Cannabis effects on driving lateral control with and without alcohol

Drug and Alcohol Dependence Available online 23 June 2015;  doi:10.1016/j.drugalcdep.2015.06.015

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 Δ9-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 500 mg placebo, low (2.9%)-THC, or high (6.7%)-THC vaporized cannabis over 10 min ad libitum in separate sessions (within-subject design, 6 conditions). Participants drove (National Advanced Driving Simulator, University of Iowa) simulated drives (∼0.8 h duration). Blood, oral fluid (OF), and breath alcohol samples were collected before (0.17 h, 0.42 h) and after (1.4 h, 2.3 h) driving that occurred 0.5–1.3 h 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 13.1 μg/L during driving increased SDLP similar to 0.05 and 0.08 g/210 L breath alcohol concentrations, the most common legal alcohol limits. Cannabis-alcohol SDLP effects were additive rather than synergistic, with 5 μg/L THC + 0.05 g/210 L alcohol showing similar SDLP to 0.08 g/210 L 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 ≥8.2 μg/L increased SDLP similar to notably-impairing alcohol concentrations. Despite OF’s screening value, OF variability poses challenges in concentration-based effects interpretation.

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Synthetic Cannabinoids.[Review]

American Journal of the Medical Sciences. 350(1):59-62, July 2015.

Synthetic cannabinoids (SCBs), also known under the brand names of “Spice,” “K2,” “herbal incense,” “Cloud 9,” “Mojo” and many others, are becoming a large public health concern due not only to their increasing use but also to their unpredictable toxicity and abuse potential. There are many types of SCBs, each having a unique binding affinity for cannabinoid receptors. Although both [DELTA]9-tetrahydrocannabinol (THC) and SCBs stimulate the same receptors, cannabinoid receptor 1 (CB1) and cannabinoid receptor 2 (CB2), studies have shown that SCBs are associated with higher rates of toxicity and hospital admissions than is natural cannabis. This is likely due to SCBs being direct agonists of the cannabinoid receptors, whereas THC is a partial agonist. Furthermore, the different chemical structures of SCBs found in Spice or K2 may interact in unpredictable ways to elicit previously unknown, and the commercial products may have unknown contaminants. The largest group of users is men in their 20s who participate in polydrug use. The most common reported toxicities with SCB use based on studies using Texas Poison Control records are tachycardia, agitation and irritability, drowsiness, hallucinations, delusions, hypertension, nausea, confusion, dizziness, vertigo and chest pain. Acute kidney injury has also been strongly associated with SCB use. Treatment mostly involves symptom management and supportive care. More research is needed to identify which contaminants are typically found in synthetic marijuana and to understand the interactions between different SBCs to better predict adverse health outcomes.

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A non-fatal self-poisoning attempt with sildenafil

J Anal Toxicol (2 July 2015) doi: 10.1093/jat/bkv071

The phosphodiesterase type 5 inhibitor, sildenafil, is not generally known for its use as a self-poisoning drug. However, intoxication cases with lethal outcome have been described. The case presented here is of a 56-year-old man who claimed to have undertaken an unsuccessful suicide attempt by mono-ingestion of 65 tablets of 100 mg sildenafil. He arrived at the emergency department 24 h after intake with severe vomiting and symptoms of blurred vision. Clinical examination revealed no priapism. Of note was a sinus tachycardia of 100 bpm without signs of hypotension. To quantify the sildenafil concentration in serum, an high-performance liquid chromatography photo-diode array method was developed and validated according to European Medicines Agency guidelines. The intoxicated patient had a serum concentration of 22.2 µg/mL sildenafil, at the time of presentation, which is far above the therapeutic peak concentration. The serum concentration further declined to 9.2 and 2.3 µg/mL, respectively, 5 and 14 h later, revealing a biological half-life of 4.2 h. To the best of our knowledge, this patient took the highest sildenafil dose, which resulted in the highest serum concentration, ever reported. In this subject, sildenafil showed good tolerability because few symptoms occurred and only moderate supportive therapy was needed for full recovery without sequelae.

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Postmortem quetiapine reference concentrations in brain and blood

J Anal Toxicol (9 July 2015) doi: 10.1093/jat/bkv072

Brain tissue is a useful alternative to blood in postmortem forensic investigations, but scarcity of information on reference concentrations in brain tissue makes interpretation challenging. Here we present a study of 43 cases where the antipsychotic drug quetiapine was quantified in brain tissue and related to concentrations in postmortem blood. For cases, where quetiapine was unrelated to the cause of death (N = 36), the 10–90 percentiles for quetiapine concentrations in brain tissue were 0.030–1.54 mg/kg (median 0.48 mg/kg, mean 0.79 mg/kg). Corresponding blood 10–90 percentile values were 0.007–0.39 mg/kg (median 0.15 mg/kg, mean 0.19 mg/kg), giving brain–blood ratio 10–90 percentiles of 2.31–6.54 (median 3.87, mean 4.32). Both correspond well to the limited amount of data found in the literature. For cases where quetiapine was a contributing factor to death (N = 5), the median value in brain tissue of 8.02 mg/kg (range 2.69–22.98 mg/kg) was more than 15 times higher than the median of the nontoxic values, and about the same relationship occurred for blood with a median of 3.19 mg/kg (range 1.00–6.90 mg/kg). The brain–blood ratios for toxic concentrations were in the range of 2.08–6.05, which correspond to those of the nontoxic concentrations. A single case, where quetiapine was ruled as the sole cause of death, a suicide by quetiapine overdose, had an even higher value of 25.74 mg/kg in brain tissue. The blood concentration was 8.99 mg/kg, giving a brain–blood ratio of 2.86. Thus, on average the brain concentrations were about four times the blood concentrations. The brain concentrations of quetiapine observed in cases, where quetiapine was unrelated to death, may serve as a reference, when evaluating postmortem cases with no blood available. The recorded concentrations, where quetiapine was contributing to death, give an indication of likely toxic concentrations.

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Distinction between saltwater drowning and freshwater drowning by assessment of sinus fluid on post-mortem computed tomography

European Radiology  July 11, 2015

OBJECTIVE:

To evaluate the difference in sinus fluid volume and density between saltwater and freshwater drowning and diagnose saltwater drowning in distinction from freshwater drowning.

METHODS:

Ninety-three drowning cases (22 saltwater and 71 freshwater) were retrospectively investigated; all had undergone post-mortem CT and forensic autopsy. Sinus fluid volume and density were calculated using a 3D-DICOM workstation, and differences were evaluated. Diagnostic performance of these indicators for saltwater drowning was evaluated using a cut-off value calculated by receiver operating characteristic (ROC) analysis.

RESULTS:

The median sinus fluid volume was 5.68 mL in cases of saltwater drowning (range 0.08 to 37.55) and 5.46 mL in cases of freshwater drowning (0.02 to 27.68), and the average densities were 47.28 (14.26 to 75.98) HU and 32.56 (-14.38 to 77.43) HU, respectively. While sinus volume did not differ significantly (p = 0.6000), sinus density was significantly higher in saltwater than freshwater drowning cases (p = 0.0002). ROC analysis for diagnosis of saltwater drowning determined the cut-off value as 37.77 HU, with a sensitivity of 77 %, specificity of 72 %, PPV of 46 % and NPV of 91 %.

CONCLUSION:

The average density of sinus fluid in cases of saltwater drowning was significantly higher than in freshwater drowning cases; there was no significant difference in the sinus fluid volume.

KEY POINTS:

• Sinus fluid density of saltwater drowning is significantly higher than freshwater drowning. • Cut-off value was 37.77 HU based on the ROC analysis. • The cut-off value translated to 91 % NPV for diagnosis of saltwater drowning.

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Alcohol Hangover as a Cause of Impairment in Apprehended Drivers

Traffic Injury Prevention  Volume 16, Issue 4, 2015

Objective: Previous studies have already shown the possibility of impairment during a hangover phase, after alcohol ingestion, when the blood alcohol concentration has returned to zero. The prevalence of drivers being in a hangover phase, in the driving population, and the relation to impairment relevant for traffic safety has, however, not been previously studied. The aim of this study was to investigate the prevalence and the concentrations of the 2 ethanol metabolites, ethyl glucuronide (EtG) and ethyl sulfate (EtS), in blood, indicating very recent alcohol intake, among apprehended drivers, in which no psychoactive substances, including alcohol, were detected. The aim was also to study these findings in relation to the impairment observed in these drivers.

Methods: Blood samples, drawn from suspected drunk or drugged drivers, were analyzed for a broad repertoire of psychoactive substances, with a clinical test for impairment (CTI) being performed at the same time. One hundred and forty-six cases, in which no psychoactive substances were detected and where a valid CTI was performed, were analyzed for EtG and EtS in blood. The prevalence and concentrations were related to the conclusions of the CTIs.

Results: EtS and EtG were detected in a total of 19 of the 146 cases (13%). Among the “impaired” drivers, EtG and EtS were detected in 16 cases (18%), whereas among “not impaired” drivers they were detected in 3 cases (5%). There were significantly more detections of EtS (and EtG) among the impaired group of drivers compared to the nonimpaired drivers (P =.030), and the concentrations of both EtG (P =.027) and EtS (P =.026) were significantly higher in the group of impaired drivers compared to the nonimpaired drivers. There was a statistically significant positive correlation between the concentrations of EtG (Spearman’s rho = 0.170, P =.041) and EtS (Spearman’s rho = 0.189, P =.022) and the degree of impairment.

Conclusions: EtG and EtS were prevalent findings in blood collected from the apprehended drivers, testing negative for all psychoactive substances. The higher rates of detections of EtG and EtS in impaired compared to nonimpaired drivers, and also the positive correlation between concentrations of EtG and EtS and the degree of impairment, indicate that hangover symptoms may be relevant for traffic safety.

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Legal consequences for alcohol-impaired drivers injured in motor vehicle collisions: A systematic review

Accident Analysis & Prevention Volume 80, July 2015, Pages 106–116

The treatment of alcohol-impaired drivers injured in a motor vehicle collision (MVC) is a complex public health issue. We conducted a systematic review to describe the legal consequences for alcohol-impaired drivers injured in a MVC and taken to a hospital or trauma center. Methods We searched MEDLINE, Embase, and CINAHL databases from inception until August 2014. We included studies that reported legal consequences including charges or convictions of injured drivers taken to a hospital or trauma center after a MVC with a blood alcohol concentration (BAC) exceeding the legal limit.Results Twenty-six studies met inclusion criteria; twenty studies were conducted in the USA, five in Canada, and one in Sweden. All were cohort studies (23 retrospective, 3 prospective) and included 11,409 patients overall. A total of 5,127 drivers had a BAC exceeding the legal limit, with legal consequences reported in 4937 cases. The median overall DUI/DWI conviction rate was 13% (range 0–85%). The median percentage of drivers with a previous conviction on their record for driving under the influence (DUI) or driving while intoxicated (DWI) was 15.5% (range 6–40%). The median percentage of drivers convicted again for DUI/DWI during the study period was 3.5% (range 2–10%). Heterogeneity between study designs, legal jurisdictions, institutional procedures and policies for obtaining a legally admissible BAC measurement precluded a meta-analysis. Conclusions The majority of intoxicated drivers injured in MVCs and seen in the emergency department are never charged or convicted. A substantial proportion of injured intoxicated drivers had more than one conviction for DUI/DWI on their police record.

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