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.

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.

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.

Risperidone versus clonidine in the treatment of children and adolescents with Tourette's syndrome.

OBJECTIVE: To evaluate the efficacy and tolerability of risperidone in comparison with clonidine in the treatment of children and adolescents with Tourette's syndrome (TS). METHOD: Following a 7- to 14-day single-blind, placebo lead-in, 21 subjects aged 7 to 17 years were randomly assigned to 8 weeks of double-blind treatment with clonidine or risperidone. Research scales evaluated tics and comorbid obsessive-compulsive and attention-deficit/hyperactivity symptoms. RESULTS: Risperidone and clonidine appeared equally effective in the treatment of tics in an intent-to-treat analysis, as rated by the Yale Global Tic Severity Scale (YGTSS). Risperidone produced a mean reduction in the YGTSS of 21%; clonidine produced a 26% reduction. Among subjects with comorbid obsessive-compulsive symptoms, 63% of the risperidone group and 33% of the clonidine group responded to treatment (not significant). The most common adverse event seen with both treatments was sedation, which was mild to moderate in severity. Sedation subsequently resolved with continued administration of the medication or with a dose reduction. No clinically significant extrapyramidal symptoms were observed. CONCLUSIONS: In this pilot study, risperidone demonstrated efficacy equivalent to clonidine in the treatment of tic symptoms in children and adolescents with TS. Further research is needed to clarify the role of atypical antipsychotics in TS and to delineate potential benefits for comorbid obsessive-compulsive and attention-deficit/hyperactivity symptoms.