Endocannabinoid regulation of acute and protracted nicotine withdrawal: effect of FAAH inhibition.

Evidence shows that the endocannabinoid system modulates the addictive properties of nicotine. In the present study, we hypothesized that spontaneous withdrawal resulting from removal of chronically implanted transdermal nicotine patches is regulated by the endocannabinoid system. A 7-day nicotine dependence procedure (5.2 mg/rat/day) elicited occurrence of reliable nicotine abstinence symptoms in Wistar rats. Somatic and affective withdrawal signs were observed at 16 and 34 hours following removal of nicotine patches, respectively. Further behavioral manifestations including decrease in locomotor activity and increased weight gain also occurred during withdrawal. Expression of spontaneous nicotine withdrawal was accompanied by fluctuation in levels of the endocannabinoid anandamide (AEA) in several brain structures including the amygdala, the hippocampus, the hypothalamus and the prefrontal cortex. Conversely, levels of 2-arachidonoyl-sn-glycerol were not significantly altered. Pharmacological inhibition of fatty acid amide hydrolase (FAAH), the enzyme responsible for the intracellular degradation of AEA, by URB597 (0.1 and 0.3 mg/kg, i.p.), reduced withdrawal-induced anxiety as assessed by the elevated plus maze test and the shock-probe defensive burying paradigm, but did not prevent the occurrence of somatic signs. Together, the results indicate that pharmacological strategies aimed at enhancing endocannabinoid signaling may offer therapeutic advantages to treat the negative affective state produced by nicotine withdrawal, which is critical for the maintenance of tobacco use.

Moderate-Vigorous Physical Activity across Body Mass Index in Females: Moderating Effect of Endocannabinoids and Temperament.

BACKGROUND Endocannabinoids and temperament traits have been linked to both physical activity and body mass index (BMI) however no study has explored how these factors interact in females. The aims of this cross-sectional study were to 1) examine differences among distinct BMI groups on daytime physical activity and time spent in moderate-vigorous physical activity (MVPA), temperament traits and plasma endocannabinoid concentrations; and 2) explore the association and interaction between MVPA, temperament, endocannabinoids and BMI. METHODS Physical activity was measured with the wrist-worn accelerometer Actiwatch AW7, in a sample of 189 female participants (43 morbid obese, 30 obese, and 116 healthy-weight controls). The Temperament and Character Inventory-Revised questionnaire was used to assess personality traits. BMI was calculated by bioelectrical impedance analysis via the TANITA digital scale. Blood analyses were conducted to measure levels of endocannabinoids and endocannabinoid-related compounds. Path-analysis was performed to examine the association between predictive variables and MVPA. RESULTS Obese groups showed lower MVPA and dysfunctional temperament traits compared to healthy-weight controls. Plasma concentrations of 2-arachidonoylglyceryl (2-AG) were greater in obese groups. Path-analysis identified a direct effect between greater MVPA and low BMI (b = -0.13, p = .039) and high MVPA levels were associated with elevated anandamide (AEA) levels (b = 0.16, p = .049) and N-oleylethanolamide (OEA) levels (b = 0.22, p = .004), as well as high Novelty seeking (b = 0.18, p<.001) and low Harm avoidance (b = -0.16, p<.001). CONCLUSIONS Obese individuals showed a distinct temperament profile and circulating endocannabinoids compared to controls. Temperament and endocannabinoids may act as moderators of the low MVPA in obesity.