Dr. Matthew Hill

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.

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.

So even though the majority of CB1 receptors seem to be on these inhibitory GABA neurons, It's the CB1 on the glutamatergic excitatory neurons that mediate most of the classic signs of what we would consider intoxication from THC or cannabis. But what's interesting is Biat worked with the Spanish group 10, 12 years ago.

So even though the majority of CB1 receptors seem to be on these inhibitory GABA neurons, It's the CB1 on the glutamatergic excitatory neurons that mediate most of the classic signs of what we would consider intoxication from THC or cannabis. But what's interesting is Biat worked with the Spanish group 10, 12 years ago.

So even though the majority of CB1 receptors seem to be on these inhibitory GABA neurons, It's the CB1 on the glutamatergic excitatory neurons that mediate most of the classic signs of what we would consider intoxication from THC or cannabis. But what's interesting is Biat worked with the Spanish group 10, 12 years ago.

Then they showed they're looking at anxiety that if you delete CB1 only off of excitatory neurons, you lose the anti-anxiety anxiolytic effects of THC. but you still have the panicky, anxiogenic effects of high dose. If you delete CB1 off of only the inhibitory GABA neurons, you still have the low dose anti-anxiety effect, but now you don't have the high dose, anxiogenic, panicky effect.

Then they showed they're looking at anxiety that if you delete CB1 only off of excitatory neurons, you lose the anti-anxiety anxiolytic effects of THC. but you still have the panicky, anxiogenic effects of high dose. If you delete CB1 off of only the inhibitory GABA neurons, you still have the low dose anti-anxiety effect, but now you don't have the high dose, anxiogenic, panicky effect.

Then they showed they're looking at anxiety that if you delete CB1 only off of excitatory neurons, you lose the anti-anxiety anxiolytic effects of THC. but you still have the panicky, anxiogenic effects of high dose. If you delete CB1 off of only the inhibitory GABA neurons, you still have the low dose anti-anxiety effect, but now you don't have the high dose, anxiogenic, panicky effect.

So what that was suggesting was that For some reason, THC will initially hit CB1 on kind of glutamatergic neurons. And essentially, the thought is this will reduce excitatory transmission and probably quiet down circuits. And if we're talking about something like the amygdala, this is probably how it's reducing anxiety.

So what that was suggesting was that For some reason, THC will initially hit CB1 on kind of glutamatergic neurons. And essentially, the thought is this will reduce excitatory transmission and probably quiet down circuits. And if we're talking about something like the amygdala, this is probably how it's reducing anxiety.

So what that was suggesting was that For some reason, THC will initially hit CB1 on kind of glutamatergic neurons. And essentially, the thought is this will reduce excitatory transmission and probably quiet down circuits. And if we're talking about something like the amygdala, this is probably how it's reducing anxiety.

Whereas as dosing starts to increase and you start to saturate the CB1 on the GABA neurons and turn off inhibition, then the network effect is more of an amplification. And that seems to result in the development of kind of an anxiogenic pro-anxiety response that's obviously undesirable. Why there's this differential shift, it's not exactly clear.

Whereas as dosing starts to increase and you start to saturate the CB1 on the GABA neurons and turn off inhibition, then the network effect is more of an amplification. And that seems to result in the development of kind of an anxiogenic pro-anxiety response that's obviously undesirable. Why there's this differential shift, it's not exactly clear.

Whereas as dosing starts to increase and you start to saturate the CB1 on the GABA neurons and turn off inhibition, then the network effect is more of an amplification. And that seems to result in the development of kind of an anxiogenic pro-anxiety response that's obviously undesirable. Why there's this differential shift, it's not exactly clear.

I mean, it's probably either due to some of the biology of exactly where the CB1 receptors sit, on excitatory or inhibitory neurons relative to all the machinery that regulates transmitter release. I mean, Beat Lutz has definitely done some stuff looking at the ability of cannabinoid receptors to evoke signaling responses in a cell.

I mean, it's probably either due to some of the biology of exactly where the CB1 receptors sit, on excitatory or inhibitory neurons relative to all the machinery that regulates transmitter release. I mean, Beat Lutz has definitely done some stuff looking at the ability of cannabinoid receptors to evoke signaling responses in a cell.

I mean, it's probably either due to some of the biology of exactly where the CB1 receptors sit, on excitatory or inhibitory neurons relative to all the machinery that regulates transmitter release. I mean, Beat Lutz has definitely done some stuff looking at the ability of cannabinoid receptors to evoke signaling responses in a cell.

And on glutamate neurons, they're much more sensitive than they are in GABA neurons. So there's probably a dose threshold. So it does look like this kind of low dosing, what most people are trying to achieve, I would assume, when they consume cannabis is probably these effects mediated by quieting down excitatory transmission.

And on glutamate neurons, they're much more sensitive than they are in GABA neurons. So there's probably a dose threshold. So it does look like this kind of low dosing, what most people are trying to achieve, I would assume, when they consume cannabis is probably these effects mediated by quieting down excitatory transmission.

And on glutamate neurons, they're much more sensitive than they are in GABA neurons. So there's probably a dose threshold. So it does look like this kind of low dosing, what most people are trying to achieve, I would assume, when they consume cannabis is probably these effects mediated by quieting down excitatory transmission.