Acute administration of alprazolam, alcohol and their combination on cognitive performance and mood: A randomised, double-blind, placebo-controlled study.

BACKGROUND: Recreational co-consumption of benzodiazepines and alcohol is a common practise; yet, the cognitive effects of this combination remain poorly understood. This study aimed to investigate the acute cognitive effects of combining a 1 mg dose of alprazolam with a moderate dose of alcohol (target 0.04% blood alcohol concentration (BAC)) in a non-clinical population. METHODS: In this randomised, double-blind, placebo-controlled, crossover trial, participants completed computerised cognitive assessments and the brief biphasic alcohol effects scale (B-BAES) after consuming 1 mg of alprazolam, both with and without a moderate dose of alcohol (target 0.04% BAC). RESULTS: Among 20 healthy participants (mean age = 28.6, SD ± 4.0 years, 60% female), we found that a peak BAC of 0.03% had no significant impact on cognitive performance. Both the individual use of alprazolam and its combination with alcohol resulted in impaired reaction time, digit vigilance, and verbal, spatial and numeric working memory tasks, although an additive effect when alcohol and alprazolam were consumed together was not evident. The most pronounced cognitive effects occurred at 100 min after dosing, coinciding with increased alprazolam concentrations. Sedative effects were heightened with alcohol, alprazolam and their combination while no stimulative effects were reported. CONCLUSIONS: Our findings highlight the significant implications of a therapeutic dose of alprazolam on impairing cognitive performance. This is particularly relevant considering the frequency of non-medical alprazolam use. Future studies should explore different dosages, administration timings and long-term effects to inform the development of public health policies and guidelines regarding the combined use of alcohol and benzodiazepines.

Driving impairment and altered ocular activity under the effects of alprazolam and alcohol: A randomized, double-blind, placebo-controlled study.

BACKGROUND: Alprazolam, also known by trade-name Xanax, is regularly detected along with alcohol in blood samples of drivers injured or killed in traffic collisions. While their co-consumption is principally legal, policy guidelines concerning fitness-to-drive are lacking and methods to index impairment are underdeveloped. METHODS: In this randomized, double-blind, placebo-controlled, crossover trial, we examined whether legally permissible levels of alcohol [target 0.04% blood alcohol concentration (BAC)], alprazolam (1mg), and their combination impacts driving performance, and whether driving impairment can be indexed by ocular activity. Participants completed a test battery consisting of a 40-minute simulated highway drive with ocular parameters assessed simultaneously, the Karolinska Sleepiness Scale, and a confidence to drive assessment following four separate treatment combinations. The predictive efficacy of ocular parameters to identify alcohol and alprazolam-related driving impairment was also examined. RESULTS: Among 21 healthy, fully licensed drivers (37% female, mean age 28.43, SD ± 3.96), driving performance was significantly impacted by alprazolam, alcohol, and their combination. Linear regression models revealed that the odds of an out-of-lane event occurring increased five-fold under the influence alprazolam alone and when combined with alcohol. An increase in gaze transition entropy (GTE) demonstrated the strongest association with the odds of an out-of-lane event occurring in the same minute, with both microsleeps and fixation rate achieving moderate accuracy across treatments. CONCLUSIONS: Alprazolam and alcohol, alone and in combination, impaired select aspects of vehicle control over time. GTE, microsleeps, and fixation rate show potential as real-time indicators of driving impairment and crash risk associated with alcohol and alprazolam consumption.

The prevalence of alcohol use and risky driving practises among individuals who consume sedatives nonmedically: findings from the NESARC-III.

Background: Worldwide, 1.3 million people die because of a road traffic collision each year, with over half (57.7%) of such deaths in the United States involving a psychoactive substance. The prevalence of drink-drivers is slowly declining; however, the number of drivers under the influence of other drugs, such as sedatives, continues to rise.Objectives: This study aimed to examine alcohol use and risky driving practices among individuals who consume sedatives nonmedically.Methods: A total of 36,309 US adults (48.1% male) who participated in wave 3 (2012) of the National Epidemiologic Survey on Alcohol and Related Conditions were included for analysis.Results: Overall, 827 respondents reported past-year nonmedical sedative use. Almost two-third (64.9%) of these individuals exceeded recommended drinking guidelines and 42.5% met the criteria for a past-year DSM-5 alcohol use disorder. When controlling for demographic, lifestyle, and health factors, they were 1.84 times as likely to drink-drive (95% confidence interval = 1.46-2.33, p < .001) compared to those not using sedatives or using them as prescribed. Among those who reported both drink-driving and driving under the influence of sedatives in the last 12 months, 68.1% met the criteria for a past-year DSM-5 sedative use disorder.Conclusion: Several driving outcomes relevant to road safety, such as driving under the influence of alcohol or sedatives, are impacted by sedative consumption. Given that individuals who consume sedatives nonmedically may be unaware or misperceive the impacts of substance use on safe driving, interventions to reduce such behavior should be targeted among this high-risk group.

The effects of amphetamines alone and in combination with alcohol on functional neurocognition: A systematic review.

Due to their desirable synergistic and/or additive pharmacological effects, amphetamines and alcohol are frequently co-consumed; yet, their combined functional neurocognitive effects remain poorly defined. The PubMed, Scopus, SafetyLit, CINAHL Complete and Medline databases were examined from inception to December 2020. Study selection, data extraction and Cochrane Risk of Bias (RoB2) assessments were conducted according to PRISMA guidelines, and the review was registered on the PROSPERO database (CRD42020189168). A total of 39 full-text articles were included which examined the effects of six amphetamine analogues alone (n = 33) and in combination with alcohol (n = 6) on measures of attention, working memory and reaction time. Amphetamine alone produced limited inverted-U shaped improvement in select behavioural domains, particularly among poor baseline performers. Combined amphetamine and alcohol impaired psychomotor speed and motor control comparable to alcohol alone, and co-consumption with high doses of alcohol (0.08 %BAC) protracted behavioural deficits. Co-consumption of amphetamine with high doses of alcohol impairs response discrimination and psychomotor speed, and their combination is not sufficient to overcome alcohol-induced motor impairment.

The Combined Effects of Alcohol and Benzodiazepines on Driving-Related Neurocognitive Skills: A Systematic Review.

OBJECTIVE: Research concerning the combined effects of alcohol and benzodiazepines on driving-related skills is largely inconsistent. Because as many as 88% of benzodiazepine users report the additional consumption of alcohol, this review aims to provide an updated and concise synthesis of the available high-quality research. METHOD: We searched EBSCOhost, PubMed, Scopus, and Web of Science until April 1, 2020, for double-blind, placebo-controlled, repeated-measures intervention trials that examined the effects of alcohol (any dose provided as blood alcohol concentration [BAC]) in combination with oral benzodiazepines on neurocognitive tasks related to driving. RESULTS: We identified evidence of a substance and timing-dependent interaction for measures of reaction time, tracking, divided attention, and visual functioning. Administering alcohol in conjunction with or shortly after a benzodiazepine resulted in a stronger interactive effect than when administration occurred further apart. An additive and/or synergistic effect often occurred when a therapeutic dose of benzodiazepine was combined with alcohol at a BAC below .05%. CONCLUSIONS: Combined alcohol and benzodiazepine use was associated with significant impairments in driving-related neurocognitive skills. There is a clear need for more high-quality research in this area to better elucidate the mechanisms of alcohol and benzodiazepine interactions. Drivers may be unaware of impairments following the combination of these drugs at legal driving limits. Thus, drivers should be warned to take caution when consuming even small amounts of alcohol while under treatment with benzodiazepines.

Driver monitoring systems (DMS): The future of impaired driving management?

OBJECTIVE: Driver monitoring systems (DMS) are the next generation of vehicle safety technology. Broadly, these refer to the embedded, aftermarket wearable or vehicle-mounted devices that collect observable information about the operator to make real-time assessment of their capacity to perform the driving task. Integrating biobehavioral monitoring (primarily ocular metrics) with driving performance assessments, these systems function to infer driver state in real time to identify operator conditions that negatively affect driving (such as fatigue, inattention, or distraction). METHOD: We review available methods used to infer driver state, as referenced against accepted models for optimal performance. Modeling our observations on deviation from predetermined performance thresholds used to trigger graded safety alerts, we suggest that many psychoactive substances produce alterations to biobehavioral processes including attentional and motor control, which affect performance indices in a manner already arguably captured by these technologies. RESULTS: Using these existing frameworks, there is considerable potential to similarly catalogue the effect of many common intoxicants known to negatively affect driving ability. This will provide safety-relevant and practical biological models for the development of next-generation multimodal DMS that integrate ocular and physiological variables sensitive to the effects of common and emergent psychoactive substances. CONCLUSION: These devices have tangible potential application across all areas of transportation, including aviation, rail, and all commercial and private vehicle systems.

Shared Demands Between Cognitive and Physical Tasks May Drive Negative Effects of Fatigue: A Focused Review.

Over the last decade, there has been increasing interest in the effects of cognitive fatigue on physical performance. This review aims to provide an understanding of these effects with an emphasis on different types of physical tasks requiring different cognitive loads. We specifically focus on understanding the similarity or difference between the cognitive and physical task to help formulate a hypothesis for when there is a decline in the subsequent physical task and when there is not. Taken together, the research shows that endurance performance and perceptual-cognitive skills seem to decline following the completion of a cognitive task, while anaerobic performance remains unaffected. Consistent with the limited-resource model of self-control, the completion of a cognitively demanding task may deplete or inhibit cognitive resources, resulting in impaired performance on a subsequent physical task that relies on similar resources. In other words, physical tasks involving central executive functioning may be significantly more impaired by cognitive fatigue compared to tasks that utilize an all-out strategy. It is recommended that future research continues examining the impact of cognitive fatigue on different types of physical tasks while controlling for other variables.