Residual effects of esmirtazapine on actual driving performance: overall findings and an exploratory analysis into the role of CYP2D6 phenotype

INTRODUCTION: Esmirtazapine is evaluated as a novel drug for treatment of insomnia. PURPOSE: The present study was designed to assess residual effects of single and repeated doses of esmirtazapine 1.5 and 4.5 mg on actual driving in 32 healthy volunteers in a double-blind, placebo-controlled study. Treatment with single doses of zopiclone 7.5 mg was included as active control. METHODS: Treatments were administered in the evening. Driving performance was assessed in the morning, 11 h after drug intake, in a standardized on-the-road highway driving test. The primary study parameter was standard deviation of lateral position (SDLP), a measure of "weaving". All subjects were subjected to CYP2D6 phenotyping in order to distinguish poor metabolizers from extensive metabolizers of esmirtazapine. RESULTS: Overall, esmirtazapine 1.5 mg did not produce any clinically relevant change in SDLP after single and repeated dosing. Driving impairment, i.e., a rise in SDLP, did occur after a single-dose administration of esmirtazapine 4.5 mg but was resolved after repeated doses. Acute driving impairment was more pronounced after both doses of esmirtazapine in a select group of poor metabolizers (N = 7). A single-dose zopiclone 7.5 mg also increased SDLP as expected. CONCLUSION: It is concluded that single and repeated doses of 1.5 mg esmirtazapine are generally not associated with residual impairment. Single-dose administration of 4.5 mg esmirtazapine was associated with residual impairment that generally resolved after repeated administration. Exploratory analysis in a small group of poor CYP 2D6 metabolizers suggested that these subjects are more sensitive to the impairing effects of esmirtazapine on car driving

Tolerance and cross-tolerance to neurocognitive effects of THC and alcohol in heavy cannabis users

and cross-tolerance to neurocognitive effects of THC and alcohol in heavy cannabis user

Evaluating the effects of bilingual traffic signs on driver performance and safety

Variable Message Signs (VMS) can provide immediate and relevant information to road users and bilingual VMS can provide great flexibility in countries where a significant proportion of the population speak an alternative language to the majority. The study reported here evaluates the effect of various bilingual VMS configurations on driver behaviour and safety. The aim of the study was to determine whether or not the visual distraction associated with bilingual VMS signs of different configurations (length, complexity) impacted on driving performance. A driving simulator was used to allow full control over the scenarios, road environment and sign configuration and both longitudinal and lateral driver performance was assessed. Drivers were able to read one and two-line monolingual signs and two-line bilingual signs without disruption to their driving behaviour. However, drivers significantly reduced their speed in order to read four-line monolingual and four-line bilingual signs, accompanied by an increase in headway to the vehicle in front. This implies that drivers are possibly reading the irrelevant text on the bilingual sign and various methods for reducing this effect are discussed

Psychedelic resting-state neuroimaging: a review and perspective on balancing replication and novel analyses

Clinical research into serotonergic psychedelics is expanding rapidly, showing promising efficacy across myriad disorders. Resting-state functional magnetic resonance imaging (rs-fMRI) is a commonly used strategy to identify psychedelic-induced changes in neural pathways in clinical and healthy populations. Here we, a large group of psychedelic imaging researchers, review the 42 research articles published to date, based on the 17 unique studies evaluating psychedelic effects on rs-fMRI, focusing on methodological variation. Prominently, we observe that nearly all studies vary in data processing and analysis methodology, two datasets are the foundation of over half of the published literature, and there is lexical ambiguity in common outcome metric terminology. We offer guidelines for future studies that encourage coherence in the field. Psychedelic rs-fMRI will benefit from the development of novel methods that expand our understanding of the brain mechanisms mediating its intriguing effects; yet, this field is at a crossroads where we must also consider the critical importance of consistency and replicability to effectively converge on stable representations of the neural effects of psychedelics

Predictors for patient knowledge and reported behaviour regarding driving under the influence of medicines: a multi-country survey

<p>Abstract</p> <p>Background</p> <p>Reports on the state of knowledge about medicines and driving showed an increased concern about the role that the use of medicines might play in car crashes. Much of patient knowledge regarding medicines comes from communications with healthcare professionals. This study, part of the DRUID (Driving Under the Influence of Drugs, alcohol and medicines) project, was carried out in four European countries and attempts to define predictors for knowledge of patients who use driving-impairing medicines. The influence of socio-demographic variables on patient knowledge was investigated as well as the influence of socio-demographic factors, knowledge and attitudes on patients' reported behaviour regarding driving under the influence of medicines.</p> <p>Methods</p> <p>Pharmacists handed out questionnaires to patients who met the inclusion criteria: 1) prevalent user of benzodiazepines, antidepressants or first generation antihistamines for systemic use; 2) age between 18 and 75 years old and 3) actual driver of a motorised vehicle. Factors affecting knowledge and reported behaviour towards driving-impairing medicines were analysed by means of multiple linear regression analysis and multiple logistic regression analysis, respectively.</p> <p>Results</p> <p>A total of 633 questionnaires (out of 3.607 that were distributed to patients) were analysed. Patient knowledge regarding driving under the influence of medicines is better in younger and higher educated patients. Information provided to or accessed by patients does not influence knowledge. Patients who experienced side effects and who have a negative attitude towards driving under the influence of impairing medicines are more prone to change their driving frequency behaviour than those who use their motorised vehicles on a daily basis or those who use anti-allergic medicines.</p> <p>Conclusions</p> <p>Changes in driving behaviour can be predicted by negative attitudes towards driving under the influence of medicines but not by patients' knowledge regarding driving under the influence of medicines. Future research should not only focus on information campaigns for patients but also for healthcare providers as this might contribute to improve communications with patients regarding the risks of driving under the influence of medicines.</p

Two cases of "cannabis acute psychosis" following the administration of oral cannabis

BACKGROUND: Cannabis is the most commonly used illegal drug and its therapeutic aspects have a growing interest. Short-term psychotic reactions have been described but not clearly with synthetic oral THC, especially in occasional users. CASE PRESENTATIONS: We report two cases of healthy subjects who were occasional but regular cannabis users without psychiatric history who developed transient psychotic symptoms (depersonalization, paranoid feelings and derealisation) following oral administration of cannabis. In contrast to most other case reports where circumstances and blood concentrations are unknown, the two cases reported here happened under experimental conditions with all subjects negative for cannabis, opiates, amphetamines, cocaine, benzodiazepines and alcohol, and therefore the ingested dose, the time-events of effects on behavior and performance as well as the cannabinoid blood levels were documented. CONCLUSION: While the oral route of administration achieves only limited blood concentrations, significant psychotic reactions may occur

Extended Driving Impairs Nocturnal Driving Performances

Though fatigue and sleepiness at the wheel are well-known risk factors for traffic accidents, many drivers combine extended driving and sleep deprivation. Fatigue-related accidents occur mainly at night but there is no experimental data available to determine if the duration of prior driving affects driving performance at night. Participants drove in 3 nocturnal driving sessions (3–5am, 1–5am and 9pm–5am) on open highway. Fourteen young healthy men (mean age [±SD] = 23.4 [±1.7] years) participated Inappropriate line crossings (ILC) in the last hour of driving of each session, sleep variables, self-perceived fatigue and sleepiness were measured. Compared to the short (3–5am) driving session, the incidence rate ratio of inappropriate line crossings increased by 2.6 (95% CI, 1.1 to 6.0; P<.05) for the intermediate (1–5am) driving session and by 4.0 (CI, 1.7 to 9.4; P<.001) for the long (9pm–5am) driving session. Compared to the reference session (9–10pm), the incidence rate ratio of inappropriate line crossings were 6.0 (95% CI, 2.3 to 15.5; P<.001), 15.4 (CI, 4.6 to 51.5; P<.001) and 24.3 (CI, 7.4 to 79.5; P<.001), respectively, for the three different durations of driving. Self-rated fatigue and sleepiness scores were both positively correlated to driving impairment in the intermediate and long duration sessions (P<.05) and increased significantly during the nocturnal driving sessions compared to the reference session (P<.01). At night, extended driving impairs driving performances and therefore should be limited

A European study on alcohol and drug use among young drivers : The TEND by night study design and methodology

Background. Young individuals are the age group with the highest risk of car accidents. One of main explanations relies on the use of psychoactive substances (alcohol, illegal and medicinal drugs), which are known to be major risk factors of road accidents, and whose consumption is almost universally more common among younger drivers. Although the correlation between psychoactive substances use and decrease in driving performance has been established in controlled experimental or laboratory settings, few studies were conducted in naturalistic circumstances. The TEND by Night project has been designed to evaluate the relationship between driving performance and psychoactive substances assumption in young drivers enrolled at typical places of consumption. Methods/Design. The TEND by Night project, endorsed by the European Commission, is a multidisciplinary, multi-centric, cross-sectional study conducted in six European countries (Italy, Belgium/Netherlands, Bulgaria, Spain, Poland and Latvia). The study population consists of 5000 young drivers aged 16-34 years, attending recreational sites during weekend nights. The intervention is based on the portal survey technique and includes several steps at the entrance and exit of selected sites, including the administration of semi-structured questionnaires, breath alcohol test, several drug assumption test, and measurement of the reaction time using a driving simulator. The main outcome is the difference in reaction time between the entrance and exit of the recreation site, and its correlation with psychoactive substances use. As a secondary outcome it will be explored the relationship between reaction time difference and the amount of consumption of each substance. All analyses will be multivariate. Discussion. The project methodology should provide some relevant advantages over traditional survey systems. The main strengths of the study include the large and multicentric sample, the objective measurement of substance assumption (which is typically self-reported), the application of a portal survey technique and the simultaneous evaluation of several psychoactive substances.publishersversionPeer reviewe