WARNING: No bleach or battery acid was used in the production of this blog posting… or anything else that comes out of our lab, for that matter!
Today we’re going to discuss two forms of THC: specifically Δ⁸-THC & Δ⁹-THC. Both forms have gained a large amount of attention in the past few years in the form of popularity as well as scrutiny. Just like many other cannabinoids, they are highly related to each other: they both have the same atoms in nearly the exact same layout and orientation. The only difference is the placement of the double bond (Fig.1) in the third (or first, depending on how you look at it) ring structure. Check it out below!
(Fig.1 - Comparison of the molecular structure of Δ⁹-THC & Δ⁸-THC)
Now, before we dive in, I must preface by stating this is going to get real scientific at times. Science is the base of everything here at Blackhouse Botanicals, as it should be for anyone working with Cannabis, and without it this subject is subject to hearsay. We’re also going to discuss some arguments regarding safety, the as-of-late scrutiny, and actual research that has been done regarding Δ⁸-THC - there’s more out there than many people may realize.
First off, we’ve discussed the basic pathway of how cannabinoids are made in previous blog posts, but as a refresher:
Hexanoyl-CoA is broken down through hydrolysis, then enzymatically changed within the trichomes of Cannabis sativa to Olivetolic Acid.
Combining Geranyl Diphosphate with Olivetolic Acid and the use of Aromatic Prenyltransferase (an enzyme) creates Cannabigerolic acid, the “mother of all cannabinoids”.
From there, different enzymes specific to the creation of CBDa, THCa, and CBCa create those three cannabinoids specifically. Other enzymes are thought to exist as well that may relate to other minor cannabinoids, but this outline of production for cannabinoids that Cannabis very efficiently enacts within the trichomes will be our baseline of discussion.
Now, THCa and CBDa are very closely related as well; they have the same molecular weight, meaning they contain the same number and types of atoms, just arranged differently. Keep that in mind, because Δ⁸-THC & Δ⁹-THC are even more closely related, as stated and seen above (Fig.1). Before we get down to the nitty-gritty, let’s compare the two.
Anyone that has tried the major forms of THC (Δ⁸-THC & Δ⁹-THC) will more than likely know about the similarities and important minor differences. Both are psychoactive, both have been shown to be appetite stimulants, both are effective for pain and inflammation, and both act as powerful anti-nausea medications. Many assume these comparisons don’t go beyond generalities of colloquial experience, but much of these effects have been clinically studied and (of course) have a strong basis in science when you look at the structure of both, their relation to the CB1 receptor, and also their breakdown products in other areas of the body such as the liver. A public commentary here in Utah on the safety of Δ⁸-THC recently discussed a study on pediatric cancer patients and the possible anti-nausea effect it could have, touting it as ‘not enough’ regarding research due to the fact only 8 children were involved in the study. Clarification was never given for the study as it followed those children over (sadly) years of chemotherapy treatments and totaled over 480 data points with Δ⁸-THC being the only one with a 100% success rate at preventing vomiting following chemotherapy. The study compared Δ⁸-THC, Δ⁹-THC, and metoclopramide (an anti-nausea pharmaceutical) and while Δ⁹-THC was a close second in efficacy, the higher potency of Δ⁹-THC led to many more complications past preventing nausea and vomiting.
There have also been clinical studies done comparing Δ⁸-THC & Δ⁹-THC by both oral and intravenous administration and the effects seen afterward, a study on their effect and comparison on human cells in culture, and another regarding the metabolism of both, just to name a few. Granted, we fully admit we would love to see just as many published and peer-reviewed studies done on Δ⁸-THC for as many numerous specific topics as there have been for Δ⁹-THC in the last 10-15 years, but the general knowledge that is backed by science gives us enough information to make some direct inferences on the safety and efficacy of both, as well as supported facts on Δ⁸-THC alone. Regarding metabolism, for example, the end products that are produced (11-hydroxy-THC and later 11-nor-Δ-hydroxy-THC / THC-Acetate) are the same.
Regarding Δ⁸-THC on the market, there absolutely needs to be a concern for the safety of the composition of consumer products… but that safety of products for our customers or any others regarding Δ⁸-THC is no different than any other Cannabis s. product containing cannabinoids. This safety all relates back to transparency regarding certificates of analysis (you can find these on our website) for finished and raw products, as well as the care taken in all steps of the process; extraction, purification, isolation, and so on. Adherence to local state and federal guidelines (which of course we strictly follow here at Blackhouse Botanicals) is also a clearly important factor.
The basis of approach to Δ⁸-THC is the same as CBN: the “degradation” pathway. After THCa is produced in the plant, it is subject to all sorts of stresses. Heat, oxidative elements, and light are all-natural (yet harmful) stresses the plant comes into contact with that, in turn, can change Δ⁹-THCa into both Δ⁸-THC(a) and CBN(a) (Cannabinol) purposefully as the plant protects itself. This is the basis of how Δ⁸-THC is created and found in Cannabis, as well as CBN (fig.2). There is no enzymatic pathway to create it as there is with CBG(a)/CBD(a)/THC(a)/CBC(a). So how does this relate to the safety of properly treated Δ⁸-THC? Simply put, Δ⁸-THC is more stable than Δ⁹-THC, so when Δ⁹-THC is subjected to any of those harmful stresses mentioned above, the energy from those is diverted into ‘moving’ the double bond from the ninth-to-tenth carbon position to the eight-to-ninth carbon position. The stability stems from moving available hydrogen atoms from an accessible place on the ‘side’ of THC to a placement more internal. If the stress is extremely harsh or harmful enough, when Δ⁹-THC is subjected to it, the exposed hydrogen atoms on the outermost side of the third cyclical structure will leave, which transforms it into CBN. These changes in cannabinoids are all pathways the plant has available to redirect harmful stresses & energy away from its genetic makeup. This is similar to the way melanin in our skin aptly absorbs UV radiation from the sun, protecting genetic information in our cells from mutations such as those that lead to skin cancer.
(Fig.2 - The THC shown is Δ⁹-THC. As you can see in this example, when compared to the CBN molecule, two sets of hydrogen have been removed leaving a fully aromatic third cyclical structure changing Δ⁹-THC into Cannabinol. Cannabinol does not have the same molecular weight as THC for this reason.)
As those of us who have been paying attention to the scrutiny Δ⁸-THC has been getting in the marketplace lately, it is surprising that CBN is not getting the same type of microscope put on it. The stresses required to obtain CBN in any quantifiable way are much more intense and require more care and expertise, as well as cleanup. Expertise is the limiting factor in the market and a main reason as to why Δ⁸-THC has had a label of “be-warned” put upon it. For example, if we look at the change that occurs when cannabinoids are decarboxylated (Fig.3), it is correct to say the change from an acidic form to a decarboxylated form is more of a change molecularly than Δ⁹-THC changing to Δ⁸-THC is, or for that matter, CBD to Δ⁹-THC. To be fair, decarboxylation from heat energy is a fairly straightforward and safe process that happens both on a laboratory scale all the way down to a personal scale when Cannabis flower is ignited for inhalation, although our decarboxylation process removes the CO2 and combustibles from reaching the customer.
(Fig.3 - The stress of high heat (one way to decarboxylate) causes CO2 to leave CBDa, leaving us with CBD, the non-acidic and ‘activated’ form of the cannabinoid)
Science also explains why Δ⁸-THC has been shown to generally be less potent than Δ⁹-THC but still acts directly on the CB1 receptor in the same way and causes similar results. The most apparent reason is the structure (Fig.1). The CB1, and CB2 (any receptors for that matter) work on a “lock & key” basis. If the key fits, the door opens, and if it doesn’t, the door does not - it’s that simple. Δ⁹-THC, Δ⁸-THC, and CBN all fit into the CB1 receptor because of their similarities and in turn, the effects are different because of their minor structural differences. This is where the importance of the placement of the double bond comes into play in our discussion.
The CB1 receptor (Fig.4) is made up of 7 main protein helices as well as a few protein loops and makes up different polar and nonpolar pockets. These pockets, the amino acid residues they relate to in the surrounding helices and loops, and the shape of the pockets are what differentiate CB1 from CB2, other receptors, and make it selective for specific cannabinoids. Since the only difference is the placement of the double bond when comparing Δ⁹-THC & Δ⁸-THC, it stands to reason that the difference in effect is related to this. This is where science really comes out to shine. On Helix Ⅱ there is a residue called F174. What this residue is isn’t as important as what it does, and that is it stabilizes THC within the pockets of the CB1 receptor. When THC binds within the CB1 receptor and subsequently causes a conformational change in the shape of CB1, it in turn blocks GABA from affecting inhibitory neurons, causing dopamine to be released. This in part plays a role in the quintessential “high” related to THC.
(Fig.4 - The CB1 Receptor shown in a 3D rendered model to outline the structure)
Now, that was a LOT to take in, but the take-away is this: the placement of the double bond in regards to Δ⁹-THC stabilizes it within the CB1 receptor more strongly and for longer than when Δ⁸-THC binds to CB1. The reason for this is how far away the double bond is in relation to the F174 residue and what type of bond it is in both cases. The same goes when playing with magnets, for example - the farther away, the more weak the pull is. All the other stabilizing and binding points within the helices of CB1 and the different points on THC that bind to them are the same. Many of the other bonds produced between THC and CB1 are much stronger than the type between F174 and the double bond in question, so by moving that bond farther away from that stabilizing residue, Δ⁸-THC binds for less time and is in turn ‘kicked out’ of the CB1 receptor faster. It’s that simple. In the future, there is, of course, going to be more research into Δ⁸-THC and we look forward to that, but from all that has been learned not only from Δ⁹-THC and CBD (including other cannabinoids such as CBN) and their actions within our bodies, there is nothing that can’t be explained at least to a reasonable point regarding Δ⁸-THC.
Lastly, this all comes down to safety. What can be explained about how Δ⁸-THC is formed at a laboratory level? How do I know the products that I'm choosing to put in my body are safe? How do I know they don’t contain products I shouldn’t ingest? We’ve received many questions from other extractors and companies looking to uncover our methods as well as inquiries from customers looking for an explanation on where our Δ⁸-THC comes from. While our methods are proprietary and I won’t be sharing them today, we do want to say this: everything that comes from Blackhouse Botanicals starts as hemp biomass and is treated with care at every step. Everything is tested at every step in our process for safety for not only our customers, but for our employees as well. Metals, residual solvents, pesticides, toxins, and potency are all tested and meet state requirements. Most important of all, every one of our methods are based on scientific research, including our Δ⁸-THC. Scientists have been aware of Δ⁸-THC since 1941 and has been at minimum a side interest and tagalong of Cannabis research since 1964 when Raphael Mechoulam synthesized it successfully from olivetolic acid along with CBD and Δ⁹-THC. In fact, the first study published where Δ⁸-THC was a major star was in 1975, over 40 years ago! Although Δ⁹-THC has been the focus of CB1 cannabinoid studies for many years, due to its extreme similarities with Δ⁸-THC, much of that research is being shown to be the same and relevant for both delta variants. There is published research on the specificity of different types of stresses on different cannabinoids, what the end result from those stresses are and the purity, and is what we based our R&D on for over a year and a half (not to mention thousands of dollars in testing and laboratory equipment) before we ever put out a product that contained Δ⁸-THC. These pathways are well known and the information regarding obtaining specific products is out. Ring closure and isomerization has been continually used in almost every industry (including heavily in pharmaceuticals) and is the basis of aldose-ketose carbohydrate chemistry that occurs in every person when we consume glucose. On top of this, a good example of safety in the market is most of the cannabinoid-containing vape cartridges. These are found in both the medical and public markets and are generally made with 85-90% distillate oil (with added terpenes), yet they are approved for use and sale to the public after proper testing. The other 10-15% of that distillate oil is non-cannabinoid products of distillation and can’t be accounted for by any standardized test, other than checking for contaminants such as metals and pesticides. It’s the reason that a 1 gram (1000mg) cartridge only has anywhere from 750-850mg total cannabinoid content on average. This is the reason we put up a blog post previously about reading a certificate of analysis - it’s important to know what’s in your products and why the amounts are what they are.
Battery acid and bleach are not something that would make any reputable company (including us) any amount of consumer-worthy cannabinoids of any kind, and certainly isn’t the basis of anything except the mop-bucket and the cars we drive to work here at Blackhouse Botanicals. Instead what you’ll find is 5 degrees, 3 minors, 25+ years of chemistry and botany experience, and a family-owned and operated small business filled only with employees that love and respect not only our customers but Cannabis and all its forms as well. There’s no acting in our lab, otherwise, our products wouldn’t be as effective as they are. The only costumes here are PPE!
These blog posts usually end with an invitation to send questions you’d like to hear discussed in the future to firstname.lastname@example.org. Instead, I invite anyone that has concerns regarding Δ⁸-THC or any of our products to send us an email and open a dialogue - we’d love to quell any concerns you may have and answer any questions we can. There are a lot of fantastic cannabinoid products on the market, and many great people in different parts of the industry both medical and hemp-related striving to bring clean, effective products to the public. We are grateful if you’ve ever chosen us to fill that hole in your endocannabinoid system-shaped heart. If not, feel free to check out the testimonials section of our website, our certificates of analysis, and try one for yourself!
We hope to hear from you in the future. See you next time!
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