Gamma-aminobutyric acid (GABA)

Gamma-aminobutyric acid, or GABA, is the main inhibitory neurotransmitter in the brain and spinal cord, the chemical that tells neurons to fire less.

Neurons make GABA from glutamate, the brain's chief excitatory messenger, using the enzyme glutamate decarboxylase, so the two exist in a kind of chemical balance. Released GABA binds two receptor types: GABA-A, an ion channel that lets chloride into the cell and makes it harder to fire within milliseconds, and GABA-B, a slower G protein-coupled receptor. A substantial share of brain neurons are GABAergic, and their inhibition shapes everything from muscle tone to the pacing of sleep. Alcohol, benzodiazepines and most anesthetics act on GABA-A receptors.

GABA enters cannabinoid discussions because CB1 receptors sit on many GABA-releasing terminals, where endocannabinoids briefly reduce GABA release. CBD does not act as a GABA-like sedative; a few laboratory studies describe it as a weak positive modulator of GABA-A receptors, and that finding has not been shown to explain any effect in people.