Cholecystokinin (CCK) is a well-characterized endogenous gut-brain peptide hormone released by I-cells in the duodenum and jejunum in response to dietary fat and protein. It is one of the most extensively studied satiety hormones, with decades of research confirming its role in meal termination, gallbladder contraction, and pancreatic enzyme secretion. CCK acts via CCK-A (peripheral) and CCK-B (central) receptors. While its physiology is firmly established, therapeutic use for weight loss is limited by rapid tachyphylaxis (tolerance).
Category: Satiety / Gut-Brain Axis. Evidence rating: B (meaningful human data).
Clinical status: Well-characterized endogenous hormone. CCK-based drugs have not succeeded clinically for obesity due to tachyphylaxis.
CCK is released postprandially and activates CCK-A receptors on vagal afferent neurons, sending satiety signals to the nucleus tractus solitarius (NTS) in the brainstem. It simultaneously stimulates gallbladder contraction and pancreatic enzyme secretion to aid digestion. CCK-B receptors in the…
Safety considerations: Sincalide (CCK-8 analog) is FDA-approved as a diagnostic agent for gallbladder function, establishing a clinical safety profile; Common side effects: nausea, abdominal cramping, urgency; CCK-B receptor activation can trigger anxiety and panic attacks (CCK-4 is used as a panicogen in research).
Reviewed by the PeptideAtlas Editorial Team.
| Molecular weight | ~1143 g/mol (CCK-8 sulfated) |
|---|---|
| Half-life | 1-2 minutes (rapid enzymatic degradation) |
| Production method | bioactive |
| Anti-doping status | not-listed |
| US regulatory status | Sincalide (Kinevac) is FDA-approved as a diagnostic agent for gallbladder and pancreatic imaging. Not approved for weight loss. |
Acute CCK administration reduces meal size, but the body develops tolerance (tachyphylaxis) within days of repeated dosing. This has prevented development of CCK-based obesity drugs. Combination with other satiety signals (e.g., leptin, PYY) is an active area of research.
Sincalide (Kinevac) is a synthetic octapeptide analog of CCK-8 that is FDA-approved for diagnostic imaging of gallbladder contraction and pancreatic function. It is the only approved clinical application of CCK.
CCK-B receptors in the brain are anxiogenic when activated. CCK-4, a tetrapeptide fragment, is potent enough to reliably induce panic attacks in research settings and is used as a pharmacological tool to study panic disorder.
CCK is one of several hormones that contribute to postprandial satiety, along with PYY, GLP-1, and mechanical stretch receptors. It primarily mediates the meal-terminating signal rather than sustained fullness.