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

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. C...

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Main Authors: 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
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Published: Nature Publishing Group 2017
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Online Access:https://eprints.nottingham.ac.uk/47445/
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author 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
author_facet 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
author_sort Zgair, Atheer
building Nottingham Research Data Repository
collection Online Access
description 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.
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spelling nottingham-474452020-05-04T19:16:23Z https://eprints.nottingham.ac.uk/47445/ 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 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. Nature Publishing Group 2017-11-06 Article PeerReviewed 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. 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 Autoimmune diseases Lymphatic system Translational research http://www.nature.com/articles/s41598-017-15026-z
spellingShingle Autoimmune diseases
Lymphatic system
Translational research
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
Oral administration of cannabis with lipids leads to high levels of cannabinoids in the intestinal lymphatic system and prominent immunomodulation
title Oral administration of cannabis with lipids leads to high levels of cannabinoids in the intestinal lymphatic system and prominent immunomodulation
title_full Oral administration of cannabis with lipids leads to high levels of cannabinoids in the intestinal lymphatic system and prominent immunomodulation
title_fullStr Oral administration of cannabis with lipids leads to high levels of cannabinoids in the intestinal lymphatic system and prominent immunomodulation
title_full_unstemmed Oral administration of cannabis with lipids leads to high levels of cannabinoids in the intestinal lymphatic system and prominent immunomodulation
title_short Oral administration of cannabis with lipids leads to high levels of cannabinoids in the intestinal lymphatic system and prominent immunomodulation
title_sort oral administration of cannabis with lipids leads to high levels of cannabinoids in the intestinal lymphatic system and prominent immunomodulation
topic Autoimmune diseases
Lymphatic system
Translational research
url https://eprints.nottingham.ac.uk/47445/
https://eprints.nottingham.ac.uk/47445/