How Rare Cannabinoids Are Making Their Way into Edibles

Evidence outside the endocannabinoid system alarmed Dr. Vrana, however. “What we got interested in was based on one of its reported activities in a non-cannabinoid receptor called Alpha-2,” he says. “That receptor, 40 years ago, was a target for hypertension. So, my colleagues administered CBG to mice and we saw a dramatic drop in blood pressure. For me, that strikes me as a potential side effect that nobody’s thinking about.”

The paper predicts that, due to CBG’s effects on Alpha-2, pure or highly enriched CBG will have unintended consequences that will also be unexpected because they’ll come from outside the endocannabinoid system. “[CBG is] not just working on CB1 or CB2,” he says. “It’s potentially working on a dozen other receptors, all of which have differing activities, and no one’s ever taken CBG at high concentrations,” including, he notes, in the studies, which were conducted on mice. He says there is no data at all regarding humans and CBG, let alone CBG in a concentrated form.

For Dr. Vrana, that concentration is the very essence of the discussion about CBG, which under normal conditions appears in tiny amounts. “For CBG in particular, it’s important for people to hear that no one is experienced with high concentrations of CBG, because, historically, it hasn’t existed. Under normal conditions, I don’t believe [consumers feel the effects of CBG]. Cannabis doesn’t express a ton of this. The fact that the plant makes it en route to making THC and CBD does not make it ‘all natural.’ There’s also the misrepresentation of it as ‘the mother of all cannabinoids,’ which gives you the impression if you eat it, your body will convert that into THC and CBD. That’s simply not the case.”

Churchill concurs, saying, “There simply aren’t a large enough number of studies, specifically clinical studies in humans, for us to draw any firm conclusions about the effects of CBN and CBG. The studies that do exist rarely control for these cannabinoids in particular. That may be changing, but for now, any claims about effects are based on speculation or anecdotal evidence.”

Long-Term Research Still Needed

At the same time, Churchill also acknowledges there hasn’t been any proof that CBN or CBG are unsafe for consumption either orally or by inhalation. “It’s hard to ground their safety in science at this time, but the lack of reports of negative effects, even with cannabis use becoming increasingly common, is encouraging.” Because THC, CBD, and CBN all derive from CBG, and they share a similar chemical structure, Churchill thinks it’s likely that “CBN and CBG are no more dangerous than their more well-known cousins, THC and CBD.”

That’s nothing more than an educated guess, though. Churchill is quick to stress that we simply don’t have very much information about CBG and CBN, and it will take time and study to figure out exactly what these compounds do—or don’t do. He adds that long-term studies on cannabis use are still needed to be able to fully grasp the benefits and the risks that come with frequent cannabis consumption. “Until we know more about how [minor cannabinoids] interact with other cannabis constituents, we cannot predict the strength of physiological effects these cannabinoids may produce,” he says.

Dr. Le agrees that the safety profile for rare cannabinoids remains unknown, and he too calls for further testing. “It’s one thing to have rare cannabinoids at low concentrations as a side product of cannabis production. It’s another thing entirely to deliver therapeutic levels of these compounds to consumers.”

The good news, says Dr. Vrana, is that the concerns he has about CBG causing harm to consumers are limited to CBG being smoked or vaped. “If it’s not being smoked,” he says, “if it’s being taken orally, it’s not going to achieve terribly high concentrations and it’s going to be a slow onset. That’s why with edibles, you have such high concentrations [of cannabinoids]: It’s not well-absorbed into circulation from the GI tract. These compounds are metabolized by the liver very assiduously.”