Oral administration of cannabis with lipids leads to high levels of cannabinoids in the intestinal lymphatic system and prominent immunomodulation

Zgair, Atheer and Lee, Jong Bong and Wong, Jonathan Chi Man and Taha, Dhiaa A. and Aram, Jehan and Virgilio, Daisy Di and McArthur, Andrew G. and Cheng, Yu-Kit and Hennig, Ivo M. and Barrett, David A. and Fischer, Peter M. and Constantinescu, Cris S. and Gershkovich, Pavel (2017) Oral administration of cannabis with lipids leads to high levels of cannabinoids in the intestinal lymphatic system and prominent immunomodulation. Scientific Reports, 7 . 14542/1-14542/12. ISSN 2045-2322

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Abstract

Cannabidiol (CBD) and Δ9-tetrahydrocannabinol (THC) have well documented immunomodulatory effects in vitro, but not following oral administration in humans. Here we show that oral co-administration of cannabinoids with lipids can substantially increase their intestinal lymphatic transport in rats. CBD concentrations in the lymph were 250-fold higher than in plasma, while THC concentrations in the lymph were 100-fold higher than in plasma. Since cannabinoids are currently in clinical use for the treatment of spasticity in multiple sclerosis (MS) patients and to alleviate nausea and vomiting associated with chemotherapy in cancer patients, lymphocytes from those patients were used to assess the immunomodulatory effects of cannabinoids. The levels of cannabinoids recovered in the intestinal lymphatic system, but not in plasma, were substantially above the immunomodulatory threshold in murine and human lymphocytes. CBD showed higher immunosuppressive effects than THC. Moreover, immune cells from MS patients were more susceptible to the immunosuppressive effects of cannabinoids than those from healthy volunteers or cancer patients. Therefore, administering cannabinoids with a high-fat meal or in lipid-based formulations has the potential to be a therapeutic approach to improve the treatment of MS, or indeed other autoimmune disorders. However, intestinal lymphatic transport of cannabinoids in immunocompromised patients requires caution.

Item Type: Article
Keywords: Autoimmune diseases, Lymphatic system, Translational research
Schools/Departments: University of Nottingham, UK > Faculty of Medicine and Health Sciences > School of Medicine > Division of Clinical Neuroscience
University of Nottingham, UK > Faculty of Science > School of Pharmacy
Depositing User: Eprints, Support
Date Deposited: 07 Nov 2017 11:44
Last Modified: 14 Nov 2017 16:17
URI: http://eprints.nottingham.ac.uk/id/eprint/47445

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