Cholecystokinin
CCK, CCK-8 (sulfated C-terminal octapeptide), CCK-33 / CCK-58 (longer native forms), pancreozymin (historical name), sincalide, Kinevac (US brand), ceruletide / Takus (frog-derived analogue, historical)
1What it is
Cholecystokinin ("gallbladder mover") was identified in 1928 by Ivy and Oldberg as the duodenal factor that makes the gallbladder contract after a meal. It is made by I cells of the upper small intestine in several lengths (8, 22, 33, 58 amino acids), all sharing the same active C-terminal end. The 8-amino-acid fragment with a sulfated tyrosine, CCK-8, is as active as the full hormone, and that is what sincalide is. CCK is also one of the most abundant peptides in the brain, where it acts as a neurotransmitter.
In medicine sincalide has been used since 1976 to make the gallbladder contract on demand. Combined with a hepatobiliary (HIDA) nuclear scan it gives a gallbladder ejection fraction, used to diagnose biliary dyskinesia; it is also used with secretin to collect pancreatic juice and to hurry barium through the small bowel. In research, CCK is famous as the first gut "satiety hormone": in 1973 Gibbs, Young and Smith showed that CCK injections made rats stop eating, which launched the modern field of gut–brain appetite signalling. Community/self-directed use: essentially none documented; CCK is far too short-acting to be useful outside a clinic, and the nausea it causes at effective doses has stopped every attempt to turn it into a weight-loss drug.
2How it's thought to work
3What the research shows
Gallbladder imaging and biliary dyskinesia
Pancreatic function and barium transit
Satiety in humans
Panic and anxiety (CCK-4)
Satiety and gut function in animals
4Reported side effects and interactions
Literature-reported
Literature (sincalide). abdominal discomfort or cramping and nausea are the most common (≥20% with bolus dosing; much less with slow infusion). Less often: vomiting, flushing, dizziness, headache, hypotension or hypertension, bradycardia, syncope, urge to defecate; rare serious hypersensitivity including anaphylaxis (the vial contains sulfite). Contraction can move small gallstones into the bile duct. Contraindicated in intestinal obstruction. The label warns it may cause preterm labour or miscarriage, so it is avoided in pregnancy.
Community-reported
none documented.Theoretical. sustained CCK exposure in animals causes pancreatic growth; no relevance to single diagnostic doses.
Interactions. opioids and anticholinergics alter gallbladder and sphincter response and can confound the test; secretin is given deliberately in combination for pancreatic testing.
Markers researchers commonly monitor
Sincalide is a diagnostic probe; the relevant readouts are: No long-term markers apply.
| Marker | Why it's watched |
|---|---|
| Gallbladder ejection fraction (cholescintigraphy) | the primary result of a sincalide-HIDA scan; <38% after a 60-minute infusion is the usual abnormal threshold. |
| Duodenal fluid enzyme output (lipase, amylase, trypsin) | in secretin–CCK pancreatic function testing. |
| Serum amylase/lipase | if post-test pain is prolonged. |
| Fasting/postprandial plasma CCK | a research measure only; assays are difficult and not clinically standardised. |
Free for everyone. Safety information is never behind a paywall.
5Reconstitution and handling
Supplied as 5 µg single-dose vials, in the clinic with 5 mL sterile water (1 µg/mL) and diluted further for infusion. Doses are in the microgram-per-kilogram range — a 70 kg adult receives 1.4 µg for a standard bolus. This is a hospital diagnostic; the site calculator is not relevant and no self-administered dose exists.
6Commonly studied alongside
Secretin (combined secretin–CCK pancreatic function test), GLP-1 and PYY (as fellow satiety hormones, often co-infused in physiology studies), semaglutide and other GLP-1 agonists (which, unlike CCK, became medicines). Discussed in relation to amylin and oxyntomodulin in multi-hormone obesity research.
Informational cross-links. Not stack recommendations.
7Regulatory status by region
| Region | Status (checked —) |
|---|---|
| United States | FDA-approved (Kinevac, Bracco; generic sincalide from several manufacturers). Recurrent shortages reported in 2016–2017 and 2022 † |
| European Union | No centrally authorised sincalide; ceruletide (Takus) was marketed historically and is largely discontinued. Availability via national/unlicensed routes † |
| United Kingdom | Not licensed; unlicensed import for specialist use † |
| Australia | Not on the ARTG; Special Access Scheme † |
| South Africa | Not registered † |
| Sport | Not listed by WADA |
8Open questions
- Does a low sincalide-stimulated ejection fraction reliably identify people who benefit from gallbladder removal?
- Can CCK1 agonism contribute usefully to multi-hormone obesity drugs without the nausea ceiling?
- What role does brain CCK play in human anxiety beyond the CCK-4 challenge model?
9References
- 1Bracco Diagnostics. Kinevac (sincalide for injection) — US prescribing information (2023 label). PubMed
- 2Gibbs J, Young RC, Smith GP (1973). Cholecystokinin decreases food intake in rats. J Comp Physiol Psychol. PubMed · DOI
- 3Kissileff HR et al. (1981). C-terminal octapeptide of cholecystokinin decreases food intake in man. Am J Clin Nutr. PubMed · DOI
- 4Lieverse RJ et al. (1995). Satiety effects of a physiological dose of cholecystokinin in humans. Gut. PubMed · DOI
- 5Beglinger C et al. (2001). Loxiglumide, a CCK-A receptor antagonist, stimulates calorie intake and hunger feelings in humans. Am J Physiol Regul Integr Comp Physiol. PubMed · DOI
- 6Jordan J et al. (2008). Stimulation of cholecystokinin-A receptors with GI181771X does not cause weight loss in overweight or obese patients. Clin Pharmacol Ther. PubMed · DOI
- 7Ziessman HA et al. (2001). Sincalide-stimulated cholescintigraphy: a multicenter investigation to determine optimal infusion methodology and gallbladder ejection fraction normal values. J Nucl Med. PubMed
- 8Bradwejn J, Koszycki D, Meterissian G (1990). Cholecystokinin-tetrapeptide induces panic attacks in patients with panic disorder. Can J Psychiatry. PubMed · DOI
- 9Rehfeld JF (2017). Cholecystokinin — from local gut hormone to ubiquitous messenger. Front Endocrinol. PubMed · DOI
References are being resolved to PubMed/DOI identifiers; links search PubMed for the citation until then.
† Being confirmed by our reviewers against current sources.
10Community
Threads and protocols are visible to members. Joining is free.
Self-reported side effects Phase 2
11Page history
Licensed CC BY-NC-SA 4.0. Found an error? Report it · Editorial standards — corrections are logged here.