These authors contributed equally to this work.
Effects of cannabinoids and cannabinoid-enriched Cannabis extracts on TRP channels and endocannabinoid metabolic enzymes
Article first published online: 12 JUL 2011
© 2011 The Authors. British Journal of Pharmacology © 2011 The British Pharmacological Society
British Journal of Pharmacology
Special Issue: Cannabinoids in Biology and Medicine, Part I. Guest Editors: Itai Bab and Steve Alexander
Volume 163, Issue 7, pages 1479–1494, August 2011
How to Cite
De Petrocellis, L., Ligresti, A., Moriello, A. S., Allarà, M., Bisogno, T., Petrosino, S., Stott, C. G. and Di Marzo, V. (2011), Effects of cannabinoids and cannabinoid-enriched Cannabis extracts on TRP channels and endocannabinoid metabolic enzymes. British Journal of Pharmacology, 163: 1479–1494. doi: 10.1111/j.1476-5381.2010.01166.x
- Issue published online: 12 JUL 2011
- Article first published online: 12 JUL 2011
- Accepted manuscript online: 22 DEC 2010 11:48AM EST
- Received; 20 October 2010; Revised; 17 November 2010; Accepted; 19 November 2010
- botanical extract;
- TRP channel;
- monoacylglycerol lipase;
- diacylglycerol lipase
BACKGROUND AND PURPOSE Cannabidiol (CBD) and Δ9-tetrahydrocannabinol (THC) interact with transient receptor potential (TRP) channels and enzymes of the endocannabinoid system.
EXPERIMENTAL APPROACH The effects of 11 pure cannabinoids and botanical extracts [botanical drug substance (BDS)] from Cannabis varieties selected to contain a more abundant cannabinoid, on TRPV1, TRPV2, TRPM8, TRPA1, human recombinant diacylglycerol lipase α (DAGLα), rat brain fatty acid amide hydrolase (FAAH), COS cell monoacylglycerol lipase (MAGL), human recombinant N-acylethanolamine acid amide hydrolase (NAAA) and anandamide cellular uptake (ACU) by RBL-2H3 cells, were studied using fluorescence-based calcium assays in transfected cells and radiolabelled substrate-based enzymatic assays. Cannabinol (CBN), cannabichromene (CBC), the acids (CBDA, CBGA, THCA) and propyl homologues (CBDV, CBGV, THCV) of CBD, cannabigerol (CBG) and THC, and tetrahydrocannabivarin acid (THCVA) were also tested.
KEY RESULTS CBD, CBG, CBGV and THCV stimulated and desensitized human TRPV1. CBC, CBD and CBN were potent rat TRPA1 agonists and desensitizers, but THCV-BDS was the most potent compound at this target. CBG-BDS and THCV-BDS were the most potent rat TRPM8 antagonists. All non-acid cannabinoids, except CBC and CBN, potently activated and desensitized rat TRPV2. CBDV and all the acids inhibited DAGLα. Some BDS, but not the pure compounds, inhibited MAGL. CBD was the only compound to inhibit FAAH, whereas the BDS of CBC > CBG > CBGV inhibited NAAA. CBC = CBG > CBD inhibited ACU, as did the BDS of THCVA, CBGV, CBDA and THCA, but the latter extracts were more potent inhibitors.
CONCLUSIONS AND IMPLICATIONS These results are relevant to the analgesic, anti-inflammatory and anti-cancer effects of cannabinoids and Cannabis extracts.
LINKED ARTICLES This article is part of a themed issue on Cannabinoids in Biology and Medicine. To view the other articles in this issue visit http://dx.doi.org/10.1111/bph.2011.163.issue-7