Endocannabinoid Signaling in the Brain

The primary psychoactive ingredient in cannabis, Delta9-tetrahydrocannabinol (Delta9-THC), affects the brain mainly by activating a specific receptor (CB1). CB1 is expressed at high levels in many brain regions, and several endogenous brain lipids have been identified as CB1 ligands. In contrast to classical neurotransmitters, endogenous cannabinoids can function as retrograde synaptic messengers: They are released from postsynaptic neurons and travel backward across synapses, activating CB1 on presynaptic axons and suppressing neurotransmitter release. Cannabinoids may affect memory, cognition, and pain perception by means of this cellular mechanism.