Dr. Matthew Hill

Both. So I think there's some contextual component to it. There was like, I mean, back in the 70s when they did more, let's say, interesting studies, there's one where basically they dosed people on THC and then had them undergo oral surgery, which seems like, in hindsight, a very bad idea. And I think virtually everyone in that study had a panic attack.

So it really potentiated the stress of what they were undergoing. And Had they been given that same dose in a different setting, I'm not sure it would have evoked that kind of response. But there is definitely a dose effect to this in terms of like, you know, the kind of classic low dose aspects of THC or cannabis that are usually considered more the positive, pleasurable aspects.

So it really potentiated the stress of what they were undergoing. And Had they been given that same dose in a different setting, I'm not sure it would have evoked that kind of response. But there is definitely a dose effect to this in terms of like, you know, the kind of classic low dose aspects of THC or cannabis that are usually considered more the positive, pleasurable aspects.

So it really potentiated the stress of what they were undergoing. And Had they been given that same dose in a different setting, I'm not sure it would have evoked that kind of response. But there is definitely a dose effect to this in terms of like, you know, the kind of classic low dose aspects of THC or cannabis that are usually considered more the positive, pleasurable aspects.

responses that are why people use, like it reduces anxiety, it relaxes, blah, blah, blah. That is more of like a low to normal-ish dose, let's say, of what someone consumes to produce those responses. If they start going upwards, though, it's not like it's graded. It's like a full flip. Like it's not linear at all. It's almost like it goes in the opposite direction.

responses that are why people use, like it reduces anxiety, it relaxes, blah, blah, blah. That is more of like a low to normal-ish dose, let's say, of what someone consumes to produce those responses. If they start going upwards, though, it's not like it's graded. It's like a full flip. Like it's not linear at all. It's almost like it goes in the opposite direction.

responses that are why people use, like it reduces anxiety, it relaxes, blah, blah, blah. That is more of like a low to normal-ish dose, let's say, of what someone consumes to produce those responses. If they start going upwards, though, it's not like it's graded. It's like a full flip. Like it's not linear at all. It's almost like it goes in the opposite direction.

So, you know, someone can use cannabis to reduce anxiety, but then cannabis can also trigger anxiety in other people and even in the same person if they consume too much. And a lot of this, at least, we think has to do with the ability of it to regulate both excitatory neurotransmission and inhibitory.

So, you know, someone can use cannabis to reduce anxiety, but then cannabis can also trigger anxiety in other people and even in the same person if they consume too much. And a lot of this, at least, we think has to do with the ability of it to regulate both excitatory neurotransmission and inhibitory.

So, you know, someone can use cannabis to reduce anxiety, but then cannabis can also trigger anxiety in other people and even in the same person if they consume too much. And a lot of this, at least, we think has to do with the ability of it to regulate both excitatory neurotransmission and inhibitory.

For reasons that we don't totally understand, there's way more cannabinoid receptors on inhibitory neurons than there is on excitatory neurons. But in the early days of creating the genetic lines, Giovanni Marsicano and Beat Lutz were over in Europe created deletion of CB1 only from excitatory neurons or only from inhibitory neurons.

For reasons that we don't totally understand, there's way more cannabinoid receptors on inhibitory neurons than there is on excitatory neurons. But in the early days of creating the genetic lines, Giovanni Marsicano and Beat Lutz were over in Europe created deletion of CB1 only from excitatory neurons or only from inhibitory neurons.

For reasons that we don't totally understand, there's way more cannabinoid receptors on inhibitory neurons than there is on excitatory neurons. But in the early days of creating the genetic lines, Giovanni Marsicano and Beat Lutz were over in Europe created deletion of CB1 only from excitatory neurons or only from inhibitory neurons.

full body deletion of CB1 and you give a mouse THC, it doesn't respond to it at all. Not surprisingly. That's a comforting experiment.

full body deletion of CB1 and you give a mouse THC, it doesn't respond to it at all. Not surprisingly. That's a comforting experiment.

full body deletion of CB1 and you give a mouse THC, it doesn't respond to it at all. Not surprisingly. That's a comforting experiment.

Yeah, exactly. So that's how we know CB1 drives all the kind of psychoactive effects of THC. So if you delete CB1 off of inhibitory GABA neurons, even though that removes like 70% of the CB1 receptors in the brain, those animals look just like wild type.

Yeah, exactly. So that's how we know CB1 drives all the kind of psychoactive effects of THC. So if you delete CB1 off of inhibitory GABA neurons, even though that removes like 70% of the CB1 receptors in the brain, those animals look just like wild type.

Yeah, exactly. So that's how we know CB1 drives all the kind of psychoactive effects of THC. So if you delete CB1 off of inhibitory GABA neurons, even though that removes like 70% of the CB1 receptors in the brain, those animals look just like wild type.

They still exhibit all the classic signs of intoxication in terms of how that would respond to pain sensitivity or locomotion or these other assays we use in mice to tell if they're high. If you delete the CB1 only off of excitatory neurons, the glutamate neurons, then you see what looks like the full knockout. So now the animals don't seem to get high.