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Alchemica

Cannabimimetic plants: are they new cannabinoidergic modulators?

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Really good review, some people here will likely be interested. One I'm surprised didn't get mentioned is β-caryophyllene for it's notable CB2 affinity. I've never been interested in potent CB1 agonists but these other plants interest me. New to me is seeing anthocyanins as cannabinoid modulators
 
Cannabimimetic plants: are they new cannabinoidergic modulators?
 
In nature, surprisingly many molecules act on the endocannabinoid system through cannabinoid receptors, degradation or synthesis enzymes. Phytochemicals and secondary metabolites able to interact with the endocannabinoid system have been recently described in a broad range of plants and fruits.
 
It's interesting how changes to diet have likely altered our endocannabinoid system:
 
"...the transition from high-protein hunting and gathering society, to one based on agriculture, and hyper-glucidic and -lipidic, has favored the over-activation of CB1R"
 
Some plants
 
Cannabigerol-like phytocannabinoids called amorfrutins have been identified in the genus Helichrysum
 
Several amorfrutins have been isolated from liverwort belonging to the genus Radula and from two species of the Fabaceae family, Amorpha fruticosa and Glycyrrhiza acanthocarpa
 
Molecules structurally similar to CBD are ferruginene compounds and methylpenanol analogs of CBD extracted from Rhododendron ferrugineum, species belonging to the Ericaceae family. Rhododendron dauricum, a flowering plant belonging to the family Ericaceae native to the North Asian forests, produces daurichromenic acid (DCA)
 
Guineensine belongs to a class of N-alkylamide alkaloids, first isolated from West African pepper (Piper guineense). They are also abundant in numerous other species of Piper genus, such as in P. longum and P. nigrum (the dietary pepper species) guineensine has ability to inhibit the central reuptake of the major endocannabinoids
 
Chelerythrine, present in the plants Chelidonium majus, Zanthoxylum clavaherculis, and Zanthoxylum rhoifolium, and sanguinarine, extracted from Sanguinaria canadensis, Argemone mexicana, Chelidonium majus, and Macleaya cordata, are two benzophen-anthridine alkaloid with potential cannabimimetic action
 
Out of six kavalactones, yangonin has shown good selectivity for CB1R compared to CB2R
 
γ-Sanshool is another alkaloid, extracted from plant genus Zanthoxylums uch as Z. clava-herculis, Z. armatum, Z. bungeanum, Z. piperitum. γ-Sanshool displayed an antagonist profile for CB1R and simultaneously an agonist activity for CB2R
 
From Voacanga africana, three alkaloids with CB1R antagonism, voacamine, 3,6-oxidovoacangine, and 5-hydroxy-3,6-oxidovoacangine, have been isolated. The crude extract of Voacanga africana has been used for the treatment of diseases connected to endocannabinoid systems such as chronic inflammation, mental disorders, and convulsions in children. Indeed, based on binding studies, it was established that these three alkaloids could be considered modulators of CB1R.
 
α-Amyrin and β-amyrin are pentacyclic triterpenes, ubiquitously distributed in the plant kingdom, known to have a number of biological effects produced via indi-rect cannabimimetic mechanisms. α-amyrin is isolated from the resins of Bursera and Protium species of the Burseraceae family. The key sources for β-amyrin include Amphipterygium adstringens, Eucalyptus globulus, Ficus carica, Ficus cordata, Nelumbo nucifera and Byrsonima crassa
 
Even betulinic acid, a pentacyclic triterpenoid, can bind to both CB1R and CB2R
 
Falcarinol, found in many plants of the Apiaceae family (Daucus carota specifically), exhibits binding affinity to both CB1R and CB2R but selec-tively acts as a covalent inverse agonist in CB1R
 
Polyphenols:
 
Biochanin A has cannabimimetic activity seems linked to inhibition of fatty acid amide hydrolase, an enzyme for anandamide degradation
 
A growing body of evidence suggests that anthocyanins incl. cyanidin may have analgesic, neuroprotective and anti-inflammatory properties, and these biological effects are tied to its potential action on cannabinoid receptors. Cyanidin is a ligand with moderate affinity to human CB1R and CB2R
 
There is moderate affinity of catechins to CB1R.
 
Curcumin is an antagonist/inverse agonist towards CB1R but contradictory results have been also produced
 
Magnolol showed a profile of partial agonist with selectivity for the CB2R, while honokiol possesses a signifi-cantly lower affinity for the CB1R
 
The cannabimimetic action of kaempferol may be due to its inhibitory capacity towards the FAAH degradation enzyme. Quercetin, a flavonol associated with rutinose to form the glycoside rutin, showed an upregulation of CB1R
 
Maca - Lepidium meyenii - has action on the endocannabinoid system
 
N-alkylamide lipids show structural similarity with anandamide and bind to CB2R more potently than endogenous cannabinoids. N-alkylamides have been isolated from Echinacea purpureaand Echinacea angustifolia. Moreover, other extracts of Echinacea spp. have demonstrated anti-inflammatory property by PPAR activity. Even Otanthus maritimus (family: Asteraceae) possesses N-alkylamides with a good CB2R affinity
 
 
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Posted (edited)

Very interesting. You must have a background in pharmacology. Is the anandamide in chocolate from the cacao plant?

Edited by Cimi

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Posted (edited)
On 14/04/2019 at 5:57 PM, Cimi said:

Is the anandamide in chocolate from the cacao plant?

 

If it is present to an appreciable degree, it is theoretically degraded so quickly by FAAH after oral administration that it's likely not that relevant but some propose there are N-acylethanolamines that slow degradation also in the chocolate. That said some of the fatty acid amides I've found orally sometimes do something at high enough doses. It may be that the abundant catechin flavonols, which seem to have moderate affinity to cannabinoid receptors (and other receptors) are more active. You've got a good lot of fatty acids, some with affinity to CNS receptors, that could also alter endocannabinoid tone. The pharmacology of the tetrahydro-beta-carbolines and isoquinolines in chocolate isn't well established from my understanding

 

One fairly recent review links most of the psychoactivity to these main constituents:

 

"...we would like to propose the “mood pyramid” as a model, summarizing the more general up to the more specific psychopharmacological actions of cocoa and chocolate. There is a large amount of scientific evidence that the flavonoids, more in particular CF, are involved in the cognition-enhancing effects, although this may not be very specific for cocoa or chocolate, since these constituents are widely distributed in nature and in food. At the second level, the methylxanthines caffeine and theobromine have additive and maybe synergistic effects on cognition and alertness, although the role of theobromine remains unclear. Methylxanthines are less common in nature than flavanols, but still not restricted to T. cacao. At the third and gradually more specific level, the tetrahydro-isoquinoline alkaloids, more in particular salsolinol, may exert additive or synergistic activities" [1].

Edited by Alchemica
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Posted (edited)
1 hour ago, Alchemica said:

 

If it is present to an appreciable degree, it is theoretically degraded so quickly by FAAH after oral administration that it's likely not that relevant but some propose there are N-acylethanolamines that slow degradation also in the chocolate.

 

Yes, I saw this here: http://www.herbmuseum.ca/content/anandamide-chocolate

 

1 hour ago, Alchemica said:

One fairly recent review links most of the psychoactivity to these main constituents:

 

"...we would like to propose the “mood pyramid” as a model, summarizing the more general up to the more specific psychopharmacological actions of cocoa and chocolate. There is a large amount of scientific evidence that the flavonoids, more in particular CF, are involved in the cognition-enhancing effects, although this may not be very specific for cocoa or chocolate, since these constituents are widely distributed in nature and in food. At the second level, the methylxanthines caffeine and theobromine have additive and maybe synergistic effects on cognition and alertness, although the role of theobromine remains unclear. Methylxanthines are less common in nature than flavanols, but still not restricted to T. cacao. At the third and gradually more specific level, the tetrahydro-isoquinoline alkaloids, more in particular salsolinol, may exert additive or synergistic activities" [1].

 

Yeah very interesting. It's one of those many things that is near impossible to tease apart into all its individual constituents because of interaction effects, and their interactions, and so on. The whole is greater than the sum of its parts.

 

The facilitation of improved alertness and cognitive functioning is a nice bonus as well. Thanks for the info.

Edited by Cimi
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