Cholecystokinin
Also known as: CCK, CCK-8, CCK-33, CCK-58, sincalide, Kinevac, cholecystokinin-pancreozymin, CCK-PZ, sulfated CCK-8, sCCK-8
Endogenous gastrointestinal peptide hormone; neuropeptide; gut-brain axis signaling molecule
What it is
Cholecystokinin (CCK) is a hormone your gut releases naturally after eating fat and protein, triggering gallbladder contraction, pancreatic enzyme release, and a powerful fullness signal to your brain. A synthetic form called sincalide (Kinevac) is FDA-approved for diagnostic gallbladder imaging, but CCK itself is not approved as a therapeutic drug.
The scientific side
Cholecystokinin is described as a peptide hormone produced and released primarily by enteroendocrine I-cells of the upper small intestine in response to dietary fat and protein. CCK exists in multiple molecular forms (CCK-8, CCK-33, CCK-58) all sharing an identical sulfated C-terminal octapeptide bioactive core. Its actions are mediated through two main G protein-coupled receptors: CCK1R (formerly CCKA) and CCK2R (formerly CCKB), both of which activate phospholipase C and adenylyl cyclase signaling cascades. CCK1R is the dominant peripheral receptor expressed in gallbladder smooth muscle, pancreatic acinar cells, gastric smooth muscle, and the vagal afferent neurons of the gut-brain axis. CCK2R is distributed more broadly in both the gastrointestinal tract and the central nervous system, including the cerebral cortex and hippocampus. Through CCK1R, CCK induces gallbladder contraction (via acetylcholine release from the myenteric cholinergic network), relaxes the sphincter of Oddi to permit bile flow into the duodenum, stimulates pancreatic enzyme secretion, and inhibits gastric emptying, all of which coordinate digestion of fat and protein. Centrally, CCK — particularly through hindbrain CCK1R — suppresses food intake by inducing satiety; postprandial CCK release interacts with vagal afferents projecting to the nucleus tractus solitarius, and inhibits orexigenic peptides in the hypothalamus. Although postprandial CCK elevation alone is insufficient for complete satiety signaling, it acts synergistically with other gut hormones. CCK also stimulates beta-cell proliferation in the pancreas, potentially enhancing insulin secretory capacity. In cardiac tissue, sulfated CCK-8 acting on CCK1R on sinoatrial node pacemaker cells slows spontaneous firing by reducing phase 4 depolarization. CCK2R expressed in the central nervous system is a historic target for pain management, modulating opioid analgesia in both naive and chronic pain states. Prior clinical attempts to exploit CCK1R agonism for obesity treatment with full agonists failed, potentially due to receptor desensitization and disruption of normal CCK1R signaling by cellular cholesterol. Newer strategies exploring biased agonists and positive allosteric modulators aim to preserve receptor specificity and avoid tachyphylaxis.
Class: Endogenous gastrointestinal peptide hormone; neuropeptide; gut-brain axis signaling molecule
Administration & storage
- Administration
- Intravenous infusion over 60 minutes (sincalideFDA-approved diagnostic use for gallbladder ejection fraction)Intravenous bolus injection (historic — now discouraged for GBEF due to falsely low ejection fractions from rapid receptor stimulation)Intravenous infusion for pancreatic function stimulation (diagnostic use)Subcutaneous or intravenous infusion in experimental human satiety studies (research use only)
- Storage
- Sincalide (Kinevac) lyophilized vials: store at room temperature, 15–30°C (59–86°F). Protect from light. Reconstituted solution should be used promptly; discard unused portions. Research-grade CCK peptides: typically stored lyophilized at -20°C or lower; reconstituted peptide solutions should be stored at -80°C and avoid repeated freeze-thaw cycles.
- Cautions
- Sincalide is for diagnostic use only and must be administered under the supervision of a physician trained in nuclear medicine or diagnostic radiology.,Rapid IV bolus of sincalide can cause nausea, abdominal cramping, and dizziness; slow 60-minute infusion substantially reduces these adverse effects.,CCK1R agonist administration (including sincalide) can produce abdominal pain and nausea mediated by gallbladder smooth muscle contraction — particularly in patients with active gallstones or biliary obstruction.,Exogenous CCK infusion in research settings has produced panic-like anxiety symptoms in some human subjects via central CCK2R activation; this effect is dose-dependent.,No therapeutic CCK formulation is approved for self-administration; research-grade CCK peptides should not be used outside controlled clinical or research settings.
Legal & regulatory status
CCK as an endogenous peptide is not approved as a therapeutic drug. Sincalide (synthetic CCK-8, brand name Kinevac, Bracco Diagnostics), a C-terminal octapeptide fragment of CCK, is FDA-approved as a diagnostic imaging…
Cholecystokinin and its analogs (including sincalide) are not listed on the current WADA Prohibited List. CCK is an endogenous hormone with no established performance-enhancing application in sport. Its diagnostic use…
No Health Canada approval has been identified for CCK or sincalide as therapeutic agents in the reviewed literature. Sincalide/Kinevac is recognized in Canadian nuclear medicine practice for hepatobiliary scintigraphy…
What it's studied for
- Gallbladder function assessment and cholescintigraphy (sincalide diagnostic use) FDA-approved diagnostic use; multiple retrospective and prospective clinical studies
- Satiety signaling and appetite/food intake regulation Human and animal studies; prior Phase II clinical evidence; mechanism established
- Pancreatic enzyme secretion stimulation (diagnostic and physiological) Established physiological mechanism; human studies
- Gastrointestinal motility regulation (gallbladder contraction and gastric emptying) Established physiological and mechanistic studies
- Pain modulation and opioid system interaction (CCK2R-targeted research) Preclinical and early-stage research; historic clinical investigation
- Cardiac pacemaker rate modulation (CCK1R signaling in sinoatrial node) Preclinical — mechanistic study
- Anxiety and neuropsychiatric effects (CNS CCK2R signaling) Preclinical; limited clinical data
Safety signals
- Nausea, abdominal cramping, and dizziness from rapid sincalide infusion
- Panic-like anxiety and psychoactive effects from exogenous CCK infusion (CCK2R-mediated)
- Potential pancreatic hypertrophy and carcinogenesis promotion (CCK1R overstimulation)
- Cardiac chronotropic effect (slowing of heart rate via CCK1R on pacemaker cells)
- Biliary colic or pain in patients with cholelithiasis
- CCK system genetic variants associated with neuropsychiatric risk
Contraindications
About these dose ranges
Dose ranges below reflect commonly reported community protocols. Where published research cites a specific dose, the PMID is linked. Doses without citations are not clinical recommendations — they reflect what practitioners and researchers commonly report using.
Community-reported dosing
| Route | Dose | Frequency / Duration | Population / context | Source tier |
|---|---|---|---|---|
| Unspecified | 0.02 µg/kg IV sincalide | — | Adults — hepatobiliary scintigraphy / gallbladder ejection fraction (diagnostic) | Research |
| Unspecified | 0.02 µg/kg IV sincalide | — | Adults — pancreatic secretion stimulation (diagnostic) | Research |
| Unspecified | Nanomolar concentrations (typically 0.5–3 nmol/kg/h IV infusion); species and protocol variable | — | Human experimental volunteers — satiety/food intake studies | Research |
| Unspecified | Variable; oral CCK1R agonists studied at mg-level doses | — | Obese patients — failed clinical trials (CCK1R agonist; not sincalide) | Research |
| intravenous infusion | 0.02 µg/kg sincalide IV | single dose per diagnostic study | adults undergoing hepatobiliary scintigraphy for suspected gallbladder dysfunction |
No peer-reviewed studies indexed for this peptide yet.