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

Abstract

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 ³ 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.

The safety and efficacy of low oral doses of cannabidiol: An evaluation of the evidence

“…Abbotts et al 73 examined the pharmacokinetics of five different oral CBD formulations each dosed at 30 mg in healthy participants. The water‐soluble CBD formulations containing various excipients (sorbitol, gum arabic, or maltodextrin) attained much greater plasma concentrations of CBD and metabolites than standard formulations, such as medium chain triglyceride oil or CBD as a crystalline powder.…”

“… 94 Pharmacovigilance of liver enzymes may be required even at low CBD doses, as we identified one study in which elevated liver enzymes were observed in four out of 59 participants following repeated oral dosing with 300 mg CBD. 55 However, in a more recent study, a single dose of 30 mg CBD did not affect liver enzymes, 73 highlighting lower doses may be of less concern. Future studies are needed to assess liver function following repeated lower doses.…”

“…Birnbaum et al 81 showed that a high‐fat meal increased plasma concentrations of CBD following an oral dose of 300 mg CBD. More recently, prior food consumption was shown to elevate plasma concentrations of CBD and its metabolites following an oral dose of 30 mg CBD 73 . It is conceivable that this “food effect” could have implications for therapeutic and adverse effects but more research is needed.…”

The molecular activity of cannabidiol in the regulation of Nrf2 system interacting with NF-κB pathway under oxidative stress

“…In both cases, however, the safety of using CBD as a therapeutic agent must also be considered. In this context, recent studies have shown that CBD is not harmful to metabolism and liver functions when used at low doses [ 117 ]. Together with this, the need to use CBD in long-term therapy, such as e.g.…”

Improved Therapeutic Efficacy of CBD with Good Tolerance in the Treatment of Breast Cancer through Nanoencapsulation and in Combination with 20(S)-Protopanaxadiol (PPD)

“…While liposomes and liposomal drugs tend to accumulate in the liver after intravenous administration, this may increase hepatic injury or hepatotoxicity and result in safety issues, such as when the encapsulated drug itself had hepatotoxicity, as did many chemotherapeutics. Fortunately, as an FDA-approved medicine, CBD has very good tolerance; so far, there has been no report about significant hepatotoxicity or obvious liver injury for CBD [ 48 , 49 ]. Meanwhile, PPD shows no hepatoxicity either [ 50 ].…”