Adding tobacco to cannabis: its frequency and likely implications.

INTRODUCTION: Young cannabis users are at increased risk of later cigarette initiation and progression to nicotine addiction. The present study addresses the frequency at which mulling (adding tobacco to cannabis smoked as joints) is performed and in which way this practice varies according to cigarette smoking status. METHODS: Data were issued from the Swiss 2007 European School Survey Project on Alcohol and other Drugs (ESPAD). A total of 881 past month cannabis users (mean age 15 years, boys 60.1%) were inquired on mulling using an anonymous self-administered questionnaire. Participants were further grouped according to their cigarette smoking status (daily, occasional, former, and never-smokers). RESULTS: Four of every 5 cannabis users depicted mulling as frequently performed. The highest occurrence was found among daily cigarette smokers (DSC; 90.3%), while former cigarette smokers reported the lowest (58.9%). The multinomial logistic regression showed DSC more likely reporting mulling as frequent compared with never-smokers (risk ratio = 3.56 [95% CI 1.55-8.21]). Conclusions: Mulling appears to be a very common process among young cannabis users, especially among concomitant cigarette smokers. Nevertheless, the majority of cigarette abstainers also reported frequently adding tobacco to the cannabis they smoke. Because it may represent a significant exposition to nicotine, mulling should be taken into account when assessing substance use among adolescents and in supporting their quitting attempts.

Weed or wheel! FMRI, behavioural, and toxicological investigations of how cannabis smoking affects skills necessary for driving.

Marijuana is the most widely used illicit drug, however its effects on cognitive functions underling safe driving remain mostly unexplored. Our goal was to evaluate the impact of cannabis on the driving ability of occasional smokers, by investigating changes in the brain network involved in a tracking task. The subject characteristics, the percentage of Δ(9)-Tetrahydrocannabinol in the joint, and the inhaled dose were in accordance with real-life conditions. Thirty-one male volunteers were enrolled in this study that includes clinical and toxicological aspects together with functional magnetic resonance imaging of the brain and measurements of psychomotor skills. The fMRI paradigm was based on a visuo-motor tracking task, alternating active tracking blocks with passive tracking viewing and rest condition. We show that cannabis smoking, even at low Δ(9)-Tetrahydrocannabinol blood concentrations, decreases psychomotor skills and alters the activity of the brain networks involved in cognition. The relative decrease of Blood Oxygen Level Dependent response (BOLD) after cannabis smoking in the anterior insula, dorsomedial thalamus, and striatum compared to placebo smoking suggests an alteration of the network involved in saliency detection. In addition, the decrease of BOLD response in the right superior parietal cortex and in the dorsolateral prefrontal cortex indicates the involvement of the Control Executive network known to operate once the saliencies are identified. Furthermore, cannabis increases activity in the rostral anterior cingulate cortex and ventromedial prefrontal cortices, suggesting an increase in self-oriented mental activity. Subjects are more attracted by intrapersonal stimuli ("self") and fail to attend to task performance, leading to an insufficient allocation of task-oriented resources and to sub-optimal performance. These effects correlate with the subjective feeling of confusion rather than with the blood level of Δ(9)-Tetrahydrocannabinol. These findings bolster the zero-tolerance policy adopted in several countries that prohibits the presence of any amount of drugs in blood while driving.

Comparison of cannabinoid concentrations in oral fluid and whole blood between occasional and regular cannabis smokers prior to and after smoking a cannabis joint.

A cross-over controlled administration study of smoked cannabis was carried out on occasional and heavy smokers. The participants smoked a joint (11 % Δ9-tetrahydrocannabinol (THC)) or a matching placebo on two different occasions. Whole blood (WB) and oral fluid (OF) samples were collected before and up to 3.5 h after smoking the joints. Pharmacokinetic analyses were obtained from these data. Questionnaires assessing the subjective effects were administered to the subjects during each session before and after the smoking time period. THC, 11-hydroxy-THC (11-OH-THC) and 11-nor-9-carboxy-THC (THCCOOH) were analyzed in the blood by gas chromatography or liquid chromatography (LC)-tandem mass spectrometry (MS/MS). The determination of THC, THCCOOH, cannabinol (CBN), and Δ9-tetrahydrocannabinolic acid A (THC-A) was carried out on OF only using LC-MS/MS. In line with the widely accepted assumption that cannabis smoking results in a strong contamination of the oral cavity, we found that THC, and also THC-A, shows a sharp, high concentration peak just after smoking, with a rapid decrease in these levels within 3 h. No obvious differences were found between both groups concerning THC median maximum concentrations measured either in blood or in OF; these levels were equal to 1,338 and 1,041 μg/L in OF and to 82 and 94 μg/L in WB for occasional and heavy smokers, respectively. The initial WB THCCOOH concentration was much higher in regular smokers than in occasional users. Compared with the occasional smokers, the sensation of confusion felt by the regular smokers was much less while the feeling of intoxication remained almost unchanged.

Temperature dependence of the magnetization processes in Co/Al oxide/Permalloy trilayers

The magnetization process of Co/Al oxide/Py trilayers and its evolution with the temperature have been analyzed. The particular behavior of the Co layers, including the shift of the hysteresis loops and a coercivity increase with the decrease of temperature, is related with the apparition of a CoO layer at the Co/Al-oxide interface.

Systematic study of the temperature dependence of the saturation magnetization in Fe, Fe-Ni and Co-based amorphous alloys

Magnetization versus temperature in the temperature interval 2-200 K was measured for amorphous alloys of three different compositions: Fe 81.5B14.5Si4, Fe40Ni38 Mo4B18, and Co70Fe5Ni 2Mo3B5Si15. The measurements were performed by means of a SQUID (superconducting quantum interference device) magnetometer. The aim was to extract information about the different mechanisms contributing to thermal demagnetization. A powerful data analysis technique based on successive minimization procedures has demonstrated that Stoner excitations of the strong ferromagnetic type play a significant role in the Fe-Ni alloy studied. The Fe-rich and Co-rich alloys do not show a measurable contribution from single-particle excitations.

Degree of multicollinearity and variables involved in linear dependence in additive-dominant models

The objective of this work was to assess the degree of multicollinearity and to identify the variables involved in linear dependence relations in additive-dominant models. Data of birth weight (n=141,567), yearling weight (n=58,124), and scrotal circumference (n=20,371) of Montana Tropical composite cattle were used. Diagnosis of multicollinearity was based on the variance inflation factor (VIF) and on the evaluation of the condition indexes and eigenvalues from the correlation matrix among explanatory variables. The first model studied (RM) included the fixed effect of dam age class at calving and the covariates associated to the direct and maternal additive and non-additive effects. The second model (R) included all the effects of the RM model except the maternal additive effects. Multicollinearity was detected in both models for all traits considered, with VIF values of 1.03 - 70.20 for RM and 1.03 - 60.70 for R. Collinearity increased with the increase of variables in the model and the decrease in the number of observations, and it was classified as weak, with condition index values between 10.00 and 26.77. In general, the variables associated with additive and non-additive effects were involved in multicollinearity, partially due to the natural connection between these covariables as fractions of the biological types in breed composition.

Revisión sobre la comorbilidad psiquiátrica del consumo de cannabis y la esquizofrenia

El consumo habitual de cannabis conlleva graves consecuencias a la población. Dicho consumo a una edad temprana, se ha visto que puede ser un factor de riesgo a tener en cuenta en poblaciones vulnerables al desarrollo de trastornos psicóticos, principalmente, en la esquizofrenia. Los objetivos de este trabajo son: analizar la prevalencia de personas que sufren esquizofrenia y a la vez son consumidoras de cannabis, conocer la existente correlación entre el consumo de cannabis y la esquizofrenia, y por último, determinar cuál de los dos factores es el precipitante del otro. Para ello se llevará a cabo una revisión de la literatura, en la que se recogerán y se analizarán artículos de carácter científico, publicados en revistas indexadas en las bases de datos seleccionadas y en las que generalmente se haga revisión por pares. Y dichos artículos tratarán el área de conocimiento y de interés para esta revisión. Se revisarán todas las publicaciones que cumplan su publicación en mayo del 2013, en idioma inglés y castellano. El tipo de población a estudiar debía ser juvenil, con un rango de edad entre los 15 y los 34 años y con un consumo habitual de cannabis. Se seleccionaron, finalmente, 19 artículos de los cuales son: otras revisiones sistemáticas, meta-análisis, estudios de cohortes, estudios longitudinales y de casos-control.

Fitness to drive and cannabis: Experimental and real-life case study validation of two blood THCCOOH thresholds to distinguish occasional users from heavy smokers

Introduction: THC-COOH has been proposed as a criterion to help to distinguish between occasional from regular cannabis users. However, to date this indicator has not been adequately assessed under experimental and real-life conditions. Methods: We carried out a controlled administration study of smoked cannabis with a placebo. Twenty-three heavy smokers and 25 occasional smokers, between 18 and 30 years of age, participated in this study [Battistella G et al., PloS one. 2013;8(1):e52545]. We collected data from a second real case study performed with 146 traffic offenders' cases in which the whole blood cannabinoid concentrations and the frequency of cannabis use were known. Cannabinoid levels were determined in whole blood using tandem mass spectrometry methods. Results: Significantly high differences in THC-COOH concentrations were found between the two groups when measured during the screening visit, prior to the smoking session, and throughout the day of the experiment. Receiver operating characteristic (ROC) curves were determined and two threshold criteria were proposed in order to distinguish between these groups: a free THC-COOH concentration below 3 μg/L suggested an occasional consumption (≤ 1 joint/week) while a concentration higher than 40 μg/L corresponded to a heavy use (≥ 10 joints/month). These thresholds were successfully tested with the second real case study. The two thresholds were not challenged by the presence of ethanol (40% of cases) and of other therapeutic and illegal drugs (24%). These thresholds were also found to be consistent with previously published experimental data. Conclusion: We propose the following procedure that can be very useful in the Swiss context but also in other countries with similar traffic policies: If the whole blood THC-COOH concentration is higher than 40 μg/L, traffic offenders must be directed first and foremost toward medical assessment of their fitness to drive. This evaluation is not recommended if the THC-COOH concentration is lower than 3 μg/L. A THC-COOH level between these two thresholds can't be reliably interpreted. In such a case, further medical assessment and follow up of the fitness to drive are also suggested, but with lower priority.

Alcohol and cannabis use as risk factors for injury--a case-crossover analysis in a Swiss hospital emergency department.

BACKGROUND: There is sufficient and consistent evidence that alcohol use is a causal risk factor for injury. For cannabis use, however, there is conflicting evidence; a detrimental dose-response effect of cannabis use on psychomotor and other relevant skills has been found in experimental laboratory studies, while a protective effect of cannabis use has also been found in epidemiological studies. METHODS: Implementation of a case-crossover design study, with a representative sample of injured patients (N = 486; 332 men; 154 women) from the Emergency Department (ED) of the Lausanne University Hospital, which received treatment for different categories of injuries of varying aetiology. RESULTS: Alcohol use in the six hours prior to injury was associated with a relative risk of 3.00 (C.I.: 1.78, 5.04) compared with no alcohol use, a dose-response relationship also was found. Cannabis use was inversely related to risk of injury (RR: 0.33; C.I.: 0.12, 0.92), also in a dose-response like manner. However, the sample size for people who had used cannabis was small. Simultaneous use of alcohol and cannabis did not show significantly elevated risk. CONCLUSION: The most surprising result of our study was the inverse relationship between cannabis use and injury. Possible explanations and underlying mechanisms, such as use in safer environments or more compensatory behavior among cannabis users, were discussed.

On the inclusion of channel's time dependence in a hidden Markov model for blind channel estimation

In this paper, the theory of hidden Markov models (HMM) isapplied to the problem of blind (without training sequences) channel estimationand data detection. Within a HMM framework, the Baum–Welch(BW) identification algorithm is frequently used to find out maximum-likelihood (ML) estimates of the corresponding model. However, such a procedureassumes the model (i.e., the channel response) to be static throughoutthe observation sequence. By means of introducing a parametric model fortime-varying channel responses, a version of the algorithm, which is moreappropriate for mobile channels [time-dependent Baum-Welch (TDBW)] isderived. Aiming to compare algorithm behavior, a set of computer simulationsfor a GSM scenario is provided. Results indicate that, in comparisonto other Baum–Welch (BW) versions of the algorithm, the TDBW approachattains a remarkable enhancement in performance. For that purpose, onlya moderate increase in computational complexity is needed.

Hemispheric language asymmetry in first episode psychosis and schizotypy : the role of cannabis consumption and cognitive disorganization

Cannabis use has been related to an elevated psychosis risk and attenuated cognitive functioning. Cannabis-related cognitive impairments are also observed in populations along the psychosis dimension. We here investigated whether a potential behavioural marker of the psychosis dimension (attenuated functional hemispheric asymmetry) is even further attenuated in individuals using cannabis (CU) versus those not using cannabis (nCU). We tested 29 patients with first episode psychosis (FEP; 11 CU) and 90 healthy controls (38 CU) on lateralized lexical decisions assessing left hemisphere language dominance. In patients, psychotic symptoms were assessed (PANSS). In controls, self-reported schizotypy was assessed (O-LIFE questionnaire). Results indicated that nCU FEP patients had a relative reduced hemispheric asymmetry, as did controls with increasing cognitive disorganisation scores, in particular when belonging to the group of nCU controls. Positive, disorganised and negative PANSS scores in patients and negative and positive schizotypy in controls were unrelated to hemispheric asymmetry. These findings suggest that cannabis use balances rather than exacerbates uncommon hemispheric laterality patterns. Moreover, in healthy populations, the potential stabilisation of typical hemispheric asymmetry in CU might be most relevant to individuals with elevated cognitive disorganisation. We discuss the potential beneficial and harmful effects of cannabis use along the psychosis dimension together with propositions for future studies that should account for the mediating role of additional substances (e.g. nicotine), cannabis composition (e.g. cannabidiol content), and individual differences (e.g. physical health, or absence of significant polysubstance use).

Challenging the "inoffensiveness" of regular cannabis use by its associations with other current risky substance use--a census of 20-year-old Swiss men.

3,537 men enrolling in 2007 for mandatory army recruitment procedures were assessed for the co-occurrence of risky licit substance use among risky cannabis users. Risky cannabis use was defined as at least twice weekly; risky alcohol use as 6+ drinks more than once/monthly, or more than 20 drinks per week; and risky tobacco use as daily smoking. Ninety-five percent of all risky cannabis users reported other risky use. They began using cannabis earlier than did non-risky users, but age of onset was unrelated to other risky substance use. A pressing public health issue among cannabis users stems from risky licit substance use warranting preventive efforts within this age group.

Enhanced cytotoxicity and decreased CD8 dependence of human cancer-specific cytotoxic T lymphocytes after vaccination with low peptide dose.

In mice, vaccination with high peptide doses generates higher frequencies of specific CD8+ T cells, but with lower avidity compared to vaccination with lower peptide doses. To investigate the impact of peptide dose on CD8+ T cell responses in humans, melanoma patients were vaccinated with 0.1 or 0.5 mg Melan-A/MART-1 peptide, mixed with CpG 7909 and Incomplete Freund's adjuvant. Neither the kinetics nor the amplitude of the Melan-A-specific CD8+ T cell responses differed between the two vaccination groups. Also, CD8+ T cell differentiation and cytokine production ex vivo were similar in the two groups. Interestingly, after low peptide dose vaccination, Melan-A-specific CD8+ T cells showed enhanced degranulation upon peptide stimulation, as assessed by CD107a upregulation and perforin release ex vivo. In accordance, CD8+ T cell clones derived from low peptide dose-vaccinated patients showed significantly increased degranulation and stronger cytotoxicity. In parallel, Melan-A-specific CD8+ T cells and clones from low peptide dose-vaccinated patients expressed lower CD8 levels, despite similar or even stronger binding to tetramers. Furthermore, CD8+ T cell clones from low peptide dose-vaccinated patients bound CD8 binding-deficient tetramers more efficiently, suggesting that they may express higher affinity TCRs. We conclude that low peptide dose vaccination generated CD8+ T cell responses with stronger cytotoxicity and lower CD8 dependence.