Cannabigerol

Clinical data
Other names	CBG
ATC code	None
Legal status
Legal status	US: Unscheduled
Identifiers
IUPAC name 2-[(2E)-3,7-Dimethylocta-2,6-dienyl]-5-pentyl-benzene-1,3-diol
CAS Number	25654-31-3 Y
PubChemCID	5315659
IUPHAR/BPS	11094
DrugBank	DB14734
ChemSpider	4474921 Y
UNII	J1K406072N
KEGG	C20219
ChEBI	CHEBI:69477
ChEMBL	ChEMBL497318 Y
CompTox Dashboard(EPA)	DTXSID701014168
ECHA InfoCard	100.346.098
Chemical and physical data
Formula	C21H32O2
Molar mass	316.485 g·mol−1
3D model (JSmol)	Interactive image
SMILES Oc1cc(cc(O)c1C/C=C(\C)CC\C=C(/C)C)CCCCC
InChI InChI=1S/C21H32O2/c1-5-6-7-11-18-14-20(22)19(21(23)15-18)13-12-17(4)10-8-9-16(2)3/h9,12,14-15,22-23H,5-8,10-11,13H2,1-4H3/b17-12+ Y Key:QXACEHWTBCFNSA-SFQUDFHCSA-N Y
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Cannabigerol (CBG) is a non-psychoactivecannabinoid and minor constituent ofcannabis.^[1][2][3][4] It is one of more than 120 identified cannabinoids found in the plant genusCannabis.^[5][6] The compound is thedecarboxylated form ofcannabigerolic acid (CBGA), the parent molecule from which other cannabinoids arebiosynthesized.^[2][7]

During plant growth, most of the CBG is converted into other cannabinoids, primarilytetrahydrocannabinol (THC) orcannabidiol (CBD), leaving about 1% CBG in finished plant material.^[8] Somestrains, however, produce larger amounts of CBG and CBGA, while having low quantities of other cannabinoids, like THC and CBD.^[9]

Thepharmacodynamics of CBG are complex.^[1][2][3] It is a relatively weakligand of thecannabinoid receptors, where it acts as a weakpartial agonist.^[1][2][3] Conversely, it is a much morepotentagonist of theα₂-adrenergic receptor,antagonist of theserotonin5-HT_1A receptor, and antagonist of thetransient receptor potential channelTRPM8.^[1][2][3] CBG also has a variety of other actions that may additionally contribute to its effects.^[1][2][3]

CBG is sold as adietary supplement.^[2] Safety concerns have been raised due to the potent activation of α₂-adrenergic receptors by CBG, which may producesedation and potentially undesirablecardiovascular effects such as decreasedheart rate andblood pressure.^[2]

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In vitro, CBG has identifiedpharmacodynamic actions and itsmechanism of action appears to be from interactions with multipletargets.^[1][2][3]

CBG is a weakligand of thecannabinoidCB₁ andCB₂ receptors withaffinities (K_i) of 380–2,600 nM and 153–3,460 nM, respectively.^{[1][2][10][11][12]} It is a weakpartial agonist orantagonist of both of these receptors.^[1][2][3] There is no information on the binding or activity of CBG at theGPR55 (the potential non-homologous CB₃ receptor).^[2][3] CBG has relatively low affinity for the cannabinoid receptors, with approximately 5-fold lower affinity for the CB₁ receptor and 27-fold lower affinity for the CB₂ receptor than THC.^{[citation needed]}

CBG is a highlypotentagonist of theα₂-adrenergic receptor (EC₅₀Tooltip half-maximal effective concentration = 0.2–72.8 nM) and a moderately potentantagonist of theserotonin5-HT_1A receptor (K_B = 51.9 nM).^[2][1][13] Activation of the α₂-adrenergic receptor by CBG might produce effects includingsedation,dry mouth, and decreasedheart rate andblood pressure.^[2] This has raisedsafety concerns about CBG.^[2] The actions of CBG at the α₂-adrenergic receptor and 5-HT_1A receptor are of far greater potency than its interactions with the cannabinoid receptors and are more likely to be involved in its pharmacodynamic effects.^{[citation needed]}

The compound is a weak agonist of thetransient receptor potential channelsTRPA1 (EC₅₀ = 700 nM),TRPV1 (EC₅₀ = 1,300 nM),TRPV2 (EC₅₀ = 1,720 nM),TRPV3 (EC₅₀ = 1,000 nM), andTRPV4 (EC₅₀ = 5,100 nM) (efficacy 18–100% at these targets) and a more potent antagonist of the transient receptor potential channelTRPM8 (IC₅₀Tooltip half-maximal inhibitory concentration = 160 nM).^{[10][2][1][11][3]} It is also a weak agonist of theperoxisome proliferator-activated receptorPPAR-γ (EC₅₀ = 1,270–15,700 nM).[2]^[1][11]

CBG is avoltage-gated sodium channel (VGSC)blocker (Na_v1.1,Na_v1.2,Na_v1.5, andNa_v1.7) andvoltage-dependent calcium channel (VDCC) blocker.^[3][1][14] Inhibition of VGSCs may be involved in the analgesic effects of CBG.^[3]

It shows noinhibition of severalendocannabinoid-metabolizingenzymes includingfatty acid amide hydrolase (FAAH),diacylglycerol lipase (DGL), andN-acylethanolamine acid amide hydrolase (NAAA).^[11] However, other research has found that CBG does inhibit FAAH and DGL, as well asmonoacylglycerol lipase (MAGL), although it is less potent as an inhibitor of FAAH thancannabidiol (CBD). Aside from endocannabinoid-metabolizing enzymes, CBG is a weak inhibitor of thecyclooxygenaseCOX-1 andCOX-2 enzymes (30% inhibition of each at 25,000 nM).^[1] In addition, it has been found to inhibit both themetabolism andreuptake ofanandamide.^[1]

Thepharmacokinetics of CBG have been studied in animals and to a lesser extent in humans.^[1] CBG ismetabolized in theliver byCYP2J2, similarly to other cannabinoids as well asendocannabinoids.^[1]

CBG is a highlylipophilic andhydrophobic compound.^[3] Its predictedlog P ranges from 7.0 to 7.5.^[7][15][16]

Syntheticderivatives of CBG have beensynthesized and studied.^[1]

CBG was isolated from cannabis in 1964.

CBG is not scheduled by theUnited NationsConvention on Psychotropic Substances.^{[citation needed]} In the United States, CBG derived from marijuana is illegal under theControlled Substances Act, while CBG derived from hemp is legal, as long as the hemp THC content is less than 0.3% of dry weight.^[17][18]

InSwitzerland, it is legal to produce hemp rich in CBG as a tobacco substitute, as long as its THC content remains below 1.0%.^[19]

As of 2022, the USFood and Drug Administration has issued numerouswarning letters to American companies for illegally marketing cannabis supplement products,^[17] including one selling CBG products with unproven illegal claims of efficacy against theCOVID-19 virus andinflammation.^[20]

Thebiosynthesis of CBG begins by loading hexanoyl-CoA onto apolyketide synthase assembly protein and subsequentcondensation with three molecules ofmalonyl-CoA.^[21] Thispolyketide is cyclized toolivetolic acid viaolivetolic acid cyclase, and thenprenylated with a ten carbonisoprenoid precursor,geranyl pyrophosphate, using an aromatic prenyltransferase enzyme,geranyl-pyrophosphate—olivetolic acid geranyltransferase, to biosynthesizecannabigerolic acid, which can then bedecarboxylated to yield CBG.^[2][4]

CBG is underlaboratory research to determine itspharmacological properties and potential effects in disease conditions, with no conclusions about therapeutic effects or safety, as of 2021.^[2][12][22] Aclinical trial published in July 2024 assessed the effects of CBG onanxiety,stress, andmood.^[23][24] CBG has been determined to have antimicrobial properties both in in vivo and in vitro models.^[25] The clinical development has, however, been hindered by its poor drug metabolism and pharmacokinetic properties.^[26]

• Drugs not assigned an ATC code
• 5-HT1A antagonists
• Alpha2-adrenergic agonists
• Calcium channel blockers
• CB1 receptor antagonists
• Phytocannabinoids
• Resorcinols
• Terpeno-phenolic compounds
• Transient receptor potential channel modulators
• Voltage-gated sodium channel blockers
• Drugs with unknown mechanisms of action

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