title: Effects of cannabinoids and cannabinoid-enriched Cannabis extracts on TRP channels and endocannabinoid metabolic enzymes.
abstract: OBJECTIVE
  Cannabidiol (CBD) and Δ(9) -tetrahydrocannabinol (THC) interact with transient receptor potential (TRP) channels and enzymes of the endocannabinoid system.
  
  
  METHODS
  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.
  
  
  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
  These results are relevant to the analgesic, anti-inflammatory and anti-cancer effects of cannabinoids and Cannabis extracts.
authors.affiliation: Endocannabinoid Research Group, Institute of Cybernetics, CNR, Pozzuoli (NA), Italy.
authors.forename: Luciano
authors.initials: L
authors.lastname: De Petrocellis
authors.forename: Alessia
authors.initials: A
authors.lastname: Ligresti
authors.forename: Aniello Schiano
authors.initials: AS
authors.lastname: Moriello
authors.forename: Marco
authors.initials: M
authors.lastname: Allarà
authors.forename: Tiziana
authors.initials: T
authors.lastname: Bisogno
authors.forename: Stefania
authors.initials: S
authors.lastname: Petrosino
authors.forename: Colin G
authors.initials: CG
authors.lastname: Stott
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Di Marzo
mesh_terms: D000577:Amides; D000581:Amidohydrolases / Q000378:metabolism; D000818:Animals; D001095:Arachidonic Acids / Q000378:metabolism; D019556:COS Cells; D063385:Cannabinoid Receptor Modulators / Q000378:metabolism*; D002186:Cannabinoids / Q000494:pharmacology*; D002188:Cannabis / Q000737:chemistry*; D002522:Chlorocebus aethiops; D063388:Endocannabinoids; D004983:Ethanolamines; D005989:Glycerides / Q000378:metabolism; D057809:HEK293 Cells; D006801:Humans; D008071:Lipoprotein Lipase / Q000378:metabolism; D008994:Monoacylglycerol Lipases / Q000378:metabolism; D010169:Palmitic Acids / Q000378:metabolism; D010936:Plant Extracts / Q000494:pharmacology; D053284:Polyunsaturated Alkamides / Q000378:metabolism; D051381:Rats; D050051:Transient Receptor Potential Channels / Q000819:agonists* / Q000037:antagonists & inhibitors* / Q000378:metabolism; D000099252:Fatty Acid Amide Hydrolases
chemical_list: D000577:Amides; D000581:Amidohydrolases; D001095:Arachidonic Acids; D063385:Cannabinoid Receptor Modulators; D002186:Cannabinoids; D063388:Endocannabinoids; D004983:Ethanolamines; D005989:Glycerides; D008071:Lipoprotein Lipase; D008994:Monoacylglycerol Lipases; D010169:Palmitic Acids; D010936:Plant Extracts; D053284:Polyunsaturated Alkamides; D050051:Transient Receptor Potential Channels; D000099252:Fatty Acid Amide Hydrolases; C005958:palmidrol; C094503:glyceryl 2-arachidonate; C480280:DAGLA protein, human; C523108:NAAA protein, human; C078814:anandamide