Cannabidiol and Cannabidiol Metabolites: Pharmacokinetics, Interaction with Food, and Influence on Liver Function.

Cannabidiol (CBD) is widely available and marketed as having therapeutic properties. Over-the-counter CBD is unregulated, many of the therapeutic claims lack scientific support, and controversy exists as to the safety of CBD-liver interaction. The study aims were to compare the pharmacokinetics of commercial CBD and CBD metabolites following the ingestion of five different CBD formulations, determine the influence of CBD on food induced thermogenesis, determine the influence of food on CBD pharmacokinetics, and determine the influence of CBD on markers of liver function. Fourteen males (body mass index ≥ 25 kg/m2) were studied in a placebo-controlled, randomized, crossover design. On five occasions, different CBD formulations were ingested (one per visit). On two additional occasions, CBD or placebo was ingested following a meal. CBD servings were standardized to 30 mg. Considerable pharmacokinetic variability existed between formulations; this pharmacokinetic variability transferred to several of the metabolites. CBD did not influence food induced thermogenesis but did favorably modify early insulin and triglyceride responses. Food appreciably altered the pharmacokinetics of CBD. Finally, CBD did not evoke physiologically relevant changes in markers of liver function. Collectively, these data suggest that consumers should be aware of the appreciable pharmacokinetic differences between commercial CBD formulations, CBD is unlikely to influence the caloric cost of eating but may prove to be of some benefit to initial metabolic responses, consuming CBD with food alters the dynamics of CBD metabolism and increases systemic availability, and low-dose CBD probably does not represent a risk to normal liver function.

Pharmacokinetic Investigation of Commercially Available Edible Marijuana Products in Humans: Potential Influence of Body Composition and Influence on Glucose Control.

The purpose of the study was to describe and compare the pharmacokinetics of five commercial edible marijuana products, determine the influence of body composition on pharmacokinetics, and, in light of epidemiology suggesting marijuana may offer diabetes protection, explore the influence of edible marijuana on glucose tolerance. Seven regular users of marijuana self-administered five edible products in a randomized crossover design; each product contained 10 mg of delta-9-tetrahydrocannabinol (THC). Thirty minutes following marijuana ingestion, participants imbibed a 75 g glucose beverage. Time-to-peak plasma THC concentration ranged between 35 and 90 min; maximal plasma THC concentration (Cmax) ranged between 3.2 and 5.5 ng/mL. Differences between products in plasma THC concentration during the first 20-30 min were detected (p = 0.019). Relations were identified between body composition and pharmacokinetic parameters for some products; however, none of these body composition characteristics were consistently related to pharmacokinetics across all five of the products. Edible marijuana had no effect on oral glucose tolerance compared with a marijuana-free control (Matsuda Index; p > 0.395). Commercially available edible marijuana products evoke different plasma THC concentrations shortly after ingestion, but do not appear to influence acute glucose regulation. These data may allow recreational marijuana users to make informed decisions pertaining to rates of edible marijuana ingestion and avoid overdose.