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Chemical compound
Chemical compound
Biosynthesis of
tetrahydrocannabinolic acid (THCA). In the first step, geranyl pyrophosphate and olivetolic acid form cannabigerolic acid, which is then enzymatically rearranged to THCA in the second step.
Cannabigerolic acid (CBGA ) is the acidic form of
cannabigerol (CBG). It is a
dihydroxybenzoic acid and
olivetolic acid in which the hydrogen at position 3 is substituted by a geranyl group. It is a biosynthetic precursor to
Delta-9-tetrahydrocannabinol , which is the principal psychoactive constituent of the
Cannabis plant. It is also a
meroterpenoid (i.e. a
polyketide and a
terpenoid ), a member of resorcinols and a
phytocannabinoid . It derives from an olivetolic acid. It is a conjugate acid of a cannabigerolate.
[1]
In the Cannabis plant, olivetolic acid and
geranyl diphosphate are synthesized into CBGA.
[2] : 6
[3] : 17 CBGA is converted in the plant by CBCA synthase,
CBDA synthase and
THCA synthase into
CBCA ,
CBDA and
THCA respectively.
[2] : 6–7 Afterwards, THCA and CBDA can be
decarboxylated into THC and CBD by drying and heating plant material. CBGA has emerging pharmacological properties; for example, it had anticonvulsant effects in a mouse model of
Dravet syndrome , a form of epilepsy.
[4]
COVID-19
In an analysis by the
University of Rhode Island on
phytocannabinoids it was found that CBGA had the 2nd highest
3C-like protease inhibitor activity against
COVID-19 out of all the phytocannabinoids tested within that study but not as high as the
antiviral drug
GC376 (72% CBGA vs 24% CBG vs 100% GC376).
[5]
A 2022 pre-clinical study by researchers from the
Oregon State University and
Oregon Health & Science University found that CBGA (along with CBDA and THCA) could prevent infection by
SARS-CoV-2 . They found that CBGA was able to block infection by the
reference strain (WA-1/2020),
alpha variant (B.1.1.7) and
beta variant (B.1.351) at micromolar concentrations (
IC50 values 37 μg/mL, 26 μg/mL, and 35 μg/mL, respectively). The results, however, are yet to be replicated in animal models or clinical trials. Out of the cannabinoids studied, CBGA was the only one capable of
allosteric binding , in addition to
orthosteric binding .
[6]
References
^
"Cannabigerolic acid" .
PubChem .
United States National Library of Medicine . Retrieved April 7, 2020 .
^
a
b Thomas BF, ElSohly MA (2015).
The Analytical Chemistry of Cannabis: Quality Assessment, Assurance, and Regulation of Medicinal Marijuana and Cannabinoid Preparations . Emerging Issues in Analytical Chemistry.
Elsevier Science .
ISBN
978-0-12-804670-8 .
^ Degenhardt VF, Stehle F, Kayser O (2016). "The biosynthesis of cannabinoids". In Preedy VR (ed.). Handbook of Cannabis and Related Pathologies: Biology, Pharmacology, Diagnosis, and Treatment .
Academic Press . pp. 13–23.
ISBN
978-0128008270 .
^ Anderson LL, Heblinski M, Absalom NL, Hawkins NA, Bowen MT, Benson MJ, et al. (December 2021).
"Cannabigerolic acid, a major biosynthetic precursor molecule in cannabis, exhibits divergent effects on seizures in mouse models of epilepsy" . British Journal of Pharmacology . 178 (24): 4826–4841.
doi :
10.1111/bph.15661 .
PMC
9292928 .
PMID
34384142 .
S2CID
236997090 .
^ Liu C, Puopolo T, Li H, Cai A, Seeram NP, Ma H (September 2022).
"Identification of SARS-CoV-2 Main Protease Inhibitors from a Library of Minor Cannabinoids by Biochemical Inhibition Assay and Surface Plasmon Resonance Characterized Binding Affinity" . Molecules . 27 (18): 6127.
doi :
10.3390/molecules27186127 .
PMC
9502466 .
PMID
36144858 .
^ van Breemen, Richard B.; Muchiri, Ruth N.; Bates, Timothy A.; Weinstein, Jules B.; Leier, Hans C.; Farley, Scotland; Tafesse, Fikadu G. (2022-01-28).
"Cannabinoids Block Cellular Entry of SARS-CoV-2 and the Emerging Variants" . Journal of Natural Products . 85 (1): 176–184.
doi :
10.1021/acs.jnatprod.1c00946 .
ISSN
0163-3864 .
PMC
8768006 .
PMID
35007072 .
Further reading
Phytocannabinoids (
comparison )
Cannabibutols Cannabichromenes Cannabicyclols Cannabidiols Cannabielsoins Cannabigerols Cannabiphorols Cannabinols Cannabitriols Cannabivarins Delta-8-tetrahydrocannabinols Delta-9-tetrahydrocannabinols Delta-10-Tetrahydrocannabinols Miscellaneous cannabinoids Active metabolites
Endocannabinoids
Synthetic cannabinoid receptor agonists / neocannabinoids
Classical cannabinoids (dibenzopyrans) Non-classical cannabinoids Adamantoylindoles Benzimidazoles Benzoylindoles Cyclohexylphenols
Eicosanoids
Hydrocarbons Indazole carboxamides Indazole-3- carboxamides Indole-3-carboxamides Indole-3-carboxylates Naphthoylindazoles
Naphthoylindoles Naphthoylpyrroles Naphthylmethylindenes Naphthylmethylindoles Phenylacetylindoles Pyrazolecarboxamides Pyrrolobenzoxazines Quinolinyl esters Tetramethylcyclo- propanoylindazoles Tetramethylcyclo- propanoylindoles Tetramethylcyclo- propylindoles Others
Allosteric
CBR Tooltip Cannabinoid receptor
ligands
Endocannabinoid enhancers (inactivation inhibitors)
Anticannabinoids (antagonists/inverse agonists/antibodies)
TRPA
Activators
4-Hydroxynonenal
4-Oxo-2-nonenal
4,5-EET
12S-HpETE
15-Deoxy-Δ12,14 -prostaglandin J2
α-Sanshool (
ginger ,
Sichuan and
melegueta peppers )
Acrolein
Allicin (
garlic )
Allyl isothiocyanate (
mustard ,
radish ,
horseradish ,
wasabi )
AM404
ASP-7663
Bradykinin
Cannabichromene (
cannabis )
Cannabidiol (
cannabis )
Cannabigerol (
cannabis )
Cinnamaldehyde (
cinnamon )
CR gas (dibenzoxazepine; DBO)
CS gas (2-chlorobenzal malononitrile)
Cuminaldehyde (
cumin )
Curcumin (
turmeric )
Dehydroligustilide (
celery )
Diallyl disulfide
Dicentrine (
Lindera spp.)
Farnesyl thiosalicylic acid
Formalin
Gingerols (
ginger )
Hepoxilin A3
Hepoxilin B3
Hydrogen peroxide
Icilin
Isothiocyanate
JT-010
Ligustilide (
celery ,
Angelica acutiloba )
Linalool (
Sichuan pepper ,
thyme )
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wintergreen )
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tobacco )
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olive oil )
Paclitaxel (
Pacific yew )
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PF-4840154
Phenacyl chloride
Polygodial (
Dorrigo pepper )
Shogaols (
ginger ,
Sichuan and
melegueta peppers )
Tear gases
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cannabis )
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onion )
Umbellulone (Umbellularia californica )
WIN 55,212-2
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Activators
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9-oxoODE
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13-HODE
13-oxoODE
20-HETE
α-Sanshool (
ginger ,
Sichuan and
melegueta peppers )
Allicin (
garlic )
AM404
Anandamide
Bisandrographolide (
Andrographis paniculata )
Camphor (
camphor laurel ,
rosemary ,
camphorweed ,
African blue basil ,
camphor basil )
Cannabidiol (
cannabis )
Cannabidivarin (
cannabis )
Capsaicin (
chili pepper )
Carvacrol (
oregano ,
thyme ,
pepperwort ,
wild bergamot , others)
DHEA
Diacyl glycerol
Dihydrocapsaicin (
chili pepper )
Estradiol
Eugenol (
basil ,
clove )
Evodiamine (
Euodia ruticarpa )
Gingerols (
ginger )
GSK1016790A
Heat
Hepoxilin A3
Hepoxilin B3
Homocapsaicin (
chili pepper )
Homodihydrocapsaicin (
chili pepper )
Incensole (
incense )
Lysophosphatidic acid
Low
pH (acidic conditions)
Menthol (
mint )
N-Arachidonoyl dopamine
N-Oleoyldopamine
N-Oleoylethanolamide
Nonivamide (PAVA) (
PAVA spray )
Nordihydrocapsaicin (
chili pepper )
Paclitaxel (
Pacific yew )
Paracetamol (acetaminophen)
Phenylacetylrinvanil
Phorbol esters (e.g.,
4α-PDD )
Piperine (
black pepper ,
long pepper )
Polygodial (
Dorrigo pepper )
Probenecid
Protons
RhTx
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Ruta graveolens )
Resiniferatoxin (RTX) (
Euphorbia resinifera /
pooissonii )
Shogaols (
ginger ,
Sichuan and
melegueta peppers )
Tetrahydrocannabivarin (
cannabis )
Thymol (
thyme ,
oregano )
Tinyatoxin (
Euphorbia resinifera /
pooissonii )
Tramadol
Vanillin (
vanilla )
Zucapsaicin
Blockers