Predicting changes in driving performance in individuals who use cannabis following acute use based on self-reported readiness to drive.

OBJECTIVE: It is unclear to what extent individuals who use cannabis can accurately assess their ability to drive safely following cannabis use, and lack of understanding as to what factors influence changes in driving performance following cannabis use. This research explores whether self-reported readiness to drive (RTD) and previous experience (PE) using cannabis within 2 h of driving can predict observed changes in driving performance following acute cannabis use. METHODS: Individuals who used cannabis at least monthly completed a baseline simulated drive, were dosed with cannabis of approximately 6.18% THC, then drove at approximately 30-minutes, 90-minutes, and 180-minutes post-dose. Before each drive, participants were asked if they felt safe to drive (on real roadways, not the simulator), a yes/no question (RTD-yes/RTD-no). Venous blood was drawn at baseline and approximately 15-minutes post-dose. Cannabis use history was obtained and included whether the participant had ever driven within 2 h of use (PE-yes/PE-no) and how many days out of the past 30 they had done so (NPD). Drives were segmented into events delineated by changes in the driving environment. Within events, standard deviation of lateral position (SDLP), average speed, and number of lane departures were calculated, and differences from baseline were modeled using mixed-effects regression. Models considered covariates of time, event, and speed, and used RTD-yes/RTD-no, PE-yes/PE-no, NPD, and their interactions as potential predictors. Conditional R2 was used to compare the predictive ability of RTD versus change in Delta-9-THC. DATA SOURCES: Data were collected from 30 individuals who use cannabis and included cannabis use patterns, driving behaviors after use, self-reported RTD, measures of driving performance, and cannabinoid blood levels. RESULTS: RTD-no predicted a 2.60 cm increase in SDLP relative to baseline (95 % CI: 0.43, 4.73, p = 0.018). Average speeds generally decreased relative to baseline, except for RTD-yes with PE-yes (+1.08 mph, 95 % CI: 0.05, 2.11). NPD predicted increased speed among RTD-yes (+0.11 mph per additional day, 95 % CI: 0.01, 0.22) and decreased speed among RTD-no (-0.06 mph per additional day, 95 % CI: -0.18, 0.32). The difference in these effects was statistically significant (p = 0.038). RTD, PE, and NPD were not significant predictors of changes in number of lane departures. For all outcomes, models using RTD achieved higher conditional R2 than models that replaced this variable with change in Delta-9-THC. Differences were most prominent when modeling change in speed with NPD (R2=0.544 with RTD vs. R2=0.481 with change in Delta-9-THC). SIGNIFICANCE OF RESULTS: These results suggest individuals who use cannabis can somewhat self-identify when they are likely to exhibit greater degraded lateral control, although RTD does not fully explain observed degradation in performance. Past research suggests drivers may reduce speed to compensate for recognized impairment following acute cannabis use. Our findings suggest this to be true for those who reported never having previously driven within 2 h of cannabis use or reported RTD-no, but not for those who had previously driven within 2 h of cannabis use and reported RTD-yes. This indicates compensatory behavior is not uniform and helps focus public health outreach efforts.

A study of self-reported personal cannabis use and state legal status and associations with engagement in and perceptions of cannabis-impaired driving.

Objective: The objectives of the current study were to (1) characterize predictors of perceived risk of driving within 2 h of cannabis use and driving after cannabis use in a sample of adults who have used cannabis in the past year and (2) determine whether the influence of these predictors vary by state legalizations status.Methods: Data for this study were from online surveys. Study participants from Colorado, Iowa, and Illinois were included if they reported being between 25 and 40 years old and had a history of cannabis use. Outcome variables included (1) days of cannabis use per month, (2) reported driving within 2 h of cannabis use (vs. not driving within 2 h as reference), (3) proportion of driving after cannabis use days per month (days of driving a car within 2 h of cannabis use per month/days of cannabis use per month), and (4) perception of safety of driving after cannabis use. Potential predictors included age of first use of cannabis, gender, education status, and state of residence. The SAS GLMSELECT Procedure was used for the analysis.Results: Increased age of first use of cannabis was associated with decreased days of cannabis use per month (B = -0.51 days/month per year), a reduction in the proportion of driving after cannabis use days per month (B = -0.02 per month), and decreased perception of safety of driving after cannabis use (B = -0.06 per year). Female gender was also associated with less use (B = -2.3 days per month), a lower proportion of driving following use (B = -0.06 days driving/days used), and decreased perception of safety (B = -0.29). In addition, residents of Colorado reported using the most days, had the highest likelihood of driving within 2 h of use, and had the most positive perceptions of being able to safely drive after cannabis use.Conclusions: The delay in onset of cannabis use may mitigate its use among adults and driving after cannabis use. This has important implications for driver safety. Intervention programs for reducing cannabis's effects on driving should focus on individuals with early onset of use, male drivers, and drivers in states where cannabis for adult recreational use is legalized.

Perceived effects of cannabis: Generalizability of changes in driving performance.

OBJECTIVE: The objective of this analysis was to determine the generalizability of the relationship between different samples of a driver's perceived state after cannabis use and related performance while operating a motor vehicle. METHODS: Data were collected from 52 subjects in a study examining the effects of cannabis on driving performance. Data were analyzed using the SAS GLM Select procedure, using stepwise selection, with subjective effects, dosing condition (placebo vs. 6.18% delta-9-tetrahydrocannabinol [THC]), and driving context as independent measures. Correlation matrices of measures of driving performance against subjective responses and dosing condition used Pearson's and Spearman's test statistics, respectively. Results were compared to a prior study from a sample of 10 subjects. RESULTS: Subjective perceptions of acute cannabis impairment remain significant predictors of driving performance and explain individual variability in driving performance degradation as well as the data, beyond that which can be explained by acute use of cannabis alone. However, the significant subjective predictors of driving performance differ between the current and prior studies. To better understand these differences, correlations between subjective effects and performance measures were evaluated, which revealed that most correlations matched directionally (e.g., an increase in "good drug effect" was correlated with an increase in standard deviation of lane position [SDLP]). When there was a mismatch, 1 or more correlations were insignificant. Dosing condition and "stoned" were perfectly consistent; "high" and "sedated" contained 1 mismatch; and "anxious," "good drug effect" and "restless" contained 3 or more mismatches. CONCLUSIONS: The results indicate that across both studies, differences in the perceived effects of cannabis are reflected in changes in both lateral and longitudinal control beyond the acute effects of cannabis, which may help explain individual variability in response to acute intoxication. However, the generalizability of these findings is lacking, as shown by inconsistencies in when and where subjective effects were significant. Other factors such as frequency of use, usage type, the evolving profile of a cannabis user, as well as other individual differences should be considered to explain this additional variability.

Perceived effects of cannabis and changes in driving performance under the influence of cannabis.

OBJECTIVE: Reports indicate that cannabis users will adapt their driving to compensate for the perceived drug effects of cannabis. This analysis examined the relationship between driver perceptions of their state contrasted with objective measures of their performance while operating a motor vehicle. METHODS: Data was collected from ten subjects in a study examining the effects of cannabis on driving performance. Driving performance was collected on the NADS quarter-cab miniSim, a limited field of view non-motion simulator, approximately two hours after cannabis inhalation. Driving measures of both lateral and longitudinal control were included in our analysis. Subjective measures of the effects of cannabis were collected at peak and prior to driving, using visual analog scales. Data were analyzed using the SAS GLM Select procedure with subjective effect, dosing condition (placebo vs 6.9% THC), and driving event as independent measures. The stepwise selection method was used. RESULTS: The analysis of each of the subjective effects showed significant differences between the placebo and the active cannabis dosed conditions. While we found variance in difference between group means, there was greater variability between subject values. We found that subjective measures were predictive of variance in driver inputs, such as steering frequency and steering reversal rate. Variance in SDLP and other driving performance measures, however, were predicted by dosing condition. CONCLUSIONS: Overall, some of the effects perceived by the driver were better related to changes in driver inputs rather than the presence of cannabis itself. Changes in performance measures such as SDLP are better explained by dosing condition. Thus, driver's perceptions may result in changes to driving behavior that could mitigate the effect of cannabis. For both lateral and longitudinal control, an increasing perception of stimulation produced a positive effect on performance. Our results provide a better understanding of how different strains of cannabis, which produce different subjective experiences for users, could impact driving safety. Specifically, we found drug effects that produce more stimulation results in less impact on driving, while those that produce a more stoned or high feeling results in a greater negative effect on driving.

Impact of cannabis and low alcohol concentration on divided attention tasks during driving.

OBJECTIVE: To assess divided-attention performance when driving under the influence of cannabis with and without alcohol. Three divided-attention tasks were performed following administration of placebo, cannabis, and/or alcohol. METHODS: Healthy adult cannabis users participated in 6 sessions, receiving combinations of cannabis (placebo/low-THC/high-THC) and alcohol (placebo/active) in randomized order, separated by washout periods of ≥1 week. At 0.5 hours post-dosing, participants performed simulator drives in the University of Iowa National Advanced Driving Simulator (NADS-1), a full vehicle cab simulator with a 360° horizontal field of view and motion base that provides realistic feedback. Drives contained repeated instances of three tasks: a side-mirror task (reaction to a triangle appearing in the side-mirrors), an artist-search task (select a specified artist from a navigable menu on the vehicle's console), and a message-reading task (read aloud a message displayed on the console). Blood THC and breath alcohol concentration (BrAC) were interpolated using individual power curves from samples collected approximately 0.17, 0.42, 1.4, and 2.3 hours post-dose. Driving measures during tasks were compared to equal-duration control periods occurring just prior to the task. Performance shifts, task completion, and lane departures were modeled relative to blood THC and BrAC using mixed-effects regression models. RESULTS: Each 1 µg/L increase in blood THC concentration predicted increased odds of failing to complete the artist-search task (OR: 1.05, 95% CI: 1.01-1.11, p = 0.046), increased odds of selecting at least one incorrect response (OR: 1.05, 95% CI: 1.00-1.09, p = 0.041), declines in speed during the side-mirror task (0.005 m/s, 95% CI: 0.001-0.009, p = 0.023), and longer lane departure durations during the artist-search task (0.74% of task-period, 95% CI: 0.12-1.36 p = 0.020). BrAC (approximately 0.05%) was not associated with task performance, though each 0.01 g/210 L increase predicted longer departure durations during the side-mirror task (1.41% of task-period, 95% CI: 0.08-2.76, p = 0.040) and increased standard deviation of lane position in the message-reading task (0.61 cm, 95% CI: 0.14-1.08, p = 0.011). CONCLUSIONS: With increasing medical and legal cannabis use, understanding the impact of acute cannabis use on driving performance, including divided-attention, is essential. These data indicate that impaired divided-attention performance is a safety concern.

EEG biomarkers acquired during a short, straight-line simulated drive to predict impairment from cannabis intoxication.

OBJECTIVE: As cannabis use becomes more widely accepted, there is growing interest in its effects on brain function, specifically how it may impact daily functional activities such as driving, operating machinery, and other safety-related tasks. There are currently no validated methods for quantifying impairment from acute cannabis intoxication. The objective of this study was to identify neurophysiological correlates associated with driving simulator performance in subjects who were acutely intoxicated with cannabis. These signatures could help create an EEG-based profile of impairment due to acute cannabis intoxication. METHODS: Each subject completed a three-visit study protocol. Subjects were consented and screened on the first visit. On the second and third visits, subjects were administered either 500 mg of cannabis with 6.7% delta-9-tetrahydrocannabinol (THC) or placebo using a Volcano© Digit Vaporizer in a counterbalanced fashion. EEG was acquired from subjects as they performed a series of neurocognitive tasks and an approximately 45-minute simulated drive that included a rural straight-away absent of any other cars or obstacles during the final 10 minutes.EEG data was acquired using a STAT X24 wireless sensor headset during a simulated driving scenario from 10 subjects during the THC and placebo visits. Metrics of driving performance were extracted from the driving simulator and synchronized with EEG data using a common clock. RESULTS: A within-subjects analysis showed that the standard deviation of lane position (SDLP) was significantly worse and heart rate was elevated during the dosed visit compared to the placebo visit. Consistent with our prior findings, EEG power in the Theta frequency band (4-7 Hz) in the dosed condition was significantly decreased from the placebo condition. Theta power was negatively correlated with the SDLP driving performance metric, while there were no significant correlations between any EEG measure and SDLP in the placebo condition. CONCLUSIONS: These results, in combination with prior work on the effect of cannabis intoxication during neurocognitive tasks, suggest that neurophysiological signatures associated with acute cannabis intoxication are robust and consistent across tasks, and that these signatures are significantly correlated with impaired performance in a driving simulator. Taken together, EEG data acquired during a short neurocognitive testbed and during a simulated drive may provide specific profiles of impairment associated with acute cannabis intoxication. Further research is needed to establish the impaired cognitive processes associated with these EEG biomarkers.

Variability of baseline vehicle control among sober young adult cannabis users: A simulator-based exploratory study.

Objective: The objective of this study was to compare the variability in vehicle control for sober young adult drivers (18-23 years old) who either use cannabis but are not acutely exposed or do not use cannabis.Methods: The data analyzed in the study were from 4 prospective driving simulation studies (completed at the National Advanced Driving Simulator at the University of Iowa) that examined vehicle control metrics in cannabis users and nonusers across high-fidelity simulated urban, interstate, and rural driving environments. Data were collected for segments of consistent driving environments including urban driving, urban curves, interstate, interstate curves, dark rural, and rural straight. Dependent measures included measures of lateral and longitudinal vehicle control.Results: Thirty out of 72 (12 users and 18 nonusers) met the age requirements for inclusion in the analysis. Between the cohorts, we identified differences in lateral and longitudinal driving performance. For lateral control there were no observed effects on variability in lane keeping. Cannabis users exhibited lower frequency steering and fewer and less variable steering reversals compared to nonusers. For longitudinal control, cannabis users drove slower than nonusers and more accelerator pedal holds and a lower accelerator pedal reversal rate were observed.Conclusions: Young adult drivers who use cannabis in our study drove slower and produced significantly less frequent steering and accelerator pedal inputs than drivers who did not use cannabis. This suggests that lasting effects of cannabis use persist and may lead to detrimental driving behaviors even after intoxication has subsided. These findings have implications for legislation in support of legalizing cannabis because sober cannabis-using drivers may still be a public health concern. Further study is needed to evaluate whether these differences persist even with longer term abstinence and whether differences are found in other age demographics.

Correlation of EEG biomarkers of cannabis with measured driving impairment.

Objective: The objective of this study was to use electroencephalogram (EEG) biomarkers derived from a short, easily administered neurocognitive testbed to determine acute cannabis intoxication and its effect on driving performance in a driving simulator.Methods: The data analyzed were from a study examining the relationship between psychomotor task performance, EEG data, and driving performance in a simulator. EEG data were collected using a STAT® X-24 EEG Wireless Sensor Headset, which was worn during the psychomotor and driving tasks. Driving data were collected for segments of consistent driving environments, including urban driving, urban curves, interstate, interstate curves, dark rural, and rural straightaways. Dependent measures included measures of lateral and longitudinal vehicle control.Results: There was a significant relationship between impaired driving performance as indicated by increased standard deviation of lane position and EEG power in slow theta band (3-5 Hz) in parietal and occipital areas.Conclusions: These results, combined with our prior reported results, suggest that EEG and electrocardiogram (ECG) acquired concurrent with neuropsychological tests hold potential to provide a highly sensitive, specific, and dose-dependent profile of cannabis intoxication and level of impairment.

Evaluating drugged driving: Effects of exemplar pain and anxiety medications.

OBJECTIVE: Distracted and drug-influenced driving presents a major risk for traffic safety morbidity and mortality. As part of an ongoing research program, we examined the effects of a commonly prescribed combination of medications for pain relief: alprazolam, a benzodiazepine, and a hydrocodone preparation, a combination opiate and acetaminophen, on a simulated driving protocol. METHODS: Utilizing a within-subjects design, we recruited 8 healthy experienced drivers without major physical and psychological histories. Using a double-blind, placebo-controlled crossover design, we administered placebo, alprazolam alone, hydrocodone/acetaminophen, and the combination of the 2 drugs in a standardized simulated driving protocol. Measures of lateral and longitudinal control were collected and the data were reduced and statically analyzed. RESULTS: The study observed clear detrimental effects of alprazolam on driving measures of lateral control and longitudinal control. Driving appeared to more aberrant at higher speeds and in rural scenarios. There were no statistical differences between hydrocodone and placebo. A measure of sedation showed that subjects rated alprazolam as more sedating than both hydrocodone and placebo. CONCLUSIONS: The findings suggest that impairing effects of this commonly prescribed combination of pharmacologic agents impact simulated driving performance. Negative changes in driving performance included measures of lateral and longitudinal control, although the deleterious effects on lateral control measures such as standard deviation of lane position (SDLP) were larger and more robust. Although the number of subjects was small, thus making it more difficult to draw conclusions on the narcotic effects, these results suggest that in this combination of central nervous system (CNS)-active drugs the benzodiazepine alprazolam accounted for the majority of impairing drug effects. The effect sizes associated with the hydrocodone preparation ranged from very small to medium. These results have potential implications for prescribing physicians and dispensing pharmacists, traffic safety experts, law enforcement officers, and patients themselves.

Measuring the attitudes of novice drivers with autism spectrum disorder as an indication of apprehensive driving: Going beyond basic abilities.

For some individuals with autism spectrum disorder, driving apprehension may interfere with the acquisition and application of driving privileges. The Driving Attitude Scale Parent-Report provides an indication of novice drivers' positive and negative attitudes toward driving. Responses were compared for parents of 66 autism spectrum disorder and 166 neuro-typical novice drivers. After the autism spectrum disorder drivers completed 3 months of driver training, 60 parents repeated the Driving Attitude Scale Parent-Report. Parents reported autism spectrum disorder drivers to have less positive and more negative attitudes toward driving than parents of neuro-typical drivers. Parents of autism spectrum disorder drivers who received driving training in a safe/low-threat virtual reality driving simulator demonstrated a significant increase in positive attitudes and reduction in negative attitudes, compared to parents of autism spectrum disorder drivers undergoing routine driver training. The reports of parents of autism spectrum disorder drivers suggest potential problems with learning to drive that can go beyond general abilities and include driving apprehension.

Can Youth with Autism Spectrum Disorder Use Virtual Reality Driving Simulation Training to Evaluate and Improve Driving Performance? An Exploratory Study.

Investigate how novice drivers with autism spectrum disorder (ASD) differ from experienced drivers and whether virtual reality driving simulation training (VRDST) improves ASD driving performance. 51 novice ASD drivers (mean age 17.96 years, 78% male) were randomized to routine training (RT) or one of three types of VRDST (8-12 sessions). All participants followed DMV behind-the-wheel training guidelines for earning a driver's license. Participants were assessed pre- and post-training for driving-specific executive function (EF) abilities and tactical driving skills. ASD drivers showed worse baseline EF and driving skills than experienced drivers. At post-assessment, VRDST significantly improved driving and EF performance over RT. This study demonstrated feasibility and potential efficacy of VRDST for novice ASD drivers.

Cannabis effects on driving longitudinal control with and without alcohol.

Although evidence suggests cannabis impairs driving, its driving-performance effects are not fully characterized. We aimed to establish cannabis' effects on driving longitudinal control (with and without alcohol, drivers' most common drug combination) relative to psychoactive ∆(9) -tetrahydrocannabinol (THC) blood concentrations. Current occasional (≥1×/last 3 months, ≤3 days per week) cannabis smokers drank placebo or low-dose alcohol, and inhaled 500 mg placebo, low (2.9%), or high (6.7%) THC vaporized cannabis over 10 min ad libitum in separate sessions (within-subject, six conditions). Participants drove (National Advanced Driving Simulator, University of Iowa) simulated drives 0.5-1.3 h post-inhalation. Blood and breath alcohol samples were collected before (0.17 and 0.42 h) and after (1.4 and 2.3 h) driving. We evaluated the mean speed (relative to limit), standard deviation (SD) of speed, percent time spent >10% above/below the speed limit (percent speed high/percent speed low), longitudinal acceleration, and ability to maintain headway relative to a lead vehicle (headway maintenance) against blood THC and breath alcohol concentrations (BrAC). In N=18 completing drivers, THC was associated with a decreased mean speed, increased percent speed low and increased mean following distance during headway maintenance. BrAC was associated with increased SD speed and increased percent speed high, whereas THC was not. Neither was associated with altered longitudinal acceleration. A less-than-additive THC*BrAC interaction was detected in percent speed high (considering only non-zero data and excluding an outlying drive event), suggesting cannabis mitigated drivers' tendency to drive faster with alcohol. Cannabis was associated with slower driving and greater headway, suggesting a possible awareness of impairment and attempt to compensate. Copyright © 2016 John Wiley & Sons, Ltd.

Effect of Blood Collection Time on Measured Δ9-Tetrahydrocannabinol Concentrations: Implications for Driving Interpretation and Drug Policy.

BACKGROUND: In driving-under-the-influence cases, blood typically is collected approximately 1.5-4 h after an incident, with unknown last intake time. This complicates blood Δ(9)-tetrahydrocannabinol (THC) interpretation, owing to rapidly decreasing concentrations immediately after inhalation. We evaluated how decreases in blood THC concentration before collection may affect interpretation of toxicological results. METHODS: Adult cannabis smokers (≥1×/3 months, ≤3 days/week) drank placebo or low-dose alcohol (approximately 0.065% peak breath alcohol concentration) 10 min before inhaling 500 mg placebo, 2.9%, or 6.7% vaporized THC (within-individuals), then took simulated drives 0.5-1.3 h postdose. Blood THC concentrations were determined before and up to 8.3 h postdose (limit of quantification 1 µg/L). RESULTS: In 18 participants, observed Cmax (at 0.17 h) for active (2.9 or 6.7% THC) cannabis were [median (range)] 38.2 µg/L (11.4-137) without alcohol and 47.9 µg/L (13.0-210) with alcohol. THC Cmax concentration decreased 73.5% (3.3%-89.5%) without alcohol and 75.1% (11.5%-85.4%) with alcohol in the first half-hour after active cannabis and 90.3% (76.1%-100%) and 91.3% (53.8%-97.0%), respectively, by 1.4 h postdose. When residual THC (from previous self-administration) was present, concentrations rapidly decreased to preinhalation baselines and fluctuated around them. During-drive THC concentrations previously associated with impairment (≥8.2 µg/L) decreased to median <5 µg/L by 3.3 h postdose and <2 µg/L by 4.8 h postdose; only 1 participant had THC ≥5 µg/L after 3.3 h. CONCLUSIONS: Forensic blood THC concentrations may be lower than common per se cutoffs despite greatly exceeding them while driving. Concentrations during driving cannot be back-extrapolated because of unknown time after intake and interindividual variability in rates of decrease.

Controlled vaporized cannabis, with and without alcohol: subjective effects and oral fluid-blood cannabinoid relationships.

Vaporized cannabis and concurrent cannabis and alcohol intake are commonplace. We evaluated the subjective effects of cannabis, with and without alcohol, relative to blood and oral fluid (OF, advantageous for cannabis exposure screening) cannabinoid concentrations and OF/blood and OF/plasma vaporized-cannabinoid relationships. Healthy adult occasional-to-moderate cannabis smokers received a vaporized placebo or active cannabis (2.9% and 6.7% Δ(9) -tetrahydrocannabinol, THC) with or without oral low-dose alcohol (~0.065g/210L peak breath alcohol concentration [BrAC]) in a within-subjects design. Blood and OF were collected up to 8.3 h post-dose and subjective effects measured at matched time points with visual-analogue scales and 5-point Likert scales. Linear mixed models evaluated subjective effects by THC concentration, BrAC, and interactions. Effects by time point were evaluated by dose-wise analysis of variance (ANOVA). OF versus blood or plasma cannabinoid ratios and correlations were evaluated in paired-positive specimens. Nineteen participants (13 men) completed the study. Blood THC concentration or BrAC significantly associated with subjective effects including 'high', while OF contamination prevented significant OF concentration associations <1.4 h post-dose. Subjective effects persisted through 3.3-4.3 h, with alcohol potentiating the duration of the cannabis effects. Effect-versus-THC concentration and effect-versus-alcohol concentration hystereses were counterclockwise and clockwise, respectively. OF/blood and OF/plasma THC significantly correlated (all Spearman r≥0.71), but variability was high. Vaporized cannabis subjective effects were similar to those previously reported after smoking, with duration extended by concurrent alcohol. Cannabis intake was identified by OF testing, but OF concentration variability limited interpretation. Blood THC concentrations were more consistent across subjects and more accurate at predicting cannabis' subjective effects. Copyright © 2015 John Wiley & Sons, Ltd.

Cannabis effects on driving lateral control with and without alcohol.

BACKGROUND: Effects of cannabis, the most commonly encountered non-alcohol drug in driving under the influence cases, are heavily debated. We aim to determine how blood Δ(9)-tetrahydrocannabinol (THC) concentrations relate to driving impairment, with and without alcohol. METHODS: Current occasional (≥1×/last 3 months, ≤3days/week) cannabis smokers drank placebo or low-dose alcohol, and inhaled 500mg placebo, low (2.9%)-THC, or high (6.7%)-THC vaporized cannabis over 10min ad libitum in separate sessions (within-subject design, 6 conditions). Participants drove (National Advanced Driving Simulator, University of Iowa) simulated drives (∼0.8h duration). Blood, oral fluid (OF), and breath alcohol samples were collected before (0.17h, 0.42h) and after (1.4h, 2.3h) driving that occurred 0.5-1.3h after inhalation. We evaluated standard deviations of lateral position (lane weave, SDLP) and steering angle, lane departures/min, and maximum lateral acceleration. RESULTS: In N=18 completers (13 men, ages 21-37years), cannabis and alcohol increased SDLP. Blood THC concentrations of 8.2 and 13.1µg/L during driving increased SDLP similar to 0.05 and 0.08g/210L breath alcohol concentrations, the most common legal alcohol limits. Cannabis-alcohol SDLP effects were additive rather than synergistic, with 5µg/L THC+0.05g/210L alcohol showing similar SDLP to 0.08g/210L alcohol alone. Only alcohol increased lateral acceleration and the less-sensitive lane departures/min parameters. OF effectively documented cannabis exposure, although with greater THC concentration variability than paired blood samples. CONCLUSIONS: SDLP was a sensitive cannabis-related lateral control impairment measure. During drive blood THC ≥8.2µg/L increased SDLP similar to notably-impairing alcohol concentrations. Despite OF's screening value, OF variability poses challenges in concentration-based effects interpretation.

Controlled Cannabis Vaporizer Administration: Blood and Plasma Cannabinoids with and without Alcohol.

BACKGROUND: Increased medical and legal cannabis intake is accompanied by greater use of cannabis vaporization and more cases of driving under the influence of cannabis. Although simultaneous Δ(9)-tetrahydrocannabinol (THC) and alcohol use is frequent, potential pharmacokinetic interactions are poorly understood. Here we studied blood and plasma vaporized cannabinoid disposition, with and without simultaneous oral low-dose alcohol. METHODS: Thirty-two adult cannabis smokers (≥1 time/3 months, ≤3 days/week) drank placebo or low-dose alcohol (target approximately 0.065% peak breath-alcohol concentration) 10 min before inhaling 500 mg placebo, low-dose (2.9%) THC, or high-dose (6.7%) THC vaporized cannabis (6 within-individual alcohol-cannabis combinations). Blood and plasma were obtained before and up to 8.3 h after ingestion. RESULTS: Nineteen participants completed all sessions. Median (range) maximum blood concentrations (Cmax) for low and high THC doses (no alcohol) were 32.7 (11.4-66.2) and 42.2 (15.2-137) µg/L THC, respectively, and 2.8 (0-9.1) and 5.0 (0-14.2) µg/L 11-OH-THC. With alcohol, low and high dose Cmax values were 35.3 (13.0-71.4) and 67.5 (18.1-210) µg/L THC and 3.7 (1.4-6.0) and 6.0 (0-23.3) µg/L 11-OH-THC, significantly higher than without alcohol. With a THC detection cutoff of ≥1 µg/L, ≥16.7% of participants remained positive 8.3 h postdose, whereas ≤21.1% were positive by 2.3 h with a cutoff of ≥5 µg/L. CONCLUSIONS: Vaporization is an effective THC delivery route. The significantly higher blood THC and 11-OH-THC Cmax values with alcohol possibly explain increased performance impairment observed from cannabis-alcohol combinations. Chosen driving-related THC cutoffs should be considered carefully to best reflect performance impairment windows. Our results will help facilitate forensic interpretation and inform the debate on drugged driving legislation.

A retrospective study of amitriptyline in youth with autism spectrum disorders.

We performed a retrospective chart review of 50 youths with Autism Spectrum Disorder (ASD), prescribed amitriptyline (AMI) for hyperactivity and impulsivity. Data was systematically extracted from 50 outpatient clinic charts, including AMI treatment duration, dose, trough levels and adverse events. Mean age was 9.4 years (4.6-17.9); 40 were males and 10 females. 30 % had failed atomoxetine and 40 % had failed ≥3 ADHD medications. Mean dose was 1.3 ± 0.6 mg/kg/day, mean trough level 114.1 ± 50.5 ng/ml, mean duration 3.4 years. Clinical Global Impressions Scale-Improvement (CGI-I) was ≤2 in 60 % of patients at the final visit, and in 82 % of patients for at least 50 % of follow-ups. Cautious use of low dose AMI shows promise for treatment-resistant youth with ASD accompanied by hyperactivity, impulsivity, aggression and self injury.

Subclinical obsessive-compulsive disorder in children and adolescents: additional results from a "high-risk" study.

INTRODUCTION: The concept of subclinical obsessive-compulsive disorder is explored using data from a "high-risk" study of offspring of persons with (OCD) and offspring of controls. Offspring with OCD were compared to those with subclinical OCD, and those without either condition. Subclinical OCD is defined as the presence of obsessions and/or compulsions without functional impairment. METHODS: Adults with OCD and their offspring 7-18 years of age were recruited through a tertiary care center psychiatric outpatient clinic, while controls (and their children) were recruited via advertisement. Parents and offspring were assessed using structured interviews and validated questionnaires at baseline and follow-up interviews. RESULTS: Offspring from both proband groups were pooled to create three subject groups: group 1, offspring with neither condition (n=43); group 2, offspring with subclinical OCD (n=24); and group 3, offspring with full OCD (n=11). Offspring with subclinical OCD held the middle ground for most comparisons. They were more symptomatic than offspring without either condition (group 1), but less symptomatic than subjects with OCD (group 3). Across the board, comparisons of diagnoses, Child Behavior Checklist (CBCL) results; Motor tic, Obsessions and compulsions, Vocal tic Evaluation Survey results; and Leyton Obsessional Inventory (LOI) results were associated with subject group at baseline and follow-up. In post-hoc comparisons, subjects with subclinical OCD had fewer comorbid anxiety disorders and lower CBCL internalizing scale scores at follow-up. Parents of children with OCD had higher LOI symptom and severity scores than parents in those of groups 1 or 2. CONCLUSION: The findings suggest that subclinical OCD holds the middle ground between full-blown OCD and having neither condition in terms of obsessive-compulsive symptoms and severity, tics, associated mood/anxiety disorders, and general functioning. At least in persons at risk for OCD, the presence of subclinical OCD may herald the onset of OCD, though in others may be an independent condition that does not lead to full OCD.

Gene doping: a review of performance-enhancing genetics.

Unethical athletes and their mentors have long arrogated scientific and medical advances to enhance athletic performance, thus gaining a dishonest competitive advantage. Building on advances in genetics, a new threat arises from athletes using gene therapy techniques in the same manner that some abused performance-enhancing drugs were used. Gene doping, as this is known, may produce spectacular physiologic alterations to dramatically enhance athletic abilities or physical appearance. Furthermore, gene doping may present pernicious problems for the regulatory agencies and investigatory laboratories that are entrusted to keep sporting events fair and ethical. Performance-enhanced genetics will likewise present unique challenges to physicians in many spheres of their practice.