Cannabis Research for Cannabidiolic Acid (CBDA)
Cannabidiolic Acid (CBDA) is a non-psychoactive cannabinoid that will not cause the euphoric feeling of being “high.” It is one of the four possible outcomes of Cannabigerolic acid (CBGa) being processed into cannabigerol (CBG), Cannabichromic acid (CBCa), Tetrahydrocannabibolic acid (THCa), and CBDa. CBGa is processed into other cannabinoids by synthase enzymes, and the CBDa synthase was first purified and isolated in 1996. Coincidentally, this was the same year California passed Prop 215 and became the first medical cannabis state.
While there hasn’t been much research done on CBDa yet, the research that has been done is quite promising. It appears to have antiemetic effects as well as anti-proliferative effects, making it ideal for fighting cancer.It also has been shown to be an anti-inflammatory and to possess antibacterial properties.
Below is a Library of Cannabis Research Studies for Cannabidiolic Acid (CBDA).
In Vitro and In Vivo Pharmacological Activity of Minor Cannabinoids Isolated From Cannabis Sativa
Scientific Reports | November 2020Abstract: “The Cannabis sativa plant contains more than 120 cannabinoids. With the exceptions of ∆9-tetrahydrocannabinol (∆9-THC) and cannabidiol (CBD), comparatively little is known about the pharmacology of the less-abundant plant-derived (phyto) cannabinoids. The best-studied transducers of cannabinoid-dependent effects are type 1 and type 2 cannabinoid receptors (CB1R, CB2R). Partial agonism of CB1R by ∆9-THC is known to bring about the ‘high’ associated with Cannabis use, as well as the pain-, appetite-, and anxiety-modulating effects that are potentially therapeutic. CB2R activation by certain cannabinoids has been associated with anti-inflammatory activities. We assessed the activity of 8 phytocannabinoids at human CB1R, and CB2R in Chinese hamster ovary (CHO) cells stably expressing these receptors and in C57BL/6 mice in an attempt to better understand their pharmacodynamics. Specifically, ∆9-THC, ∆9-tetrahydrocannabinolic acid (∆9-THCa), ∆9-tetrahydrocannabivarin (THCV), CBD, cannabidiolic acid (CBDa), cannabidivarin (CBDV), cannabigerol (CBG), and cannabichromene (CBC) were evaluated. Compounds were assessed for their affinity to receptors, ability to inhibit cAMP accumulation, βarrestin2 recruitment, receptor selectivity, and ligand bias in cell culture; and cataleptic, hypothermic, anti-nociceptive, hypo locomotive, and anxiolytic effects in mice. Our data reveal partial agonist activity for many phytocannabinoids tested at CB1R and/or CB2R, as well as in vivo responses often associated with activation of CB1R. These data build on the growing body of literature showing cannabinoid receptor-dependent pharmacology for these less-abundant phytocannabinoids and are critical in understanding the complex and interactive pharmacology of Cannabis-derived molecules.” — Study
Sleep and Neurochemical Modulation by Cannabidiolic Acid Methyl Ester in Rats
Brain Research Bulletin | February 2020Abstract: “Cannabidiolic acid methyl ester (HU-580) is a more stable compound than cannabidiolic acid (CBDA) which has been shown to be effective in reducing nausea, anxiety, depression behaviors in animal models. Here we extend the investigation of this compound to determine its effect on the sleep-wake cycle in male Wistar rats. HU-580 dose-dependently (0.1, 1.0 or 100 μg/Kg, i.p.) prolonged wakefulness (W) and decreased slow wave sleep (SWS) duration whereas rapid eye movement sleep (REMS) showed no statistical change. In addition, the brain microdialysis probes either placed at nucleus accumbens (NAc) or into the basal forebrain in freely moving animals were used to evaluate the effects of HU-580 treatment on neurotransmitters related to the sleep-wake cycle modulation. HU-580 enhanced extracellular levels of dopamine, serotonin collected from NAc while adenosine and acetylcholine were increased in basal forebrain. In summary, HU-580 seems to possess wake-promoting pharmacological properties and enhances the levels of wake-related neurochemicals. This is the first report of effects of HU-580 on sleep modulation expanding the very limited existent data on the neurobiological effects of HU-580 on rats.” — Study
Cannabidiolic Acid-Mediated Selective Down-Regulation of C-FOS in Highly Aggressive Breast Cancer MDA-MB-231 cells: Possible Involvement of its Down-Regulation in the Abrogation of Aggressiveness
Journal of Natural Medicines | January 2017Abstract: “The physiological activities of cannabidiolic acid (CBDA), a component of fiber-type cannabis plants, have been demonstrated and include its function as a protector against external invasion by inducing cannabinoid-mediated necrosis (Shoyama et al., Plant Signal Behav 3:1111-1112, 2008). The biological activities of CBDA have been attracting increasing attention. We previously identified CBDA as an inhibitor of the migration of MDA-MB-231 cells, a widely used human breast cancer cell line in cancer biology, due to its highly aggressive nature. The chemical inhibition and down-regulation of cyclooxygenase-2 (COX-2), the expression of which has been detected in ~40 % of human invasive breast cancers, are suggested to be involved in the CBDA-mediated abrogation of cell migration. However, the molecular mechanism(s) responsible for the CBDA-induced down-regulation of COX-2 in MDA-MB-231 cells have not yet been elucidated. In the present study, we describe a possible mechanism by which CBDA abrogates the expression of COX-2 via the selective down-regulation of c-fos, one component of the activator protein-1 (AP-1) dimer complex, a transcription factor for the positive regulation of the COX-2 gene.” — Study
Sequence Heterogeneity of Cannabidiolic and Tetrahydrocannabinolic Acid-Synthase in Cannabis Sativa L. and its Relationship with Chemical Phenotype.
Phytochemistry | August 2015Abstract: “Sequence variants of THCA- and CBDA-synthases were isolated from different Cannabis sativa L. strains expressing various wild-type and mutant chemical phenotypes (chemotypes). Expressed and complete sequences were obtained from mature inflorescences. Each strain was shown to have a different specificity and/or ability to convert the precursor CBGA into CBDA and/or THCA type products. The comparison of the expressed sequences led to the identification of different mutations, all of them due to SNPs. These SNPs were found to relate to the cannabinoid composition of the inflorescence at maturity and are therefore proposed to have a functional significance. The amount of variation was found to be higher within the CBDAS sequence family than in the THCAS family, suggesting a more recent evolution of THCA-forming enzymes from the CBDAS group. We therefore consider CBDAS as the ancestral type of these synthases.” — Study
Synergy Between Cannabidiol, Cannabidiolic Acid, and Δ9-Tetrahydrocannabinol in the Regulation of Emesis in the Suncus Murinus (House Musk Shrew).
Behavioral Neuroscience | June 2015Abstract: “Smoked marijuana contains over 100 different cannabinoids, including the psychoactive compound Δ9-tetrahydrocannabinol (THC) and cannabidiol (CBD). THC, CBD, and its acidic precursor, cannabidiolic acid (CBDA), have all been shown to have antiemetic properties in the Suncus murinus (S. murinus; house musk shrew). Here we show that when subthreshold antiemetic doses of CBD (2.5 mg/kg ip) or CBDA (0.05 mg/kg ip) are combined with a subthreshold antiemetic dose of THC (1 mg/kg ip) in the S. murinus, both lithium-chloride-induced vomiting and abdominal retching are dramatically suppressed. These results suggest that combined effects of these compounds may lead to better control of vomiting with fewer side effects.” — Study
Down-Regulation of Cyclooxygenase-2 (COX-2) by Cannabidiolic Acid in Human Breast Cancer Cells
The Journal of Toxicology | June 2014Abstract: “Cannabidiol (CBD), a major constituent of the fiber-type cannabis plant, exhibits a wide range of biological activities, such as anti-cancer cell proliferation, anti-cerebral infarction, and the inhibition of 15-lipoxygenase. In fresh plant materials, most CBD exists in its acid form, cannabidiolic acid (CBDA, Fig. 1A). The specific use of the acidic cannabinoid as an active pharmaceutical ingredient has not yet been achieved because CBDA is recognized as the pharmacologically inactive form (Yamauchi et al., 1967; Razdan, 1986; Burstein, 1999). However, recent studies including ours demonstrated that, in addition to CBD, CBDA by itself exhibits biological actions, such as antibacterial effects, the inhibition of cyclooxygenase-2 (COX-2) (Takeda et al., 2008), and anti-nausea/emetic effects” — Study
The Cannabinoid Acids, Analogs and Endogenous Counterparts
Bioorganic & Medicinal Chemistry | March 2014Abstract: “The cannabinoid acids are a structurally heterogeneous group of compounds some of which are endogenous molecules and others that are metabolites of phytocannabinoids. The prototypic endogenous substance is N-arachidonoyl glycine (NAgly) that is closely related in structure to the cannabinoid agonist anandamide. The most studied phytocannabinoid is D9-THC-11-oic acid, the principal metabolite of D9-THC. Both types of acids have in common several biological actions such as low affinity for CB1 anti-inflammatory activity and analgesic properties. This suggests that there may be similarities in their mechanism of action, a point that is discussed in this review. Also presented are reports on analogs of the acids that provide opportunities for the development of novel therapeutic agents, such as ajulemic acid.” — Study
Suppression of Lithium Chloride-Induced Conditioned Gaping (a Model of Nausea-Induced Behaviour) in Rats (Using the taste Reactivity Test) with Metoclopramide is Enhanced by Cannabidiolic Acid
Pharmacology Biochemistry and Behavior | October 2013Abstract: “We aimed to determine the potential of various doses of metoclopramide (MCP, a dopamine antagonist) to reduce lithium chloride (LiCl)-induced conditioned gaping (a nausea-induced behaviour) in rats, using the taste reactivity test. We then evaluated whether an ineffective low dose of cannabidiolic acid (CBDA, 0.1 μg/kg, Rock and Parker, 2013), the potent acidic precursor of cannabidiol (CBD, a non-psychoactive component of cannabis) could enhance the anti-nausea effects of an ineffective low dose of MCP. MCP (3.0 mg/kg) reduced conditioned gaping responses…These data suggest that CBDA could be a powerful adjunct treatment to anti-emetic regimens for chemotherapy-induced nausea”. — Study
Effect of low Doses of Cannabidiolic Acid and Ondansetron on LiCl-Induced Conditioned Gaping (a Model of Nausea-Induced Behaviour) in Rats
British Journal of Pharmacology | May 2013Abstract: “We investigated the efficacy of low doses of CBDA to suppress acute nausea, assessed by the establishment of conditioned gaping to a LiCl-paired flavour in rats. The potential of threshold and subthreshold doses of CBDA to enhance the reduction of nausea-induced conditioned gaping by OND were then determined…CBDA potently reduced conditioned gaping in rats, even at low doses and enhanced the anti-nausea effect of a low dose of OND. These findings suggest that combining low doses of CBDA and OND will more effectively treat acute nausea in chemotherapy patients.” — Study
Streptococcus Gordonii Collagen-Binding Domain Protein CBDA may EnhanceBacterial Survival in Instrumented Root Canalsex vivo
Journal of Endodontics | January 2013Abstract: “A Streptococcus gordonii gene similar to ace was identified by genome sequence searches in silico. An isogenic derivative of strain DL1 with a disruption in the identified gene was constructed by allelic replacement. Parent and mutant strains were characterized for their ability to bind immobilized collagen type-1 in a microtiter plate binding assay. Survival of the strains in a human tooth ex vivo instrumented root canal model was compared by inoculating canals with parental or mutant bacteria and determining the CFUs recovered at various time points over a 12-day period…A gene encoding a putative collagen-binding protein was identified in S. gordonii. Fewer S. gordonii cbdA-deficient cells survived ex vivo compared with parental cells, suggesting that collagen-binding proteins may contribute to persistence of oral streptococci in instrumented root canals.” — Study
Cannabidiolic Acid, a Major Cannabinoid in Fiber-Type Cannabis, is an Inhibitor of MDA-MB-231 Breast Cancer Cell Migration.
Toxicology | November 2012Abstract: “Cannabidiol (CBD), a major non-psychotropic constituent of fiber-type cannabis plant, has been reported to possess diverse biological activities, including anti-proliferative effect on cancer cells. Although CBD is obtained from non-enzymatic decarboxylation of its parent molecule, cannabidiolic acid (CBDA), few studies have investigated whether CBDA itself is biologically active…The data presented in this report suggest for the first time that as an active component in the cannabis plant, CBDA offers potential therapeutic modality in the abrogation of cancer cell migration, including aggressive breast cancers.” — Study
The Effects of Cannabidiolic Acid and Cannabidiol on Contractility of the Gastrointestinal Tract of Suncus Murinus.
Archives of Pharmacal Research | September 2011Abstract: “Cannabidiol (CBD) has been shown to inhibit gastrointestinal (GI) transit in pathophysiologic in vivo models, while having no effect in physiologic controls. The actions of the precursor of CBD, cannabidiolic acid (CBDA), have not been investigated in the GI tract. The actions of these phytocannabinoids on the contractility of the GI tract of Suncus murinus were investigated in the current study…The data suggest that CBDA and CBD have inhibitory actions on the intestines of S. murinus that are not neurally mediated or mediated via CB1 or CB2 receptors.” —Study
Non-psychotropic Plant Cannabinoids: New Therapeutic Opportunities from an Ancient Herb
Trends in Pharmacological Sciences | 2009Abstract: “D9-tetrahydrocannabinol binds cannabinoid (CB1 and CB2) receptors, which are activated by endogenous compounds (endocannabinoids) and are involved in a wide range of physiopathological processes (e.g. modulation of neurotransmitter release, regulation of pain perception, and of cardiovascular, gastrointestinal and liver functions). The well-known psychotropic effects of D9- tetrahydrocannabinol, which are mediated by activation of brain CB1 receptors, have greatly limited its clinical use. However, the plant Cannabis contains many cannabinoids with weak or no psychoactivity that, therapeutically, might be more promising than D9- tetrahydrocannabinol. Here, we provide an overview of the recent pharmacological advances, novel mechanisms of action, and potential therapeutic applications of such non-psychotropic plant-derived cannabinoids. Special emphasis is given to cannabidiol, the possible applications of which have recently emerged in inflammation, diabetes, cancer, affective and neurodegenerative diseases, and to D9-tetrahydrocannabivarin, a novel CB1 antagonist which exerts potentially useful actions in the treatment of epilepsy and obesity.” — Study
Cannabidiolic Acid as a Selective Cyclooxygenase-2 Inhibitory Component in Cannabis
Drug Metabolism and DispositionAbstract: “In the present study it was revealed that cannabidiolic acid (CBDA) selectively inhibited cyclooxygenase (COX)-2 activity with an IC50 value (50% inhibition concentration) around 2 μM, having 9-fold higher selectivity than COX-1 inhibition. In contrast, Δ9-tetrahydrocannabinolic acid (Δ9-THCA) was a much less potent inhibitor of COX-2 (IC50 > 100 μM). Nonsteroidal anti-inflammatory drugs containing a carboxyl group in their chemical structures such as salicylic acid are known to inhibit nonselectively both COX-1 and COX-2. CBDA and Δ9-THCA have a salicylic acid moiety in their structures. Thus, the structural requirements for the CBDA-mediated COX-2 inhibition were next studied. There is a structural difference between CBDA and Δ9-THCA; phenolic hydroxyl groups of CBDA are freed from the ring formation with the terpene moiety, although Δ9-THCA has dibenzopyran ring structure. It was assumed that the whole structure of CBDA is important for COX-2 selective inhibition because β-resorcylic acid itself did not inhibit COX-2 activity. Methylation of the carboxylic acid moiety of CBDA led to disappearance of COX-2 selectivity. Thus, it was suggested that the carboxylic acid moiety in CBDA is a key determinant for the inhibition. Furthermore, the crude extract of cannabis containing mainly CBDA was shown to have a selective inhibitory effect on COX-2. Taken together, these lines of evidence in this study suggest that naturally occurring CBDA in cannabis is a selective inhibitor for COX-2.” — Study
Cannabidiolic-Acid Synthase, the Chemotype-Determining Enzyme in the Fiber-Type Cannabis Sativa.
Febs Letters | May 2007Abstract: “Cannabidiolic-acid (CBDA) synthase is the enzyme that catalyzes oxidative cyclization of cannabigerolic-acid into CBDA, the dominant cannabinoid constituent of the fiber-type Cannabis sativa. We cloned a novel cDNA encoding CBDA synthase by reverse transcription and polymerase chain reactions with degenerate and gene-specific primers. Biochemical characterization of the recombinant enzyme demonstrated that CBDA synthase is a covalently flavinylated oxidase. The structural and functional properties of CBDA synthase are quite similar to those of tetrahydrocannabinolic-acid (THCA) synthase, which is responsible for the biosynthesis of THCA, the major cannabinoid in drug-type Cannabis plants.” — Study
Cannabis 25 (1), Biotransformation of Cannabidiol and Cannabidiolic Acid
Plant Cell Reports | August 1996Abstract: “Two marihuana constituents, cannabidiol (1) and cannabidiolic acid (4) were each converted mainly to two metabolites using tissue segments of Pinellia ternata tuber. The structures of the metabolites formed from 1 were determined to be 1-Oβ-D-glucopyranoside and 1-Oβ-D-diglucopyranoside by (1)H nmr, (13)C nmr and fabms. Those from 4 were determined as 4-Oβ-D-glucopyranoside and 10′-hydroxyl 4-Oβ-D-glucopyranoside. In time course experiments, 1 was absorbed rapidly by the tissues and glucosylated. Hydroxylation subsequent to the glucosylation occurred at the pentyl group in 4.” — Study
Purification and Characterization of Cannabidiolic-Acid Synthase from Cannabis Sativa L.. Biochemical Analysis of a Novel Enzyme That Catalyzes the Oxidocyclization of Cannabigerolic acid to Cannabidiolic acid.
The Journal of Biological Chemistry | July 1996Abstract: “We identified a unique enzyme that catalyzes the oxidocyclization of cannabigerolic acid to cannabidiolic acid (CBDA) in Cannabis sativa L. (CBDA strain). The enzyme, named CBDA synthase, was purified to apparent homogeneity by a four-step procedure. These results indicate that CBDA synthase is neither an oxygenase nor a peroxidase and that the enzymatic cyclization does not proceed via oxygenated intermediates. CBDA synthase catalyzes the formation of CBDA from cannabinerolic acid as well as cannabigerolic acid, although the kcat for the former (0.03 s−1) is lower than that for the latter (0.19 s−1). Therefore, we conclude that CBDA is predominantly biosynthesized from cannabigerolic acid rather than cannabinerolic acid.” — Study
Cannabinoid Acids Analysis.
PubMed | March 1992Abstract: “The Cannabinoid pattern of vegetable preparations from Cannabis sativa (hashish, marijuana) allows to recognize the phenotype of the plants, to be used as drug or for fiber. Cannabinoid determination by analytical point of view has represented some problems caused by the complex composition of the hexane extract…The identification of the compounds shows their nature of cannabinoid acids, which the main by quantitative point of view results the cannabidiolic acid (CBDA). It is known that the cannabinoid acids are thermally unstable and are transformed in the corresponding cannabinoids by decarboxylation. This is of interest in forensic analysis with the aim to establish the total amount of THC in the Cannabis preparations, as the active component.” — Study
Determination of Cannabinoid Acids by High-Performance Liquid Chromatography of Their Neutral Derivatives Formed by Thermal Decarboxylation: I. Study of the Decarboxylation Process in Open Reactors
Journal of Chromatography A | November 1990Abstract: “Decarboxylation of cannabidiolic and tetrahydrocannabinolic acids was studied in open reactors in order to investigate the accuracy and reliability of the decarboxylation sample preparation process applied prior to indirect methods, which has been widely used for the determination of cannabinoid acids. The rate of the decarboxylation reaction was followed by the high-performance liquid chromatographic determination of the neutral cannabinoids formed. The effects of different parameters (temperature, solvents, sorbent phases, salts) on decarboxylation were investigated. Reliable results could only be obtained by the mathematical correction of data obtained from experiments in an open reactor.” — Study
Cannabis Research Library
Over 1000 studies covering over 130 topics compiled for easy browsing.
