Driving Under the Influence of Cannabis: Impact of Combining Toxicology Testing with Field Sobriety Tests.

BACKGROUND: Cannabis is increasingly used both medically and recreationally. With widespread use, there is growing concern about how to identify cannabis-impaired drivers. METHODS: A placebo-controlled randomized double-blinded protocol was conducted to study the effects of cannabis on driving performance. One hundred ninety-one participants were randomized to smoke ad libitum a cannabis cigarette containing placebo or delta-9-tetrahydrocannabinol (THC) (5.9% or 13.4%). Blood, oral fluid (OF), and breath samples were collected along with longitudinal driving performance on a simulator (standard deviation of lateral position [SDLP] and car following [coherence]) over a 5-hour period. Law enforcement officers performed field sobriety tests (FSTs) to determine if participants were impaired. RESULTS: There was no relationship between THC concentrations measured in blood, OF, or breath and SDLP or coherence at any of the timepoints studied (P > 0.05). FSTs were significant (P < 0.05) for classifying participants into the THC group vs the placebo group up to 188 minutes after smoking. Seventy-one minutes after smoking, FSTs classified 81% of the participants who received active drug as being impaired. However, 49% of participants who smoked placebo (controls) were also deemed impaired at this same timepoint. Combining a 2 ng/mL THC cutoff in OF with positive findings on FSTs reduced the number of controls classified as impaired to zero, 86 minutes after smoking the placebo. CONCLUSIONS: Requiring a positive toxicology result in addition to the FST observations substantially improved the classification accuracy regarding possible driving under the influence of THC by decreasing the percentage of controls classified as impaired.

Variable Delta-9-Tetrahydrocannabinol Pharmacokinetics and Pharmacodynamics After Cannabis Smoking in Regular Users.

BACKGROUND: Despite its federally restricted status, cannabis is widely used medicinally and recreationally. The pharmacokinetics (PK) and central nervous system (CNS) effects of tetrahydrocannabinol (THC), the major psychoactive cannabinoid, are not well understood. The objective of this study was to develop a population PK model of inhaled THC, including sources of variability, and to conduct an exploratory analysis of potential exposure-response relationships. METHODS: Regular adult cannabis users smoked a single cannabis cigarette containing 5.9% THC (Chemovar A) or 13.4% THC (Chemovar B) ad libitum. THC concentrations in whole blood were measured and used to develop a population PK model to identify potential factors contributing to interindividual variability in THC PK and to describe THC disposition. Relationships between model-predicted exposure and heart rate, change in composite driving score on a driving simulator, and perceived highness were evaluated. RESULTS: From the 102 participants, a total of 770 blood THC concentrations were obtained. A two-compartment structural model adequately fit the data. Chemovar and baseline THC (THC BL ) were found to be significant covariates for bioavailability, with Chemovar A having better THC absorption. The model predicted that heavy users-those with the highest THC BL -would have significantly higher absorption than those with lighter previous use. There was a statistically significant relationship between exposure and heart rate, and exposure and perceived highness. CONCLUSIONS: THC PK is highly variable and related to baseline THC concentrations and different chemovars. The developed population PK model showed that heavier users had higher THC bioavailability. To better understand the factors affecting THC PK and dose-response relationships, future studies should incorporate a wide range of doses, multiple routes of administration, and different formulations relevant to typical community use.

A longitudinal study of cannabis use and risk for cognitive and functional decline among older adults with HIV.

Cannabis use is rapidly increasing among older adults in the United States, in part to treat symptoms of common health conditions (e.g., chronic pain, sleep problems). Longitudinal studies of cannabis use and cognitive decline in aging populations living with chronic disease are lacking. We examined different levels of cannabis use and cognitive and everyday function over time among 297 older adults with HIV (ages 50-84 at baseline). Participants were classified based on average cannabis use: frequent (> weekly) (n = 23), occasional (≤ weekly) (n = 83), and non-cannabis users (n=191) and were followed longitudinally for up to 10 years (average years of follow-up = 3.9). Multi-level models examined the effects of average and recent cannabis use on global cognition, global cognitive decline, and functional independence. Occasional cannabis users showed better global cognitive performance overall compared to non-cannabis users. Rates of cognitive decline and functional problems did not vary by average cannabis use. Recent cannabis use was linked to worse cognition at study visits when participants had THC+ urine toxicology-this short-term decrement in cognition was driven by worse memory and did not extend to reports of functional declines. Occasional (≤ weekly) cannabis use was associated with better global cognition over time in older adults with HIV, a group vulnerable to chronic inflammation and cognitive impairment. Recent THC exposure may have a temporary adverse impact on memory. To inform safe and efficacious medical cannabis use, the effects of specific cannabinoid doses on cognition and biological mechanisms must be investigated in older adults.

RESUMEN: El consumo de cannabis está aumentando rápidamente entre los adultos mayores en los Estados Unidos, en parte para tratar síntomas de afecciones de salud comunes (p. ej. dolor crónico, problemas de dormir). Actualmente, hay pocos estudios longitudinales sobre el consumo de cannabis y el deterioro cognitivo en poblaciones que envejecen y viven con enfermedades crónicas. Examinamos diferentes niveles del consumo de cannabis y funciones cognitivas a lo largo del tiempo entre 297 adultos mayores con VIH (de 50 a 84 años al principio de la investigación). Los participantes se clasificaron según el consumo promedio de cannabis: consumidores de cannabis frecuentes (> semanal) (n = 23) ocasionales (≤ semanal) (n = 83), y no consumidores de cannabis (n=191) fueron seguidos longitudinalmente hasta por 10 años (promedio = 3,9 años). Los modelos multinivel investigaron los efectos del consumo promedio y reciente de cannabis en la cognición global, el deterioro cognitivo global, y la independencia funcional. Los consumidores ocasionales de cannabis mostraron un mejor rendimiento cognitivo global en comparación con los no consumidores. El nivel de deterioro cognitivo y problemas funcionales no estuvieron asociado con el uso de cannabis. El consumo reciente de cannabis se vinculó con una peor cognición en las visitas del estudio cuando los participantes tenían toxicología de orina de THC positivo­esta disminución a corto plazo de la cognición se debió a una peor memoria, pero no se extendió a los informes de deterioros funcionales. El consumo ocasional (≤ semanal) de cannabis se asoció con una mejor cognición global a lo largo del tiempo en adultos mayores con VIH, un grupo susceptible a la inflamación crónica y la disfunción cognitiva. La exposición reciente al THC puede tener un impacto negativo temporal en la memoria. Los efectos de dosis específicas de cannabinoides en la cognición y sus mecanismos de acción biológicos deben ser investigados en personas mayores con el fin de informar el uso seguro y eficaz del cannabis medicinal.

Daily Cannabis Use is Associated With Lower CNS Inflammation in People With HIV.

OBJECTIVE: Recent cannabis exposure has been associated with lower rates of neurocognitive impairment in people with HIV (PWH). Cannabis's anti-inflammatory properties may underlie this relationship by reducing chronic neuroinflammation in PWH. This study examined relations between cannabis use and inflammatory biomarkers in cerebrospinal fluid (CSF) and plasma, and cognitive correlates of these biomarkers within a community-based sample of PWH. METHODS: 263 individuals were categorized into four groups: HIV- non-cannabis users (n = 65), HIV+ non-cannabis users (n = 105), HIV+ moderate cannabis users (n = 62), and HIV+ daily cannabis users (n = 31). Differences in pro-inflammatory biomarkers (IL-6, MCP-1/CCL2, IP-10/CXCL10, sCD14, sTNFR-II, TNF-α) by study group were determined by Kruskal-Wallis tests. Multivariable linear regressions examined relationships between biomarkers and seven cognitive domains, adjusting for age, sex/gender, race, education, and current CD4 count. RESULTS: HIV+ daily cannabis users showed lower MCP-1 and IP-10 levels in CSF compared to HIV+ non-cannabis users (p = .015; p = .039) and were similar to HIV- non-cannabis users. Plasma biomarkers showed no differences by cannabis use. Among PWH, lower CSF MCP-1 and lower CSF IP-10 were associated with better learning performance (all ps < .05). CONCLUSIONS: Current daily cannabis use was associated with lower levels of pro-inflammatory chemokines implicated in HIV pathogenesis and these chemokines were linked to the cognitive domain of learning which is commonly impaired in PWH. Cannabinoid-related reductions of MCP-1 and IP-10, if confirmed, suggest a role for medicinal cannabis in the mitigation of persistent inflammation and cognitive impacts of HIV.

Assessing HIV provider knowledge, screening practices, and training needs for HIV-associated neurocognitive disorders. A short report.

Management of HIV-associated neurocognitive disorders (HAND) is becoming increasingly important with HIV-positive people living normal life spans. We aimed to establish the level of HAND awareness among doctor and nurse occupational health practitioners, screening used to detect impairment, factors limiting screening for HAND, and training needs. One-hundred-and-five members of the nursing and physician professional societies for occupational health practitioners in South Africa and Occupational Health Departments at five South African universities responded to an email invitation to complete an online survey addressing demographics, HAND knowledge, screeners being used to screen for HAND and related training needs. While 80% had heard of HAND, few (13.3%) were aware of the Frascati criteria. Only 2% had received training addressing HAND; 11.4% screened for HAND; 45.7% did not know what screening tool to us; 80% preferred spending <15 min on screening. The largest obstacle to screening was lack of expertise (77.1%) but 77.3% thought it important to screen for HAND. 94.3% wanted screening training. Health providers are poorly informed about HAND and lack expertise and tools to screen for HAND in their treatment programs. While few had relevant training, they recognize the importance of screening for HAND in the workplace and desire training.

Paresthesia Predicts Increased Risk of Distal Neuropathic Pain in Older People with HIV-Associated Sensory Polyneuropathy.

OBJECTIVE: Distal sensory polyneuropathy (DSP) is a disabling consequence of human immunodeficiency virus (HIV), leading to poor quality of life and more frequent falls in older age. Neuropathic pain and paresthesia are prevalent symptoms; however, there are currently no known curative treatments and the longitudinal course of pain in HIV-associated DSP is poorly characterized. METHODS: This was a prospective longitudinal study of 265 people with HIV (PWH) enrolled in the CNS HIV Antiretroviral Therapy Effects Research (CHARTER) study with baseline and 12-year follow-up evaluations. Since pain and paresthesia are highly correlated, statistical decomposition was used to separate the two symptoms at baseline. Multivariable logistic regression analyses of decomposed variables were used to determine the effects of neuropathy symptoms at baseline on presence and worsening of distal neuropathic pain at 12-year follow-up, adjusted for covariates. RESULTS: Mean age was 56 ± 8 years, and 21% were female at follow-up. Nearly the entire cohort (96%) was on antiretroviral therapy (ART), and 82% had suppressed (≤50 copies/mL) plasma viral loads at follow-up. Of those with pain at follow-up (n = 100), 23% had paresthesia at the initial visit. Decomposed paresthesia at baseline increased the risk of pain at follow-up (odds ratio [OR] 1.56; 95% confidence interval [CI] 1.18, 2.07), and decomposed pain at baseline predicted a higher frequency of pain at follow-up (OR 1.96 [95% CI 1.51, 2.58]). CONCLUSIONS: Paresthesias are a clinically significant predictor of incident pain at follow-up among aging PWH with DSP. Development of new therapies to encourage neuroregeneration might take advantage of this finding to choose individuals likely to benefit from treatment preventing incident pain.

Validation of a liquid chromatography tandem mass spectrometry (LC-MS/MS) method to detect cannabinoids in whole blood and breath.

Background The widespread availability of cannabis raises concerns regarding its effect on driving performance and operation of complex equipment. Currently, there are no established safe driving limits regarding ∆9-tetrahydrocannabinol (THC) concentrations in blood or breath. Daily cannabis users build up a large body burden of THC with residual excretion for days or weeks after the start of abstinence. Therefore, it is critical to have a sensitive and specific analytical assay that quantifies THC, the main psychoactive component of cannabis, and multiple metabolites to improve interpretation of cannabinoids in blood; some analytes may indicate recent use. Methods A liquid chromatography tandem mass spectrometry (LC-MS/MS) method was developed to quantify THC, cannabinol (CBN), cannabidiol (CBD), 11-hydroxy-THC (11-OH-THC), (±)-11-nor-9-carboxy-Δ9-THC (THCCOOH), (+)-11-nor-Δ9-THC-9-carboxylic acid glucuronide (THCCOOH-gluc), cannabigerol (CBG), and tetrahydrocannabivarin (THCV) in whole blood (WB). WB samples were prepared by solid-phase extraction (SPE) and quantified by LC-MS/MS. A rapid and simple method involving methanol elution of THC in breath collected in SensAbues® devices was optimized. Results Lower limits of quantification ranged from 0.5 to 2 µg/L in WB. An LLOQ of 80 pg/pad was achieved for THC concentrations in breath. Calibration curves were linear (R2>0.995) with calibrator concentrations within ±15% of their target and quality control (QC) bias and imprecision ≤15%. No major matrix effects or drug interferences were observed. Conclusions The methods were robust and adequately quantified cannabinoids in biological blood and breath samples. These methods will be used to identify cannabinoid concentrations in an upcoming study of the effects of cannabis on driving.

Neurocognitive functioning among HIV-positive adults in southern India.

The validity of a comprehensive international neuropsychological (NP) test battery for detection of HIV-associated neurocognitive disorders (HAND) in a Tamil speaking southern Indian cohort (69 HIV+ and 67 HIV-) was explored. The prevalence of HAND was significantly higher in the HIV+ vs. HIV- group (33 vs.13%; p < 0.01). Impairment rates were highest in the motor and speed of information processing domains. An NP battery translated into Tamil appears to be a valid tool for assessing HAND because the prevalence it found of HAND in southern India is similar to that found elsewhere.

Neurocognitive change in the era of HIV combination antiretroviral therapy: the longitudinal CHARTER study.

BACKGROUND: Human immunodeficiency virus (HIV)-associated neurocognitive disorders (HAND) can show variable clinical trajectories. Previous longitudinal studies of HAND typically have been brief, did not use adequate normative standards, or were conducted in the context of a clinical trial, thereby limiting our understanding of incident neurocognitive (NC) decline and recovery. METHODS: We investigated the incidence and predictors of NC change over 16-72 (mean, 35) months in 436 HIV-infected participants in the CNS HIV Anti-Retroviral Therapy Effects Research cohort. Comprehensive laboratory, neuromedical, and NC assessments were obtained every 6 months. Published, regression-based norms for NC change were used to generate overall change status (decline vs stable vs improved) at each study visit. Survival analysis was used to examine the predictors of time to NC change. RESULTS: Ninety-nine participants (22.7%) declined, 265 (60.8%) remained stable, and 72 (16.5%) improved. In multivariable analyses, predictors of NC improvements or declines included time-dependent treatment status and indicators of disease severity (current hematocrit, albumin, total protein, aspartate aminotransferase), and baseline demographics and estimated premorbid intelligence quotient, non-HIV-related comorbidities, current depressive symptoms, and lifetime psychiatric diagnoses (overall model P < .0001). CONCLUSIONS: NC change is common in HIV infection and appears to be driven by a complex set of risk factors involving HIV disease, its treatment, and comorbid conditions.

The effects of antiretroviral treatment initiation on cognition in HIV-infected individuals with advanced disease in Pune, India.

There has been a reduction in the most severe cases of HIV-associated neurocognitive disorders (HAND) with advances in antiretroviral treatment (ART). But the prevalence of milder forms of HAND still remains high. Data from systematically conducted studies on the effects of ART on cognition are scanty in India, where HIV-1 clade C is prevalent. The purpose of the present study was to assess the effect of antiretroviral therapy in HIV-seropositive (HIV+) individuals (n = 92) with CD4 cell counts <200 cells/mm(3). The overall and domain-specific levels of cognitive functioning were determined using a locally recruited normative sample, and a change in neurocognitive functioning at the 1-year follow-up visit was analyzed. Results revealed cognitive impairment in 44.6 % of the HIV+ group at baseline. At the 1-year follow-up, the group showed significant improvement in the Learning domain (p < 0.05). HIV+ individuals showing improvement in the global cognitive scores had a significantly lower baseline CD4 cell count compared to others. Overall, the degree of improvement associated with the magnitude of rise in CD4 suggests the possibility that early, mild subclinical deficits may also benefit from treatment.

Genetic attributes of blood-derived subtype-C HIV-1 tat and env in India and neurocognitive function.

Genetic elements in HIV-1 subtype B tat and env are associated with neurotoxicity yet less is known about other subtypes. HIV-1 subtype C tat and env sequences were analyzed to determine viral genetic elements associated with neurocognitive impairment in a large Indian cohort. Population-based sequences of HIV-1 tat (exon 1) and env (C2-V3 coding region) were generated from blood plasma of HIV-infected patients in Pune, India. Participants were classified as cognitively normal or impaired based on neuropsychological assessment. Tests for signature residues, positive and negative selection, entropy, and ambiguous bases were performed using tools available through Los Alamos National Laboratory (http://www.hiv.lanl.gov) and Datamonkey (http://www.datamonkey.org). HIV-1 subtype C tat and env sequences were analyzed for 155 and 160 participants, of which 34-36% were impaired. Two signature residues were unique to impaired participants in exon 1 of tat at codons 29 (arginine) and 68 (proline). Positive selection was noted at codon 29 among normal participants and at codon 68 in both groups. The signature at codon 29 was also a signature for low CD4+ (<200 cells/mm(3)) counts but remained associated with impairment after exclusion of those with low CD4+ counts. No unique genetic signatures were noted in env. In conclusion, two signature residues were identified in exon 1 of HIV-1 subtype C tat that were associated with neurocognitive impairment in India and not completely accounted for by HIV disease progression. These signatures support a linkage between diversifying selection in HIV-1 subtype C tat and neurocognitive impairment.

Neurocognitive functioning in a Romanian cohort of young adults with parenterally-acquired HIV-infection during childhood.

The Romanian cohort can provide valuable information about the effect of chronic HIV-infection and exposure to combined antiretroviral therapy (cART) on the developing brain, based on its unique characteristics: young adults infected parenterally with HIV clade F in the late 1980s and exposed to cART for a decade. We conducted a prospective study using a neuropsychological test battery validated in other international HIV cohorts, in order to evaluate the rate and severity of neurocognitive impairment in a group of young Romanian adults. The 49 HIV-infected (HIV+) participants and the 20 HIV negative (HIV-) controls were similar for age and gender, although the HIV- group tended to be more educated. We found higher cognitive impairment prevalence in the HIV+ group (59.1 %) versus the HIV- group (10 %), and the impairment rate remained significantly higher even when the groups were matched based on the educational level (38.7 % for the HIV+ group vs. 10.0 % for the HIV- controls; p = 0.025). The nadir CD4 count was <200 in 71.4 % of patients, but at the time of neurocognitive assessment, 89.5 % of patients had normal immunological status and 81.8 % undetectable HIV load. Among the HIV-impaired group, 26 % of the participants had syndromic impairment while the other 74 % had asymptomatic neurocognitive impairment. We found a high prevalence of neurocognitive dysfunction in the Romanian young adults growing-up with HIV. The greatest HIV-related cognitive deficits were in the domains of executive and motor functioning, consistent with a frontosubcortical pattern.

Vaporized Cannabis versus Placebo for Acute Migraine: A Randomized Controlled Trial.

Background: Preclinical and retrospective studies suggest cannabinoids may be effective in migraine treatment. However, there have been no randomized clinical trials examining the efficacy of cannabinoids for acute migraine. Methods: In this randomized, double-blind, placebo-controlled, crossover trial, adults with migraine treated up to 4 separate migraine attacks, 1 each with vaporized 1) 6% Δ9-tetrahydrocannabinol (THC-dominant); 2) 11% cannabidiol (CBD-dominant); 3) 6% THC+11% CBD; and 4) placebo cannabis flower in a randomized order. Washout period between treated attack was ≥1 week. The primary endpoint was pain relief and secondary endpoints were pain freedom and most bothersome symptom (MBS) freedom, all assessed at 2 hours post-vaporization. Results: Ninety-two participants were enrolled and randomized, and 247 migraine attacks were treated. THC+CBD was superior to placebo at achieving pain relief (67.2% vs 46.6%, Odds Ratio [95% Confidence Interval] 2.85 [1.22, 6.65], p=0.016), pain freedom (34.5% vs. 15.5%, 3.30 [1.24, 8.80], p=0.017) and MBS freedom (60.3% vs. 34.5%, 3.32 [1.45, 7.64], p=0.005) at 2 hours, as well as sustained pain freedom at 24 hours and sustained MBS freedom at 24 and 48 hours. THC-dominant was superior to placebo for pain relief (68.9% vs. 46.6%, 3.14 [1.35, 7.30], p=0.008) but not pain freedom or MBS freedom at 2 hours. CBD-dominant was not superior to placebo for pain relief, pain freedom or MBS freedom at 2 hours. There were no serious adverse events. Conclusions: Acute migraine treatment with 6% THC+11% CBD was superior to placebo at 2 hours post-treatment with sustained benefits at 24 and 48 hours.

California Cannabis Research Briefing, April 2023: Meeting Summary.

On April 28, 2023, the University of California Office of the President, in partnership with the California Department of Cannabis Control (DCC), hosted the California Cannabis Research Briefing. The California Cannabis Research Briefing brought together researchers and state agencies/policymakers to discuss pertinent policy issues on cannabis within the state. Researchers across six different topic areas (environment, cannabis markets, social equity matters, public health, medicinal cannabis use, and public safety) provided brief explanations of their research and its policy implications. A moderated discussion with stakeholders followed these presentations. The goals of this event were to highlight research that can inform policy issues relevant to the state, and to discuss how research can be incorporated into the cannabis policy landscape.

Global NeuroAIDS roundtable.

In May 2012, the Division of AIDS Research at the National Institute of Mental Health (NIMH) organized the "Global NeuroAIDS Roundtable" in conjunction with the 11th International Symposium on Neurovirology and the 2012 Conference on HIV in the Nervous System. The meeting was held in New York, NY, USA and brought together NIMH-funded investigators who are currently working on projects related to the neurological complications of AIDS (NeuroAIDS) in Africa, Asia, Eastern Europe, and Latin America in order to provide an opportunity to share their recent findings and discuss the challenges encountered within each country. The major goals of the roundtable were to evaluate HIV-associated neurocognitive impairment and determine if it may be directly attributable to distinct HIV subtypes or clades and to discuss the future priorities for global NeuroAIDS research. At the "Global NeuroAIDS Roundtable", presentations of preliminary research indicated that HIV-associated neurocognitive impairment is prevalent in all countries examined regardless of which HIV clade is present in the region. The only clear-cut difference between HIV-1 clades was in relation to subtypes A and D in Uganda. However, a key point that emerged from the discussions was that there is an urgent need to standardize neurocognitive assessment methodologies across the globe before definitive conclusions can be drawn regarding the relationship between HIV clade diversity and neuropathogenesis. Future research directions were also discussed at the roundtable with particular emphasis on the potential of viral and host factor molecular interactions to impact the pathophysiology of HIV-associated neurocognitive disorders (HAND) from a global perspective.

Evaluation of Field Sobriety Tests for Identifying Drivers Under the Influence of Cannabis: A Randomized Clinical Trial.

Importance: With increasing medicinal and recreational cannabis legalization, there is a public health need for effective and unbiased evaluations for determining whether a driver is impaired due to Δ9-tetrahydrocannabinol (THC) exposure. Field sobriety tests (FSTs) are a key component of the gold standard law enforcement officer-based evaluations, yet controlled studies are inconclusive regarding their efficacy in detecting whether a person is under the influence of THC. Objective: To examine the classification accuracy of FSTs with respect to cannabis exposure and driving impairment (as determined via a driving simulation). Design, Setting, and Participants: This double-blind, placebo-controlled parallel randomized clinical trial was conducted from February 2017 to June 2019 at the Center for Medicinal Cannabis Research, University of California, San Diego. Participants were aged 21 to 55 years and had used cannabis in the past month. Data were analyzed from August 2021 to April 2023. Intervention: Participants were randomized 1:1:1 to placebo (0.02% THC), 5.9% THC cannabis, or 13.4% THC cannabis smoked ad libitum. Main Outcome and Measures: The primary end point was law enforcement officer determination of FST impairment at 4 time points after smoking. Additional measures included officer estimation as to whether participants were in the THC or placebo group as well as driving simulator data. Officers did not observe driving performance. Results: The study included 184 participants (117 [63.6%] male; mean [SD] age, 30 [8.3] years) who had used cannabis a mean (SD) of 16.7 (9.8) days in the past 30 days; 121 received THC and 63, placebo. Officers classified 98 participants (81.0%) in the THC group and 31 (49.2%) in the placebo group as FST impaired (difference, 31.8 percentage points; 95% CI, 16.4-47.2 percentage points; P < .001) at 70 minutes after smoking. The THC group performed significantly worse than the placebo group on 8 of 27 individual FST components (29.6%) and all FST summary scores. However, the placebo group did not complete a median of 8 (IQR, 5-11) FST components as instructed. Of 128 participants classified as FST impaired, officers suspected 127 (99.2%) as having received THC. Driving simulator performance was significantly associated with results of select FSTs (eg, ≥2 clues on One Leg Stand was associated with impairment on the simulator: odds ratio, 3.09; 95% CI, 1.63-5.88; P < .001). Conclusions and Relevance: This randomized clinical trial found that when administered by highly trained officers, FSTs differentiated between individuals receiving THC vs placebo and driving abilities were associated with results of some FSTs. However, the high rate at which the participants receiving placebo failed to adequately perform FSTs and the high frequency that poor FST performance was suspected to be due to THC-related impairment suggest that FSTs, absent other indicators, may be insufficient to denote THC-specific impairment in drivers. Trial Registration: ClinicalTrials.gov Identifier: NCT02849587.

Genetic features of cerebrospinal fluid-derived subtype B HIV-1 tat.

Since HIV-1 Tat has been associated with neurocognitive dysfunction, we investigated 60 HIV-1 subtype B-infected individuals who were characterized for neurocognitive functioning and had paired CSF and blood plasma samples available. To avoid issues with repeated sampling, we generated population-based HIV-1 tat sequences from each compartment and evaluated these data using a battery of phylogenetic, statistical, and machine learning tools. These analyses identified position HXB2 5905 within the cysteine-rich domain of tat as a signature of CSF-derived HIV-1, and a higher number of mixed bases in CSF, as measure of diversity, was associated with HIV-associated neurocognitive disorder. Since identified mutations were synonymous, we evaluated the predicted secondary RNA structures, which showed that this mutation altered secondary structure. As a measure of divergence, the genetic distance between the blood and CSF-derived tat was inversely correlated with current and nadir CD4+ T cell counts. These data suggest that specific HIV-1 features of tat influence neurotropism and neurocognitive impairment.

Effects of Marathi-Hindi bilingualism on neuropsychological performance.

The present study aimed to examine if bilingualism affects executive functions and verbal fluency in Marathi and Hindi, two major languages in India, with a considerable cognate (e.g., activity is actividad in Spanish) overlap. A total of 174 native Marathi speakers from Pune, India, with varying levels of Hindi proficiency were administered tests of executive functioning and verbal performance in Marathi. A bilingualism index was generated using self-reported Hindi and Marathi proficiency. After controlling for demographic variables, the association between bilingualism and cognitive performance was examined. Degree of bilingualism predicted better performance on the switching (Color Trails-2) and inhibition (Stroop Color-Word) components of executive functioning; but not for the abstraction component (Halstead Category Test). In the verbal domain, bilingualism was more closely associated with noun generation (where the languages share many cognates) than verb generation (which are more disparate across these languages), as predicted. However, contrary to our hypothesis that the bilingualism "disadvantage" would be attenuated on noun generation, bilingualism was associated with an advantage on these measures. These findings suggest distinct patterns of bilingualism effects on cognition for this previously unexamined language pair, and that the rate of cognates may modulate the association between bilingualism and verbal performance on neuropsychological tests.

Smoked cannabis for spasticity in multiple sclerosis: a randomized, placebo-controlled trial.

BACKGROUND: Spasticity is a common and poorly controlled symptom of multiple sclerosis. Our objective was to determine the short-term effect of smoked cannabis on this symptom. METHODS: We conducted a placebo-controlled, crossover trial involving adult patients with multiple sclerosis and spasticity. We recruited participants from a regional clinic or by referral from specialists. We randomly assigned participants to either the intervention (smoked cannabis, once daily for three days) or control (identical placebo cigarettes, once daily for three days). Each participant was assessed daily before and after treatment. After a washout interval of 11 days, participants crossed over to the opposite group. Our primary outcome was change in spasticity as measured by patient score on the modified Ashworth scale. Our secondary outcomes included patients' perception of pain (as measured using a visual analogue scale), a timed walk and changes in cognitive function (as measured by patient performance on the Paced Auditory Serial Addition Test), in addition to ratings of fatigue. RESULTS: Thirty-seven participants were randomized at the start of the study, 30 of whom completed the trial. Treatment with smoked cannabis resulted in a reduction in patient scores on the modified Ashworth scale by an average of 2.74 points more than placebo (p < 0.0001). In addition, treatment reduced pain scores on a visual analogue scale by an average of 5.28 points more than placebo (p = 0.008). Scores for the timed walk did not differ significantly between treatment and placebo (p = 0.2). Scores on the Paced Auditory Serial Addition Test decreased by 8.67 points more with treatment than with placebo (p = 0.003). No serious adverse events occurred during the trial. INTERPRETATION: Smoked cannabis was superior to placebo in symptom and pain reduction in participants with treatment-resistant spasticity. Future studies should examine whether different doses can result in similar beneficial effects with less cognitive impact.

High-risk driving behaviors among adolescent binge drinkers.

BACKGROUND: Binge drinking is common among adolescents. Alcohol use, particularly binge drinking, has been associated with neurocognitive deficits and increased risk-taking behaviors, which may contribute to negative driving outcomes among adolescents even while sober. OBJECTIVES: To examine potential differences in self-reported risky driving behaviors between adolescent binge drinkers and a matched sample of controls on measures of (1) compliance with graduated licensing laws, (2) high-risk driving behaviors, and (3) driving outcomes (i.e., crashes, traffic tickets). METHODS: This study examined driving behaviors and outcomes in adolescent recent binge drinkers (n = 21) and demographically and driving history matched controls (n = 17) between the ages of 16-18 years. RESULTS: Binge drinkers more frequently violated graduated licensing laws (e.g., driving late at night) and engaged in more "high-risk" driving behaviors, such as speeding and using a cell phone while driving. Binge drinkers had more traffic tickets, crashes, and "near crashes" than the control group. Speeding was the behavior most associated with crashes within the binge drinkers. CONCLUSION: In this study, binge-drinking teens consistently engage in more dangerous driving behaviors and experience more frequent crashes and traffic tickets. They are also less compliant with preventative restrictions placed on youth while they are learning critical safe driving skills. SCIENTIFIC SIGNIFICANCE: These findings highlight a need to examine the contribution of underlying traits (such as sensation seeking) and binge-related cognitive changes to these high-risk driving behaviors, which may assist researchers in establishing alternative prevention and policy efforts targeting this population.