine-type stimulants on driving are of considerable importance and indeed are in need of further research to clarify their specific effects.
This research was partially funded by a grant from VicRoads, Melbourne, Australia, and an Australian Research Council Discovery grant (DP0772762) to Professor Con Stough, Katherine Papafotiou and Edward Ogden.