Modulation of the endocannabinoids N-Arachidonoylethanolamine (AEA) and 2-Arachidonoylglycerol (2-AG) on Executive Functions in Humans

Animal studies point to an implication of the endocannabinoid system on executive functions. In humans, several studies have suggested an association between acute or chronic use of exogenous cannabinoids (Δ9-tetrahydrocannabinol) and executive impairments. However, to date, no published reports establish the relationship between endocannabinoids, as biomarkers of the cannabinoid neurotransmission system, and executive functioning in humans. The aim of the present study was to explore the association between circulating levels of plasma endocannabinoids N-arachidonoylethanolamine (AEA) and 2-Arachidonoylglycerol (2-AG) and executive functions (decision making, response inhibition and cognitive flexibility) in healthy subjects. One hundred and fifty seven subjects were included and assessed with the Wisconsin Card Sorting Test; Stroop Color and Word Test; and Iowa Gambling Task. All participants were female, aged between 18 and 60 years and spoke Spanish as their first language. Results showed a negative correlation between 2-AG and cognitive flexibility performance (r = −.37; p<.05). A positive correlation was found between AEA concentrations and both cognitive flexibility (r = .59; p<.05) and decision making performance (r = .23; P<.05). There was no significant correlation between either 2-AG (r = −.17) or AEA (r = −.08) concentrations and inhibition response. These results show, in humans, a relevant modulation of the endocannabinoid system on prefrontal-dependent cognitive functioning. The present study might have significant implications for the underlying executive alterations described in some psychiatric disorders currently associated with endocannabinoids deregulation (namely drug abuse/dependence, depression, obesity and eating disorders). Understanding the neurobiology of their dysexecutive profile might certainly contribute to the development of new treatments and pharmacological approaches

Effects of the cannabinoid CB1 receptor antagonist rimonabant on distinct measures of impulsive behavior in rats

Rationale Pathological impulsivity is a prominent feature in several psychiatric disorders, but detailed understanding of the specific neuronal processes underlying impulsive behavior is as yet lacking. Objectives As recent findings have suggested involvement of the brain cannabinoid system in impulsivity, the present study aimed at further elucidating the role of cannabinoid CB1 receptor activation in distinct measures of impulsive behavior. Materials and methods The effects of the selective cannabinoid CB1 receptor antagonist, rimonabant (SR141716A) and agonist WIN55,212-2 were tested in various measures of impulsive behavior, namely, inhibitory control in a five-choice serial reaction time task (5-CSRTT), impulsive choice in a delayed reward paradigm, and response inhibition in a stop-signal paradigm. Results In the 5-CSRTT, SR141716A dose-dependently improved inhibitory control by decreasing the number of premature responses. Furthermore, SR141716A slightly improved attentional function, increased correct response latency, but did not affect other parameters. The CB1 receptor agonist WIN55,212-2 did not change inhibitory control in the 5-CSRTT and only increased response latencies and errors of omissions. Coadministration of WIN55,212-2 prevented the effects of SR141716A on inhibitory control in the 5-CSRTT. Impulsive choice and response inhibition were not affected by SR141716A at any dose, whereas WIN55,212-2 slightly impaired response inhibition but did not change impulsive choice. Conclusions The present data suggest that particularly the endocannabinoid system seems involved in some measures of impulsivity and provides further evidence for the existence of distinct forms of impulsivity that can be pharmacologically dissociated

Cardiorespiratory fitness and body mass index of 9-11-year-old English children: a serial cross-sectional study from 1998 to 2004.

OBJECTIVE: To examine the changes over time in cardiorespiratory fitness and body mass index (BMI) of children. DESIGN: Serial cross-sectional, population-based study. SETTING: Primary schools in Liverpool, UK. PARTICIPANTS: A total of 15,621 children (50% boys), representing 74% of eligible 9-11-year olds in the annual school cohorts between 1998/9 and 2003/4, who took part in a 20m multi-stage shuttle run test (20mMST). MAIN OUTCOME MEASURES: Weight, height, BMI (kg/m(2)) and obesity using the International Obesity Taskforce definition. RESULTS: Median (95% confidence interval) 20mMST score (number of runs) fell in boys from 48.9 (47.9-49.9) in 1998/9 to 38.1 (36.8-39.4) in 2003/4, and in girls from 35.8 (35.0-36.6) to 28.1 (27.2-29.1) over the same period. Fitness scores fell across all strata of BMI (P&lt;0.001). Moreover, BMI increased over the same 6-year period even among children in fittest third of 20mMST. CONCLUSION: In a series of uniform cross-sectional assessments of school-aged children, BMI increased whereas cardiorespiratory fitness levels decreased within a 6-year period. Even among lean children, fitness scores decreased. Public health measures to reduce obesity, such as increasing physical activity, may help raise fitness levels among all children - not just the overweight or obese