Hemp oil also contains small amounts of other cannabinoids, for example: CBC, CBG or CBN.
INGREDIENTS: Cannabis Sativa Seed Oil, Cannabis Sativa Leaf / Stem Extract (6% CBD + CBDA)
NATURAL PRODUCT. SUITABLE FOR VEGANS.
The presence of the carboxylic function was highlighted in the 13 C-NMR experiment, which showed the relative carbon resonating at δC 177.2. The 13 C-NMR data were in accordance with an aromatic nucleus, binding the CBDA monoterpene core, stabilized by the formation of a stable intramolecular hydrogen bond, which massively influenced the C-1’ resonance, bringing it to δC 116.0.
The potential CBDA anti-inflammatory activity continues to be the main focus for deepened investigations. In this context, studies based on systemic or oral administration before and/or after the inflammatory and irritating carrageenan were carried out . In particular, it was evidenced that CBDA at 10 μg/kg exerted an anti-inflammatory action when administered intraperitoneally 60 min prior to carrageenan, whereas in rodents pre-treated with 100 μg/kg, delivered by oral gavage, carrageenan-induced hyperalgesia favorably decreased . CBDA, intraperitoneally administered at 0.1 μg·kg −1 dose, also showed anxiolytic-like effects under conditions of high stress . The brain and plasma pharmacokinetic profile of CBDA, as well as of other acidic cannabinoids, has been recently defined; the rapid absorption at plasma level and the extremely low brain/plasma ratio were positively modulated when CBDA was administered in an alternate Tween 80-based vehicle. The anticonvulsant in a mouse model of Dravet syndrome is also reported . PPARγ, a nuclear receptor expressed in several tissues and cell types, involved in inflammation and neurodegeneration, was found to be activated in 293T cells transfected with a pair of GAL4-PPARγ/GAL4-luc plasmids by CBDA in a more efficacious way in respect to CBD at high concentrations .
1 H-NMR and 13 C-NMR spectra were acquired and compared with literature data .
5. CBDA Isolation and Chemical Characterization from Hemp Pollen: Our New Goal
The renewal of interest in industrial hemp (Cannabis sativa L.) launched new scientific research goals worldwide for its therapeutic, nutraceutical, and food applications [1,2,3]. Over time, hemp is reacquiring its role as green and sustainable crop, able to be a good alternative and ingredients resource for health foods, organic body care, biomaterials, and more . Indeed, the hemp growing industrial market cannot disregard its diversity in chemical compounds, among which phytocannabinoids are the most described. These secondary metabolites phytochemically praise the uniqueness of Cannabis species, but also, in a puzzling scenario, dictated the denial of the plant use for almost 40 years of our history. The psychoactive/psychotropic Δ 9 -tetrahydrocannabinol (Δ 9 -THC or simply THC) was widely condemned as the guilty substance; nowadays, it is recognized as CB1 and CB2 partial agonist, whereas another abundant cannabinoid, namely cannabidiol (CBD), is identified as an “entourage compound”, able to modulate THC effects . Indeed, Cannabis plant produces cannabinoids as prenylated aromatic carboxylic acids, which are converted in their more discussed neutral forms thanks to light, heat, or prolonged storage. In particular, on the basis of the concentrations of the main acidic cannabinoids, five Cannabis chemotypes occur. Chemotype I consist in drug-type plants for which the tetrahydrocannabinolic acid (THCA)/ cannabidiolic acid (CBDA) ratio is >>1.0, chemotype III describes plants whose aerial parts contain a THCA/CBDA ratio <<1.0, whereas an intermediate ratio corresponds to chemotype II. The high content of cannabigerolic acid (CBGA) is related to chemotype IV, and finally, chemotype V designates all the fiber-plants that completely lack cannabinoids .
Cannabidiolic acid (CBDA) is the main phytocannabinoid in fiber and seed-oil hemp (Cannabis sativa L.) plants, but its potential health-related capabilities have been masked for years by a greater scientific interest towards its neutral derivative cannabidiol (CBD). This review aims to collect from the literature and critically discuss all the information about this molecule, starting from its biosynthesis, and focusing on its bioactivity, as an anti-inflammatory, anti-emetic, anti-convulsant, and anti-cancerogenic drug. Furthermore, in the awareness that, despite its multiple bioactive effects, currently poor efforts have been made to achieve its reliable purification, herein, we propose a relatively simple, fast, and inexpensive procedure for its recovery from pollen of industrial hemp cultivars. Spectroscopic and spectrometric techniques allowed us to unequivocally identify pure isolated CBDA and to distinguish it from the constitutional isomer tetrahydrocannabinolic acid (THCA-A).
Number of papers dealing with the concept “CBD” or “CBDA” published in year range 1960–2020 (source: PubMed database, 18 April 2020). Data are plotted also through a radial chart that enhances, at one glance, the different interest in the two highly related compounds.
2. CBDA and Its Biosynthesis
In recent years, Italy, as other European countries, was hit by the industrial hemp revolution. The food sector, more than others, has acquired the benefits of hemp cultivation, launching on the market products mostly deriving from the processing of hemp seed. Concurrently, the fear of the presence of possible contamination of edible products with cannabinoids, instead present in other parts of the plant, has given way to a whole series of analyses, also through the use of the most advanced techniques, to define the presence, the relative abundance, and the origin (e.g., leaf, florescence) of these substances during the processing [53,54,55]. Indeed, hemp seed oil contains, among its constituents, acidic cannabinoids, some of them highly oxygenated. Cannabidiolic acid is the most representative cannabinoid compound in hemp seed oil, and the CBDA/CBD ratio was proposed as a marker of storage conditions and production process . Furthermore, the CBDA content could be particularly elevated in waste materials, as trimming materials or hemp pollen. Thus, based also on recent interest in the CBDA’s bioactivities, studies aimed at its isolation and purification have been carried out in order to obtain its high qualitative and quantitative “recovery”. This need has prompted us to use multiple, combined, and alternative techniques that “simplify” the chemical composition of two different hemp-derived products, such as hemp seed oil and hemp pollen. Even in this case, there are few studies in the literature concerning the CBDA purification, where great attention is paid to the neutral analogue. It is noteworthy that identification studies in which liquid chromatography techniques coupled with DAD or MS detection are the masters [56,57], while there have been few real attempts to achieve the molecule’s purification.
Recent in silico study was carried out to investigate drug-like properties of CBDA and other phytocannabinoids . Molecular properties, such as number of hydrogen bond acceptor (HBA) and hydrogen bond donor (HBD), partition coefficient (cLogP), polar surface area (PSA), and the number of rotatable bonds (NROTB), were calculated using Molinspiration Cheminformatics software ( Table 1 ). CBDA molecular structure, obtained in the form of Simplified Molecular-Input Line-Entry System (SMILE), was imported using PubChem Compound. CBDA’s topological PSA (TPSA) was in line with an absorptivity of more than 90%. Furthermore, when drug likeness score for G protein-coupled receptors (GPCRs) ligands, ion channel modulators, kinase inhibitors, nuclear receptor ligands, and protease inhibitors were predicted, it was observed that CBDA is moderately active in all bioactive scores . Unfortunately, the more recent drug discovery approach for in silico pharmacokinetic profile did not consider CBDA among the compounds investigated to get structural insights into the selection of cannabinoid scaffolds for the development of antitumor drugs .