The endocannabinoid system & CB1 retrograde signaling |

1.5-minute animation created for CME event.

Our assignment included the development of the science story and creation of key events that would inform and educate viewers on the physiologic functions associated with the endocannabinoid system (ECS), the role of CB1 retrograde signaling, as well as the enzymes involved in the degradation of endocannabinoids.

We had the pleasure and honor of collaborating closely with the speaker of this event; she is also noted for her discovery of the CB1 receptor for cannabinoid agonists.

The target audience included neurologists, primary care physicians, and pediatricians.

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As the animation opens, we bring our focus to a single synapse within the central nervous system where we can see excessive presynaptic neuronal activity, as well as excessive neurotransmitter release.

Our view pushes in towards the postsynaptic neuron.

Activation of the post-synaptic receptors stimulates the synthesis of 2-AG from the membrane of the postsynaptic neuron. We can see 2-AG endocannabinoids emerging from the phospholipid bilayer, traveling upwards across the synaptic cleft, and arriving on the presynaptic side.

Here on the presynaptic neuron, we can see Ca2+ membrane channels and CB1 receptors on the surface. Ca2+ flows into/through the open membrane channels.

As our hero 2-AG binds to a CB1 receptor on the presynaptic neuron, we can see that activated CB1 receptors lead to a reduction in Ca2+ influx – and a reduction in neurotransmitter release from the presynaptic neuron.

The final two sequences show 2-AG being removed by hydrolysis (FAAH and MAGL are involved), and how THC acts as an agonist at the CB1 receptor, effectively performing the same action as 2-AG by directly targeting CB1 receptors on the presynaptic cleft.