CBD Not Just Innocent Bystander in Weed

This transcript has been edited for clarity.

Welcome to Impact Factor, your weekly dose of commentary on a new medical study. I’m Dr F. Perry Wilson of the Yale School of Medicine.

I visited a legal cannabis dispensary in Massachusetts a few years ago, mostly to see what the hype was about. There I was, knowing basically nothing about pot, as the gentle stoner behind the counter explained to me the differences between the various strains. Acapulco Gold is buoyant and energizing; Purple Kush is sleepy, relaxed, dissociative. Here’s a strain that makes you feel nostalgic; here’s one that helps you focus. It was as complicated and as oddly specific as a fancy wine tasting — and, I had a feeling, about as reliable.

And while a strain that evokes memories of your first kiss is beyond the reach of modern cultivation practices, it is true that not all marijuana is created equal. It’s a plant, after all, and though delta-9-tetrahydrocannabinol (THC) is the chemical responsible for its euphoric effects, it is far from the only substance in there.

The second most important compound in cannabis is cannabidiol (CBD), and most people will tell you that CBD is the gentle yin to THC’s paranoiac yang. Hence your local ganja barista reminding you that, if you don’t want all those anxiety-inducing side effects of THC, grab a strain with a nice CBD balance.


But is it true? A new study appearing in JAMA Network Open suggests, in fact, that it’s quite the opposite. This study is from Dr Austin Zamarripa and colleagues, who clearly sit at the researcher cool kids table.

Eighteen adults who had abstained from marijuana use for at least a month participated in this trial (which is way more fun than anything we do in my lab at Yale). In random order, separated by at least a week, they ate some special brownies.


Condition one was a control brownie, condition two was a brownie containing 20 mg of THC, and condition three was a brownie containing 20 mg of THC and 640 mg of CBD. Participants were assigned each condition in random order, separated by at least a week.

A side note on doses for those of you who, like me, are not totally weed literate. A dose of 20 mg of THC is about a third of what you might find in a typical joint these days (though it’s about double the THC content of a joint in the ’70s — I believe the technical term is “doobie”). And 640 mg of CBD is a decent dose, as 5 mg per kilogram is what some folks start with to achieve therapeutic effects.

Both THC and CBD interact with the cytochrome p450 system in the liver. This matters when you’re ingesting them instead of smoking them because you have first-pass metabolism to contend with. And, because of that p450 inhibition, it’s possible that CBD might actually increase the amount of THC that gets into your bloodstream from the brownie, or gummy, or pizza sauce or whatever.

Let’s get to the results, starting with blood THC concentration. It’s not subtle. With CBD on board the THC concentration rises higher faster, with roughly double the area under the curve.


And, unsurprisingly, the subjective experience correlated with those higher levels. Individuals rated the “drug effect” higher with the combo. But, interestingly, the “pleasant” drug effect didn’t change much, while the unpleasant effects were substantially higher. No mitigation of THC anxiety here — quite the opposite. CBD made the anxiety worse.


Cognitive effects were equally profound. Scores on a digit symbol substitution test and a paced serial addition task were all substantially worse when CBD was mixed with THC.


And for those of you who want some more objective measures, check out the heart rate. Despite the purported “calming” nature of CBD, heart rates were way higher when individuals were exposed to both chemicals.


The picture here is quite clear, though the mechanism is not. At least when talking edibles, CBD enhances the effects of THC, and not necessarily for the better. It may be that CBD is competing with some of the proteins that metabolize THC, thus prolonging its effects. CBD may also directly inhibit those enzymes. But whatever the case, I think we can safely say the myth that CBD makes the effects of THC more mild or more tolerable is busted.

F. Perry Wilson, MD, MSCE, is an associate professor of medicine and director of Yale’s Clinical and Translational Research Accelerator. His science communication work can be found in the Huffington Post, on NPR, and here on Medscape. He tweets @fperrywilson and his new bookHow Medicine Works and When It Doesn’tis available now.

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