How High? Words By Psy-23

Despite its controversial reputation, Cannabis sativa continues to develop a more positive perception through its countless uses in industry, textiles, manufacturing and, ever-more-increasingly, as a potential treatment for a wide range of maladies.

Courtesy of the now-all-but-defunct ‘War on Drugs’ , medical research into its numerous properties has been incredibly limited in much of the Western world until fairly recently but recent studies have managed to isolate a range of components in the hope of providing a more complete understanding of the plant’s innumerate complexities. Recently, our attention was drawn to a newly-published study into cannabinoids which managed to isolate and identify two new phytocannabinoids which could prove to be incredibly significant for future medical purposes.

The study focuses on the ‘extreme variability’ of cannabis strains in terms of their cannabinoid composition. Cannabinoids ‘derive from an enzymatic reactions between a resorcinol and an isoprenoid group’ which uses the ‘modularity of these two parts’ to produce almost ‘150 different cannabinoids’. A condensation reaction occurs which results in the formation of CBGA (cannbigerolic acid) and this is then converted to form either CBDA, CBCA or THCA.

Once these have formed through biosynthesis they exist in the carboxylated form, however this can be ‘converted into the corresponding decarboxylated (neutral) form using heat’. As you are most likely aware, the two primary neutral cannabinoids are Delta-9 Tetrahydrocannabinol (commonly referred to as THC) and cannabidiol (CBD).

For argument’s sake, it is easiest to consider and label these by their effects: THC is recognized for its psychoactive potential and intoxicant effects; CBD is an antioxidant, anti-convulsant and anti-inflammatory. CBD also acts as an antagonistic inhibitor of THC and counteracts or balances out many of its effects.As part of the study (and the previous research which has led up to this point) the team were aiming to explore the ‘alkyl side chain on the resorcinyl moiety [which is usually] made of five carbon atoms’.

The quantity of carbon atoms on the side chain seems to be influential in determining the resulting phytocannabinoid leading to the recognition and categorizing of ‘varinoids’ (which possess three carbon atoms) and ‘orcinoids’ (possessing only one). Currently, varinoids include CBDV and THCV (cannabidivarin and tetrahydrocannabivarin respectively) while orcinoids include CBD-C and THC-C (cannabidiorcol and tetrahydrocannabiorcal). The study explains that ‘both [of these] series [of cannabinoids] are biosynthesized in the plant as the specific ketide synthases have been identified’. In essence this means that both varinoids and orcinoids are naturally-occurring phytocannabinoids.

Additional studies ‘reported the presence of [two] butyl phytocannabinoid with a four-term alkyl chain’ which have been labeled as CBDB and THC-B (cannabidibutol and tetrahydrocannabutol, however neither of these presented significant evidence of plant enzymes which would be ‘responsible for the biosynthesis of these butyl phytocannabinoids’.

Although the exact reason has not been identified, suggestions indicated that this could be due to the influence of external factors such as ‘microbial oxidation or decarboxylation of their corresponding homologs’ i.e. an external factor acted as a catalystThroughout this study, the team began to contemplate and hypothesize the impact of synthesizing alkyll side-chains which were longer in length than would occur naturally.

This aimed to replicate the influence of external factors but also allowed the team to test the capacity of the plant by lab-engineering homologs with more than five carbon atoms on the side chain. In their own words, ‘to the best of [their] knowledge, a phytocannabinoid with a linear alkyll side chain containing more than five carbon atoms has never been reported as naturally occurring’.

As part of this research, the team were able to synthesize ‘seven-term homologs of CBD and ∆9-THC in a medical cannabis variety, the Italian FM2, provided by the Military Chemical Pharmaceutical Institute in Florence.[…] According to the International Non-proprietary Name (INN), [they] suggested for these CBD and THC analogues the name “cannabidiphorol” (CBDP) and “tetrahydrocannabiphoral” (THCP), respectively.

The suffix “-phorol” comes from “sphaerophorol” common name for 5-heptyl-benzen-1,3-diol, which constitutes the resorcinyl moiety of these two new phytocannabinoids.’In order to test the strength and varied effects of these two new phytocannabinoids, a number of different conditions were administered and monitored.

This tetrad of testing sought to investigate the impact of THCP on hypomotility (open field test – to see how much distance is covered in a given period of time), hypothermia (body temperature changes), antinociceptive (hot plate test – to assess nerve response to external heat changes) and cataleptic (bar test – recording length of time spent on a gradually heating bar before subjects stepped down) effects. An abridged overview of the results is given below.This ‘tetrad includes the assessment of spontaneous activity, immobility index (catalepsy), analgesia and changes in rectal temperature.

Decrease of locomotor activity, catalepsy, analgesia and hypothermia are well-known signs of physiological manifestations of cannabinoid activity. After intraperitoneal (i.p.) administrations, ∆9-THCP at 2.5mg/kg markedly reduced the spontaneous activity of mice in the open field, while at 5mg/kg it induced catalepsy on the ring with the immobility as compared to the vehicle treated mice.

In the hot plate test, [it] induced antinociceptive effect at 10 and 5 mg/kg.’Currently, most of the major studies into cannabis as a potential medicine have focused their efforts on THC but these studies indicate that ‘THCP is endowed of an even higher binding affinity for CB1 receptor and a greater cannabimimetic activity than THC itself’ and the results have been verified through a series of lab tests including in vitro studies and in ‘tetrad behavioral tests in mice’ as outlined above. To be frank, the results are staggering.

THCP was proven to be 33 times more active than THC against the CB1 receptor and almost 10 times more active against the CB2 receptor. Now, I’m not a research scientist but this is undoubtedly impressive. One would assume that the potential for THCP and CBDP to be used in the treatment of a multitude of conditions is fantastically vast (assuming that the resulting phytocannabinoids are stable and tested to be proven safe).

In essence, and if I have fully understood what these results indicate, this study presents us with the idea that there is the potential to develop the potency of phytocannabinoids through synthesis and synthetic adaptation. The research team also believe that there is a distinct possibility of further forms of THCP and CBDP to be found in a range of strains which could potentially be even stronger than those established here.

Whilst the work on developing synthetic cannabinoids is something which is not to everyone’s preference, the impact of studies like this on furthering our understanding of how cannabinoids are formed and developed could prove invaluable.Note: all information for this article was taken directly from the published source material as listed in the references below. Any misinterpreted data or incorrect statement of facts is unintentional.

Source: A novel phytocannabinoid isolated from Cannabis sativa L. with an in vivo cannabimimetic activity higher than Δ9-tetrahydrocannabinol: Δ9-Tetrahydrocannabiphorol – https://www.nature.com/articles/s41598-019-56785-1

Published and Written By Psy-23 In Weed World Magazine Issue 145

The post How High? Words By Psy-23 appeared first on Weed World Magazine.

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