cannabinoid

Endocannabinoids are retrograde neurotransmitters, meaning that they pass 'backwards' (from dendrite to axon) through the synaptic cleft.

Two types of cannabinoid receptors: CB1 is found mostly in the brain and CB2 mostly in the immune system. Most endocannabinoids bind to both, but other non-endogenous cannabinoids like THC only bind to one or the other (THC is a partial agonist of CB1).

Cannabinoids are lipid-based, which gives them unusual properties: they can diffuse through cell membranes (lipid bilayers), but because they're hydrophobic they can't travel far through extracellular fluids.

Youtube comments imply that THC is effective because it hits uniformly, whereas endocannabinoids are more locally concentrated:

Q: I wonder why, when active THC is only a partial agonist of the CB1 receptor, it still has a greater response than the higher efficacy endogenous ligands.. Are the endogenous full agonists just present in such low concentrations, or only released by certain stimuli so we don't experience an all-time high?

A: 2-AG is actually the more common endogenous ligand for the CB1 receptor in the brain, although anandamide is definitely part of it. endocannabinoids are retrograde messengers, and because they are lipid based they can diffuse through the membrane of the postsynaptic cell and bind the CB1 receptors on the presynaptic cell, inhibiting neurotransmitter release. The mechanism is meant to be a negative feedback loop, and only active at certain synapses at specific times. THC effects pretty much the whole brain at one (CB1 is the most common g-protein-coupled receptor in the brain), suppressing a very high number of synapses for an extended amount of time.

To read: Cannabinoid signaling , for its own sake and as an example of how people think about cellular signaling