Pharmacological Foundations of Cannabis Chemovars

Abstract

An advanced Mendelian Cannabis breeding program has been developed utilizing chemical markers to maximize the yield of phytocannabinoids and terpenoids with the aim to improve therapeutic efficacy and safety. Cannabis is often divided into several categories based on cannabinoid content. Type I, -tetrahydrocannabinol-predominant, is the prevalent offering in both medical and recreational marketplaces. In recent years, the therapeutic benefits of cannabidiol have been better recognized, leading to the promotion of additional chemovars: Type II, Cannabis that contains both-tetrahydrocannabinol and cannabidiol, and cannabidiol-predominant Type III Cannabis. While high--tetrahydrocannabinol and high-myrcene chemovars dominate markets, these may not be optimal for patients who require distinct chemical profiles to achieve symptomatic relief. Type II Cannabis chemovars that display cannabidiol- and terpenoid-rich profiles have the potential to improve both efficacy and minimize adverse events associated with -tetrahydrocannabinol exposure. Cannabis samples were analyzed for cannabinoid and terpenoid content, and analytical results are presented via PhytoFacts, a patent-pending method of graphically displaying phytocannabinoid and terpenoid content, as well as scent, taste, and subjective therapeutic effect data. Examples from the breeding program are highlighted and include Type I, II, and III Cannabis chemovars, those highly potent in terpenoids in general, or single components, for example, limonene, pinene, terpinolene, and linalool. Additionally, it is demonstrated how Type I - III chemovars have been developed with conserved terpenoid proportions. Specific chemovars may produce enhanced analgesia, anti-inflammatory, anticonvulsant, antidepressant, and anti-anxiety effects, while simultaneously reducing sequelae of-tetrahydrocannabinol such as panic, toxic psychosis, and short-term memory impairment.

Chemical Characterization of Leaves, Male and Female Flowers from Spontaneous Cannabis (Cannabis sativa L.) Growing in Hungary

“…A recent work described the chemical profiling of medical cannabis extracts but with focus on cannabinoid derivatives. [21] Another recent work reported the biorefining of C. sativa var. spontanea residues to extract cannabinoids by supercritical carbon dioxide showing the presence of several flavonol glycosides that were analyzed by HR-MS but without structure elucidation.…”

Absence of entourage: Terpenoids commonly found in Cannabis sativa do not modulate the functional activity of Δ9-THC at human CB1and CB2 receptors

“…Scientific evidence for cannabinoid-terpenoid interactions is essentially absent and mostly comes from websites and dispensaries extolling the virtues of proprietary Cannabis chemical varieties, or chemovars. 12,13 However, some terpenoids do have intrinsic psychoactive and physiological effects, and modulatory effects on ∆ 9 -THC actions is not farfetched. 1,14 For example, in studies with laboratory animals, limonene displayed anxiolytic effects, pinene increased gastrointestinal motility, linalool was sedative, anticonvulsant and anxiolytic, while myrcene produced sedation, analgesia and muscle relaxant effects (summarised in Russo and Marcu 14 ).…”

“…However, compelling evidence for cannabinoid-terpenoid interactions or synergy does not yet exist, and it is also worth noting the relatively low concentrations of terpenoids present in herbal cannabis. 5,13,15,16 With so many bioactive components present in cannabis, the systematic, granular elucidation of possible entourage effects poses a substantial combinatorial puzzle and scientific challenge. As a preliminary approach to addressing this challenge, the present study examined whether the effects of ∆ 9 -THC on its cognate cannabinoid receptors (CB 1 and CB 2 ) would be modified in the presence of terpenoids that are commonly found in cannabis, either alone or in combination.…”

Vaporized cannabis extracts have reinforcing properties and support conditioned drug-seeking behavior in rats

“…Over 120 unique phytocannabinoid compounds are present in Cannabis sativa in addition to THC. These phytocannabinoids have distinct pharmacological and behavioral profiles [3], and interactions between phytocannabinoids give rise to the psychotropic or physiological effects of cannabis chemovars [4][5][6]. For example, CBD acts as a CB1R negative allosteric modulator and inhibits THC-dependent intracellular signaling and beta-arrestin-2-mediated CB1R internalization [7,8].…”