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

Zgair, Atheer; Lee, Jong Bong; Wong, Jonathan Chi Man; Taha, Dhiaa A.; Aram, Jehan; Virgilio, Daisy Di; McArthur, Andrew G.; Cheng, Yu-Kit; Hennig, Ivo M.; Barrett, David A.; Fischer, Peter M.; Constantinescu, Cris S.; Gershkovich, Pavel

Authors

Atheer Zgair

Jong Bong Lee

Jonathan Chi Man Wong jonathancmwong@gmail.com

Dhiaa A. Taha

Jehan Aram

Daisy Di Virgilio

Andrew G. McArthur

Yu-Kit Cheng

Ivo M. Hennig

David A. Barrett

Peter M. Fischer

Cris S. Constantinescu

Pavel Gershkovich



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.

Journal Article Type Article
Journal Scientific Reports
Print ISSN 2045-2322
Electronic ISSN 2045-2322
Publisher Nature Publishing Group
Peer Reviewed Peer Reviewed
Volume 7
Article Number 14542
APA6 Citation Zgair, A., Lee, J. B., Wong, J. C. M., Taha, D. A., Aram, J., Virgilio, D. D., …Gershkovich, P. (in press). Oral administration of cannabis with lipids leads to high levels of cannabinoids in the intestinal lymphatic system and prominent immunomodulation. Scientific Reports, 7,
Keywords Autoimmune diseases, Lymphatic system, Translational research
Publisher URL http://www.nature.com/articles/s41598-017-15026-z
Copyright Statement Copyright information regarding this work can be found at the following address: http://creativecommons.org/licenses/by/4.0

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Copyright Statement
Copyright information regarding this work can be found at the following address: http://creativecommons.org/licenses/by/4.0





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