Evaluation of the efficacy and safety of cannabidiol-rich cannabis extract in children with autism spectrum disorder: randomized, double-blind, and placebo-controlled clinical trial

Abstract Objective Autism spectrum disorder (ASD) is characterized by persistent deficits in social communication and social interaction and by restricted and repetitive patterns of behavior. Some studies have shown that substances derived from Cannabis sativa improve the quality of life of children with ASD without causing serious adverse effects, thus providing an alternative therapeutic option. The objective of this study was to evaluate the efficacy and safety of a cannabis extract rich in cannabidiol (CBD) in children with ASD. Methods In this randomized, double-blind, placebo-controlled clinical trial, 60 children, aged from 5 to 11 years, were selected and divided into two groups: the treatment group, which received the CBD-rich cannabis extract, and the control group, which received the placebo. They both used their respective products for a period of 12 weeks. Statistical analysis was done by two-factor mixed analysis of variance (two-way ANOVA). Results Significant results were found for social interaction (F1,116 = 14.13, p = 0.0002), anxiety (F1,116 = 5.99, p = 0.016), psychomotor agitation (F1,116 = 9.22, p = 0.003), number of meals a day (F1,116 = 4.11, p = 0.04), and concentration (F1,48 = 6.75, p = 0.01), the last of which was only significant in mild ASD cases. Regarding safety, it was found that only three children in the treatment group (9.7%) had adverse effects, namely dizziness, insomnia, colic, and weight gain. Conclusion CBD-rich cannabis extract was found to improve one of the diagnostic criteria for ASD (social interaction), as well as features that often co-exist with ASD, and to have few serious adverse effects.

Evaluation of the efficacy and safety of cannabidiol-rich cannabis extract in children with autism spectrum disorder: randomized, double-blind and controlled placebo clinical trial.

INTRODUCTION: Autism Spectrum Disorder is characterized by persistent deficits in social communication, social interaction, and restricted and repetitive patterns of behavior. Some studies have shown that substances derived from Cannabis sativa improve the quality of life of autistic children without causing serious adverse effects, thus providing a therapeutic alternative. METHOD: This was a randomized, double-blind, placebo-controlled clinical trial to evaluate the efficacy and safety of a cannabis extract rich in cannabidiol (CBD) in autistic children. Sixty children, aged between 5 and 11 years, were selected and divided into two groups: the treatment group, which received the CBD-rich cannabis extract, and the control group, which received the placebo, both used the product for a period of 12 weeks. Statistical analysis was done by two-factor mixed analysis of variance (ANOVA two way). RESULTS: Significant results were found for social interaction [F(1,116)=14.13, p=0.0002)], anxiety [F(1,116)=5.99, p=0.016], psychomotor agitation [F(1,116)=9.22, p=0.003)], number of meals a day [F(1,116)=4.11, p=0.04)] and concentration [F (1,48)=6.75, p=0.01], the latter being significant only in mild autism spectrum disorder. Regarding safety, it was found that only three children in the treatment group (9.7%) had adverse effects, namely dizziness, insomnia, colic and weight gain. CONCLUSION: CBD-rich cannabis extract was found to improve one of the diagnostic criteria for ASD (social interaction), as well as often co-existing features, and to have few serious adverse effects.

The direct correlation between oxidative stress and LDL-C levels in adults is maintained by the Friedewald and Martin equations, but the methylation levels in the MTHFR and ADRB3 genes differ.

Low-density lipoprotein (LDL-C) concentrations are a standard of care in the prevention of cardiovascular disease and are influenced by different factors. This study compared the LDL-C concentrations estimated by two different equations and determined their associations with inflammatory status, oxidative stress, anthropometric variables, food intake and DNA methylation levels in the LPL, ADRB3 and MTHFR genes. A cross-sectional population-based study was conducted with 236 adults (median age 37.5 years) of both sexes from the municipality of João Pessoa, Paraíba, Brazil. The LDL-C concentrations were estimated according to the Friedewald and Martin equations. LPL, ADRB3 and MTHFR gene methylation levels; malondialdehyde levels; total antioxidant capacity; ultra-sensitive C-reactive protein, alpha-1-acid glycoprotein, homocysteine, cobalamin, and folic acid levels; usual dietary intake; and epidemiological variables were also determined. For each unit increase in malondialdehyde concentration there was an increase in the LDL-C concentration from 6.25 to 10.29 mg/dL (p <0.000). Based on the Martin equation (≥70 mg/dL), there was a decrease in the DNA methylation levels in the ADRB3 gene and an increase in the DNA methylation levels in the MTHFR gene (p <0.05). There was a positive relation of homocysteine and cholesterol intake on LDL-C concentrations estimated according to the Friedewald equation and of waist circumference and age based on the two estimates. It is concluded the LDL-C concentrations estimated by the Friedewald and Martin equations were different, and the Friedewald equation values were significantly lower than those obtained by the Martin equation. MDA was the variable that was most positively associated with the estimated LDL-C levels in all multivariate models. Significant relationships were observed based on the two estimates and occurred for most variables. The methylation levels of the ADRB3 and MTHFR genes were different according to the Martin equation at low LDL-C concentrations (70 mg/dL).

Decrease of the DNA methylation levels of the ADRB3 gene in leukocytes is related with serum folate in eutrophic adults.

BACKGROUND: DNA methylation has been evidenced as a potential epigenetic mechanism related to various candidate genes to development of obesity. Therefore, the objective of this study was to evaluate the DNA methylation levels of the ADRB3 gene by body mass index (BMI) in a representative adult population, besides characterizing this population as to the lipid profile, oxidative stress and food intake. METHODS: This was a cross-sectional population-based study, involving 262 adults aged 20-59 years, of both genders, representative of the East and West regions of the municipality of João Pessoa, Paraíba state, Brazil, in that were evaluated lifestyle variables and performed nutritional, biochemical evaluation and DNA methylation levels of the ADRB3 gene using high resolution melting method. The relationship between the study variables was performed using analyses of variance and multiple regression models. All results were obtained using the software R, 3.3.2. RESULTS: From the stratification of categories BMI, was observed a difference in the average variables values of age, waist-to-height ratio, waist-to-hip ratio, waist circumference, triglycerides and intake of trans fat, which occurred more frequently between the categories "eutrophic" and "obesity". From the multiple regression analysis in the group of eutrophic adults, it was observed a negative relationship between methylation levels of the ADRB3 gene with serum levels of folic acid. However, no significant relation was observed among lipid profile, oxidative stress and food intake in individuals distributed in the three categories of BMI. CONCLUSIONS: A negative relationship was demonstrated between methylation levels of the ADRB3 gene in eutrophic adults individuals with serum levels of folic acid, as well as with the independent gender of BMI, however, was not observed relation with lipid profile, oxidative stress and variables of food intake. Regarding the absence of relationship with methylation levels of the ADRB3 gene in the categories of overweight, mild and moderate obesity, the answer probably lies in the insufficient amount of body fat to initiate inflammatory processes and oxidative stress with a direct impact on methylation levels, what is differently is found most of the times in exacerbated levels in severe obesity.