Oral delivery of cannabidiol: Revealing the formulation and absorption challenges

Cannabidiol (CBD) is a pharmacologically active, non-psychoactive cannabinoid derived from natural sources. Currently, it is available in prescription oral dosage forms for its anti-epileptic properties. The global market for CBD food supplements and nutraceutical products is showing rapid growth, driven by its wide-ranging pharmacological benefits and good safety profile. Numerous ongoing pharmacological studies aim to uncover new potential indications for CBD. While oral CBD formulations are highly desirable due to the ease of use, their development is challenged by various complexities. The aim of this review was to investigate published literature and gather useful information aimed at better formulation and the improvement of oral bioavailability in drug delivery of CBD. Our investigation explored the CBD physicochemical properties, its permeation and absorption from the gastrointestinal tract to the systemic circulation, as well as its distribution, metabolism and excretion. The review has revealed numerous controversies, yet a consensus emerges regarding the low stability and poor oral bioavailability of CBD. Simultaneously, discrepancies remain regarding the CBD apparent permeability, the impact of CBD degradation products on its absorption, the involvement of lymphatic transport, and processes associated with CBD excretion. It is widely acknowledged that CBD is chemically unstable, especially in acidic environments, and undergoes extensive metabolism, resulting in the formation of pharmacologically active metabolites. Food and lipid-based vehicles enhance the oral bioavailability and reduce absorption variability of CBD-containing products. The formulation challenges for CBD primarily revolve around issues of chemical instability, biological membrane permeability, and presystemic metabolism.