Effects of cannabinoids and cannabinoid-enriched Cannabis extracts on TRP channels and endocannabinoid metabolic enzymes.

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De Petrocellis L, Ligresti A, Moriello AS, Allara M, Bisogno T, Petrosino S, Stott CG, Di Marzo V

Effects of cannabinoids and cannabinoid-enriched Cannabis extracts on TRP channels and endocannabinoid metabolic enzymes.

Br J Pharmacol. 2011 Aug;163(7):1479-94. doi: 10.1111/j.1476-5381.2010.01166.x.

PubMed ID

21175579 [ View in PubMed

]

Abstract

BACKGROUND AND PURPOSE: Cannabidiol (CBD) and Delta(9) -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 alpha (DAGLalpha), 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 DAGLalpha. 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.

DrugBank Data that Cites this Article

Drugs

Tetrahydrocannabivarin

Cannabidivarin

Drug Targets

Drug	Target	Kind	Organism	Pharmacological Action	Actions
Cannabidiol	Transient receptor potential cation channel subfamily A member 1	Protein	Humans	Unknown	Agonist	Details
Cannabidiol	Transient receptor potential cation channel subfamily V member 1	Protein	Humans	Unknown	Activator	Details
Cannabidiol	Transient receptor potential cation channel subfamily V member 2	Protein	Humans	Unknown	Activator	Details
Cannabidivarin	Transient receptor potential cation channel subfamily A member 1	Protein	Humans	Yes	Agonist	Details
Cannabidivarin	Transient receptor potential cation channel subfamily V member 1	Protein	Humans	Yes	Agonist	Details
Cannabidivarin	Transient receptor potential cation channel subfamily V member 2	Protein	Humans	Yes	Agonist	Details

Drug Enzymes

Drug	Enzyme	Kind	Organism	Pharmacological Action	Actions
Cannabidiol	Fatty-acid amide hydrolase 1	Protein	Humans	Unknown	Inhibitor	Details