Objective: To determine the safety and tolerability of escalating doses of three cannabis oil formulations, containing predominantly CBD, THC, or CBD and THC (1.5:1) vs. placebo in dogs.Design: Randomized, placebo-controlled, blinded, parallel study.Animals: Twenty healthy Beagle dogs (10 males, 10 females).Methods: Dogs were randomly assigned to one of five treatment groups (n = 4 dogs per group balanced by sex): CBD-predominant oil, THC-predominant oil, CBD/THC-predominant oil (1.5:1), sunflower oil placebo, medium-chain triglyceride oil placebo. Up to 10 escalating doses of the oils were planned for administration via oral gavage, with at least 3 days separating doses. Clinical observations, physical examinations, complete blood counts, clinical chemistry, and plasma cannabinoids were used to assess safety, tolerability, and the occurrence of adverse events (AEs). AEs were rated as mild, moderate, or severe/medically significant.Results: Dose escalation of the CBD-predominant oil formulation was shown to be as safe as placebo and safer than dose escalation of oils containing THC (CBD/THC oil or THC oil). The placebo oils were delivered up to 10 escalating volumes, the CBD oil up to the tenth dose (640.5 mg; ∼62 mg/kg), the THC oil up to the tenth dose (597.6 mg; ∼49 mg/kg), and the CBD/THC oil up to the fifth dose (140.8/96.6 mg CBD/THC; ∼12 mg/kg CBD + 8 mg/kg THC). AEs were reported in all dogs across the five groups and the majority (94.9%) were mild. Moderate AEs (4.4% of all AEs) and severe/medically significant AEs (0.8% of all AEs) manifested as constitutional (lethargy, hypothermia) or neurological (ataxia) symptoms and mainly occurred across the two groups receiving oils containing THC (CBD/THC oil or THC oil).Conclusions and clinical significance: Overall, dogs tolerated dose escalation of the CBD oil well, experiencing only mild AEs. The favorable safety profile of 10 escalating doses of a CBD oil containing 18.3-640.5 mg CBD per dose (∼2-62 mg/kg) provides comparative evidence that, at our investigated doses, a CBD-predominant oil formulation was safer and more tolerated in dogs than oil formulations containing higher concentrations of THC.

Sports beverages formulated with fructose and glucose composites enhance exogenous carbohydrate oxidation, gut comfort, and endurance performance, relative to single-saccharide formulations. However, a critical review of performance data is absent. We conducted a comprehensive literature review of the effect of fructose:glucose/maltodextrin (glucose or maltodextrin) composites versus glucose/maltodextrin on endurance performance. Mechanistic associations were drawn from effects on carbohydrate metabolism, gut, and other sensory responses. Overall, 14 studies contained estimates of 2.5-3.0-h endurance performance in men, mostly in cycling. Relative to isocaloric glucose/maltodextrin, the ingestion of 0.5-1.0:1-ratio fructose:glucose/maltodextrin beverages at 1.3-2.4 g carbohydrate·min(-1) produced small to moderate enhancements (1-9 %; 95 % confidence interval 0-19) in mean power. When 0.5:1-ratio composites were ingested at ≥1.7 g·min(-1), improvements were larger (4-9 %; 2-19) than at 1.4-1.6 g·min(-1) (1-3 %; 0-6). The effect sizes at higher ingestion rates were associated with increased exogenous carbohydrate oxidation rate, unilateral fluid absorption, and lower gastrointestinal distress, relative to control. Solutions containing a 0.7-1.0:1 fructose:glucose ratio were absorbed fastest; when ingested at 1.5-1.8 g·min(-1), a 0.8:1 fructose:glucose ratio conveyed the highest exogenous carbohydrate energy and endurance power compared with lower or higher fructose:glucose ratios. To conclude, ingesting 0.5-1.0:1-ratio fructose:glucose/maltodextrin beverages at 1.3-2.4 g·min(-1) likely benefits 2.5-3.0 h endurance power versus isocaloric single saccharide. Further ratio and dose-response research should determine if meaningful performance benefits of composites accrue with ingestion <1.3 g·min(-1), relative to higher doses. Effects should be established in competition, females, other food formats, and in heat-stress and ultra-endurance exercise where carbohydrate demands may differ from the current analysis.

OBJECTIVE To determine the safety and pharmacokinetics of various doses of plant-derived cannabidiol (CBD) versus placebo following repeated oral administration. ANIMALS 20 healthy adult Beagles. PROCEDURES In a randomized, blinded, placebo-controlled trial, dogs were randomized to 5 groups balanced in body weight and sex (n = 4 dogs/group) and received a CBD (1, 2, 4, or 12 mg/kg; from cannabis extract) or placebo oil formulation PO once daily for 28 days. Outcome variables were assessed through daily health observations, veterinary examinations, CBC, and serum biochemical analysis. Blood samples were collected at various time points to estimate 24-hour pharmacokinetic profiles of CBD and selected metabolites (7-carboxy-CBD and 7-hydroxy-CBD). RESULTS Repeated CBD administration was well tolerated by dogs, with no clinically important changes in measured safety outcomes. Veterinary examinations revealed no clinically important abnormal findings. Adverse events were mild in severity. Relative to placebo administration, CBD administration at 12 mg/kg/d resulted in more gastrointestinal adverse events (mainly hypersalivation) and significantly higher serum alkaline phosphatase activity. Total systemic exposure to CBD increased on a dose-dependent basis following both acute (first dose) and chronic (28 days) administration. Within each CBD dose group, repeated administration increased total systemic exposure to CBD 1.6- to 3.3-fold. The 24-hour trough plasma CBD concentrations were also dose dependent, with a steady state reached following 2 weeks of administration. CONCLUSIONS AND CLINICAL RELEVANCE Repeated, daily oral administration of the CBD formulation led to dose-dependent increases in total systemic exposure to CBD and 24-hour trough plasma concentrations in healthy dogs. These findings could help guide dose selection.

A systematic review and meta-analysis of randomised controlled trials was undertaken to determine the effects of almond consumption on blood lipid levels, namely total cholesterol (TC), LDL-cholesterol (LDL-C), HDL-cholesterol (HDL-C), TAG and the ratios of TC:HDL-C and LDL-C:HDL-C. Following a comprehensive search of the scientific literature, a total of eighteen relevant publications and twenty-seven almond-control datasets were identified. Across the studies, the mean differences in the effect for each blood lipid parameter (i.e. the control-adjusted values) were pooled in a meta-analysis using a random-effects model. It was determined that TC, LDL-C and TAG were significantly reduced by −0·153 mmol/l (P < 0·001), −0·124 mmol/l (P = 0·001) and −0·067 mmol/l (P = 0·042), respectively, and that HDL-C was not affected (−0·017 mmol/l; P = 0·207). These results are aligned with data from prospective observational studies and a recent large-scale intervention study in which it was demonstrated that the consumption of nuts reduces the risk of heart disease. The consumption of nuts as part of a healthy diet should be encouraged to help in the maintenance of healthy blood lipid levels and to reduce the risk of heart disease.

Objectives The aim of this study was to determine the safety and tolerability of escalating doses of orally delivered cannabis oils predominant in cannabidiol (CBD), tetrahydrocannabinol (THC), or both CBD and THC in healthy cats. Methods In this placebo-controlled, blinded study, 20 healthy adult cats were randomized to one of five treatment groups (n = 4 per group): two placebo groups (sunflower oil [SF] or medium-chain triglyceride oil [MCT]), or three plant-derived cannabinoid oil groups (CBD in MCT, THC in MCT or CBD/THC [1.5:1] in SF). Up to 11 escalating doses of each formulation were delivered orally via syringe to fasted subjects, with at least 3 days separating doses. Safety and tolerability were determined from clinical observations, complete blood counts (CBCs) and clinical chemistry. Plasma cannabinoids (CBD, THC) and metabolites (7-COOH-CBD, 11-OH-THC) were assessed. Results Titration to maximum doses of 30.5 mg/kg CBD (CBD oil), 41.5 mg/kg THC (THC oil) or 13.0:8.4 mg/kg CBD:THC (CBD/THC oil) was safely achieved in all subjects. All observed adverse events (AEs) were mild, transient and resolved without medical intervention. Gastrointestinal AEs were more common with formulations containing MCT. Constitutional (lethargy, hypothermia), neurologic (ataxia) and ocular (protrusion membrana nictitans) AEs were more common with oils containing THC (CBD/THC and THC oils). There were no clinically significant changes in CBC or clinical chemistry across treatment groups. Higher plasma levels of the cannabinoids and their metabolites following administration of the CBD/THC combination product are suggestive of a pharmacokinetic interaction. Conclusions and relevance This is the first feline study to explore the safety and tolerability of CBD and THC, alone and in combination, in a controlled research setting. These findings will inform veterinarians of the safety profile of cannabinoids, particularly when considering the potential therapeutic use of CBD in cats or recognizing clinical signs associated with accidental exposure to THC-containing products.