Dr. Matthew Hill

Whereas 2-AG seems to require a bit more concentration in the synapse to be able to bind to the receptor. So it has a lower affinity for the receptor. But once it binds to the receptor, it's like... pretty heavy duty. So it evokes a very robust intracellular signaling response. Why we have two endocannabinoids, we're not totally sure. Some of us have theories.

I'm of the camp that I think they may play somewhat differential roles, either based on the synapse or the circuit that they're working in, or this idea that maybe anandamide might be more of a tonic molecule. And what I mean by that is, we'll say it's like a stage setter. So like anandamide might just be kind of made by neurons on an ongoing basis and just released.

I'm of the camp that I think they may play somewhat differential roles, either based on the synapse or the circuit that they're working in, or this idea that maybe anandamide might be more of a tonic molecule. And what I mean by that is, we'll say it's like a stage setter. So like anandamide might just be kind of made by neurons on an ongoing basis and just released.

I'm of the camp that I think they may play somewhat differential roles, either based on the synapse or the circuit that they're working in, or this idea that maybe anandamide might be more of a tonic molecule. And what I mean by that is, we'll say it's like a stage setter. So like anandamide might just be kind of made by neurons on an ongoing basis and just released.

And its job may be to kind of keep the steady state of a brain circuit and a desired range. So that under resting conditions, it's not too active or too quiet.

And its job may be to kind of keep the steady state of a brain circuit and a desired range. So that under resting conditions, it's not too active or too quiet.

And its job may be to kind of keep the steady state of a brain circuit and a desired range. So that under resting conditions, it's not too active or too quiet.

So in that context, it kind of is like just the thermostat of the house. Whereas 2AG is like, let's say the pinch hitter. who gets brought in to do the heavy lifting. 2AG during a situation like, let's say, something even like a seizure as an extreme example, we have a huge amount of neural activity.

So in that context, it kind of is like just the thermostat of the house. Whereas 2AG is like, let's say the pinch hitter. who gets brought in to do the heavy lifting. 2AG during a situation like, let's say, something even like a seizure as an extreme example, we have a huge amount of neural activity.

So in that context, it kind of is like just the thermostat of the house. Whereas 2AG is like, let's say the pinch hitter. who gets brought in to do the heavy lifting. 2AG during a situation like, let's say, something even like a seizure as an extreme example, we have a huge amount of neural activity.

Those neurons that are getting heavily activated during massive amounts of neural activity start dumping out huge amounts of 2AG and that acts as the, okay, we really need to turn off this circuit very quickly in this situation.

Those neurons that are getting heavily activated during massive amounts of neural activity start dumping out huge amounts of 2AG and that acts as the, okay, we really need to turn off this circuit very quickly in this situation.

Those neurons that are getting heavily activated during massive amounts of neural activity start dumping out huge amounts of 2AG and that acts as the, okay, we really need to turn off this circuit very quickly in this situation.

And in most of these forms of like synaptic plasticity, like I was saying earlier, where you need to either strengthen or weaken a synapse in response to a change in the environment or in response to an experience or something that's going on, most of that is driven by 2AG signaling.

And in most of these forms of like synaptic plasticity, like I was saying earlier, where you need to either strengthen or weaken a synapse in response to a change in the environment or in response to an experience or something that's going on, most of that is driven by 2AG signaling.

And in most of these forms of like synaptic plasticity, like I was saying earlier, where you need to either strengthen or weaken a synapse in response to a change in the environment or in response to an experience or something that's going on, most of that is driven by 2AG signaling.

And so, you know, all these forms of like turning things up or down in a kind of rapid and on-demand manner, that's mostly 2AG. So most... people who study like neurophysiology and like record activity in neurons and look at endocannabinoids, they're almost entirely talking about 2-AG when they play with stuff. So yeah, that's kind of one of the ways we do it.

And so, you know, all these forms of like turning things up or down in a kind of rapid and on-demand manner, that's mostly 2AG. So most... people who study like neurophysiology and like record activity in neurons and look at endocannabinoids, they're almost entirely talking about 2-AG when they play with stuff. So yeah, that's kind of one of the ways we do it.

And so, you know, all these forms of like turning things up or down in a kind of rapid and on-demand manner, that's mostly 2AG. So most... people who study like neurophysiology and like record activity in neurons and look at endocannabinoids, they're almost entirely talking about 2-AG when they play with stuff. So yeah, that's kind of one of the ways we do it.

We say that anandamide may be more tonic and 2-AG might be more phasic and like brought online when needed, but doesn't do a lot. There is some evidence that 2-AG may also have a role to regulate some circuits under kind of resting conditions as well. And there certainly are some situations where anandamide might get brought into play. to affect plasticity, but