Acute and short-term administrations of delta-9-tetrahydrocannabinol modulate major gut metabolomic regulatory pathways in C57BL/6 mice

Megha Oza,Travis Dias,Li Chen,Prakash Nagarkatti,Phani M Gummadidala,Anindya Chanda,Mathew Sajish,Paramita Chakraborty,Koyeli Banerjee,Rubaiya Jesmin,Mitzi Nagarkatti,Mayomi H Omebeyinje,Peter D R Moeller,Qian Wang,Lorne J Hofseth,William Becker,Chandrani Mitra

doi:10.1038/s41598-019-46478-0

Abstract

Delta-9-tetrahydrocannabinol (THC) is the primary psychoactive compound in Cannabis, which is studied extensively for its medicinal value. A central gap in the science is the underlying mechanisms surrounding THC’s therapeutic effects and the role of gut metabolite profiles. Using a mass-spectrometry based metabolomics, we show here that intraperitoneal injection of THC in C57BL/6 mice modulates metabolic profiles that have previously been identified as integral to health. Specifically, we investigated the effects of acute (single THC injection denoted here as ‘1X’) and short -term (five THC injections on alternate days denoted as ‘5X’) THC administration on fecal and intestinal tissue metabolite profiles. Results are consistent with the hypothesis that THC administration alters host metabolism by targeting two prominent lipid metabolism pathways: glycerophospholipid metabolism and fatty acid biosynthesis.

Highlights

The medical use of Cannabis, a product from the plant, Cannabis sativa, is becoming increasingly popular worldwide for its medicinal value[1,2,3]
It is well established that THC can be useful in preventing and ameliorating the symptoms of intestinal inflammation such as abdominal pain, diarrhea and reduced appetite in patients suffering from inflammatory bowel disease (IBD)[16,17,18,19]
We have shown here that lipid metabolism, especially glycerophospholipid metabolism and fatty acid biosynthesis, is a key metabolic pathway targeted by THC following i.p. administration

Summary

Introduction

The medical use of Cannabis (commonly termed ‘marijuana’), a product from the plant, Cannabis sativa, is becoming increasingly popular worldwide for its medicinal value[1,2,3]. THC can be used for the treatment of multiple acute and chronic health disorders[9,10,11] These include treatment of nausea and vomiting associated with cancer chemotherapy, anorexia, and cachexia associated with HIV and AIDS patients, pain and muscle spasms in multiple sclerosis[12]. Www.nature.com/scientificreports sulphonic acid-induced mucosal damage of the intestine, neutrophil infiltration and in vitro motility disturbances It has been shown[20,21,22] that the epithelial wound healing, inhibition of pro-inflammatory cytokine and chemokine release, immune cell recruitment, are mediated through activation of cannabinoid receptors (CB1 and CB2) of the endogenous cannabinoid system.

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