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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

Description du projet

Améliorer les denrées comestibles à base de cannabis

En pharmacologie, la biodisponibilité est la proportion de médicament susceptible d’avoir un effet actif après avoir été introduit dans le corps. Malgré une facilité d’administration et de potentiels bénéfices thérapeutiques, l’ingestion orale de cannabidiol (CBD) — un cannabinoïde actif trouvé dans les plantes de cannabis — n’offre qu’une faible biodisponibilité. En outre, le mouvement du CBD ingéré dans le corps dépend du patient, et son métabolisme éventuel reste incompris. Le projet CBDHIGHBIO, financé par le programme MSCA, recueillera des données qui permettront de remédier à ces problèmes. Il utilisera des acides gras à longue chaîne pour améliorer l’administration et l’absorption. Il recourra également à des composés spéciaux qui inhibent la dégradation par des enzymes métaboliques du foie. Les résultats devraient augmenter la biodisponibilité du CBD et mener au développement de produits à base de cannabidiol plus efficaces, vendus sous la forme de denrées comestibles au cannabis.

Objectif

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.

Coordinateur

UNIVERSIDADE DO MINHO
Contribution nette de l'UE
€ 172 618,56
Adresse
LARGO DO PACO
4704 553 Braga
Portugal

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Région
Continente Norte Cávado
Type d’activité
Higher or Secondary Education Establishments
Liens
Coût total
Aucune donnée

Partenaires (1)