Beyond CBD, THC: 'Minor' Cannabinoids Flood Market

On the heels of the cannabidiol (CBD) craze come three other cannabinoids touted as potential treatments for various medical issues: cannabigerol (CBG), cannabinol (CBN), and delta-8 THC (tetrahydrocannabinol). While companies are freely selling products featuring these compounds, especially delta-8, practitioners and industry insiders note little evidence exists regarding any of the three.

They especially question delta-8, which has captivated the market over the last year despite a dearth of research.

"Given the nature of these compounds (on their own), it's unlikely that they're unsafe," Jordan Tishler, MD, president of the Association of Cannabis Specialists, wrote in an email to MedPage Today. They are "great to sell but not necessarily safe or useful medically," however, he added. "The evidence for use in humans is very thin."

Next Batch of Medicinal Cannabinoids?

Delta-8 is similar to delta-9 THC, the component primarily responsible for the cannabis "high." That effect is reportedly much diminished with delta-8 THC and perhaps absent entirely. Proponents say it offers the same medical benefits -- such as addressing nausea and stimulating appetite -- as delta-9.

Unlike naturally occurring CBG and CBN, delta-8 is a synthetic made from hemp-derived CBD. It is "normal THC with a fake mustache on," said Trevor Yahn-Grode, a hemp industry analyst with New Frontier Data. It has attracted consumers who eschew CBD-based products for THC benefits and mild psychoactivity -- but not as much as delta-9 products typically induce, said John Kagia, a New Frontier executive.

All cannabinoids originate from CBG, but the compound is present in only very small quantities (often less than 1%) of naturally-harvested cannabis. CBG could treat anxiety, pain, inflammation, and nausea, among other potential uses, proponents say.

CBN often develops in aging cannabis flowers as the THC degrades and also is only present in very small quantities of natural cannabis. CBN has especially been touted as a potential insomnia treatment, in addition to addressing inflammation and stimulating appetite.

CBN and CBG, like CBD, are not psychoactive. Their existence has been known for decades, while delta-8 has emerged only recently.

But CBG and CBN have been examined at large scale only in animals; MedPage Today found no record of any human studies.

And delta-8 THC has scarcely been researched at all. "It clearly activates CB1&2 [endocannabinoid system] receptors and gets you high, but is less efficacious than delta 9," Samoon Ahmad, MD, co-author of Medical Marijuana: A Clinical Handbook, emailed MedPage Today. "Unique effects haven't been studied enough yet."

Safety also remains an open question. "Since none of them are regulated at this time, and we know from the CBD literature" about unregulated products sometimes being contaminated, Tishler wrote, "many products may be unsafe to use until proven otherwise."

'Minor' Cannabinoids, Major Market Growth

These three compounds make up only a small piece of the cannabis market, Kagia and Yahn-Grode said, with sales probably less than 5% of CBD's. But these so-called "minor cannabinoids" represent a fast-growing sector. "This is all happening in real time," Kagia said.

Delta-8 "exploded out of nowhere," Yahn-Grode said, with retail sales of at least $10 million last year and now dominating the minor cannabinoid market. That's largely due to suppliers reacting to gluts of CBD, on one hand, and fears on the other that regulators could soon ban delta-8, Yahn-Grode and Kagia said.

Supplies of all three compounds have been boosted by the 2018 Farm Bill, which legalized hemp agriculture. For example: CBG- and CBN-based products are becoming more popular as harvesters have transformed what used to be costly cultivation by hand into an industrial process. Novel production methods have also yielded products with higher concentrations of CBG and CBN, at lower cost.

Unlike delta-9 THC, federal regulations are silent on these compounds, enabling anyone to legally purchase products in states that haven't banned them either.

In addition, cannabis companies are attempting to differentiate themselves in this newly competitive marketplace, said Jonathan P. Caulkins, PhD, a public policy professor with Carnegie Mellon University in Pittsburgh.

"Nobody wants to sell just plain cannabis," he said. "There is enormous creativity in the marketplace right now" and that is "a driver" of CBG and CBN products in particular, he added.

The result: Many patients and some practitioners are trying these products.

Practitioners report mixed results. Tishler and Mikhail Kogan, MD, who direct George Washington University's Center for Integrative Medicine, have tried CBN in insomnia patients. But Tishler has "not found it to be better than standard THC-dominant cannabis products," he wrote.

Kogan has trialed CBG as an appetite stimulant, especially for older adults -- but "it seems to be unpredictable," he said.

Neither Kogan, Tishler, nor Ahmad (also a New York University professor) indicated they have used delta-8 with patients, nor are they considering doing so any time soon. The Association of Cannabis Specialists is working on an advisory statement outlining its concerns regarding delta-8, Tishler wrote.

"It could all just be a commercial gimmick for all I know; none of this has been demonstrated anywhere so I'd be very cautious," Kogan said.

Regarding all three compounds, Tishler wrote, "I would not recommend them."

But, Kogan said, "The reality is it's going to move forward whether we like it or not."

For example, Biomedican, a biosynthesis company, hopes to have a CBG-based pharmaceutical drug ready for production within a year, officials told MedPage Today. And CBG- and CBN-based products will continue to emerge on the market, said Michael Sassano, CEO of SOMAI Pharmaceuticals.

That's partly because manufacturers are ahead of research and regulation. "This is going to be consumer-driven," Kagia said.

Still, that will likely take some time. About half of the general public knows nothing about THC, he said, citing a New Frontier survey conducted last year.

The bottom line: "There's a lot of controversy around all three [compounds]," Kogan said. "None of them have any significant evidence; that's the problem."

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