Science
The Cannabis plant’s use as a medicine dates back nearly 9,000 years. The active ingredients in the cannabis plant are known collectively as cannabinoids.
The most prominent cannabinoid is tetrahydrocannabinol or THC, which is found in the marijuana variety of cannabis and is the cannabinoid that is responsible for the “high” one gets when one smokes cannabis flower. The other prominent cannabinoid is cannabidiol , which is found in the hemp variety of cannabis and is the cannabinoid that has been discovered to have many popular benefits. The cannabinoid complex is a prolific profile that also contains cannabidiolic acid (CBDa), tetrahydrocannabinolic acid (THCa), cannabigerol (CBG), cannabigerolic acid (CBGa) and cannabinol (CBN).
The cannabinoids’ importance in maintaining human health is related to the cannabinoid system in our bodies, which include the body’s own naturally produced endocannabinoids and their receptors upon which endocannabinoids bind. Endocannabinoids, and, for that matter, all naturally produced molecules, were designed by nature over millions of years (i.e. evolution) to benefit the organism’s ability to survive. These naturally evolved molecules express their healthful benefits inside the organism’s body through a myriad of biochemical processes, such as binding and interacting with their corresponding naturally designed receptors. This evolutionary process starts from the simplest organism and continues to the most complex.3 Indeed, receptors of vertebrates (e.g. humans) and their receptor binders (also known as ligands) likely evolved from the corresponding receptors and ligands in microbes (e.g. antibiotics) and plants (e.g. cannabinoids). The evolutionary pressure placed on plants to produce natural products, such as cannabinoids, could very well have come from the vertebrates and the plants interacting with each other and sharing the benefits of co-evolution over millions of years.
Cannabinoids participate in keeping all of the functions in the body in a normal operating mode even though the body is exposed to all kinds of attacks from the environment such as from the toxins we breathe and the toxins we eat. This maintenance of normal body function is known as homeostasis. Homeostasis also comes from endocannabinoids and cannabinoids acting at the intersection of the body’s various systems, allowing communication and coordination between the different parts of the body from the organs all the way down to the cells. The endocannabinoid system, with its complex actions in our immune system, nervous system, and all of the body’s organs, is literally a bridge between body and mind.
It is intriguing to think that the intersection of plant and animal during the evolutionary process of both plant and animal manifest this beautifully designed symbiosis. ChyloCure is participating in the further enhancement of cannabis’ revolutionary benefits by applying science to this evolutionary remedy.
Cannabidiolic Acid Value
The health benefits of cannabinoids have been known and practiced for centuries. More than 26,000 studies and reviews referencing cannabis plants and cannabinoid molecules have been published in the recent past.
This renewed interest in cannabinoid benefits can be principally attributed to the recent discovery of the endocannabinoid receptors throughout the central nervous system 4 More specifically, many of the benefits attributed to cannabinoids stem from the effects of cannabidiol, the decarboxylated congener of cannabidiolic acid on other key receptors. While its mechanisms of action remain under study, it is proposed that the decarboxylated form interacts with multiple central nervous system receptors, ion channels and neurotransmitters. Additionally, its effects on adenosine reuptake, and the GPR-55 and TRPV1 receptors are thought to contribute to its antiepileptic properties in mice. When tested at the National Institute of Neurological Disorders and Stroke (NINDS) drug testing laboratory, Cannabidiol showed an ED50 for the MBS model of epilepsy of 85 mg/kg in mice and 89 mg/kg in rats. Cannabidiol was also active in the Metrazol model, the cardiogenic model, and other chemo-convulsant models at doses between 80 and 200 mg/kg.
As touched upon, recent identification of an integrated endocannabinoid regulatory system has helped us recognize and understand many of the health benefits of cannabinoids. This is explained, in part, by the cannabinoid molecules’ variable affinity for cannabinoid receptors expressed throughout the human body (although recently discovered, cannabinoid receptors are even expressed in very rudimentary species of animals). More recently, it has been discovered that other receptors and enzymes, such as PPARγ, 5HT1A, GPCR, and COX-2, are likewise fundamental to cannabinoids’ diverse effects and mechanisms of action. Moreover, all cannabinoid acids, namely cannabidiolic acid, THCa and CBGa, outperform their corresponding neutral cannabinoids in terms of PPARγ binding. This is particularly true for THCa, which has shown potent neuroprotective activity, possibly through down regulation of expression of inflammatory genes. Thus, THCa has been proposed to treat progressive neurodegenerative disorders such as Huntington’s disease and other neuroinflammatory conditions5 Additionally, THCa has been shown in animal studies to limit the spread of prostate cancer cells.
Cannabidiolic acid, the predominant cannabinoid in many cannabis strains, demonstrates the importance of the interplay between cannabinoids and cannabinoid receptors. Much of the work demonstrating Cannabidiolic acid’s analgesic effect was conducted by Linda Parker and her associates who noted that THC’s anti-hyperalgesia was blocked by CB1 receptor antagonists, whereas cannabidiolic acid’s analogous effects were blocked by TRPV1 antagonists.6 This apparent selectivity of raw hemp extract at these transfer receptor sites is supported by Izzo7 wherein it was shown that cannabidiolic acid was an agonist for TRPA1 (nociception attenuation), TRPV1’ (cancer cell apoptosis inducer) and TRPM8.
Bolognini8 reported that cannabidiolic acid suppressed experimentally induced nausea in rats in a 5HT1A receptor-mediated manner. It was further reported that “compared with cannabidiol, cannabidiolic acid may display greater potency, efficacy and selectivity at ameliorating signs of cerebral infarction, anxiety and depression via 5HT1A receptor-dependent mechanisms in animal models.”
Considerable research on cannabidiolic acid’s interaction with COX-2 receptors has been conducted by Kazuhito Watanabe and associates at Hokuriku University. Specifically, in 2008 these researchers reported that cannabidiolic acid (~2 micromolar concentration) inhibited COX-2. It was further noted that full inhibition of the COX-2 receptor required the carboxylic acid moiety, thus cannabidiol is not nearly as active.9 Moreover, cannabidiolic acid is selective for COX-2 and does not inhibit COX-1, which is beneficial since inhibition of COX-1 may lead to unwanted side effects such as GI ulceration/bleeding and platelet dysfunction. Thus, the advantages of cannabidiolic acid’s selective inhibition of COX-2 may be quite substantial. Cannabidiolic acid’s dual inhibitory effects of COX-2 may also suppress genes associated with cancer metastasis.10 It was further determined that this COX-2 inhibition involves the down regulation of specific proto-oncogenes that promote the progression of some cancers11 Recently it has also been shown that cannabidiolic acid has the unique ability to inhibit migration of highly invasive MDA-MB-231 human breast cancer cells.12
