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Strategies to modulate the bioavailability of cannabinoids in edible products: in vitro tests, cytotoxicity, and pre-clinical assessment to generate reliable data for regulatory agencies

Project description

Enhancing cannabis edibles

In pharmaceutics, bioavailability is the proportion of a drug able to have an active effect after being introduced into the body. Despite ease-of-administration and potential therapeutic benefits, the oral ingestion of cannabidiol (CBD) — an active cannabinoid found in cannabis plants — has low bioavailability. Moreover, the movement of ingested CBD within the body is patient dependent and its eventual metabolism is not well understood. The MSCA-funded CBDHIGHBIO project will establish data to develop a means of mitigating these issues. It will use long-chain fatty acids to promote delivery and absorption. It will also use special compounds that inhibit breakdown by metabolising enzymes in the liver. Results should increase CBD bioavailability and lead to more effective cannabidiol-based products known as cannabis edibles.


Cannabis edibles (CE) are considered a big opportunity to take place in the recent and fast-growing cannabis market. However, there are big challenges on the development of these products, such as the lack of understanding of the metabolism of cannabinoids after oral ingestion, the low bioavailability of cannabinoids (including cannabidiol, CBD), and high intra- and inter-subjects’ pharmacokinetic variability. Recent approaches to enhance the oral CBD bioavailability include its incorporation into lipid-based delivery systems and the addition of compounds called bioenhancers. Lipids can enhance the oral CBD bioavailability via an increase in the transport to the systemic circulation via intestinal lymph, whereas bioenhancers may inhibit metabolizing enzymes reducing the extent of its liver first-pass effect. Piperine (PIP) is known as a powerful bioenhancer by inhibiting drug-metabolizing enzymes of cytochrome P-450 (CYP450), that are involved in the CBD metabolism. The aims of this study are to provide reliable data about the CBD metabolism after oral ingestion to help regulatory agencies to regulate the market of CE and standardize the consumption indications for these products; to increase the CBD bioavailability by using long-chain fatty acids to promote the enhancement of lymphatic absorption combined with PIP addition to inhibit the hepatic metabolism of CBD; and develop an advanced delivery carrier to enable its vehiculation into aqueous-based CE. We hypothesize that the combination of CBD and PIP can substantially improve the CBD bioavailability, thus decreasing the intra- and inter-subject variability. Systematic in vitro tests will be performed to evaluate the inhibitory effect of PIP on CYP450 activity, to determine the bioaccessibility, stability and bioavailability of CBD and PIP after oral ingestion, and to assess their cytotoxicity. Finally, in vivo studies will be performed to evaluate the CBD pharmacokinetic and bioavailability.



Net EU contribution
€ 172 618,56
Largo do paco
4704 553 Braga

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Continente Norte Cávado
Activity type
Higher or Secondary Education Establishments
EU contribution
No data

Partners (1)