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Cannabis and its major constituents, Δ9-tetrahydrocannabinol (THC) and cannabidiol (CBD), are being widely used to treat sleep disturbances. However, THC can cause acute cognitive and psychomotor impairment and there are concerns that driving and workplace safety might be compromised the day after evening use. Here, we examined possible 'next day' impairment following evening administration of a typical medicinal cannabis oil in adults with insomnia disorder, compared to matched placebo. This paper describes the secondary outcomes of a larger study investigating the effects of THC/CBD on insomnia disorder. Twenty adults [16 female; mean (SD) age, 46.1 (8.6) y] with physician-diagnosed insomnia who infrequently use cannabis completed two 24 h in-laboratory visits involving acute oral administration of combined 10 mg THC and 200 mg CBD ('THC/CBD') or placebo in a randomised, double-blind, crossover trial design. Outcome measures included 'next day' (≥9 h post-treatment) performance on cognitive and psychomotor function tasks, simulated driving performance, subjective drug effects, and mood. We found no differences in 'next day' performance on 27 out of 28 tests of cognitive and psychomotor function and simulated driving performance relative to placebo. THC/CBD produced a small decrease (-1.4%, p=.016, d=-0.6) in accuracy on the Stroop-Colour Task (easy/congruent) but not the Stroop-Word Task (hard/incongruent). THC/CBD also produced a small increase (+8.6, p=.042, d=0.3) in self-ratings of Sedated at 10 h post-treatment, but with no accompanying changes in subjective ratings of Alert or Sleepy (p's>0.05). In conclusion, we found a lack of notable 'next day' impairment to cognitive and psychomotor function and simulated driving performance following evening use of 10 mg oral THC, in combination with 200 mg CBD, in an insomnia population who infrequently use cannabis. [ABSTRACT FROM AUTHOR]

Rationale: Alcohol-induced driving impairment can occur with any departure from a zero-blood alcohol concentration (BAC). Because intoxication is characterised by impaired judgement, drivers under the influence of alcohol may overestimate their capacity to safely operate a vehicle. Objectives: This study examined the effects of alcohol on driving performance, four-choice reaction time (FCRT), and self-rated confidence in driving ability. It specifically focused on alcohol doses equal to commonly enforced legal BAC limits (i.e. 0.05% and 0.08%). Methods: A randomized, double-blind, placebo-controlled design was utilised. Seventeen participants were tested in three conditions: placebo and two alcohol conditions aiming for BACs of 0.05% and 0.08%. Participants underwent a baseline FCRT task and a 1-h simulated highway driving task before completing another FCRT task and rated their confidence in their driving ability. Results: The high and low alcohol dose conditions resulted in a mean BAC of 0.07%, and 0.04%, respectively (n = 17). The high BAC treatment significantly increased standard deviation of lateral position (SDLP) by 4.06 ± 5.21 cm and standard deviation of speed (SDS) by 0.69 ± 0.17 km/h relative to placebo, while confidence in driving ability remained unchanged across treatments. FCRT performance was impaired by the high BAC treatment (all < 0.01), but there we no significant differences between placebo and low BAC conditions. Conclusions: The findings of this study show that driving performance and associated psychomotor functioning become significantly impaired below legally permissible driving limits in some jurisdictions. We identified a dissociation between driving performance and subjective awareness of impairment. Despite a significantly diminished driving ability at 0.07% BAC, drivers were unaware of their impairment. [ABSTRACT FROM AUTHOR]

Rationale: The effects of hypnotics on automobile driving have been attracting increasing attention. However, few driving simulators (DSs) have been confirmed to have acceptable reliability and validity for assessing the next-day residual effects of zopiclone as a positive control on driving performance. Objective: To investigate whether a new DS could permit detection of the next-day residual effects of zopiclone on driving performance. Methods: In this double-blind, randomized, placebo-controlled crossover trial, 28 healthy males received zopiclone 7.5 mg at bedtime on days 1 and 8 and placebo on the other days over a period of 16 days. The participants took part in three driving tasks—road-tracking, car-following, and harsh-braking—using a DS on days 2 and 9 at 9-h post-dosing. Scores on the Karolinska Sleepiness Scale and Profile of Mood States-Second Edition were then assessed, as was the serum concentration of zopiclone. Results: The estimated differences in the standard deviation of lateral position (cm) in the road-tracking task between the zopiclone and placebo groups on days 2 and 9 were 3.75 cm (90% confidence interval (CI): 1.71–5.79) and 4.07 cm (90% CI: 2.02–6.11), respectively. The estimated differences in the distance coefficient of variation in the car-following task and in the brake reaction time in the harsh-braking task between the zopiclone and placebo groups on day 2 were 4.31 (90% CI: 1.94–6.69) and 24.6 ms (90% CI: 12.7–36.4), respectively. Conclusions: The DS used in this study has sufficient sensitivity to detect the next-day residual effects of zopiclone on driving performance. [ABSTRACT FROM AUTHOR]

Rationale: Although driving simulators (DS) are receiving increasing attention due to concern over traffic accidents under the influences of drugs, few DS are recognized for their reliability and validity. Therefore, the development of an evaluation system using DS for driving performance is urgently needed. Objectives: To investigate whether the standard deviation of lateral position (SDLP) increases with blood alcohol concentration (BAC) using a DS with reliability and calculate the SDLP threshold from the difference between BAC levels of 0 and 0.05%. Methods: Twenty healthy Japanese men performed the DS tasks up to 60 min in Study 1 and DS tasks twice at 1-week intervals in Study 2. Twenty-six healthy men conducted the same DS tasks under BAC level (0, 0.025, 0.05, and 0.09%) in double-blind, randomized, crossover trial in Study 3. The primary outcome was SDLP in a road-tracking test. The test–retest reliability of DS data was assessed, and the estimated difference in SDLP between BAC levels of 0 and 0.05% was calculated using a linear regression model. Results: The cumulative SDLP values at 5-min intervals were stable, and the intraclass correlation coefficient for its values was 0.93. SDLP increased with BAC in a concentration-dependent manner. The predicted ΔSDLP value for the difference between BAC levels of 0 and 0.05% was 9.23 cm. No participants dropped out because of simulator sickness. Conclusions: The new DS used in these studies has reliability, validity, and tolerability and is considered suitable for evaluating the influence of drugs on driving performance. [ABSTRACT FROM AUTHOR]

Rationale: The driving simulator provides a safe and controlled environment for testing driving behaviour efficiently. The question is whether it is sensitive to detect drug-induced effects. Objective: The primary aim of the current study was to investigate the sensitivity of the driving simulator for detecting drug effects. As a case in point, we investigated the dose-related effects of oral ∆-tetrahydrocannabinol (THC), i.e. dronabinol, on simulator and on-the-road driving performance in equally demanding driving tasks. Method: Twenty-four experienced driver participants were treated with dronabinol (Marinol®; 10 and 20 mg) and placebo. Dose-related effects of the drug on the ability to keep a vehicle in lane (weaving) and to follow the speed changes of a lead car (car following) were compared within subjects for on-the-road versus in-simulator driving. Additionally, the outcomes of equivalence testing to alcohol-induced effects were investigated. Results: Treatment effects found on weaving when driving in the simulator were comparable to treatment effects found when driving on the road. The effect after 10 mg dronabinol was however less strong in the simulator than on the road and inter-individual variance seemed higher in the simulator. There was, however, a differential treatment effect of dronabinol on reactions to speed changes of a lead car (car following) when driving on the road versus when driving in the simulator. Conclusion: The driving simulator was proven to be sensitive for demonstrating dronabinol-induced effects particularly at higher doses. Treatment effects of dronabinol on weaving were comparable with driving on the road but inter-individual variability seemed higher in the simulator than on the road which may have potential effects on the clinical inferences made from simulator driving. Car following on the road and in the simulator were, however, not comparable. [ABSTRACT FROM AUTHOR]

Rationale: Hypnotics are widely used to treat insomnia but adverse effects of different hypnotics, especially benzodiazepine receptor agonists, are getting more attention lately. The effects of novel hypnotics have not been fully examined. Objective: This study aims to assess the effects of two hypnotics, ramelteon and triazolam, on driving performance, cognitive function, and equilibrium function. Methods: In this double-blinded, three-way crossover trial, 17 healthy males received acute doses of 8 mg ramelteon, 0.125 mg triazolam, and placebo. The subjects were administered three driving tasks-road-tracking, car-following, and harsh-braking-using a driving simulator and three cognitive tasks-Continuous Performance Test, N-back Test, and Trail-Making Test-at baseline and at 1 and 4 h post-dosing. The Stanford Sleepiness Scale scores and computerized posturography were also assessed. Results: In the driving simulations, ramelteon and triazolam increased the number of subjects who slid off the road. Triazolam increased the standard deviation of lateral position compared to ramelteon and placebo at 1 h post-dosing. Ramelteon and triazolam significantly increased the time to complete of Trail-Making Test part A and the environmental area in posturography compared to placebo at 1 and 4 h post-dosing. Ramelteon and triazolam significantly increased subjective sleepiness compared to placebo at 1 h post-dosing. Conclusions: Ramelteon may affect road-tracking performance, visual attention and/or psychomotor speed measured by Trail-Making Test part A, and body balance in acute dosing. Lower dose of triazolam also impaired performance worse than ramelteon. Physicians should consider risks and benefits when prescribing both drugs, especially in the initial period of administration. [ABSTRACT FROM AUTHOR]

Rationale: Some recent pharmacoepidemiological studies revealed an elevated risk of driving accidents after opioid analgesics uses. Among analgesics, codeine is often associated with paracetamol in numerous pharmaceutical specialties. Objectives: The objective of this study was to evaluate the dose-effect relationship of three usual therapeutic doses of codeine/paracetamol on driving ability, psychomotor performance, subjective alertness, in link with blood concentrations in healthy young volunteers. Methods: Driving performance, responses to psychomotor vigilance tests, and scales reflecting alertness were evaluated during the morning after drug intake in a double-blind, randomized, placebo-controlled study. Sixteen healthy volunteers (23.4 ± 2.7 years old, 8 men and 8 women) participated in this balanced, cross-over study. Three doses of codeine/paracetamol (20/400, 40/800, 60/1200 mg) were evaluated against placebo. Two blood samples were collected, 1 and 4 h after drug intake. In serum, codeine and morphine concentrations were determined in serum using high-performance liquid chromatography electrospray ionization-tandem mass spectrometry, and paracetamol concentrations using fluorescence polarization immunoassay. Results: Driving and psychomotor performance were not affected by any of the three codeine/paracetamol doses. However, significant, though modest, correlations were observed between the driving parameters and both morphine and codeine blood concentrations. Conclusions: This study did not reveal any significant impairment in performance due to the three therapeutic doses used in healthy young volunteers. However, the relationships between drug blood concentration and behavioral measures suggest that an inter-subject variability in blood concentration may influence the power of the observed drug effect. [ABSTRACT FROM AUTHOR]

Rationale: Stimulant drugs are commonly abused and also used to promote wakefulness, yet their effects on driving performance during sleep deprivation have not been thoroughly researched in experimental studies. Objectives: The aims were to assess the effects on fundamental driving parameters during simulated driving of two doses of d-amphetamine and further to assess the interaction between d-amphetamine and sleep deprivation. Methods: A double-blind, placebo-controlled experiment including 18 healthy male volunteers was conducted. Results: The participants felt more alert when taking a dose of d-amphetamine than when taking placebo, and the effect was stronger for the higher dose. However, the data did not show any evidence that taking d-amphetamine prevented the subjects from becoming successively sleepier during the night. A significant main effect of the dose was found for three out of the five primary indicators where the lower dose led to improved driving. These indicators were crossing-car reaction time, and coherence and delay from a car-following event. Regarding sleep deprivation, a main effect was found for four of the primary indicators and three of the secondary indicators. The results showed overall impaired driving with respect to standard deviation of lateral position and delay in reaction time when the sleep-deprived conditions were compared to the alert condition. We found no interactions between dose and sleep deprivation for any of the performance indicators. Conclusions: Our results suggest that administration of d-amphetamine does not compensate for impairment of driving due to fatigue. The positive effects of 10 mg were not further improved or even sustained when increasing the dose to 40 mg. [ABSTRACT FROM AUTHOR]

Rationale: In party circuits dexamphetamine is frequently used in combination with alcohol. It is hypothesized that co-administration of dexamphetamine to alcohol might reduce the sedative effects of alcohol, but may potentiate risk-taking behaviour. Objectives: The study was aimed at assessing the effects of alcohol, dexamphetamine and the combination of both on simulated driving and cognitive performance. Method: Eighteen subjects participated in a randomized, crossover, placebo-controlled study employing four conditions: 10 mg dexamphetamine, 0.8 g/kg alcohol, 10 mg dexamphetamine + 0.8 g/kg alcohol, and placebo. Fundamental driving skills and risk-taking behaviour were assessed in a driving simulator. Subjects also completed vigilance and divided attention tasks, and subjective ratings. Results: Mean BAC levels during simulated driving were between 0.91‰ and 0.64‰. Subjects using alcohol showed a significantly larger mean standard deviation of lateral position and shorter accepted gap time and distance. Use of alcohol or dexamphetamine + alcohol was associated with a higher frequency of red light running and collisions than the dexamphetamine or placebo conditions. Performance of vigilance and divided attention tasks was significantly impaired in the alcohol condition and, to a lesser degree, in the dexamphetamine + alcohol condition. Conclusion: Single doses of 0.8 g/kg alcohol increased risk-taking behaviours and impaired tracking, attention and reaction time during a 3-h period after drinking when BACs declined from 0.9 to 0.2 mg/ml. The stimulatory effects of co-administration of dexamphetamine 10 mg were not sufficient to overcome the impairing effects of alcohol on skills related to driving. [ABSTRACT FROM AUTHOR]

Rational: An increasing number of fatal road-accidents have been reported in which ecstasy was found in the blood of drivers. Although, ecstasy is frequently found to have been used in combination with alcohol, studies on the acute effects of ecstasy co-administered with alcohol on driving performance are relatively rare. Objective: The present study was designed to establish the extent of driver impairment as a consequence of ecstasy or combined ecstasy and alcohol use as compared to driving under the influence of 0.3‰, 0.5‰ and 0.8‰ alcohol. Furthermore, subjective performance was also assessed. Results: Alcohol and ecstasy mainly influenced automated driving performance such as lateral and speed control. However, small to no effects of the substances were found on more complex driving behaviour. Overall, variance within the different driving measures was high especially when participants were treated with 3.4-methylenedioxy-methamphetamine (MDMA) and alcohol. Furthermore, equivalence testing showed that combined use may lead to impaired driving for some, but not all, drivers. Participants rated their own performance to be slightly worse than normal in both studies. Since driving was actually seriously deteriorated, this was a falsely positive assessment of their condition. Conclusions: The dissociation between subjective perceptions and objective performance decrements are important notions for traffic safety since this may affect a driver's judgement of whether or not it is safe to drive. For example, an intoxicated individual might decide to drive because the feelings of alertness caused by MDMA cloud the impairing effects of other drugs such as alcohol, thereby creating a potentially serious risk for traffic safety. [ABSTRACT FROM AUTHOR]

Rationale: Although hypnotics are primarily used by older people, the residual effects the morning after a single nighttime intake of the two most commonly prescribed hypnotics, zolpidem (Zp) and zopiclone (Zc), on older middle-aged drivers have not been evaluated and compared. Methods: Sixteen healthy subjects, 55 to 65 years of age, participated in this double-blind, balanced, cross-over study. Zc (7.5 mg), Zp (10 mg) and flunitrazepam (Fln) (1 mg) or a placebo was administered at each subject's home at 11.00 pm. The next morning, at 9.00 am, the subjects had to drive in a simulated monotonous driving environment for 1 h. During each morning session, two blood samples were collected, and subjective feelings of alertness were completed three times. Results: In comparison to placebo, Zp and Zc equivalently and significantly impaired the standard deviation of lateral position, the standard deviation of speed and the number of road exits. Detectable blood concentrations were found with Zp in 11 subjects at 8.30 am and at 1.30 pm. The subjective alertness factor was significantly impaired with Zp. Conclusions: This is the first study revealing residual effects of Zp on driving performance in ageing drivers which are similar to that of Zc. Studying the effects of medication in different age ranges appears useful to complete the studies on behavioural-pharmacological effects of medication. To reduce the incidence of driving accidents due to prescription drugs, patients should be warned at the time of treatment initiation that they should avoid driving. [ABSTRACT FROM AUTHOR]

Depression is a common mental disorder with cognitive deficits, but little information is available on the effects of antidepressant treatment on driving performance in depressed patients. Assessing actual driving performance and cognition of depressed patients receiving long-term antidepressant treatment. Performance was assessed in depressed patients receiving selective serotonin reuptake inhibitor (SSRI) or serotonin and noradrenalin reuptake inhibitor (SNRI) treatment for 6–52 weeks and in matched healthy controls by means of two standardised on-the-road driving tests and laboratory tests of cognition. Data showed poorer driving performance as indicated by a higher standard deviation of lateral position or ‘weaving motion’ in medicated patients relative to controls. Time to speed adaptation and critical flicker fusion threshold were also impaired in medicated patients. The Hamilton Depression Rating Scale scores in medicated patients were significantly higher as compared to that of controls. No other significant results between the two groups were demonstrated on the variables of the driving tests and laboratory tests of cognition. The depressed patients receiving long-term treatment with SSRI- and SNRI-type antidepressants show impaired driving performance. This impairment in driving performance can probably be attributed to residual depressive symptoms instead of the antidepressant treatment. [ABSTRACT FROM AUTHOR]

Rationale: The number of road fatalities related to the presence of amphetamines in drivers has been relatively constant over the past 10 years. However, there remains uncertainty as to the extent that these drugs induce driving impairment, and whether any such impairments translate to an increase in road fatalities. Objectives: To examine the acute effects of 0.42 mg/kg dexamphetamine on simulated driving performance, and to establish which, if any, simulated driving abilities become impaired following dexamphetamine administration. Methods: A repeated-measures, counter-balanced, double-blind, placebo-controlled design was employed. Twenty healthy volunteers completed two treatment conditions--0.42 mg/kg dexamphetamine and placebo. Performance was assessed using a driving simulator task. Blood and saliva samples were obtained prior to the driving tasks and immediately after task completion (120 min and 170 min post-drug administration, respectively). Results: Mean dexamphetamine blood concentrations were 83 ng/ml and 98 ng/ml at 120 min and 170 min, respectively. Results indicated a decrease in overall simulated driving ability following dexamphetamine administration during the day-time but not the nighttime scenario tasks. Contributing to this performance reduction, "incorrect signalling", "failing to stop at a red traffic light" and "slow reaction times" were the behaviours most strongly affected bydexamphetamine. Conclusions: Thedecrease in simulated driving ability observed during the daytime driving tasks are consistent with the perceptual narrowing or tunnel vision that is associated with dexamphetamine consumption. [ABSTRACT FROM AUTHOR]