PMC:3951193 / 43508-48662 JSONTXT

{"project":"2_test","denotations":[{"id":"24622769-21620566-95790300","span":{"begin":234,"end":237},"obj":"21620566"},{"id":"24622769-19875078-95790301","span":{"begin":525,"end":528},"obj":"19875078"},{"id":"24622769-18622408-95790302","span":{"begin":744,"end":747},"obj":"18622408"},{"id":"24622769-21953882-95790303","span":{"begin":821,"end":824},"obj":"21953882"},{"id":"24622769-20590565-95790304","span":{"begin":1064,"end":1067},"obj":"20590565"},{"id":"24622769-20041802-95790305","span":{"begin":1184,"end":1187},"obj":"20041802"},{"id":"24622769-19897346-95790306","span":{"begin":1295,"end":1298},"obj":"19897346"},{"id":"24622769-22525682-95790307","span":{"begin":1413,"end":1416},"obj":"22525682"},{"id":"24622769-22311129-95790308","span":{"begin":1615,"end":1618},"obj":"22311129"},{"id":"24622769-19940110-95790309","span":{"begin":1717,"end":1720},"obj":"19940110"},{"id":"24622769-12943782-95790310","span":{"begin":1803,"end":1806},"obj":"12943782"},{"id":"24622769-11678659-95790311","span":{"begin":1810,"end":1813},"obj":"11678659"},{"id":"24622769-22041081-95790312","span":{"begin":1853,"end":1856},"obj":"22041081"},{"id":"24622769-16819230-95790313","span":{"begin":1871,"end":1874},"obj":"16819230"},{"id":"24622769-12372871-95790314","span":{"begin":1878,"end":1881},"obj":"12372871"},{"id":"24622769-21667972-95790315","span":{"begin":1895,"end":1898},"obj":"21667972"},{"id":"24622769-7765609-95790316","span":{"begin":1901,"end":1904},"obj":"7765609"},{"id":"24622769-20206138-95790317","span":{"begin":2113,"end":2116},"obj":"20206138"},{"id":"24622769-11171159-95790318","span":{"begin":2226,"end":2229},"obj":"11171159"},{"id":"24622769-8751435-95790319","span":{"begin":2352,"end":2355},"obj":"8751435"},{"id":"24622769-9872309-95790320","span":{"begin":2498,"end":2501},"obj":"9872309"},{"id":"24622769-10864031-95790321","span":{"begin":2519,"end":2522},"obj":"10864031"},{"id":"24622769-11171159-95790322","span":{"begin":2884,"end":2887},"obj":"11171159"},{"id":"24622769-21999614-95790323","span":{"begin":3079,"end":3082},"obj":"21999614"},{"id":"24622769-9599279-95790324","span":{"begin":3162,"end":3165},"obj":"9599279"},{"id":"24622769-9561107-95790325","span":{"begin":3187,"end":3190},"obj":"9561107"},{"id":"24622769-16547349-95790326","span":{"begin":3682,"end":3685},"obj":"16547349"},{"id":"24622769-19303464-95790327","span":{"begin":3829,"end":3832},"obj":"19303464"},{"id":"24622769-21764086-95790328","span":{"begin":3907,"end":3910},"obj":"21764086"},{"id":"24622769-18574142-95790329","span":{"begin":4106,"end":4109},"obj":"18574142"},{"id":"24622769-21356367-95790330","span":{"begin":4203,"end":4206},"obj":"21356367"},{"id":"24622769-22326488-95790331","span":{"begin":4316,"end":4319},"obj":"22326488"},{"id":"24622769-23138934-95790332","span":{"begin":4413,"end":4416},"obj":"23138934"},{"id":"24622769-19096995-95790333","span":{"begin":4481,"end":4484},"obj":"19096995"},{"id":"24622769-18063495-95790334","span":{"begin":4579,"end":4582},"obj":"18063495"},{"id":"24622769-15934935-95790335","span":{"begin":5149,"end":5152},"obj":"15934935"}],"text":"Herbal remedies\nSome plants besides Cannabis produce vaguely cannabimimetic effects. Copal incense, extracted from Protium species (same plant family as Boswellia) contains a pentacyclic triterpene with high affinity for CB1 and CB2 [156]. Absinthe contains thujone, a constituent of wormwood, Artemisia absinthium. Thujone has weak affinity for CB1 [157]. Pristimerin, an alkaloid found in khat, Catha edulis, acts as a potent inhibitor of MAGL (IC50 = 93 nM) and causes an elevation of 2-AG levels in rat cortical neurons [158]. Salvinorin A in Salvia divinorum produces CB1-mediated effects in the gastrointestinal tract of rodents. Salvinorin A primarily acts as a kappa-opioid receptor agonist and is inactive as a ligand for CB1 and CB2 [159]; it may interact with a putative CB1-kappa-opioid receptor heterodimer [160].\nFlavonoids such as biochanin A (from red clover, Trifolium pratense), genistein (from soybean, Glycine max), and kaempferol (from tea, Camelia sinensis, and many other plants) exert modest inhibition of FAAH in the low micromolar range [161]. Cyanidin and delphinidin, two anthocyanidins found in a wide range of plants, have micromolar affinities for CB1 [162]. Epigallocatechin-3-O-gallate, the most abundant catechin in tea, also has micromolar affinities for CB1 [163].\nYangonin, a kavalactone extracted from kava, Piper methysticum, exhibits affinity for CB1 with a K i = 0.72 µM [164]. Curcumin, extracted from curry powders, elevates eCB levels and brain nerve growth factor (NGF) in a brain region-specific fashion, and pretreatment with CB1 antagonist AM4113 blocks this effect [165]. A study suggested that curcumin and resveratrol could bind to CB1, but the study was retracted [166].\nCompounds with phytocannabinoid-like moieties have been extracted from legumes [167], [168], Helichrysum [169], Rhododendron sp. [170], liverworts [171], [172], and fungi [173]–[175]. Falcarinol is a skin irritant found in several plants that causes contact dermatitis. It covalently binds with the CB1 receptor, causing potent inverse agonistic and pro-inflammatory effects in human skin [176].\nHigher plants (angiosperms and gymnosperms) produce PUFAs with acyl tails limited to 18 carbons in length [177]. Hence reports of PUFAs in plants with longer acyl tails, such as AA, AEA, and 2-AG are controversial. Di Tomaso et al. [178] detected AEA in chocolate and cocoa powder derived from Theobroma cacao. A subsequent study showed very little, if any, AEA in cocoa powder [149]. Nakane et al. [179] reportedly extracted sciadonic acid (20:3ω-6) from seeds of a pine tree, Sciadopitys verticillata. This analog of 2-AG exhibited cannabimimetic activity in NG108-15 cells expressing CB1.\nUnlike higher plants, non-vascular plants such as club mosses, mosses, and algae express Δ6-elongase enzymes, so they are capable of producing PUFAs with longer acyl tails [177]. Semiplenamide A, an AEA-like PUFA isolated from a blue-green alga, Lyngbya semiplena, has micromolar affinity for CB1 and also blocks the AEA transporter, thereby inhibiting AEA breakdown [180]. Grenadamide, a PUFA in Lyngbya majuscula, has micromolar affinities for CB1 [181]. Soderstrom et al. [182] extracted but did not identify an eCB-like compound from L. majuscula. Soderstrom also extracted a dozen eCB-like PUFAs from unidentified green algae (Chlorophyta), the brown alga Laminaria angustata, and the sponge Mycale micracanthoxea.\nSome plant ligands bind to CB2 and modulate the immune system, but have no affinity for CB1 and do not elicit psychoactivity. Alkamides from Echinacea species bind to CB2 with nanomolar affinity, and act as CB2 agonists with immunomodulatory effects [183]. Several constituents from E. purpurea root and herb produce synergistic, pleiotropic effects—they bind to CB2 as well as inhibit AEA uptake [184]. Other constituents from Echinacea purpurea act as weak CB1 antagonists [185].\nThe principal terpenoid in black pepper, (E)-β-caryophyllene (BCP), binds to CB2 with nanomolar affinity and acts as an agonist. Its anti-inflammatory effects are reduced in CB2 knockout mice [186]. The protective effects of BCP on colitis in mice are reversed by the CB2 antagonist AM630 [187]. The protective effects of BCP on cisplatin-induced nephrotoxicity in mice are absent in CB2 knockout mice [188]. Lastly, the antinociceptive effect of BCP in mice is prevented by pretreatment with AM630 [189].\nRutamarin in Ruta graveolens has micromolar affinity for CB2 [190]. An unidentified constituent in noni fruit, Morinda citrifolia, shows weak affinity for CB2 [191]. The aromatic resin extracted from mastic, Pistacia lentiscus, contains an essential oil (EO) rich with monoterpenoids and sesquiterpenoids. Rats fed mastic EO showed higher plasma levels of DHA, EPA, PEA, and OEA than control rats, with no change in AEA or 2-AG [192].\nShellfish are not herbal remedies, but they have been used medicinally. AEA and/or 2-AG have been isolated from the mussel Mytilus galloprovincialis, the clam Tapes dicussatus, the oyster Crassosterea sp. [193], the sea urchin Paracentrotus lividus [194], and the sea squirt Ciona intestinalis [195]."}

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remedies\nSome plants besides Cannabis produce vaguely cannabimimetic effects. Copal incense, extracted from Protium species (same plant family as Boswellia) contains a pentacyclic triterpene with high affinity for CB1 and CB2 [156]. Absinthe contains thujone, a constituent of wormwood, Artemisia absinthium. Thujone has weak affinity for CB1 [157]. Pristimerin, an alkaloid found in khat, Catha edulis, acts as a potent inhibitor of MAGL (IC50 = 93 nM) and causes an elevation of 2-AG levels in rat cortical neurons [158]. Salvinorin A in Salvia divinorum produces CB1-mediated effects in the gastrointestinal tract of rodents. Salvinorin A primarily acts as a kappa-opioid receptor agonist and is inactive as a ligand for CB1 and CB2 [159]; it may interact with a putative CB1-kappa-opioid receptor heterodimer [160].\nFlavonoids such as biochanin A (from red clover, Trifolium pratense), genistein (from soybean, Glycine max), and kaempferol (from tea, Camelia sinensis, and many other plants) exert modest inhibition of FAAH in the low micromolar range [161]. Cyanidin and delphinidin, two anthocyanidins found in a wide range of plants, have micromolar affinities for CB1 [162]. Epigallocatechin-3-O-gallate, the most abundant catechin in tea, also has micromolar affinities for CB1 [163].\nYangonin, a kavalactone extracted from kava, Piper methysticum, exhibits affinity for CB1 with a K i = 0.72 µM [164]. Curcumin, extracted from curry powders, elevates eCB levels and brain nerve growth factor (NGF) in a brain region-specific fashion, and pretreatment with CB1 antagonist AM4113 blocks this effect [165]. A study suggested that curcumin and resveratrol could bind to CB1, but the study was retracted [166].\nCompounds with phytocannabinoid-like moieties have been extracted from legumes [167], [168], Helichrysum [169], Rhododendron sp. [170], liverworts [171], [172], and fungi [173]–[175]. Falcarinol is a skin irritant found in several plants that causes contact dermatitis. It covalently binds with the CB1 receptor, causing potent inverse agonistic and pro-inflammatory effects in human skin [176].\nHigher plants (angiosperms and gymnosperms) produce PUFAs with acyl tails limited to 18 carbons in length [177]. Hence reports of PUFAs in plants with longer acyl tails, such as AA, AEA, and 2-AG are controversial. Di Tomaso et al. [178] detected AEA in chocolate and cocoa powder derived from Theobroma cacao. A subsequent study showed very little, if any, AEA in cocoa powder [149]. Nakane et al. [179] reportedly extracted sciadonic acid (20:3ω-6) from seeds of a pine tree, Sciadopitys verticillata. This analog of 2-AG exhibited cannabimimetic activity in NG108-15 cells expressing CB1.\nUnlike higher plants, non-vascular plants such as club mosses, mosses, and algae express Δ6-elongase enzymes, so they are capable of producing PUFAs with longer acyl tails [177]. Semiplenamide A, an AEA-like PUFA isolated from a blue-green alga, Lyngbya semiplena, has micromolar affinity for CB1 and also blocks the AEA transporter, thereby inhibiting AEA breakdown [180]. Grenadamide, a PUFA in Lyngbya majuscula, has micromolar affinities for CB1 [181]. Soderstrom et al. [182] extracted but did not identify an eCB-like compound from L. majuscula. Soderstrom also extracted a dozen eCB-like PUFAs from unidentified green algae (Chlorophyta), the brown alga Laminaria angustata, and the sponge Mycale micracanthoxea.\nSome plant ligands bind to CB2 and modulate the immune system, but have no affinity for CB1 and do not elicit psychoactivity. Alkamides from Echinacea species bind to CB2 with nanomolar affinity, and act as CB2 agonists with immunomodulatory effects [183]. Several constituents from E. purpurea root and herb produce synergistic, pleiotropic effects—they bind to CB2 as well as inhibit AEA uptake [184]. Other constituents from Echinacea purpurea act as weak CB1 antagonists [185].\nThe principal terpenoid in black pepper, (E)-β-caryophyllene (BCP), binds to CB2 with nanomolar affinity and acts as an agonist. Its anti-inflammatory effects are reduced in CB2 knockout mice [186]. The protective effects of BCP on colitis in mice are reversed by the CB2 antagonist AM630 [187]. The protective effects of BCP on cisplatin-induced nephrotoxicity in mice are absent in CB2 knockout mice [188]. Lastly, the antinociceptive effect of BCP in mice is prevented by pretreatment with AM630 [189].\nRutamarin in Ruta graveolens has micromolar affinity for CB2 [190]. An unidentified constituent in noni fruit, Morinda citrifolia, shows weak affinity for CB2 [191]. The aromatic resin extracted from mastic, Pistacia lentiscus, contains an essential oil (EO) rich with monoterpenoids and sesquiterpenoids. Rats fed mastic EO showed higher plasma levels of DHA, EPA, PEA, and OEA than control rats, with no change in AEA or 2-AG [192].\nShellfish are not herbal remedies, but they have been used medicinally. AEA and/or 2-AG have been isolated from the mussel Mytilus galloprovincialis, the clam Tapes dicussatus, the oyster Crassosterea sp. [193], the sea urchin Paracentrotus lividus [194], and the sea squirt Ciona intestinalis [195]."}