Exposing the Therapeutic Potential of Cannabigerolic Acid

What is Cannabigerolic acid (CBGa)?

CBGa or cannabigerolic acid is the first cannabinoid to be synthensized by the cannabis plant. CBGa is a direct product of olivetolic acid and geranyl phosphate. It is a dihydroxybenzoic acid with the hydrogen at position 3 substituted by a geranyl group. As a 22-carbon compound (C22H32O4), it has a ring of carbon atoms attached to long carbon chains and a carboxylic group (hence the name cannabigerolic acid).

The cannabis plant is home to over 554 phytochemicals identified as cannabinoids, terpenes, complex sugars, and flavonoids. Out of this vast number of compounds, about 120 have been identified as cannabinoids with several therapeutic benefits. The cannabinoids share similarities with anandamide and 2-Arachidonyolglycerol (2-AG), the body’s natural bliss switches, thus allowing them to interact with the cannabinoid receptors to modulate cognitive activities.

The interaction between the cannabinoids and the cannabinoid receptors has been the bedrock of cannabis research and its legalization for recreational and medical activity since 19644. At this time cannabis is legal in over 70 countries have legalized the use of cannabis for medical or recreational purposes (or both). This number is expected to increase as more people become aware of the power of the “God plant” to address all forms of oxidative-stress-related diseases of mind and body.

While neutral form-or distillate-phytocannabinoids like CBD, CBC, CBN, CBG, and THC have been the subject of intense research over the past 50 years, their acidic counterparts have remained largely unexamined by most research institutions. Most research papers dealing with cannabinoid acids like Cannabigerolic acid (CBGA), cannabidiolic acid (CBDA), cannabichromenic acid (CBCA), and tetrahydrocannabinolic acid (THCA), have focused on their conversion to neutral cannabinoids with little focus on their therapeutic benefits when the acids are preserved not decarboxylated. However, the latest findings from recent peer-reviewed research demonstrate that cannabinoid acids may possess an excellent level of therapeutic benefits, which may even outshine their neutral forms.

This article will expose the potential benefits of CBGA and how it can lead to a new medicine movement if harnessed by the cannabis industry world-wide so that its full therapeutic potential becomes the order of the day.

How is CBGA formed?

CBGA and CBGVA (cannabigerovarinic acid) are the first cannabinoids to be synthesized in the cannabis plant. While CBGA serves as the mother of most neutral cannabinoids, CBGVA serves as the mother of varin cannabinoids. CBGA is a product of interaction between olivetolic acid and geranyl phosphate,. The enzymatic reaction involves the alkylation of olivetolic acid in the presence of geranyl pyrophosphate. Olivetolic acid is a polyketide nucleus of all cannabinoids. It serves as the framework that supports the existence of all cannabinoids.

Cannabinoids contain a terpenophenolic skeleton originating from geranyl diphosphate (GPP), a monoterpene, and olivetolic acid. These frameworks are produced by polyketide synthase (PKS) and olivetolic acid cyclase. After producing the frameworks, cannabigerolic acid synthase (CBGAS) then catalyzes the transfer of the phenol group via an electrophilic aromatic substitution that helps to form CBGA. The formed CBGA can further be cyclized by other synthases (THCA synthase, CBDA synthase, and CBCA synthase) to form other acidic cannabinoids.

Most of the CBGA produced in the plant is sequentially converted into other acidic cannabinoids like THCA, CBDA, and CBCA helped by synthase enzymes (THCA synthase, CBDA synthase, and CBCA synthase). The synthase enzymes catalyze the oxidative cyclization of the monoterpene moiety of CBGA to form other acidic cannabinoids.

Before now, research on CBGA has been highly limited due to the minute quantities of the acidic cannabinoid in the cannabis plant. But recently, plant breeding created specialized strains that lack the enzymes for converting CBGA into other acidic cannabinoids. Note that all cannabinoids exist in their acidic forms and are produced in the trichomes as compounds of the plant’s own immunological self-defense: The mechanism created by the cannabis plant to combat insects, absorb ultraviolet radiation, and promote cell death of the plant’s own leaves to promote growth of the cannabis flower itself.

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CBGA is highly concentrated in young cannabis plants, usually within the rooting and vegetative phases. Although the concentration of CBGA varies based on chemovars and the plant parts involved, researchers discovered that CBGA exhibits the highest concentration in cannabis leaves in the root growing phase while the flowers have the highest CBGA concentration after between 150 to172 days of plant growth.

Besides harvesting the plants early to obtain a large concentration of CBGA, there are reports on how CBGA can be synthesized from yeast and some bacterial cells, thus promoting their synthesis and availability for research.

What is CBGA used for?

Although most research has focused on the conversion of CBGA to other cannabinoid acids, the therapeutic potential of CBGA cannot be overemphasized. CBGA is expected to supplant CBD as the medicine of choice for a variety of oxidative stress related disorders by 2030. Recently, the therapeutic potential of CBGA was put on display by the discovery that the mother molecule possesses a more active anticonvulsant property than CBD. Besides performing better at reducing seizures, CBGA was also observed to require lesser dosage and performed excellently at boosting the activities of clobazam, a choice medication for convulsion. Some of the other possible therapeutic benefits of CBGA have been summarized as follows:

Antioxidant activity of CBGa

CBGA and other cannabinoid acids (except Δ9-THCA) can scavenge free radicals and prevent the oxidation process and reduce metal ions. This is important for restoring internal balance to the calcium ion exchange necessary to convert food into ATP throughout all types of cellular activity and to reduce the spread of cancerous cells.

Cannabinoids generally exhibit an excellent antioxidant activity, usually higher than α-tocopherol or vitamin C. The antioxidant activity is controlled by the phenolic (-OH) groups in the cannabinoids, thus showing why CBGA>CBDA>Δ9-THCA in providing antioxidant activity. This trend is also observed in the activity of neutral cannabinoids with CBG>CBD>THC>CBN. The relatively low antioxidant activity of Δ9-THCA can be attributed to the presence of one OH group, which is engaged in the formation of hydrogen bond with COOH groups.

The carboxyl group plays a critical role in determining the antioxidant property of cannabinoids. Combining the acidic cannabinoids and their neutral forms increases the overall antioxidant activity of the cannabinoids with CBGA: CBG>CBDA: CBD>THCA: THC.

Anti-inflammatory properties of CBGa

The anti-inflammatory roles of CBGA and other cannabinoids in calming the inflammatory storms of COVID-19 have been explored by a research team in 2021. Their research shows how cannabis extracts containing cannabinoids, including CBGA, can decrease the level of pro-inflammatory cytokines in human 3D tissues. The extracts downregulated pathways involved in inflammation and fibrosis in COVID-19 patients. However, the extracts used in the research contained only a negligible concentration of CBGA (0.32% in the extracts and 0.1% in the flowers), with THC and CBD occupying the largest percentage.

Another research in 2011 showed how CBGA exhibited better inhibitory activity than NSAIDS in preventing the activities of prostaglandins. This may be important in proffering solutions to inflammation-induced diseases like rheumatoid arthritis (RA), chronic obstructive pulmonary diseases (COPD), asthma, and multiple sclerosis. In their research, CBGA showed over 30% inhibitory potential thus, suggesting an excellent anti-inflammatory property. Novel CBG derivatives and CBGA analogs could potentially reduce inflammation, pain, and obesity.

Anticancer properties of CBGa

The anticancer activities of CBGA have been reported on colorectal cancer, lymphocytic leukemia, brain tumor growth, and lung cancer. CBGA possesses some cytotoxic activity that can induce apoptosis in cancer cell lines and delay the growth of tumors. The success of CBGA in cancer control is further being explored in developing novel cancer drugs for treating colorectal cancer. The proposed drug will contain CBGVA and CBGA, the two mother cannabinoids.

Antimicrobial activity of CBGa

Raphael Melchoulam was the first to discover the antibacterial activity of CBGA against Gram-positive bacteria in 1965. After this, other researchers observed the moderate activity of CBGA on Multi-Drug Resistant Staphylococcus aureus (MRSA). When compared with CBD, CBGA was 4 times more effective at inhibiting MRSA. CBGA may also contribute to inhibiting the growth of Bacillus subtilis.

Apart from inhibiting the growth of bacteria, CBGA has shown a good anti-parasitic property. Its antileishmanial activity on Leishmania donovani at a concentration of 12.0 μg/mL is also considered to be effective. CBGA showed no cytotoxic effect on African green monkey fibroblast, thus showing its possible safety for human populations.

Some researchers have attributed the antimicrobial activity of CBGA to the inhibition of anthranilate synthase (AS). AS is a target enzyme for the discovery of new antimicrobial compounds, and it is important for tryptophan synthesis.

Anticonvulsant and anti-seizure activity of CBGa

CBGA possesses potent anticonvulsant and anti-seizure properties, which was more effective for seizure relief than CBD. It was the most potent phytocannabinoid against hyperthermia-induced seizures in test animals. CBGA also shows some positive interaction with clobazam thus, suggesting a possible new line of medication for Dravet syndrome. The interaction between CBGA and cannabinoid receptors can also come in handy in reducing pain and other symptoms associated with chronic epileptic episodes.

Antidiabetic properties of CBGa

The antidiabetic potentials of CBGA are largely attributed to its inhibitory activities on aldose reductase (AS). The cannabis extract used in the research contained non-psychotropic cannabinoids CBD/CBDA or CBG/CBGA. Aldose reductase converts glucose to sorbitol and fructose. Its activity supports the establishment of secondary complications of diabetes such as cataracts, retinopathy, nephropathy, and neuropathy controlled by insulin.

Neuroprotective properties of CBGa

The neuroprotective properties of CBGA and its derivatives have been extensively explored for possible pain relief from arthritis and multiple sclerosis. The derivatives interacted with peroxisome proliferator-activated receptor-γ (PPAR-γ) to protect the cells from neuro-inflammation. This may hold a promise in reducing the severity associated with neurodegenerative diseases and may promote adult neurogenesis.

Antidepressant and anxiolytic properties

Although CBG shows little affinity for CB1 and CB2 receptors, the compound and its derivatives were observed to show a promise in serving as an antidepressant, anxiolytic, and analgesic agent. It also produces a neuromodulator function that may be useful in several other diseases. CBGA also provides an excellent entourage effect which may come in handy in promoting the activities of other cannabinoids.

Eyecare

CBGA has been reported to improve the trans corneal penetration of eye care products by over 300%. There is great promise in CBGA for glaucoma patients through improved drug delivery mechanisms.

How our body interacts with CBGA

CBGA metabolism is unique since it does not interact with CB1 and CB2 receptors. The carboxyl group improves its bioavailability, thus making it less susceptible to first-pass metabolism. Although there is limited research on the fate of ingested CBGA, Some resaerchers have explained the pharmacokinetics of cannabinoid acids via intraperitoneal (I.P) administration. The 2019 research observed the fate of the molecules in adult mice and discovered that it takes 15-45 minutes for users to experience the effects of CBGA. The researchers observed a maximum plasma concentration after 15 minutes of administration while the maximum brain concentration was recorded in 30 minutes. CBGA absorption peaked at 45 minutes.

CBGA exhibited a half-life of 120 minutes in the plasma and 62 minutes in the brain cells. The lower half-life in brain cells was attributed to rapid brain interaction between CBGA and brain cells. Overall, CBGA and other cannabinoid acids exhibited low brain penetration in an oil vehicle.

Using full-spectrum products showed a considerably higher half-life for all cannabinoid acids. In full spectrum administration, the half-life increased to 298 minutes, thus supporting entourage effects and greater bioavailability at target sites.

Cannabinoid Targets of CBGa

A 2020 study demonstrated how CBGA shows a little affinity for both CB1R and CB2R receptors. This ultimately limits the pharmacological activity of the compound due to CB receptors. It is therefore pertinent to note that CBGA produces its therapeutic benefits by interacting with other cannabinoid receptors. The cannabinoid receptors responsible for the therapeutic benefits of CBGA are discussed below;

G-protein coupled receptor 55:

G-protein Coupled receptors (GPCR) are the largest and most diverse receptors in animals. They function as an inbox for messages in the form of peptides, lipids, fats, and proteins. About one-third of marketed drugs are believed to exhibit their activities by binding to these receptors.

GPR55 has been widely reported to play critical roles in the activities of cannabinoids, with CBGA acting as a non-competitive antagonist. CBGA binds to the allosteric sites of the receptors or binds to the receptor sites in an irreversible manner, thus modulating its activities. This reaction is responsible for its anticonvulsant activities.

The activities of GPCR55 are directly involved in pain sensitivity relating to inflammatory and neuropathic pain. It can initiate cellular activity and may also increase the concentration of intracellular calcium in neurons during seizures. There are also reports on how GPCR55 is associated with disease conditions like cancer, diabetes, obesity, and the proper functioning of the gastrointestinal tract, making CBGA a promising remedy for such conditions.

Transient receptor potential cation channel V1 (TRPV1)

Receptors in the Transient potential channel subfamily V member 1 (TRPV1) are also known as capsaicin receptors or vanilloid receptor 1 (VR1). They are expressed in nociceptive neurons and are responsible for the transmission of pain. TRPV1 is responsible for selectively activating the sensory neurons responsible for conveying information about unpleasant stimuli to the central nervous system. CBGA can function as an antagonist of the receptors, thus promoting pain relief.

Transient receptor potential ankyrin type 1 (TRP1A)

TRP1A responds to noxious stimuli, inflammatory cytokines, or pungent substances and plays an active role in pain signaling, taste, and inflammation. It is a member of the transient receptor potential family. CBGA functions as an agonist of TRP1A receptors, promoting anti-inflammatory properties and analgesic effects.

Transient receptor potential Melastatin 8 (TRPM8)

TRPM8 receptors are activated by chemical cooling agents like menthol or when temperatures drop below 26 degrees Celsius. They detect cold stimuli and are involved in the transmission of sensitive roles in cold evoked pain stimuli. TRPM8 has been reported to play important roles in skin anti-inflammatory properties and was initially thought to be triggered by CBG. Instead, CBGA was found to play an antagonistic role on these receptors. The therapeutic role of TRPM8 and the effect of CBGA have been reported in colorectal cancer.

Peroxisome proliferator-activated receptor gamma (PPARγ)

PPARγ or PPARG is a member of the supergene family of nuclear receptors responsible for the transcription and regulation of genes like cellular intermediary metabolism and inflammation. They are directly involved in regulating fatty acid storage and glucose metabolism, thus indicating a good point for the antidiabetic potentials of CBGA. The activation of PPRG can inhibit the growth of cultured cell lines from the human breast, prostate, and lung cancer. Researchers have discovered that Cannabinoid acids like CBGA, CBDA, and THCA are more efficient at activating the PPARG receptors and may be super active in killing cancerous cells.

Gamma-aminobutyric acid (GABA A) receptors:

GABA is an amino acid that functions as the primary neurotransmitter for the central nervous system. It reduces neuronal excitability via the inhibition of nerve transmission. The neurons are in the brainstem, hypothalamus, basal ganglia, thalamus, and hippocampus. They also participate in stabilizing neurological functions.

Low GABA activity has been associated with several neurobehavioral illnesses. It is responsible for generalized anxiety, schizophrenia, autism spectrum disorder, and depressive disorder. They are also associated with seizures and epilepsy, where CBGA is examined to increase the peak currents, thus assisting people with epilepsy and seizures.

Prospects for Future Research into CBGA and Other Cannabis Acids

Cannabinoids like CBGA, CBG, CBGVA, CBDA, THCA, and CBCA are set to supplant CBD and THC as the new kid on the block in the near future. These rare cannabinoids, especially CBGA, possess an excellent therapeutic profile that will outperform CBD when utilized. Although research in CBGA is limited, there is an increased awareness of the possible therapeutic potential of the molecule after it outperformed CBD in calming seizures.

CBGA also possesses an excellent therapeutic profile that can boost the activity of other cannabinoids while suppressing the psychoactive effects of THC and other psychoactive cannabinoids. It requires a lesser dosage and may possess a higher bioavailability. That CBGA can provide better results than CBD at a lower dosage is a breakthrough in cannabis research. Given its ubiquitous therapeutic properties, much more research regarding CBGA metabolism and interaction with other cannabinoids is needed.

References

ElSohly MA, Gul W. Constituents of Cannabis Sativa. Handb Cannabis. Published online January 22, 2015:3-22. doi:10.1093/ACPROF:OSO/9780199662685.003.0001
Andre CM, Hausman JF, Guerriero G. Cannabis sativa: The Plant of the Thousand and One Molecules. Front Plant Sci. 2016;7(FEB2016). doi:10.3389/FPLS.2016.00019
Devsi A, Kiyota B, Ouellette T, et al. A pharmacological characterization of Cannabis sativa chemovar extracts. J Cannabis Res 2020 21. 2020;2(1):1-13. doi:10.1186/S42238-020-00026-0
Pertwee RG. Cannabinoid pharmacology: the first 66 years. Br J Pharmacol. 2006;147(Suppl 1):S163. doi:10.1038/SJ.BJP.0706406
Formato M, Crescente G, Scognamiglio M, et al. (‒)-Cannabidiolic Acid, a Still Overlooked Bioactive Compound: An Introductory Review and Preliminary Research. Molecules. 2020;25(11). doi:10.3390/MOLECULES25112638
Dawidowicz AL, Olszowy-Tomczyk M, Typek R. CBG, CBD, Δ9-THC, CBN, CBGA, CBDA and Δ9-THCA as antioxidant agents and their intervention abilities in antioxidant action. Fitoterapia. 2021;152. doi:10.1016/J.FITOTE.2021.104915
McPartland JM, MacDonald C, Young M, Grant PS, Furkert DP, Glass M. Affinity and Efficacy Studies of Tetrahydrocannabinolic Acid A at Cannabinoid Receptor Types One and Two. Cannabis Cannabinoid Res. 2017;2(1):87. doi:10.1089/CAN.2016.0032
Thomas BF, ElSohly MA. Biosynthesis and Pharmacology of Phytocannabinoids and Related Chemical Constituents. Anal Chem Cannabis. Published online 2016:27-41. doi:10.1016/B978-0-12-804646-3.00002-3
Klahn P. Cannabinoids-Promising Antimicrobial Drugs or Intoxicants with Benefits? Antibiotics. 2020;9(6):1-26. doi:10.3390/ANTIBIOTICS9060297
Aizpurua-Olaizola O, Soydaner U, Öztürk E, et al. Evolution of the Cannabinoid and Terpene Content during the Growth of Cannabis sativa Plants from Different Chemotypes. J Nat Prod. 2016;79(2):324-331. doi:10.1021/ACS.JNATPROD.5B00949
Blatt-Janmaat K, Qu Y. The Biochemistry of Phytocannabinoids and Metabolic Engineering of Their Production in Heterologous Systems. Int J Mol Sci 2021, Vol 22, Page 2454. 2021;22(5):2454. doi:10.3390/IJMS22052454
Luo X, Reiter MA, d’Espaux L, et al. Complete biosynthesis of cannabinoids and their unnatural analogues in yeast. Nature. 2019;567(7746):123-126. doi:10.1038/S41586-019-0978-9
Kabiri M, Kamal SH, Pawar S V., et al. A stimulus-responsive, in situ-forming, nanoparticle-laden hydrogel for ocular drug delivery. Drug Deliv Transl Res. 2018;8(3):484-495. doi:10.1007/S13346-018-0504-X/FIGURES/9
Why CBG and Other Rare Cannabinoids Will Supplant CBD | Nasdaq. Accessed November 23, 2021. https://www.nasdaq.com/articles/why-cbg-and-other-rare-cannabinoids-will-supplant-cbd-2020-09-28
Expert: The Future of Products Containing Rare Cannabinoids is in Pharmacy. Accessed November 23, 2021. https://www.pharmacytimes.com/view/expert-the-future-of-products-containing-rare-cannabinoids-is-in-pharmacy
Mechoulam R, Gaoni Y. Hashish. IV. The isolation and structure of cannabinolic cannabidiolic and cannabigerolic acids. Tetrahedron. 1965;21(5):1223-1229. doi:10.1016/0040-4020(65)80064-3
Anderson LL, Heblinski M, Absalom NL, et al. Cannabigerolic acid, a major biosynthetic precursor molecule in cannabis, exhibits divergent effects on seizures in mouse models of epilepsy. Br J Pharmacol. Published online 2021. doi:10.1111/BPH.15661
Atalay S, Jarocka-karpowicz I, Skrzydlewskas E. Antioxidative and Anti-Inflammatory Properties of Cannabidiol. Antioxidants. 2020;9(1). doi:10.3390/ANTIOX9010021
Kovalchuk A, Wang B, Li D, et al. Fighting the storm: could novel anti-TNFα and anti-IL-6 C. sativa cultivars tame cytokine storm in COVID-19? Aging (Albany NY). 2021;13(2):1571-1590. doi:10.18632/AGING.202500
Ruhaak LR, Felth J, Karlsson PC, Rafter JJ, Verpoorte R, Bohlin L. Evaluation of the cyclooxygenase inhibiting effects of six major cannabinoids isolated from Cannabis sativa. Biol Pharm Bull. 2011;34(5):774-778. doi:10.1248/BPB.34.774
Kogan NM, Lavi Y, Topping LM, et al. Novel CBG Derivatives Can Reduce Inflammation, Pain and Obesity. Mol 2021, Vol 26, Page 5601. 2021;26(18):5601. doi:10.3390/MOLECULES26185601
Nallathambi R, Mazuz M, Namdar D, et al. Identification of synergistic interaction between cannabis-derived compounds for cytotoxic activity in colorectal cancer cell lines and colon polyps that induces apoptosis-related cell death and distinct gene expression. Cannabis Cannabinoid Res. 2018;3(1):120-135. doi:10.1089/CAN.2018.0010/ASSET/IMAGES/LARGE/FIGURE7.JPEG
Scott KA, Shah S, Dalgleish GA, Liu MW. Enhancing the Activity of Cannabidiol and Other Cannabinoids In Vitro Through Modifications to Drug Combinations and Treatment Schedules . Anticancer Res. 2013;33:4373-4380. Accessed November 22, 2021. https://ar.iiarjournals.org/content/anticanres/33/10/4373.full.pdf
Goodin AJ, Wilson DL, Cook RL, Wang Y, Brown J, Winterstein AG. Abstracts Scientific Program and Planning Committee Disclosure Statement Scientific Program and Planning Committee. doi:10.1159/000519038
Cannabics Pharmaceuticals Pioneers in Cannabis and Cancer. Accessed November 22, 2021. https://cannabics.com/
Karas JA, Wong LJM, Paulin OKA, et al. The Antimicrobial Activity of Cannabinoids. Antibiot 2020, Vol 9, Page 406. 2020;9(7):406. doi:10.3390/ANTIBIOTICS9070406
Kapoor G, Saigal S, Elongavan A. Action and resistance mechanisms of antibiotics: A guide for clinicians. J Anaesthesiol Clin Pharmacol. 2017;33(3):300-305. doi:10.4103/joacp.JOACP_349_15
Sumthong P. Antimicrobial Compounds as Side Products from the Agricultural Processing Industry. Vol Doctoral t. Division of Pharmacognosy, Section of Metabolomics, Institute of Biology, Faculty of Science, Leiden University; 2007. Accessed November 22, 2021. https://hdl.handle.net/1887/12086
Klahn P. Cannabinoids-Promising Antimicrobial Drugs or Intoxicants with Benefits? Antibiot 2020, Vol 9, Page 297. 2020;9(6):297. doi:10.3390/ANTIBIOTICS9060297
Smeriglio A, Giofrè S V., Galati EM, et al. Inhibition of aldose reductase activity by Cannabis sativa chemotypes extracts with high content of cannabidiol or cannabigerol. Fitoterapia. 2018;127:101-108. doi:10.1016/J.FITOTE.2018.02.002
Granja AG, Carrillo-Salinas F, Pagani A, et al. A cannabigerol quinone alleviates neuroinflammation in a chronic model of multiple sclerosis. J Neuroimmune Pharmacol. 2012;7(4):1002-1016. doi:10.1007/s11481-012-9399-3
Gugliandolo A, Pollastro F, Grassi G, Bramanti P, Mazzon E. In Vitro Model of Neuroinflammation: Efficacy of Cannabigerol, a Non-Psychoactive Cannabinoid. Int J Mol Sci 2018, Vol 19, Page 1992. 2018;19(7):1992. doi:10.3390/IJMS19071992
Borrelli F, Pagano E, Romano B, et al. Colon carcinogenesis is inhibited by the TRPM8 antagonist cannabigerol, a Cannabis-derived non-psychotropic cannabinoid. Carcinogenesis. 2014;35(12):2787-2797. doi:10.1093/CARCIN/BGU205
Baraldi PG, Preti D, Materazzi S, Geppetti P. Transient Receptor Potential Ankyrin 1 (TRPA1) Channel as Emerging Target for Novel Analgesics and Anti-Inflammatory Agents. J Med Chem. 2010;53(14):5085-5107. doi:10.1021/JM100062H
Anderson LL, Low IK, Banister SD, McGregor IS, Arnold JC. Pharmacokinetics of Phytocannabinoid Acids and Anticonvulsant Effect of Cannabidiolic Acid in a Mouse Model of Dravet Syndrome. J Nat Prod. 2019;82(11):3047-3055. doi:10.1021/ACS.JNATPROD.9B00600
Anderson LL, Etchart MG, Bahceci D, Golembiewski TA, Arnold JC. Cannabis constituents interact at the drug efflux pump BCRP to markedly increase plasma cannabidiolic acid concentrations. Sci Reports 2021 111. 2021;11(1):1-14. doi:10.1038/s41598-021-94212-6
Navarro G, Varani K, Lillo A, et al. Pharmacological data of cannabidiol- and cannabigerol-type phytocannabinoids acting on cannabinoid CB 1, CB 2 and CB 1/CB 2 heteromer receptors. Pharmacol Res. 2020;159. doi:10.1016/J.PHRS.2020.104940
Filipiuc LE, Ababei DC, Alexa-Stratulat T, et al. Major Phytocannabinoids and Their Related Compounds: Should We Only Search for Drugs That Act on Cannabinoid Receptors? Pharmaceutics. 2021;13(11):1823. doi:10.3390/PHARMACEUTICS13111823
GPCR | Learn Science at Scitable. Accessed November 24, 2021. https://www.nature.com/scitable/topicpage/gpcr-14047471/
Whyte LS, Ryberg E, Sims NA, et al. The putative cannabinoid receptor GPR55 affects osteoclast function in vitro and bone mass in vivo. Proc Natl Acad Sci U S A. 2009;106(38):16511-16516. doi:10.1073/PNAS.0902743106
Schicho R, Storr M. A potential role for GPR55 in gastrointestinal functions. Curr Opin Pharmacol. 2012;12(6):653-658. doi:10.1016/J.COPH.2012.09.009
Bazelot M, Whalley B. Investigating the Involvement of GPR55 Signaling in the Antiepileptic Effects of Cannabidiol (P5.244). Neurology. 2016;86(16 Supplement).
Rosenbaum T, Simon SA. TRPV1 Receptors and Signal Transduction. TRP Ion Channel Funct Sens Transduct Cell Signal Cascades. Published online April 10, 2007:91-106. doi:10.1201/9781420005844-11
De Petrocellis L, Ligresti A, Moriello AS, et al. Effects of cannabinoids and cannabinoid-enriched Cannabis extracts on TRP channels and endocannabinoid metabolic enzymes. Br J Pharmacol. 2011;163(7):1479. doi:10.1111/J.1476-5381.2010.01166.X
Gao S, Kaudimba KK, Guo S, et al. Transient Receptor Potential Ankyrin Type-1 Channels as a Potential Target for the Treatment of Cardiovascular Diseases. Front Physiol. 2020;11:836. doi:10.3389/FPHYS.2020.00836/BIBTEX
Muller C, Morales P, Reggio PH. Cannabinoid Ligands Targeting TRP Channels. Front Mol Neurosci. 2018;11. doi:10.3389/FNMOL.2018.00487
Yang C, Jo SH, Csernus B, et al. Activation of peroxisome proliferator-activated receptor gamma contributes to the survival of T lymphoma cells by affecting cellular metabolism. Am J Pathol. 2007;170(2):722-732. doi:10.2353/AJPATH.2007.060651
Nadal X, del Río C, Casano S, et al. Tetrahydrocannabinolic acid is a potent PPARγ agonist with neuroprotective activity. Br J Pharmacol. 2017;174(23):4263. doi:10.1111/BPH.14019