Originally posted on Analytical Cannabis.
In 2018, US lawmakers passed the Agriculture Improvement Act, more commonly known as the Farm Bill. Included in this bill was a provision that legalized the production of industrial hemp as well as “any part of that plant, including the seeds thereof and all derivatives, extracts, cannabinoids, isomers, acids, salts, and salts of isomers” so long as the total THC content of the plant is less than 0.3% by dry weight.
Ever since, the market for hemp-derived cannabinoids and isomers has gone from strength to strength; the US CBD market alone was estimated to be worth 4 billion USD in 2021.
But CBD is not the only hemp-derived cannabinoid that is attracting significant attention. Cannabigerol (CBG) and cannabichromene (CBC) have both demonstrated potential medical benefits, while delta-8 THC products pose challenging new questions over the legal status of hemp-derived THC isomers.
Making a hemp-derived cannabinoid extract
A typical process for making a hemp-derived cannabinoid isolate begins the same way as any other hemp or cannabis oil extraction.
“There’s primarily three methods that are out there — supercritical CO2, hydrocarbon extraction using liquid propane, and cryo-ethanol extraction. Each of these methods has their own advantages and disadvantages,” Deepank Utkhede, chief operating officer at the pharmaceutical-grade CBD producer Vantage Hemp, told Analytical Cannabis.
“You put the biomass in the equipment, it’s extracted, and you end up with what we call a crude extract. This has got all your cannabinoids — CBD, THC, CBDA, CBDV, all of them — as well as fats, lipids, and waxes that get extracted during that process, and some others like chlorophylls and other oils from the plant.”
In order to turn this crude oil into a pure cannabinoid isolate, the oil then goes through a winterization and filtration process to remove those unwanted plant lipids. After being sent through a falling film evaporator to remove any residual solvents, the producer is left with a high-quality, full-spectrum hemp extract oil.
If a manufacturer wants to go a step further and create a very pure hemp-derived isolate of a certain cannabinoid, this can be done by adding in a further distillation and crystallization step.
“It’s a liquid when it comes out, but then it solidifies because it just starts to crystallize out because it’s such a high CBD content,” Utkhede said when describing Vantage Hemp’s own process for producing CBD isolate. “The next step is crystallization, where you take that distillate, you dissolve it in pentane and then you take it down to minus 20 [degrees Celsius] to make it crash out of the solution. Once it crashes out of the solution, you can collect those crystals and that’s your crystallized isolate.”
However, while this process works well for major cannabinoids such as CBD, which are naturally present in hemp biomass in large amounts, it is less useful for creating isolates of more minor cannabinoids. In these cases, producers may go down the semi-synthetic route and choose to convert hemp-derived CBD into another cannabinoid using chemical processes.
“Hemp, while it produces a large number of cannabinoids, most of those cannabinoids are produced in very low levels. So it’s not really that efficient to get from the plant, although you can and there’s a lot of companies doing it,” Utkhede said. “For a certain number of molecules, it makes more sense to isolate a parent compound from hemp which is abundant and then do a conversion.”
What are hemp-derived cannabinoids used for?
With various studies showing that CBD can have a positive effect on anxiety-related disorders, inflammation and oxidative stress, and sleep problems, it is unsurprising that a powerful market for CBD-infused health and wellness products has materialized quickly around the globe. Since hemp-derived CBD isolates are odorless and colorless powders, the cannabinoid lends itself to being made into pills, suspended in topical creams, and even being directly applied sublingually.
“CBD, although it’s been around for a long time, it’s only been taken out of the shadows in the last two to three years,” Utkhede said. ”When you look at it, we’re at the beginning part of an asymptotic increase where we are going to start seeing just a massive amount of data come up and a massive amount of demand and utilization in various industries – pharmaceutical, health and wellness, dietary, that sort of thing.”
While CBD has attracted much of the attention from the health and wellness market, the comparatively less-abundant cannabinoid CBG is also making waves. Early research has demonstrated that this compound may have significant therapeutic applications, from treating glaucoma to killing drug-resistant bacteria such as methicillin-resistant Staphylococcus aureus (MRSA). CBC is another cannabinoid that holds a lot of promise for future drug development, having been shown to play a role in brain function and cancer cell necrosis.
In addition to hemp-derived cannabinoid isolates, broad-spectrum hemp oils are also popular products among consumers.
“You have this whole slew of these minors that are also present [in hemp oil] – it’s basically all CBG, CBN, CBDV, CBDA,” Utkhede said. “They can contribute to the entourage [effect], as opposed to using an isolate which is generally 99.5% or greater CBD.”
While the entourage effect itself has still to be definitively proven, the basic idea is that different cannabinoids may work together synergistically to boost or otherwise influence their effects when present together in a broad-spectrum extract.
Regulating hemp-derived cannabinoids
Another isomer that has recently made waves in the cannabis space is delta-8 THC.
This compound occurs naturally in hemp in small amounts and is less intoxicating than its more well-known isomer, delta-9 THC. However, it does still deliver a noticeable mellow high that is attractive to many consumers who feel that delta-9 THC is too intense.
So, why is this compound generating so much controversy? Well, that is largely down to its unclear legal standing. Much of the legal language concerning cannabis, including the Farm Bill, refers specifically to delta-9 THC when defining restricted products, and this has caused issues when considering the legality of certain delta-8 THC products.
“The industry thought process is that hemp is legal under the Farm Bill, [so] CBD extracted from hemp is natural and, therefore, legal; trace levels of delta-8 THC have been observed in [hemp] biomass and, therefore, is [sometimes viewed as] a natural product. And since delta-8 is naturally occurring, a derivative pathway from CBD [to delta-8 THC] for production should be illegal,” Chris Hudalla, president and chief scientific officer at ProVerde Laboratories, explained in a recent Analytical Cannabis webinar. “The problem with that thought process is that conversion of CBD into delta-8 THC is not a natural process.”
This lack of clear regulatory control over delta-8 THC products is concerning to many, and even prompted one group of researchers to publish a viewpoint paper in JAMA Network Open calling for more regulation. While some individual states have banned the sale of any delta-8 THC products, a federal court in California recently ruled that delta-8 THC products that “fit comfortably within the statutory definition of ‘hemp’” by containing less than 0.3% delta-9 THC would be considered legal in the state.
The regulatory landscape for CBD products can also be tricky for producers to navigate. In January of this year, the US Food and Drug Administration (FDA) announced that it would not be writing any rules to regulate the marketing of CBD as a food item or dietary supplement, saying that it was instead prepared to work with Congress to develop a new cross-agency strategy for regulating such products.
The future of the market
It is estimated that the total hemp derivative market, including materials such as hemp fiber, will be worth more than 20 billion USD by 2028. The personal care market segment is forecast to grow at the highest rate during this period, with hemp-derived CBD oil continuing to be applied to beauty care products and cosmetics.
“I think the biggest impediment to the adoption [of hemp-derived cannabinoids] is information,” Utkhede commented. “All these new cannabinoids, because they’re relatively new and up until recently they hadn’t been isolated, their effects aren’t fully known. And it’s hard to market a product when you don’t fully understand its effects.”
As a producer of pharmaceutical-grade CBD, Vantage Hemp is also beginning to see more desire for CBD that can be used in clinical trials. The company is currently already supplying three clinical trials with hemp-derived CBD formulations that are being used to monitor the effects of the cannabinoid on issues such as sleep, mobility, and viral infection.
“Ideally you want clinical data showing its effect and preferably clinical data where you’re comparing it to a placebo,” Utkhede said. “You are going to see a lot more of that, a lot more of a push towards clinical studies, and then entering markets where it’s clearly defined that it’s a medicine and here are the requirements.”
