No abstract

It is predicted that by 2030, globally, an estimated 2.16 billion adults will be overweight, and 1.12 billion will be obese. This study examined genetic data regarding Reward Deficiency Syndrome (RDS) to evaluate their usefulness in counselling patients undergoing bariatric surgery and gathered preliminary data on the potential use in predicting short term (6-month) weight loss outcomes. Methods: Patients undergoing bariatric surgery (n = 34) were examined for Genetic Addiction Risk Severity (GARS) [measures the presence of risk alleles associated with RDS]; as well as their psychosocial traits (questionnaires). BMI changes and sociodemographic data were abstracted from Electronic Health Records. Results: Subjects showed ∆BMI (M = 10.0 ± 1.05 kg/m2) and a mean % excess weight loss (56 ± 13.8%). In addition, 76% of subjects had GARS scores above seven. The homozygote risk alleles for MAO (rs768062321) and DRD1 (rs4532) showed a 38% and 47% prevalence among the subjects. Of the 11 risk alleles identified by GARS, the DRD4 risk allele (rs1800955), was significantly correlated with change in weight and BMI six months post-surgery. We identified correlations with individual risk alleles and psychosocial trait scores. The COMT risk allele (rs4680) showed a negative correlation with EEI scores (r = −0.4983, p < 0.05) and PSQI scores (r = −0.5482, p < 0.05). The GABRB3 risk allele (rs764926719) correlated positively with EEI (r = 0.6161, p < 0.01) and FCQ scores (r = 0.6373, p < 0.01). The OPRM1 risk allele showed a positive correlation with the DERS score (r = 0.5228, p < 0.05). We also identified correlations between DERS and BMI change (r = 0.61; p < 0.01). Conclusions: These data support the potential benefit of a personalized medicinal approach inclusive of genetic testing and psychosocial trait questionnaires when counselling patients with obesity considering bariatric surgery. Future research will explore epigenetic factors that contribute to outcomes of bariatric surgery.

Background: Delta-9-tetrahydrocannabinol (THC) is the main psychoactive component of cannabis. Historically, rodent studies examining the effects of THC have used intraperitoneal injection as the route of administration, heavily focusing on male subjects. However, human cannabis use is often through inhalation rather than injection. Objective: We sought to characterize the pharmacokinetic and phenotypic profile of acutely inhaled THC in female rats, compared to intraperitoneal injection, to identify any differences in exposure of THC between routes of administration. Methods: Adult female rats were administered THC via inhalation or intraperitoneal injection. Serum samples from multiple time points were analyzed for THC and metabolites 11-hydroxy-delta-9-tetrahydrocannabinol and 11-nor-9-carboxy-delta-9-tetrahydrocannabinol using ultra-performance liquid chromatography-tandem mass spectrometry. Rats were similarly treated for locomotor activity analysis. Results: Rats treated with 2 mg/kg THC intraperitoneally reached a maximum serum THC concentration of 107.7 ± 21.9 ng/mL. Multiple THC inhalation doses were also examined (0.25 mL of 40 or 160 mg/mL THC), achieving maximum concentrations of 43.3 ± 7.2 and 71.6 ± 22.5 ng/mL THC in serum, respectively. Significantly reduced vertical locomotor activity was observed in the lower inhaled dose of THC and the intraperitoneal injected THC dose compared to vehicle treatment. Conclusion: This study established a simple rodent model of inhaled THC, demonstrating the pharmacokinetic and locomotor profile of acute THC inhalation, compared to an i.p. injected THC dose in female subjects. These results will help support future inhalation THC rat research which is especially important when researching behavior and neurochemical effects of inhaled THC as a model of human cannabis use.

Emerging evidence indicates that the endogenous cannabinoid system modulates the behavioral and physiological effects of nicotine. Fatty acid-binding proteins (FABPs) are among the primary intracellular trafficking mechanisms of endogenous cannabinoids, such as anandamide. To this end, changes in FABP expression may similarly impact the behavioral manifestations associated with nicotine, particularly its addictive properties. FABP5+/+ and FABP5−/− mice were tested for nicotine-conditioned place preference (CPP) at two different doses (0.1 or 0.5 mg/kg). The nicotine-paired chamber was assigned as their least preferred chamber during preconditioning. Following 8 days of conditioning, the mice were injected with either nicotine or saline. The mice were allowed to access to all the chambers on the test day, and their times spent in the drug chamber on the preconditioning versus the test days were used to examine the drug preference score. The CPP results showed that the FABP5−/−mice displayed a higher place preference for 0.1 mg/kg nicotine than the FABP5+/+ mice, while no CPP difference was observed for 0.5 mg/kg nicotine between the genotypes. In conclusion, FABP5 plays an important role in regulating nicotine place preference. Further research is warranted to identify the precise mechanisms. The results suggest that dysregulated cannabinoid signaling may impact nicotine-seeking behavior.