Abstract:Phytocannabinoid Cannabidiol (CBD) has been shown to elicit a great many immunological benefits. It acts on the endocannabinoid system, namely through interactions with cannabinoid receptor 2 (CB2). CBD-CB2 affinity, which we refer to as bioactivity, is rarely tested for clinical samples. We believe that uncontrolled variation in bioactivity levels have been silently confounding many CBD experiments. In our four-part study, we validate an efficient bioactivity test that can enable greater scientific control over CBD studies. We use it to compare the bioactivity of CBD obtained from different plant organs, and we also studied whether processing methods play a role in determining bioactivity. We also examine the bioactivity and processing factors of a novel non-cannabis plant capable of producing CBD in commercial quantities, named Humulus Kriya (H. Kriya, U.S. Patent No. 15/932,529, 2018). We also test the bioactivity of some CBD isolates/extracts currently sold in the market, and compare them with a CBD product called ImmunAG, which was extracted from the inflorescence of H. Kriya. We find that the CBD from the inflorescence of the plant produces the highest bioactivity, followed by the apical buds/leaves, the petioles, and finally the stalk. We find that H. Kriya has a bioactivity profile similar to Cannabis Sativa. We find that the bioactivity levels among cannabis-based commercial CBD products are quite low, and variable. We find significantly higher bioactivity levels in ImmunAG.
Phytocannabinoid Cannabidiol (CBD) has been shown to elicit a great many immunological benefits. It acts on the endocannabinoid system, namely through interactions with cannabinoid receptor 2 (CB2). CBD-CB2 affinity, which we refer to as bioactivity, is rarely tested for clinical samples. We believe that uncontrolled variation in bioactivity levels have been silently confounding many CBD experiments. In our four-part study, we validate an efficient bioactivity test that can enable greater scientific control over CBD studies. We use it to compare the bioactivity of CBD obtained from different plant organs, and we also studied whether processing methods play a role in determining bioactivity. We also examine the bioactivity and processing factors of a novel non-cannabis plant capable of producing CBD in commercial quantities, named Humulus Kriya (H. Kriya, U.S. Patent No. 15/932,529, 2018). We also test the bioactivity of some CBD isolates/extracts currently sold in the market, and compare them with a CBD product called ImmunAG, which was extracted from the inflorescence of H. Kriya. We find that the CBD from the inflorescence of the plant produces the highest bioactivity, followed by the apical buds/leaves, the petioles, and finally the stalk. We find that H. Kriya has a bioactivity profile similar to Cannabis Sativa. We find that the bioactivity levels among cannabis-based commercial CBD products are quite low, and variable. We find significantly higher bioactivity levels in ImmunAG. ___________________________________________________________________________________________________ In recent years, there has been a great surge in scientific research involving the Phytocannabinoid Cannabidiol (CBD) (Burstein, 2015; Zuardi, 2008). CBD appears to have an acceptable, if not favorable safety profile (Iffland, & Grotenhermen, 2017; Devinsky et al., 2016) and has been shown to be anxiolytic, antidepressant, antipsychotic, anticonvulsant, anti-nausea, antioxidant, antiinflammatory, anti-arthritic, and anti-neoplastic (Ligresti, De Petrocellis, & Di Marzo, 2016). It has shown to be protective in animal models of epilepsy, anxiety, psychosis, and basal ganglia diseases (Ligresti, De Petrocellis, & Di Marzo, 2016). Anticancer effects have also been shown (Pisanti et al., 2017). Of the receptors upon which CBD acts, cannabinoid receptor 2 (CB2) has the most ubiquitous, well-studied presence in the immune system (Malfitano, Basu, Maresz, Bifulco, & Dittel, 2014). CB2 presents in NK cells, B cells, monocytes, CD4+ cells, CD8+ cells, T cells, and neutrophils (Malfitano,
The crystal structure of cannabidiol, C21H30O2, {2-[(1R,6R)-3-methyl-6-(prop-1-en-2-yl)cyclohex-2enyl]-5-pentylbenzene-1,3-diol}, was first determined by Jones et al. (1977) and Ottersen & Rosenqvist (1977). Mechoulam (1967) identified and represented the structure as R,R by chemical means, which was a laborious and remarkable feat. We used advanced single-crystal X-ray diffractometers to study the structure of a fraction isolated from the Humulus kriya plant. The unique Cu Kf3 wavelength radiation determined that the absolute structure was R,R-the same as the Cannabidiol structure represented by Mechoulam. We found an identical crystal structure to CBD from cannabis sativa (Mayr, Grassl, Korber, Christoffel & Bodensteiner, 2017).
It is estimated that 75-78% of all modern medicines are directly or indirectly derived from higher plants. Less than 5% of all plant species have been explored for their medical potential. Natural plant compounds rarely have side effects. This makes them a potent alternative to pharmaceutical drugs for chronic use. All active ingredients from plants are biological molecules. They have a complex biochemical pathway to produce a somatic effect on the human body. In order for plant materials to rival pharmaceutical drugs, they have to undergo the same pharmaceutical factors – namely measurement of its bioactivity, knowledge of its pharmacokinetic and pharmacodynamic properties, and standardized quantities of active ingredient with the indential bioactive properties.
Valvular interstitial cells (VICs) are integral to heart valve homeostasis and structural leaflet integrity. Aberrant calcification of VICs leads to dangerous diseases including calcific aortic valve disease. VIC calcification can be reduced through modulation of the MAPK/ERK cascade by selective antagonism of the CB2 receptor. This is a well-studied target of Cannabidiol (CBD). Recently, it has become increasingly understood that not all CBD samples have the same degree of bioactive potential (bioactivity). The present study seeks to determine whether levels of CBD bioactivity have different effects on VIC calcification reduction. VICs were isolated from porcine aortic valve leaflets, induced to calcify, and treated with CBD or left untreated. CBD of varying bioactivity was clustered into 8 different levels (.20, .30, .50, .60, .70, .80, .90, and .95.) by rounding. Concentrations of 5, 10, 25, 40, and 100 mg were examined. Means, standard deviations, minimum, and maximum calcification reduction values for each combination of bioactivity and mg concentration are provided. Two 1x5 repeated measures ANOVAs on mg concentrations, holding bioactivity at .20, and at .95 , respectively, were performed. A 2x2 robust mixed ANOVA confirmed an interaction between bioactivity and mg concentration (psihat = -36.5, p < .001). Calcification was most reduced by the .95 bioactivity, 100 mg concentration treatment (M = 55%, SD = 6.66%). These results indicate that bioactivity is of central importance when considering CBD as a treatment for VIC calcification reduction. __________________________________________________________________________________________________The valves of the human heart are supple, flowregulating membranes within a complex multichambered pump (Mohler et al., 2001;Butcher, Simmons, & Warnock, 2008). Within these valves, among an extracellular matrix, exist valvular interstitial cells (VICs), which are integral to heart valve homeostasis and structural leaflet integrity (Hjortnaes et al., 2015;Taylor, Batten, Brand, Thomas, & Yacoub, 2003). Calcification of VICs causes disruption of interstitial cell mechanical phenotype, and drives disorganization of the interstitial matrix, nodule formation, and pro-calcific signaling (Farrar, Pramil, Richards, Mosher, & Butcher, 2016). This can lead to any number of dystrophic calcification diseases of the heart, which each can increase the risk for developing other cardiovascular diseases (e.g., valvular stenosis, see Michel & Dipchand, 2017;de Simone et al., 2010;Gerdts et al., 2015).Novel therapeutic targets for cardiovascular calcification reduction include cannabinoid receptor 2 (CB2; Kaschina, 2016). CB2 is present in osteoclasts, osteoblasts, and osteocytes (Ofek et al., 2006;Idris, Sophocleous, Landao-Bassonga, van't Hof, & Ralston, 2008;Idris et al., 2005). CB2 is upregulated in calcifying heart valves (Naito et al., 2010). CB2 agonists, such as anandamide, have been shown to stimulate extracellular signal-regulated kinase (ERK) activation (McAllister & Glass, ...
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