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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

Descripción del proyecto

Mejorar los comestibles de cánnabis

En farmacología, la biodisponibilidad es la proporción de fármaco capaz de tener un efecto activo tras ser administrado a un organismo. A pesar de la facilidad de administración y los posibles beneficios terapéuticos, la ingesta oral de cannabidiol (CBD), un cannabinoide activo que se encuentra en las plantas de cánnabis, tiene una biodisponibilidad baja. Además, el movimiento del CBD ingerido dentro del organismo depende del paciente y se desconoce en gran medida su metabolismo final. El equipo del proyecto CBDHIGHBIO, financiado por las Acciones Marie Skłodowska-Curie, establecerá datos para desarrollar una forma de minimizar estos problemas. Utilizará ácidos grasos de cadena larga para facilitar la administración y la absorción. También utilizará compuestos especiales que inhiban la descomposición producida por el metabolismo de las enzimas en el hígado. Los resultados deberían aumentar la biodisponibilidad del CBD y conducir a productos derivados del cannabidiol (conocidos como «comestibles de cannabis») más efectivos.

Objetivo

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.

Régimen de financiación

HORIZON-AG-UN - HORIZON Unit Grant

Coordinador

UNIVERSIDADE DO MINHO
Aportación neta de la UEn
€ 172 618,56
Dirección
LARGO DO PACO
4704 553 Braga
Portugal

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Región
Continente Norte Cávado
Tipo de actividad
Higher or Secondary Education Establishments
Enlaces
Coste total
Sin datos

Socios (1)