Cholecystokinin, formerly called pancreozymin, is synthesized and secreted by enteroendocrine cells in the duodenum, the first segment of the small intestine.

[7][8] In 1903, the French physiologist Émile Wertheimer [fr] showed that this reflex was not mediated by the nervous system.

[9] In 1904, the French physiologist Charles Fleig showed that the discharge of bile was mediated by a substance that was conveyed by the blood.

[10] There remained the possibility that the increased flow of bile in response to the presence of acid in the duodenum might be due to secretin, which had been discovered in 1902.

The problem was finally resolved in 1928 by Andrew Conway Ivy and his colleague Eric Oldberg of the Northwestern University Medical School, who found a new hormone that caused contraction of the gall bladder and that they called "cholecystokinin".

[13][14][15] Swedish biochemists Johannes Erik Jorpes and Viktor Mutt undertook the monumental task of isolating and purifying porcine cholecystokinin and then determining its amino acid sequence.

Nonsulfated CCK peptides also occur, which consequently cannot activate the CCK-A receptor, but their biological role remains unclear.

[17][19] CCK plays important physiological roles both as a neuropeptide in the central nervous system and as a peptide hormone in the gut.

[21][22] CCK has been researched thoroughly for its role in digestion[23] In addition to its role in digestion, CCK is involved in regulating various behavioral phenomena, including satiety, appetite, anxiety, thermoregulation, sexual behavior, memory, and the response to drugs of abuse, particularly within the cortex and limbic regions of the brain.

[5][6] Bile salts form amphipathic lipids, micelles that emulsify fats, aiding in their digestion and absorption.

[26] The site of the anxiety-inducing effects of CCK seems to be central with specific targets being the basolateral amygdala, hippocampus, hypothalamus, periaqueductal grey, and cortical regions.

[26][33] The CCK tetrapeptide fragment CCK-4 (Trp-Met-Asp-Phe-NH2) reliably causes anxiety and panic attacks (panicogenic effect) when administered to humans and is commonly used in scientific research for this purpose of in order to test new anxiolytic drugs.