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

So I think that's more typically in a lab setting, how you would define if someone's high or not from it. And this is why when people do studies with something like a placebo cannabis or a very low THC cannabis, you'll see kind of a scaling. So, um,

Even if you give someone a placebo cannabis, if they think that they're getting cannabis, a lot of people still respond by saying they feel a bit high.

I'm not actually certain if you are allowed to have someone in a drug study if they've never done something before. I think they have to have had some previous experience with a drug to be enrolled.

Yeah, but I think, yeah, I don't think you can use drug-naive people. I mean, I don't run human clinical lab studies, so I can't explicitly say it, but that's my understanding is that someone has to have had even limited, like, not much, but at least once or twice. They have to have experienced the drug before.

So I don't know if you would take someone who was completely blind because I don't know how they would replicate that state if they're not expecting it.

I wouldn't say it's well worked out. There definitely seems to be some like temporal dilation, like you're saying, where people think things of, you know, someone will be high and someone will ask them, how long do you think time has passed? They would report usually longer periods of time have passed than actually have.

I feel like there is some older work I could dig up to see if I could find that is either in like, it might even be in pigeons, but it might be in rodents that's looking at like temporal ordering and they give animals cannabinoids. And that's kind of a cleaner way of seeing because they are very good at learning. Like if I wait 10 minutes and then I engage in a behavior, I get a reward.

And so you can really train animals to have this ordinal timing where they kind of know distinct periods of time. And if they give them cannabinoids, they respond differently. So in that context, it does still seem to produce some state where there's an altered perception of time passing.

And so I think if we were going to really understand the mechanism of it, that would probably be the way to go. But I'm not super familiar with the work because no one's... I mean, anything I can think of is pretty old. I can't think of anything modern where people have actually looked at this. Interesting.

I think we almost need to take a step back actually to talk about how cannabis works in the brain before we kind of go into that. So THC as a molecule exerts almost all its effects. They're acting at this one receptor for the most part that's widely expressed through the brain called the cannabinoid type 1 receptor. CB1. Yeah, CB1 is the shorthand for it.

And I think, you know, as people tend to create analogies to describe what receptors are, for those of you who don't know, most people use like a lock and key analogy that like a receptor would be a protein that sits on a cell and a molecule that binds to it like THC is the key that fits in that lock. When it activates it, it triggers some biological process in the cell, in this case a neuron.

that changes its activity in some capacity. And so THC acts on these CB1 receptors, which are very widely expressed. In fact, outside of like kind of ion channels that are expressed in the brain, the CB1 is, I think, one of the most, if not the most widely expressed receptor in the brain. It's everywhere. So it's really important.

And I think as kind of you had alluded to previously, it doesn't exist in the, you know, this didn't evolve in humans in the hopes that one day humans would find cannabis.

I know people love to leverage things. If it's a plant, it's natural and safe. And there's obviously issues we'll talk about with that. But I mean, really, this is just biological redundancy. I mean, nature only has so many ways to create something. And so there's going to be things that end up overlapping in the way that they function.

And so the receptor that's in the brain and throughout the body, the CB1, and there is also a CB2 receptor. It's not really expressed in the brain. It's in some of the immune cells in the brain and maybe some limited distribution in actual brain cell neurons. Where in the body is it expressing? It's mostly immune cells. So you'll see CB2s mostly on like macrophages or other kind of immune cells.

Cells that gobble up debris. Yeah. And that basically, you know, regulate inflammatory processes. And so the main role of CB2 seems to be much more about like regulating inflammation. So that's kind of a separate role that can certainly impact the brain in different ways.

But when we talk about the effects on the central nervous system and the brain and behavior, we're talking almost entirely about CB1. And so both the CB1 and CB2 receptors, like I said, don't exist because nature was like, humans are going to find cannabis. This will all work together now. So there are molecules our body produces, which we call endocannabinoids.

And they are kind of funny little molecules because they don't really behave. Like certainly in the brain, they don't behave like a normal neurotransmitter. So, I mean, I assume most people who listen to your podcast are relatively adept with the basic idea of how neurons work.

So you have neuron A, let's call it the presynaptic neuron because you have that gap between the two cells where they communicate called the synapse. So neuron A works. releases a transmitter, and it can be something that excites the neighboring cell, neuron B, or it can inhibit it.

And so the way that we always kind of talk about neurotransmission in the brain is neuron A releases a chemical that crosses the synapse, acts on neuron B, and it can either jack that neuron's activity up or it can scale it down. And that affects brain-wide patterns of activity.

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