Phytocannabinoids: An Introductory Guide

Phytocannabinoids

What’s the Difference Between Phytocannabinoids and Cannabinoids?

It might interest you to know that there’s actually a minimal difference between phytocannabinoids and cannabinoids. The difference is just a matter of specificity. Phytocannabinoids refer to any cannabinoid that is naturally occurring within the cannabis family of plants. Such cannabinoids include the more famous THC and CBD, but they also include other cannabinoids such as cannabigerol (CBG), which we will discuss. There are over 70 phytocannabinoids discovered and studied within the cannabis plant.

These phytocannabinoids can be considered as a contrast to endogenous cannabinoids, which are the lipids and ligands that your body makes on its own through the endocannabinoid system (ECS) without any interference or ingestion of the cannabis plant. Phytocannabinoids each have different ways of interacting with the ECS.  For this article, we will be looking at Cannabigerol (CBG), Cannabichromene (CBC), Cannabidiol (CBD), Tetrahydrocannabinols (THC), Cannabinol (CBN), and Cannabitriol (CBT), but bear in mind that this is not the all-inclusive list. Research is still underway about further details regarding many phytocannabinoids.

Cannabigerol (CBG)

Short History

This cannabinoid was discovered in 1964 by Gaoni and Mechoulam. Mechoulam is also credited as the first to elucidate the correct structure of CBD in 1963, according to “Chemistry and Analysis of Phytocannabinoids and Other Cannabis Constituents” by Rudolf Brenneisen. It was found that CBG, unlike THC, does not induce psychotropic effects.

Interaction with Receptors

In a study published in the British Journal of Pharmacology, scientists found that cannabigerol is a potent stimulator of [35S]GTP?S binding to brain membranes. The cannabinoid was also tested on isolated vas deferens in mice. (For anyone who may not have been paying attention in biology class when they talked about sex–why weren’t you paying attention to that?–the vas deferens is the duct that conveys sperm from the testicle to the urethra). Cannabigerol was found to inhibit electrically evoked contractions of the vas deferens. Since these contractions are “thought to result from the release of ATP and noradrenaline on to postjunctional P2 receptors and ?1-adrenoceptors,” that was thought to be cannabigerol’s mode of function and rather than the CB1 receptors.

Cannabigerol also behaves as a ?2-adrenoceptor agonist in mouse brain membranes.  ?2-adrenoceptor agonists are kind of a big deal. But according to the British Medical Bulletin, there is evidence that ?2-adrenoceptor agonists can have neuroprotective function. The agonists were found to attenuate neurological deficiencies in rat models that had incomplete cerebral ischaemia. This is a condition in which there is insufficient blood flow to the brain to meet metabolic demand, leading to poor oxygen supply or cerebral hypoxia and, thus, to the death of brain tissue. “Subsequent studies evaluating the possible neuroprotective value of ?2-adrenoceptor agonists have used Dex (dexmedetomidine) because of its potency and high selectivity for the ?2-adrenoceptor.”

As it pertains to CB receptors, cannabigerol has a higher affinity for CB1 than it does for CB2. But binding to CB1 receptors was only detectable at concentrations above those at which it stimulates [35S]GTP?S binding to the brain membranes. It is classified as a CB1 antagonist, not an agonist.  

Roles

According to Medical Jane, an LLC formed in June of 2012 and coined as the “WebMD® of Cannabis,” cannabigerol is a minor cannabinoid with major impact. Part of the reason for this is because cannabigerolic acid is also the main precursor for other major cannabinoid acidic precursors, THCA, CBDA (cannabidiolic acid), and CBCA. These are then metabolized by synthases that can make THC, CBD, or CBC. This can also be referred to as the degradation of CBGA. Cannabigerol is thought of as the cannabis “stem cell” because of this role it plays in producing the other cannabinoids.  

Cannabichromene (CBC)

Short History

Cannabichromene has not been studied as extensively as some of its cannabinoid brothers and sisters. But according to Alternet.org, cannabichromene was discovered in 1966, not long after the studies on cannabigerol and cannabidiol.

Interaction with Receptors

More work needs to be done on the scientific understanding of CBC’s reaction with receptors. There are a few things we can grasp from the limited information, however. For one, according to a study published in the Journal of Analytical Toxicology in September of 2011, CBC has a low affinity for the CB1 receptor. This was discovered because it was tested in conjunction with a receptor antagonist rimonabant, which was known to block the effects of THC and other cannabinoids. But it did not manage to do so with CBC. With that said, CBC has a non-CB1 receptor method of action.

In another study published in the British Journal of Pharmacology, inflammation was induced in the small intestines of mice using croton oil. To quote, “Croton oil administration was associated with decreased levels of anandamide (but not 2-arachidonoyl glycerol) and palmitoylethanolamide, up-regulation of TRPA1 and CB? receptors and down-regulation of CB? receptors.” CBC outside of the organism (tested on organs or tissue separated from the organism) did not change endocannabinoid levels. It did, however, alter the mRNA expression of TRPA1 and cannabinoid receptors. In the organism, CBC did not affect motility (a term used to describe the contraction of the muscles that mix and propel contents in the gastrointestinal tract) but normalized croton oil-induced hypermotility. The results of the study are quoted as follows: “CBC selectively reduces inflammation-induced hypermotility in vivo in a manner that is not dependent on cannabinoid receptors or TRPA1.” In other words, CBC does not really do its main work via cannabinoid receptors, as the first study pointed out.

A third study examining the effect of cannabichromene on adult neural stem/progenitor cells suggests that CBC raises the viability (self-maintenance or ability to recover) of neural stem progenitor cells (NSPCs) while inhibiting their differentiation into astroglia, possibly through up-regulation of ATP and adenosine signaling. Either way, this is kind of a big deal. You’re probably not sure or familiar with what NSCPs are, but to frame their impact in an easy-to-understand way, just think of them as stem cells for your nervous system. They hold the capacity to proliferate, self-renew, and produce things that can turn into neurons, astrocytes, and oligodendrocytes.

Roles

Cannabichromene is believed to work in tandem with THC, moderating or attenuating its effects. But on its own, it is not psychoactive. Working with THC, it seems to yield relaxing effects. A plant with high cannabichromene is also likely to have higher THC content.  However, more work needs to be done to fully understand cannabichromene’s role.

Cannabinol (CBN)

Short History

The discovery of cannabinol actually has an interesting tie-in with archaeology and industrial history. Industrial hemp can be harvested for fiber purposes, as it was for at least an area in the French Massif Central, where CBN was discovered in the sediment, according to a news report by Science 2.0. It was discovered in a sediment record from the lake, suggesting that retting took place in the area. Retting is a process used when making hemp into textiles or other high-quality applications. The bast fibers must be separated from the rest of the stalk.  It is a microbial process that breaks the chemical bonds holding these bast fibers to the woody core, effectively separating the two. You can do retting in two ways: field retting and water retting. Water retting is far more laborious and time-consuming, but it involves leaving stems immersed in water and checking them regularly. It uses a lot of water that must be clean and then treated before being discharged. This process is not really used anymore in countries that can’t afford the cost or have environmental regulations against it.

CBN was first named in 1896 by Wood et al., and its structure was elucidated in 1940. In other words, people knew about it for a good long while before moving on to other phytocannabinoids.

Interaction with Receptors

A 2012 study published in Psychopharmacology (Berl) has shown that CBN can induce effects via the CB1 receptor. The focus of the study was to examine other cannabinoids as they pertain to appetite regulation, since THC is well documented in that area and already has legalized pharmaceutical versions to help with appetite. CBN currently is not thought to be psychotropic, so the drive to eliminate such a side effect is in demand. But reports on its psychoactivity are mixed; what is agreed upon is that its psychoactivity is so small compared to that of THC that it’s negligible. The study also showed that CBN was effective in increasing appetite.

As for psychotropic effects, this study published in the Journal of Pharmacology supports some of the prior claims. Participants were given differing serving sizes of CBN alone, THC alone, and two different combinations of CBN with THC. CBN seemed to mitigate or do away with any heart rate increase normally caused by THC. The participants seemed to be a bit unable to accurately assess the passage of one minute when any THC had been involved while CBN produced no effect on their assessment of time. The combination of drugs, however, seemed to make the participants “feel” drugged, sleepy, or groggy more than they did with THC alone.

This third study published in the Journal of Neuroscience showed that both THC and CBN (cannabinol) “induce a CB(1)/CB(2) cannabinoid receptor-independent release of calcitonin gene-related peptide from capsaicin-sensitive perivascular sensory nerves.” With this said, there are certainly both CB1 and CB1 receptor reactions at play.

Roles and Synthesis/Degradation

According to Medical Jane, cannabinol is itself a degraded compound. The chemical synthesis starts with cannabigerolic acid, which is turned into THCA by THC synthase, which is then turned into cannabinolic acid via air and time and then, finally, into CBN given heat and ultraviolet light. For this reason, cannabinol has a role in telling you the age of your cannabis (if the cannabis hasn’t been preserved).       

Cannabitriol (CBT)

Short History

Strangely, though this phytocannabinoid isn’t really new, it would appear a Jamaican scientist by the name of Hawthorne Watson is attempting to take credit for its discovery when you Google its history – even though cannabitriol was first isolated by Obata and Ishikawa in 1966 according to a mini-review by Mahmoud A. ElSohly and Desmond Slade, “Chemical constituents of marijuana: The complex mixture of natural cannabinoids.” The mini-review even expands to say that nine types of cannabitriol are known. Unfortunately, this is all that seems to be solid about cannabitriol. The literature on cannabitriol is limited to just its structure and its discovery. It is definitely an area of research that needs more investigation. It appears that the other phytocannabinoids, including CBD and THC mostly, have stolen this phytocannabinoid’s thunder.

Cannabidiol (CBD) and Tetrahydrocannabinols (THC)

Luckily, these two phytocannabinoids are ones that we have spent more time talking about in depth on our website. For information about how both have their effects on receptors, this article about CB receptors tells you what you need to know. To get a better grasp on CBD’s history as a phytocannabinoid, our article about synthetic CBD covers that information as well.

In Conclusion

  • Phytocannabinoids are an ongoing area of research.
  • It is important to understand that some of them are integral to the existence of other phytocannabinoids. Cannabigerol, for example, is the cannabinoid that turns into other cannabinoids given certain synthases and exposure to heat.
  • CBD and THC are the most researched phytocannabinoids.
  • Not all cannabinoids have their mode of operation through the CB receptors but, rather, through other receptors in the body, making cannabis a true pharmacological wonder.

Please don’t hesitate to contact us with any questions. We can tell you more about the phytocannabinoids in relation to our products. Specifically, though, all our products are made to be CBD-rich from industrial hemp sources. Feel free to let us know which phytocannabinoid is the most fascinating to you in the comments below.