The cannabis plant is thought to have over 1000 molecules with hundreds of them having known biological activities. The most effective medical cannabis treatment options derive from the interaction between the human biological systems and the cannabis (product) chemical composition. There are many uses of each part of the cannabis plant: from roots to trichome covered flower tops; each expressing a unique subset of biologically active molecules. The overwhelming majority of legal medicinal and adult-use markets traditionally were focused on THC, and, only as of the last few years, on CBD, terpenes, and other phytocannabinoids and cannabis-based molecules.
Medicinal cannabis markets should be getting prepared to commercialize other phytocannabinoids, apart from THC and CBD. In fact, seasoned distributors and forward looking companies are already showing significant interest and see additional value in rare cannabis strains that are high in CBG (cannabigerol), CBDV (cannabidivarin), CBC (cannabichromene), THCV (tetrahydrocannabidivarin), and other minor phytocannabinoids and certain terpenes. Unlike the most prevalent phytocannabinoids THC(A) and CBD(A), these other minor phytocannabinoids are harder to harvest. Likewise, these plant-based cannabinoid isolates also come at a high premium, where minor cannabinoids can garner two or three times the price of CBD. Consumers are catching on to these new cannabinoids and are starting to recognize their distinct benefits and effects.
“…the most important thing for the medicinal effects of cannabis is knowing the active ingredients in each product and not the strain or brand names”
When speaking of the cannabis entourage effect, the starting point is to understand these most predominant plant components and not specific cannabis strain names. Cannabis contains a matrix of major and minor cannabinoids. However, often consumers and even healthcare practitioners recommend products based on strain names, brand names, concentration of just THC, or even the producers’ listed indications. However, the most important thing for the medicinal effects of cannabis is knowing the active ingredients in each product and not the strain or brand names. The main reason for this is that nature introduces variability in the chemical output of cannabis plants. Indeed, even the same genetics grown under the same conditions can produce a different matrix of cannabinoids and terpenes, and that matrix maybe even more different or reformulated in final cannabis flower-derived products, like oils, concentrates, edibles, salves, etc.
For example, look at two major phytocannabinoids THC and CBD and their interactions with respect to physiological targets in the brain and body. THC is an agonist of cannabinoid receptor 1 (CB1) (The Endocannabinoid System), which in the brain accounts for the high or euphoria-like effect. When used responsibly and purposefully, it can have many medicinal and even recreational benefits. Medicinal effects of THC are recognized by both markets - FDA approved pharmaceutical and state-regulated medical cannabis markets (Cannabinoid Medications). However, at very high concentrations or if used in its pure isolated form, it can lead to undesirable side effects in some individuals, like anxiety and panic attacks, increased chance of heart arrhythmias and attacks, and hyperemesis syndrome. Overall, accepted medicinal benefits of THC outweigh the negative side-effects mentioned here.
Compared to THC, CBD has a taming effect on THC and has the ability to reduce anxiety and panic attacks. On a physiological level, CBD is a negative allosteric modulator of CB1 receptor and can reduce its activity. In addition, CBD has higher binding affinity to serotonin receptors than to CB receptors and serotonin signaling is crucial in controlling anxiety. In this way, synergistic effects of cannabinoids can affect our bodies via the same receptor or pathway - CB1, or by engaging distinct, complementary body systems - CB and serotonin receptors. Finally, effects and interactions of major and minor cannabinoids depends on individual physiology and psyche, especially when it comes to THC.
Molecular and individual physiological effects of the entourage of chemicals also depend on the phytocannabinoid interactions with terpenes. Some of the terpenes target CB receptors and other overlapping targets of cannabinoids in the body and brain. Some molecules act synergistically, having and additive effect on a given receptor activity. But it may also act in an antagonistic, or even a negative fashion. Many future observational and clinical studies will delineate how some of the most common aromatic terpenes found in cannabis, such as limonene, pinene, or linalool, to mention a few, interact with the physiological cannabinoid targets. Based on this knowledge, cannabis companies and pharmaceutical companies can create tremendous market value and produce the most effective, individualized medical cannabis treatments.
Indeed, an individual approach to cannabis products is very important, because cannabinoids and terpenes get metabolized at different rates and each individual’s tone of the endocannabinoid system varies. In this respect, drug-to-drug interactions of the existing medications and known cannabis component activity must be carefully evaluated. Thus, healthcare practitioners are guided by this rule when recommending medical cannabis (THC) products: “Start low, go slow” (Cannabinoid Dosing). Start with low concentrations of active ingredients and observe the effect slowly, before increasing the doses. Doctors may recommend to titrate (add and raise slowly the concentration) cannabinoids into a treatment regiment and together with the patient identify the most effective formulations. Once the main cannabinoids and terpenes are identified, follow and seek out products that contain the desired entourage of the molecules, rather than their marketed strain names.
Certainly, it will take time and a concerted effort to create a user friendly cannabis-centric entourage (health and wellness) system. Until then, education on distinct cannabis components, the cannabis entourage, cannabis product compositions, and their uses will enable safe, effective, and supervised use of the panacea of medical cannabis products and, simultaneously, lead to the cannabis industry’s success.
REFERENCES:
Cho, K. S. et al. Terpenes from Forests and Human Health. Toxicol Res (2017).
Aizpurua-Olaizola, O. et al. Evolution of the Cannabinoid and Terpene Content during the Growth of Cannabis sativa Plants from Different Chemotypes. J Nat Products. (2016).
Takeda, S. et al. Cannabidiolic acid, a major cannabinoid in fiber-type cannabis, is an inhibitor of MDA-MB-231 breast cancer cell migration. Toxicol Lett (2012).
Russo, E. B. Taming THC: potential cannabis synergy and phytocannabinoid-terpenoid entourage effects. Br J Pharmacol (2011).
Haring, M. et al. Cannabinoid type-1 receptor signaling in central serotonergic neurons regulates anxiety-like behavior and sociability. Front Behav Neurosci (2015).
Acton, Q. A. Terpenes—Advances in Research and Application: 2013 Edition. (ScholarlyEditions, 2013).
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