ENDOCANNABINOIDS Kaitlyn Schmieder

Definition: Family of related endogenous signals that interact with cannabinoid receptors. These cannabinoid receptors are the same receptors that are
activated by cannabinoids such as THC, which is the active ingredient in Cannabis Sativa. Importantly, the endocannabinoid system is active in your body
regardless of whether you use marijuana, because it’s important for many bodily functions.
Type: Small molecule, unconventional neurotransmitters. Like the classical neurotransmitters, they are involved in neural communication and their release
is regulated by calcium, but they are not stored in vesicles or released in a traditional manner from the presynaptic terminal. The two main endocannabinoids that
we know of are anandamide and 2-arachidonylglycerol (2-AG). They are unsaturated fatty acids with polar head groups.
Precursors: Present in the lipid membrane and include a family of glycerophospholipids called NArPEs.
Synthesis: Stimulated by a second messenger in the postsynaptic cell that causes an increase in calcium ion concentration. Synthesized on demand.
Release: Signals can diffuse through the postsynaptic membrane due to their hydrophobic quality to reach cannabinoid receptors on other cells.
Receptors: Two main types of cannabinoid receptors called CB1 and CB2. Both are G-protein coupled receptors. Most research focuses on the CB1
receptors because they are most prevalent in the CNS, but more recent research focuses on the role of CB2 receptors in the immune system.
Postsynaptic Effects: Powerful influence on synaptic transmission because they can regulate neural communication via retrograde transmission.
After traveling backward from the postsynaptic cell, they bind to a receptor on the presynaptic cell. This activation inhibits calcium channels, activates potassium
channels, and interferes with vesicle release, and the result is an inhibition of presynaptic GABA or glutamate release. In this way, depolarization of the
postsynaptic neuron reduces synaptic transmission.
Location: Primary locations of CB1 receptors are the hippocampus and the cerebellum, which explains the difficulties with both memory and
coordination that marijuana users experience. CB1 receptors also found in the substantia nigra and caudate putamen, which are areas implicated in drug abuse.
Functions: Pain reduction, relaxing, eating, sleeping, and forgetting. Rodent studies show that they also play a role in memory and emotion regulation.
Research: Endocannabinoid system is implicated in anxiety and essential for forgetting avoidance behaviors that underlie anxiety.
Micale, Vincenzo; Stepan, Jens; Jurik, Anjela; et al. (July 2017). Extinction of avoidance behavior by safety learning depends on endocannabinoid signaling in
the hippocampus. Journal of Psychiatric Research, 90 (3), 46-59.