THE ENDOGENOUS CANNABINOID SYSTEM (ECS): What’s All the Fuss About?
In 1998, cannabis science pioneer, Dr. Raphael (Ralph) Mechoulam and his team first introduced the idea of the entourage effect. Their research validated the hypothesis that different cannabinoids work synergistically on the endo-cannabinoid system, enhancing their activity. The term entourage effect gets thrown around a lot, but does it mean? And beyond that, what specific cannabinoids?
If you’re reading this blog, you are definitely familiar with THC. And you’ve probably heard of CBD. (When smoked on its own, CBD has been shown to have positive physiological effects on the body. These include parasympathetic nervous system activation and appetite induction. Combined with THC, it reduces the paranoia and anxiety normally associated with cannabis use.)
Perhaps even more important than Dr. Mechoulam’s contribution of the term “entourage effect,” was his discovery of the human body’s natural cannabis receptor system—the system cannabinoids like THC and CBD act upon. This physiological system is responsible for maintaining homeostasis throughout the body at a cellular level.
At the site of the trauma, you will find cannabinoids handling three specific biological mechanisms simultaneously:
• Suppressing the release of sensitizers and activators
• Stabilizing nerve cells to reduce firing
• Inhibiting the release of inflammatory agents into nearby immune cells
All three of these “tasks” handled by the ECS serve the same function: reducing pain at the site of the injury. This same biological balancing act takes place at every level of the body all the time; the ECS is always working to maintain homeostasis This has incredible implications for medicine, as cannabis continues to gain momentum as a pain-reducing medication. Cannabinoids don’t just feel good because your body likes them; they’re fundamental components of human health.
Let’s take a quick tour of some other, less talked-about cannabinoids.
TETRAHYDROCANNABINOLIC ACID (THCA) & CANNABIDIOLIC ACID (CBDA). What does the “A” mean?
Many people don’t realize that even “high THC” cultivars of the cannabis plant produce very little psychoactive delta-9-THC; the vast majority of what’s contained inside the resin glands is THCa, the chemical precursor of THC. The same is true for CBD: High CBD strains are actual- ly high in CBDa. In both instances, the “a” stands for acid — carboxylic acid specifically, which does not easily pass through the blood-brain barrier because of its atomic structure, which is altered passively through the process of decarboxylation; the name refers to the removal of the COOH “carboxyl group.”
Although people generally refer to the total measured potency of a flower or concentrate (including acidic precursors) as “cannabinoid content,” it’s the raw cannabinoid acids that are dominant in bud. Smoking, vaporizing, or in some cases extracting the bud decarboxylates THCA to delta-9-THC, the psychoactive compound, or in the case of cannabidiol (CBD), converts CBDa to CBD.
There are several extraction and post-extraction methods for decarboxylating cannabis—but all involve heat. Whereas cold extraction processes and preserves the raw, acidic cannabinoids. Extraction methods that use high enough temperatures produce decarboxylated, neutral (versus acidic) cannabinoids.
A simple example is the difference between bud and brownies: If you take an eighth of high-potency bud and eat it, there will be little-to-no noticeable effects. That doesn’t mean there won’t be any benefits — many people swear by juicing and consuming raw cannabis for improved health and wellness — but it certainly won’t get you high. This is because the vast majority of the cannabinoids in the bud have not been decarboxylated, so they remain in their raw, non-intoxicating state.
A brownie, on the other hand, has been exposed to temperatures exceeding THC’s decarb point, which is right around 220°F. Even if you didn’t decarb your bud before making butter and baking, it is possible you still baked at a temp higher than the decarb point, so the vast majority of the cannabinoids in your brownie are active THC, meaning if you eat it, well, you know what happens. This same rule applies to CBD, only the decarb point is slightly higher — roughly 280°F.
CBN has long been considered undesirable in high concentration by most cannabis consumers and, by extension, cultivators. This is because CBN is produced through the degradation of THC through exposure to oxygen (oxidization) and THC has traditionally been the most desirable cannabinoid. CBN levels rise naturally as mature cannabis plants near harvest, because the same oxidation process that converts THCa to THC also transforms THC to CBN.
CBN levels also increase during decarboxylation; exposure to heat increases the natural degradation process, meaning THCa is being converted to delta-9-THC, which is simultaneously being converted to CBN. That balancing act has long been biased towards maximizing delta-9 levels and minimizing CBN concentration, but as the way the public consumes and relates to cannabis evolves to encompass more cannabinoids there is a small but growing interest in CBN extracts.
Traditionally, most cannabis consumer experiences with CBN have come from consuming old buds that have converted most of their THC to CBN through gradual oxidation. This experience is generally characterized by the effect most associated with CBN — somnolence, or sleep induction. Those seeking the effects they enjoyed a year ago (never mind the long since volatized terpene profile) will be disappointed, but those just trying to get a good night’s sleep might appreciate the extra CBN.
As with all cannabinoids, CBN can be isolated through fractional distillation for use in tinc- tures or consumption through dabbing, but there are very few commercial sources for these products at present. This could represent an opportunity moving forward as demand for cannabinoids beyond THC and CBD gradually expands with our understanding of their respective contribution to the entourage effect and their individual impacts.
CBGA: THE MOTHER OF ALL CANNABINOIDS
If you’ve never heard of cannabigerol or CBG you aren’t alone — many cannabis consumers are unaware of this “minor” cannabinoid, which generally only appears in minute concentration (1% or less) in harvested cannabis. However, without this precursor cannabinoid there would be no THC or CBD.
All THCa and CBDa contained in the resin glands of the cannabis plant starts out as CBGa, which is internally produced and subsequently converted by enzymes into THCa, CBDa or CBCa — another cannabinoid which is just appearing on the radars of researchers in earnest. But, as with all cannabinoids, we’re learning that CBG has its own distinct impacts on human physiology, which include inhibiting cancer cell growth and reducing intraocular pressure.
Cannabichromene (CBC) is “nonpsychoactive,” cannabinoid, in the sense that it doesn’t bind readily to CB1 cannabinoid receptors. It does seem to provide analgesic effects though, and has been shown to bond with pain receptors. Research into this cannabinoid is still thin compared to the volumi- nous data on CBD and THC, but it has been show to have a unique affect on anandamide, an endocannabinoid associated with numerous therapeutic effects, from alleviating depression to inhibiting cancer cell growth. CBC allows anandamide to remain in the bloodstream for longer, increasing its cumulative impact and boosting its efficacy. This effect has also been observed with CBD, but early research suggests it may be even more pronounced with CBC.
UNPACKING “MORE RESEARCH IS NEEDED IN THE CANNABIS SPACE”
Any discussion on cannabis medicine and the science behind how cannabis works inevitably ends up with somebody saying that phrase — the last rhetorical sanctuary of the status quo on cannabis — “more research is needed.”
And of course there is some truth to that. Any social and scientific phenomenon with as many facets and developing fronts as cannabis undoubtedly requires a monumental undertaking by researchers and scientists to better understand it. However, this ignores the mountain of very legitimate clinical research already logged on this topic, much of it originating in Israel, which has a less restrictive legal environment when it comes to cannabis research.
It is our sincere hope that research into cannabis continues forever, but we also can’t let advocates of prohibition conflate the endless need for more knowledge with an absence of sufficient data to move forward with decriminalization.
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