Dr. Matthew Hill

through various mechanisms essentially turning off the electrical activity of that presynaptic neuron so that it stops releasing neurotransmitter. They can also regulate, though, inhibitory neurotransmitter release as well. And this is usually done through a little bit more of a complex process where it's driven by excitation, but then it regulates the inhibitory pathway.

So inhibiting the inhibitor leads to more excitation. Exactly. I usually liken it to basically taking the brakes off of a car while you're going downhill kind of thing. You'd use your braking system to keep things in check, but if you want to go faster, you take the foot off the brakes and you let things accelerate. And so this can be really important for things like...

So inhibiting the inhibitor leads to more excitation. Exactly. I usually liken it to basically taking the brakes off of a car while you're going downhill kind of thing. You'd use your braking system to keep things in check, but if you want to go faster, you take the foot off the brakes and you let things accelerate. And so this can be really important for things like...

So inhibiting the inhibitor leads to more excitation. Exactly. I usually liken it to basically taking the brakes off of a car while you're going downhill kind of thing. You'd use your braking system to keep things in check, but if you want to go faster, you take the foot off the brakes and you let things accelerate. And so this can be really important for things like...

forms of synaptic plasticity or neuroplasticity, let's say, where you want synaptic strengthening to happen. So like under a learning event or something, you want that synapse to really hardwire better. And so having endocannabinoids kind of turn off the inhibitory component is one of the mechanisms to facilitate that.

forms of synaptic plasticity or neuroplasticity, let's say, where you want synaptic strengthening to happen. So like under a learning event or something, you want that synapse to really hardwire better. And so having endocannabinoids kind of turn off the inhibitory component is one of the mechanisms to facilitate that.

forms of synaptic plasticity or neuroplasticity, let's say, where you want synaptic strengthening to happen. So like under a learning event or something, you want that synapse to really hardwire better. And so having endocannabinoids kind of turn off the inhibitory component is one of the mechanisms to facilitate that.

But at the same time, if you want to have a bit more adaptive flexibility, endocannabinoids can weaken that synapse at the same time by acting right at the excitatory terminal itself. And so their ability to kind of play with the relative activity of a circuit is really dependent on which neuron they're acting on. And so they can regulate excitation or inhibition differentially.

But at the same time, if you want to have a bit more adaptive flexibility, endocannabinoids can weaken that synapse at the same time by acting right at the excitatory terminal itself. And so their ability to kind of play with the relative activity of a circuit is really dependent on which neuron they're acting on. And so they can regulate excitation or inhibition differentially.

But at the same time, if you want to have a bit more adaptive flexibility, endocannabinoids can weaken that synapse at the same time by acting right at the excitatory terminal itself. And so their ability to kind of play with the relative activity of a circuit is really dependent on which neuron they're acting on. And so they can regulate excitation or inhibition differentially.

And I mean, CB1 receptors are found on virtually every single kind of neuron in the brain, except one. I think you'll find this interesting because it's dopamine. And dopamine neurons are basically the only neurons in the brain that don't really, at least as far as we've been able to characterize to date, express cannabinoid receptors.

And I mean, CB1 receptors are found on virtually every single kind of neuron in the brain, except one. I think you'll find this interesting because it's dopamine. And dopamine neurons are basically the only neurons in the brain that don't really, at least as far as we've been able to characterize to date, express cannabinoid receptors.

And I mean, CB1 receptors are found on virtually every single kind of neuron in the brain, except one. I think you'll find this interesting because it's dopamine. And dopamine neurons are basically the only neurons in the brain that don't really, at least as far as we've been able to characterize to date, express cannabinoid receptors.

I wouldn't say that cannabinoids don't affect dopamine because what we understand in the ventral tegmental area, which is kind of a hotspot of dopamine neurons, or at least the ones that are involved in motivation and stuff, those neurons are regulated by a lot of inhibitory neurons that dump out inhibitory transmitter and keep those neurons kind of quiet.

I wouldn't say that cannabinoids don't affect dopamine because what we understand in the ventral tegmental area, which is kind of a hotspot of dopamine neurons, or at least the ones that are involved in motivation and stuff, those neurons are regulated by a lot of inhibitory neurons that dump out inhibitory transmitter and keep those neurons kind of quiet.

I wouldn't say that cannabinoids don't affect dopamine because what we understand in the ventral tegmental area, which is kind of a hotspot of dopamine neurons, or at least the ones that are involved in motivation and stuff, those neurons are regulated by a lot of inhibitory neurons that dump out inhibitory transmitter and keep those neurons kind of quiet.

So there's an opportunity for indirect response. Exactly. So what you have is those neurons that regulate the dopamine neurons are very rich in cannabinoid receptors. This is actually kind of similar to how mu opioid receptors work for things like morphine or heroin. And essentially what the cannabinoid receptors will do is when they're activated, they'll turn off that inhibitory control.

So there's an opportunity for indirect response. Exactly. So what you have is those neurons that regulate the dopamine neurons are very rich in cannabinoid receptors. This is actually kind of similar to how mu opioid receptors work for things like morphine or heroin. And essentially what the cannabinoid receptors will do is when they're activated, they'll turn off that inhibitory control.

So there's an opportunity for indirect response. Exactly. So what you have is those neurons that regulate the dopamine neurons are very rich in cannabinoid receptors. This is actually kind of similar to how mu opioid receptors work for things like morphine or heroin. And essentially what the cannabinoid receptors will do is when they're activated, they'll turn off that inhibitory control.

And that allows dopamine neurons to kind of move into a state where they're more prone to go into burst firing and have big dumps of dopamine. Whether or not that relates to, you know, the positive affect or the euphoria, I don't think anyone has... cleanly demonstrated that. I mean, obviously dopamine's very complicated in terms of its relation to endpoints and whether it's reward or motivation.