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

And you can take a sativa and an indica that have virtually identical levels of THC and yet people will report very different intoxicating states that come out of that.

I mean, I have to believe the majority of that's an expectancy bias. I have a hard time believing that these things are really driven by fundamental biological differences within... Because anything else that's... I mean, that's the thing, like... Sure.

Some of the labs now, there is a movement to start looking at, can certain compositions of other things in cannabis start to maybe modulate or influence? This is called, like I think I've said this before, the entourage effect, this idea that THC alone might do one thing, but then layering in other things. Terpenes or minor cannabinoids may influence that effect. That is a theory.

That's not a thing that we know definitively in any way. And in fact, there's virtually no research that's ever been done to test this.

There's some stuff that's starting to come out now, like Ryan Vandery at Hopkins recently published a paper where they kind of, in a dose-dependent manner, added limonene, which is one of these terpenes, like I said, I think gives it like a citrusy odor, into the THC and did find at a really high dose, Probably a dose that I don't think you could actually find in cannabis.

It's a little bit higher than what you would have gotten there. But limonene did seem to be able to curb the ability of high dose THC to make someone feel anxious. And this was done in a blinded manner. So there's, I think, some validity to the interaction, whether that's occurring in cannabis, naturally, because of the levels of THC to limonene, I don't know.

But it really was one of the first demonstrations that adding in a terpene could actually influence a component of the intoxicated state in a blinded manner, I think is interesting. And Ziva Cooper, who's here at UCLA, is doing some work with beta-caryophyllene, which is probably... probably the second most abundant terpene, I think, from Nick Chikomas' work.

I think myrcene may have been the highest prevalent terpene across all types of cannabis. Beta-caryophyllene is probably the second, and limonene, I think, is probably the third. And So I think they, I mean, and so they're looking at, I think Ziva's work is in the context of pain.

So they're trying to look at if a fixed dose of THC, if you add in varying levels of beta-caryophyllene, does this influence this? So, because again, you do see this in patient communities where they say, well, this strain helps my pain better than that strain. And so it's like, okay, is there actual legitimacy to this?

Or again, is this just an expectancy bias because someone who sold this to you told you that this strain is better for pain? And the problem is these are all subjective endpoints. I mean, this is, Like pain, sleep, anxiety, these are all how someone personally experiences it.

And we know from all the clinical trials that study pain, sleep, and anxiety, there's massive placebo effects that happen in all these conditions. And so it's very difficult to actually make any kind of sound statements about this in the absence of there being kind of clinical trials that have clearly started to do this. But it's like, as you can imagine, when you start doing the math,

given the amount of terpenes and the amount of combinations at different levels, how overwhelming this could become. Because maybe, you know, there's a few that you need in there that interact with THC, not just one. There is like a lot of work that's happened in the last few years that has really started to try and look at if these terpenes or minor cannabinoids act at the cannabinoid receptor.

which none of them seem to. So this isn't like you've got things that modulate how THC is binding to CB1. If they're doing something else, it's probably through an interaction with another neurochemical system that's influencing what THC is doing. So I'm not against the idea that different chemovars or what people call strains of cannabis could do different things subjectively.

I just am remiss to believe this until I see some blinded data because I think outside of that, we know how powerful an expectancy bias is. So it makes it very, very challenging to make any kind of firm statements. And so kind of in the context of like how you introduced this, that was – again, I think like one of the issues that I took with the other podcast was because –

As you've said, I understand the thought process you went through. Like, you know, you had this paper where people were reporting subjective effects. There's some neuroimaging data that's been done with cannabis. You kind of said, okay, this is what that was, and that was what sativa did versus this is what indica did.

Yeah, I mean, I would say that's definitely not true nowadays. That pre-legalization anywhere outside of Colorado, that was true. People were gravitating there towards it.

So, I mean, the first thing that's interesting that I think a lot of people don't understand about CBD is CBD doesn't really exist in any form of street cannabis, and it hasn't for a very long time.

There's some. There's very, very low levels of CBD. And the reason that is, is because THC and CBD are both made from the same precursor molecule. And which direction it goes in is based purely on which synthetic enzyme converts it to either THC or CBD.

And so as people have clearly chased THC and wanted cannabis that's rich in THC, and so cannabis has been bred to become higher content in THC, by default, CBD has been bred out of the plant. And it has largely been bred out of the plant for quite some time.

And so this – I always find it interesting that there's this community that's like, oh, well, THC is the recreational cannabis and CBD is the medical cannabis. And I'm always like, that's bizarre because historically there's always been like THC has been what people have bred cannabis for.

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