Three scientists break down what is known about this increasingly popular cannabinoid and its potential in the cannabis industry. Dr. Allison Justice, Ph.D., Dr. Markus Roggen, Ph.D. and Dr. Miyabe Shields, Ph.D.
The Horticulturalist: Delta-8 THC in Cannabis By Dr. Allison Justice, Ph.D. Three years ago, hemp was an extremely profitable plant, bringing in upwards of $7,000 per kilogram of crude CBD oil. Today, the average price for crude has dropped drastically to $500 per kilogram, keeping both growers and regulators on their toes. Minor cannabinoids and isomers help to bring higher value to the crop, yet in general, prices continue to fall. One unique isomer, delta-8 tetrahydrocannabinol (THC), has gained a lot of attention within the past year.
The federal government implemented the final rule for the Domestic Hemp Production Program March 22 as mandated by the Agriculture Improvement Act of 2018 (2018 Farm Bill). In this regulation, hemp is defined as, “the plant species Cannabis sativa L. and any part of that plant, including the seeds thereof and all derivatives, extracts, cannabinoids, isomers, acids, salts, and salts of isomers, whether growing or not, with a delta-9 tetrahydrocannabinol concentration of not more than 0.3 percent on a dry weight basis. … Delta-9 tetrahydrocannabinol, or THC, is the primary intoxicating component of cannabis.”
Because these regulations only define and spell out rules for delta-9, they allow the production for other cannabinoids, including delta-8 THC, even though it does have intoxicating effects. Though delta-8 THC is found naturally in cannabis, it can be made in bulk more economically from CBD (derived from hemp) in a laboratory. This has changed the game for many hemp farmers who were sitting on CBD biomass that, essentially, had become worthless. Cannabis cultivators, including multistate operator Trulieve, are also offering products with delta-8.
When extracting delta-8 THC from biomass, more than 60% of cannabinoids are lost. For example, if a grower had 22 lbs. of biomass at a potency of 10% CBD, the ending yield of delta-8 THC distillate would be approximately 340 grams. At the current price of $1,500 per kilogram of delta-8 THC distillate, according to Kush Marketplace, 22 lbs. of biomass would yield a return of $510 or approximately $23 per lb. When compared to selling CBD biomass for $2 per lb., this is a significant difference.
Even more so than CBD, many stakeholders question the production and formulation of delta-8 THC. Although delta-8 THC could be a threat to the delta-9 market, it’s much more likely that it would be an addition as a diversification of product offerings and formulations. Regardless, there are misconceptions about delta-8 and the effects it can have on the body.
The Chemist: Limitations in Understanding, Testing By Dr. Markus Roggen, Ph.D. Delta-8 THC is an isomer of the more common delta-9 THC, meaning the two molecules are made up of the same number and types of atoms, in general have the same connectivity, and differ only in one or two bonds. The difference between those two THC molecules is the location of the double bond in the cyclohexene moiety, or the top left ring in the red molecule image below. There also are other known THC isomers, e.g., delta-10 THC, but those are less common and generally not tested for.
The isomerization step, when the double bond moves from the delta-9 position to the delta-8 position, is induced by heating and/or acids. As it turns out, delta-8 THC is thermodynamically more stable than delta-9 THC, meaning delta-8 THC always is favored if heat and/or acid is applied to the system for an extended time, as it is more stable.
That does not mean that when you smoke cannabis, the THCA will decarboxylate to delta-9 THC and directly turn into delta-8 THC before you inhale it. In that scenario, the heat is not applied long enough. But for other production steps, like distillation or particularly CBD to THC conversion, this isomerization to delta-8 THC is common. It was in distillation of THC extracts that delta-8 THC was first noted as a common side product.
In particular, the conversion of CBD to THC is of interest. The patent US7399872B2, first filed in 2001, examines the use of an acid and heat to turn CBD into delta-8 THC. This idea is exploited by many hemp producers to increase the value of their hemp extracts, or to remove delta-9 THC from their extracts. But there are a few problems with this process.
The conversion of CBD to delta-8 THC is not perfectly clean if conditions are imprecise. There can be CBD left over or some delta-9 THC intermediate. Speaking of testing protocols, distinguishing between delta-9 and delta-8 in standard testing methods, like high-pressure liquid chromatography (HPLC), is quite difficult. It was only in the past few years that testing laboratories became aware of delta-8 THC contaminations and slowly updated their methods to distinguish it from delta-9 THC and separately quantify it. And as there are not federally consistent, enforced testing protocols in the cannabis industry, there will be laboratories that cannot tell the difference between delta-9 and delta-8 THC.
The Pharmacologist: Delta-8 THC’s Medical Potential By Dr. Miyabe Shields, Ph.D. When it was first discovered, delta-8 THC was considered a minor psychoactive component of cannabis or hashish. Though it is present in much smaller amounts in the plant, when isolated and evaluated on its own, it behaves very comparably to delta-9 THC. Delta-8 THC and delta-9 THC activate the CB1 and CB2 receptors in the endocannabinoid system, which help mediate the behavioral affects of cannabis, with the same potency, according to “The Structure-Function Relationships of Classical Cannabinoids: CB1/CB2 Modulation” published by Eric Bow and John Rimoldi in Perspectives in Medicinal Chemistry. In one study detailed in a 1993 article in Pharmacology Biochemistry and Behavior, when delta-8 THC was given to mice, the same amount of delta-8 THC as delta-9 THC was needed to reach the same measurable biological effects, such as changes in movement or body temperature. This does not mean that they are identical or interchangeable, but rather that delta-8 THC could be expected to share some effects of delta-9 THC. So far this appears to be true; however, there are slight differences between the effects of delta-8 THC and delta-9 THC in humans.
One of the few studies to look at delta-8-THC in humans, published in 1973 in Clinical Pharmacology and Therapeutics, compared the experiences of six men in their 30s who ate chocolate cookies containing either 20 mg delta-8 THC or 20 mg delta-9 THC. The cookies containing delta-8 THC took longer to take effect and lasted for a shorter amount of time than the equivalent dose of delta-9 THC. The overall effects the men felt from the cookies were comparable, but the participants reported delta-8 THC was less intense than the same dose of delta-9 THC. The same study looked at both delta-8 THC and delta-9 THC given intravenously at doses ranging from 1 mg to 6 mg, monitoring the onset time, duration, and intensity of the effects. Similar to when it was eaten in a cookie, the effects from delta-8 THC were less intense and lasted for a shorter amount of time before declining in comparison to delta-9 THC. This study could imply that for some consumers, delta-8 THC would have milder effects at the same dose as delta-9 THC and that the effects would not last as long. However, this study has not been replicated and had a small number of participants. The effects of cannabinoids are known to be patient-specific, and the experience will likely vary from individual to individual.
There are some preliminary studies showing that delta-8 THC does share similar therapeutic potential to delta-9 THC. In a 2001 study published in Brain Research investigating morphine withdrawal in mice, delta-8 THC was able to reduce the severity of morphine withdrawal symptoms. (This could be a possible therapeutic mechanism for the use of hemp in opioid substance abuse.) Delta-8 THC also was able to completely stop vomiting and nausea in eight children receiving chemotherapy treatment for cancer, according to a study published in 1995 in Life Sciences, which is further evidence that it may share therapeutic properties with delta-9 THC.
The full therapeutic profile of delta-8 THC has yet to be explored in detail, and some of the therapeutic effects may be from metabolic byproducts created when delta-8 THC is processed by the body. The main metabolite created when delta-8 THC is ingested, 11-hydroxy-delta-8 THC, is structurally similar to those created from delta-9 THC. This metabolite as well as another, 11-oxo-delta-8 THC, have been shown to be more potent than delta-8 THC in animal studies. It is highly likely that these metabolites are created when humans take delta-8 THC, but it’s still unclear how they contribute to the overall effects.
Overall, there are many similarities in how delta-8 THC and delta-9 THC affect humans, from their interaction with cannabinoid receptors to their metabolism. While there is still a lot to be clarified, early evidence points to delta-8 THC as less potent, but comparable in therapeutic effects to delta-9 THC. However, like with all cannabinoids, more research is needed. We see through this literature review that in the purest form, delta-8 THC can have comparable therapeutic potential to delta-9 THC, and that we should further investigate how this isomer can benefit the cannabis industry.
