An explorative approach to understanding individual differences in driving performance and neurocognition in long-term benzodiazepine users

Objective: Previous research reported cognitive and psychomotor impairments in long‐term users of benzodiazepine receptor agonists (BZRAs). This article explores the role of acute intoxication and clinical complaints. Methods: Neurocognitive and on‐road driving performance of 19 long‐term (≥6 months) regular (≥twice weekly) BZRA users with estimated plasma concentrations, based on self‐reported use, exceeding the therapeutic threshold (CBZRA+), and 31 long‐term regular BZRA users below (CBZRA−), was compared to that of 76 controls. Results: BZRA users performed worse on tasks of response speed, processing speed, and sustained attention. Age, but not CBZRA or self‐reported clinical complaints, was a significant covariate. Road‐tracking performance was explained by CBZRA only. The CBZRA + group exhibited increased mean standard deviation of lateral position comparable to that at blood‐alcohol concentrations of 0.5 g/L. Conclusions: Functional impairments in long‐term BZRA users are not attributable to self‐reported clinical complaints or estimated BZRA concentrations, except for road‐tracking, which was impaired in CBZRA + users. Limitations to address are the lack of assessment of objective clinical complaints, acute task related stress, and actual BZRA plasma concentrations. In conclusion, the results confirm previous findings that demonstrate inferior performance across several psychomotor and neurocognitive domains in long‐term BZRA users

From dusk ‘till yawn:The assessment of driving performance in clinical populations at risk of drowsy driving at the group and individual level

This dissertation discusses different strategies and methods for assessing driving performance in clinical populations, both for groups of patients and individual patients. The central assessment method in this dissertation is the Dutch standardized on-the-road driving test, which is a rather unique driving test conducted by Maastricht University in actual traffic. In addition to theoretical considerations regarding this test, two experimental studies applying the standardized on-the-road driving test for the assessment of driving performance of narcolepsy and sleep apnoea patients after treatment with a novel stimulant medication (or placebo) are presented

Driving Aptitude and Fitness to Drive

The number of annual road traffic deaths is steadily increasing. This chapter provides a general overview of the techniques for identifying risk factors for road traffic accidents and the assessment of driving performance and related functioning, as well as their strengths and weaknesses. Traffic medicine and forensic medicine are closely related disciplines that overlap a great deal. Whereas traffic medicine is mainly concerned with driving capability, forensic medicine is concerned with driver culpability. The most widely adopted study design for investigating contributing factors to road traffic accidents and at-risk drivers is the case–control study. On-road driving tests are often considered as the most ecologically valid assessments of driving performance. Epidemiological and experimental research attempts to uncover risk factors for road traffic accidents. After a driver has been judged to be unfit to drive, an assessment of driving aptitude may be necessary

Effects of Medicinal Drugs on Fitness to Drive

Driving a car is a skill that incorporates many different functions, such as cognitive processes, sensory perceptions and motor skills. Evidence that drugs impair driving ability comes from epidemiological as well as experimental studies. The chapter presents an overview of medicinal drugs that could impair driving performance as tested with the on-the-road driving test. Hypnotics are meant to induce sleep in patients who suffer from insomnia. Anxiolytic drugs are used for the treatment of anxiety. There are several different classes of anti-depressants. These classes are based on their mechanism of action. The group of anti-histamines includes chemically different compounds that all share the pharmacological capacity of preventing histamine from binding to its receptor and diminishing allergies’ symptoms. The chapter provides an overview of the studies using the on-the road driving test for measuring the impairing effects of psychoactive prescription drugs on driving performance

Langdurig gebruik van tweedegeneratieantidepressiva en rijvaardigheid

De vraag of het gebruik van tweedegeneratieantidepressiva effect heeft op de rijvaardigheid van patiënten met een klinische depressie is nog niet beantwoord. De conclusies uit epidemiologisch onderzoek zijn niet eenduidig. Experimentele studies laten weinig invloed zien van tweedegeneratieantidepressiva op de rijvaardigheid, maar deze studies wijken vaak methodologisch af van de klinische praktijk. Dit artikel beschrijft de uitkomsten van een onderzoek naar de effecten van een langdurige behandeling (6–52 weken) met tweedegeneratieantidepressiva in een steekproef van klinisch depressieve patiënten. Patiënten die werden behandeld met een medicijn uit deze groep (n = 24) werden vergeleken met patiënten die chronisch behandeld werden met een benzodiazepine (n = 31), een onbehandelde patiëntengroep (n = 10) en een controlegroep van gezonde vrijwilligers (n = 24). De uitkomsten tonen aan dat de eerste groep significant beter presteerde op een gestandaardiseerde rijtest op de weg dan de andere twee patiëntengroepen, maar dat deze groep het nog steeds slechter deed dan de controlegroep. Een correlatieanalyse liet een verband zien tussen de ernst van de depressie en de prestatie op de rijtest. De conclusie is dan ook dat depressieve klachten een probleem vormen voor de rijveiligheid en dat een behandeling met een tweedegeneratieantidepressivum dit risico kan doen afnemen

Effect of Cannabidiol and Δ9-Tetrahydrocannabinol on Driving Performance:A Randomized Clinical Trial

IMPORTANCE: Cannabis use has been associated with increased crash risk, but the effect of cannabidiol (CBD) on driving is unclear. OBJECTIVE: To determine the driving impairment caused by vaporized cannabis containing Δ(9)-tetrahydrocannabinol (THC) and CBD. DESIGN, SETTING, AND PARTICIPANTS: A double-blind, within-participants, randomized clinical trial was conducted at the Faculty of Psychology and Neuroscience at Maastricht University in the Netherlands between May 20, 2019, and March 27, 2020. Participants (N = 26) were healthy occasional users of cannabis. INTERVENTIONS: Participants vaporized THC-dominant, CBD-dominant, THC/CBD-equivalent, and placebo cannabis. THC and CBD doses were 13.75 mg. Order of conditions was randomized and balanced. MAIN OUTCOMES AND MEASURES: The primary end point was standard deviation of lateral position (SDLP; a measure of lane weaving) during 100 km, on-road driving tests that commenced at 40 minutes and 240 minutes after cannabis consumption. At a calibrated blood alcohol concentration (BAC) of 0.02%, SDLP was increased relative to placebo by 1.12 cm, and at a calibrated BAC of 0.05%, SDLP was increased relative to placebo by 2.4 cm. RESULTS: Among 26 randomized participants (mean [SD] age, 23.2 [2.6] years; 16 women), 22 (85%) completed all 8 driving tests. At 40 to 100 minutes following consumption, the SDLP was 18.21 cm with CBD-dominant cannabis, 20.59 cm with THC-dominant cannabis, 21.09 cm with THC/CBD-equivalent cannabis, and 18.28 cm with placebo cannabis. SDLP was significantly increased by THC-dominant cannabis (+2.33 cm [95% CI, 0.80 to 3.86]; P  .99), relative to placebo. At 240 to 300 minutes following consumption, the SDLP was 19.03 cm with CBD-dominant cannabis, 19.88 cm with THC-dominant cannabis, 20.59 cm with THC/CBD-equivalent cannabis, and 19.37 cm with placebo cannabis. The SDLP did not differ significantly in the CBD (−0.34 cm [95% CI, −1.77 to 1.10]; P > .99), THC (0.51 cm [95% CI, −1.01 to 2.02]; P > .99) or THC/CBD (1.22 cm [95% CI, −0.29 to 2.72]; P = .20) conditions, relative to placebo. Out of 188 test drives, 16 (8.5%) were terminated due to safety concerns. CONCLUSIONS AND RELEVANCE: In a crossover clinical trial that assessed driving performance during on-road driving tests, the SDLP following vaporized THC-dominant and THC/CBD-equivalent cannabis compared with placebo was significantly greater at 40 to 100 minutes but not 240 to 300 minutes after vaporization; there were no significant differences between CBD-dominant cannabis and placebo. However, the effect size for CBD-dominant cannabis may not have excluded clinically important impairment, and the doses tested may not represent common usage. TRIAL REGISTRATION: EU Clinical Trials Register: 2018-003945-4

Effect of Cannabidiol and Δ9-Tetrahydrocannabinol on Driving Performance: A Randomized Clinical Trial

Importance: Cannabis use has been associated with increased crash risk, but the effect of cannabidiol (CBD) on driving is unclear.Objective: To determine the driving impairment caused by vaporized cannabis containing Δ9-tetrahydrocannabinol (THC) and CBD.Design, Setting, and Participants: A double-blind, within-participants, randomized clinical trial was conducted at the Faculty of Psychology and Neuroscience at Maastricht University in the Netherlands between May 20, 2019, and March 27, 2020. Participants (N = 26) were healthy occasional users of cannabis.Interventions: Participants vaporized THC-dominant, CBD-dominant, THC/CBD-equivalent, and placebo cannabis. THC and CBD doses were 13.75 mg. Order of conditions was randomized and balanced.Main Outcomes and Measures: The primary end point was standard deviation of lateral position (SDLP; a measure of lane weaving) during 100 km, on-road driving tests that commenced at 40 minutes and 240 minutes after cannabis consumption. At a calibrated blood alcohol concentration (BAC) of 0.02%, SDLP was increased relative to placebo by 1.12 cm, and at a calibrated BAC of 0.05%, SDLP was increased relative to placebo by 2.4 cm.Results: Among 26 randomized participants (mean [SD] age, 23.2 [2.6] years; 16 women), 22 (85%) completed all 8 driving tests. At 40 to 100 minutes following consumption, the SDLP was 18.21 cm with CBD-dominant cannabis, 20.59 cm with THC-dominant cannabis, 21.09 cm with THC/CBD-equivalent cannabis, and 18.28 cm with placebo cannabis. SDLP was significantly increased by THC-dominant cannabis (+2.33 cm [95% CI, 0.80 to 3.86]; P  .99), relative to placebo. At 240 to 300 minutes following consumption, the SDLP was 19.03 cm with CBD-dominant cannabis, 19.88 cm with THC-dominant cannabis, 20.59 cm with THC/CBD-equivalent cannabis, and 19.37 cm with placebo cannabis. The SDLP did not differ significantly in the CBD (−0.34 cm [95% CI, −1.77 to 1.10]; P > .99), THC (0.51 cm [95% CI, −1.01 to 2.02]; P > .99) or THC/CBD (1.22 cm [95% CI, −0.29 to 2.72]; P = .20) conditions, relative to placebo. Out of 188 test drives, 16 (8.5%) were terminated due to safety concerns.Conclusions and Relevance: In a crossover clinical trial that assessed driving performance during on-road driving tests, the SDLP following vaporized THC-dominant and THC/CBD-equivalent cannabis compared with placebo was significantly greater at 40 to 100 minutes but not 240 to 300 minutes after vaporization; there were no significant differences between CBD-dominant cannabis and placebo. However, the effect size for CBD-dominant cannabis may not have excluded clinically important impairment, and the doses tested may not represent common usage

Influence of long-term benzodiazepine use on neurocognitive skills related to driving performance in patient populations: a review

Acute benzodiazepine intoxication produces severe impairment of neurocognitive skills related to driving. It is less clear whether such impairments also occur in patients who use benzodiazepines chronically. The current review evaluated neurocognitive skills of long-term benzodiazepine users and addressed 2 major questions: do long-term users develop tolerance for the impairing effects of benzodiazepines on neurocognitive performance, and if so, does tolerance warrant a change in driver fitness classification systems that currently deem users of benzodiazepines unfit to drive? Neurocognitive impairments were reported in patients who on average used benzodiazepines for 5-15 years. In addition, sensitivity to acute benzodiazepine impairment decreased in long-term users, suggesting (partial) tolerance. Definitions of clinical relevance of neurocognitive impairments in long-term users and how these were affected by duration of benzodiazepine use were generally lacking. Also, sensitivity of neurocognitive tasks to drug effects and their validity to predict fitness to drive were generally unknown. Because of these limitations, no firm conclusion can be drawn regarding a re-classification of long-term benzodiazepine effects on driver fitness