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

Abstract

BACKGROUND AND PURPOSE

Cannabidiol (CBD) and Δ(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 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.

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  • Authors+Show Affiliations

    ,

    Endocannabinoid Research Group, Institute of Cybernetics, CNR, Pozzuoli (NA), Italy.

    , , , , , ,

    Source

    British journal of pharmacology 163:7 2011 Aug pg 1479-94

    MeSH

    Amidohydrolases
    Animals
    Arachidonic Acids
    COS Cells
    Cannabinoid Receptor Modulators
    Cannabinoids
    Cannabis
    Cercopithecus aethiops
    Endocannabinoids
    Ethanolamines
    Glycerides
    HEK293 Cells
    Humans
    Lipoprotein Lipase
    Monoacylglycerol Lipases
    Palmitic Acids
    Plant Extracts
    Polyunsaturated Alkamides
    Rats
    Transient Receptor Potential Channels

    Pub Type(s)

    Journal Article
    Research Support, Non-U.S. Gov't

    Language

    eng

    PubMed ID

    21175579

    Citation

    TY - JOUR T1 - Effects of cannabinoids and cannabinoid-enriched Cannabis extracts on TRP channels and endocannabinoid metabolic enzymes. AU - De Petrocellis,Luciano, AU - Ligresti,Alessia, AU - Moriello,Aniello Schiano, AU - Allarà,Marco, AU - Bisogno,Tiziana, AU - Petrosino,Stefania, AU - Stott,Colin G, AU - Di Marzo,Vincenzo, PY - 2010/12/24/entrez PY - 2010/12/24/pubmed PY - 2012/1/19/medline SP - 1479 EP - 94 JF - British journal of pharmacology JO - Br. J. Pharmacol. VL - 163 IS - 7 N2 - BACKGROUND AND PURPOSE: Cannabidiol (CBD) and Δ(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 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. SN - 1476-5381 UR - https://www.unboundmedicine.com/medline/citation/21175579/abstract/Effects_of_cannabinoids_and_cannabinoid_enriched_Cannabis_extracts_on_TRP_channels_and_endocannabinoid_metabolic_enzymes_ L2 - https://doi.org/10.1111/j.1476-5381.2010.01166.x ER -