Dr. Matthew Hill

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614 appearances 1 recordings 1 series first heard Jul 2024 last heard Jul 2024

Dr. Matthew Hill’s voice in public audio — every appearance, attributed to the second.

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Huberman Lab · How Cannabis Impacts Health & the Potential Risks | Dr. Matthew Hill · 8 Jul 2024 podcast

Yeah.

That's kind of how I describe to people if they ever ask me for what the pharmacology of CBD is. I'm like, that's not the only mechanism. But the thing that was important in CC studies that I think is relevant is that it was not super high concentrations of CBD that caused that. So you could get this adenosine accumulation at...

you're not talking like micromolar levels of CBD, which is what a lot of studies have done. And so even when we're talking about the allosteric modulatory site, like yes, there's evidence for it. And it is convincing evidence. It's just the dose range in there. You're kind of like, who's getting hit with CBD at that level where you're getting these effects and more so,

when they've done the blinded work, like when Ryan Vandery at Hopkins again, who is one of the main people who's done a lot of this work, has actually blindly given people CBD dosing with THC, finds the opposite, that it actually amplifies some of the effects of THC.

And this was something we learned from the pediatric epilepsy world was that when you start giving CBD at relatively high doses, one of the things it does is saturate a lot of liver enzymes. And so some of the efficacy in the pediatric epilepsy space may be a secondary effect due to an accumulation of some of the anti-epileptics as well because they're not being metabolized the same way.

And this has now been very well replicated. We know that once you start taking CBD, when they hit doses that are at the clinical level, you're going to start having hepatic effects. So it's going to affect the liver, and it's going to affect the ability of the liver to chew up other drugs. And there's very specific –

CYP enzymes, like the cluster of enzymes that metabolize things, is very specific ones that CBD hits. And so as a consequence, one of them is what choose THC up. So you can get a potentiation of THC by inhibiting its metabolism if you have high enough CBD on board.

Yeah. I mean, so what you're saying is like what we said is the entourage effect. And I think that is a theory that is held by a lot of people that this exists. I mean, the reality is these terpenes and minor cannabinoids exist at such low levels that like, there's a couple of kinds of cannabis that might have like a high enough level where you're seeing something, but

Yeah, I mean, I agree to the extent that it would be a little wild if everyone's subjective experience across different kinds of cannabis was entirely driven by some kind of expectancy, which I can't imagine is accounting for all of it. But I think when we talk about

sativa versus indica i think there's a huge bias that's going into there um but one of the things with cbd that's interesting unlike thc is you can actually do pretty clean blinded studies because it's really hard to give someone thc and them not know they're on thc right this was the big problem with the mdma trial that happened recently is that people who got the placebo

It's very challenging to give someone a psychoactive drug and a placebo and them not know which one they have. Whereas because CBD doesn't produce an intoxicating state and it's not really perceptible from the person who's taken it that it's doing anything, that actually does make it far more amenable to do blinded trials with. And so...

I mean, the interesting thing with CBD, and this is where I get a lot of people that get angry at me as well, is that I would argue that the overwhelming majority of the effects of CBD that people report are all placebo effects. And I say that because people leverage the epilepsy stuff and some of the clinical work and say, but we know it does things.

And my response to them is, do you know what dose those people are getting? Because this is something that for some reason has not made the transition from science into pop culture. Right.

I think that's a placebo effect. And I say that because the majority of gummies are about like two megs, five megs, 20 megs maybe.

Yeah, yeah. I mean, THC and sleep is definitely a whole other thing. But sure, a lot of people report this with CBD. But again, so most CBD edibles or things that people take that are sold through commercial markets are in the range of 2 to 25 megs of CBD. So then I say to them, so you're aware that in the pediatric epilepsy studies, the dose ranges are like 1,500 to 2,000 makes.

And then you're talking about a child who weighs on the order of what, 20 kilos, maybe, you know, like 40, 60 pounds, somewhere in that range versus... So if you start dosing by weight, which is how most of these things are done, well, they'll say 20 megs per kg or whatnot.

So someone my size, so I weigh a bit over 200 pounds, for me to take that dose of CBD at let's say 20 megs per kg at like 90-odd kilos, I mean, you're talking about me taking – A liver-damaging dose of CBD. Insane. Maybe I wouldn't say damaging. It's definitely influencing how the liver metabolizes other things because it's going to saturate those enzymes. But you're taking a very high dose.

Yeah, I can't speak to that because I actually do not know the metabolism of alcohol well enough. I don't believe so because that's alcohol dehydrogenase. So that would probably be a separate enzyme pathway than the SIPS.

Yeah, but I don't know if it would have an effect in that capacity. I mean, they've definitely seen this, like they know the list of medications that this is a problem for. So it's things like warfarin and like blood thinners. Blood thinners. And the anti-epileptics funnel into the same metabolic pathway as this THC. So there's certain things that this would influence.

I don't know if I would say this would be in the context of alcohol, but I think more so, I mean, what I try and point out to people repeatedly is I have yet to see a blinded clinical study that has found any effect of CBD that's efficacious that's under 300 to 500 milligrams. And-

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