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)

Recovery, repair & tissue

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Note on this profile. Sincalide is an approved prescription diagnostic given intravenously during gallbladder imaging and pancreatic function tests. It is not a research-use or self-administered compound and there is no documented community use. This page explains the hormone and the published science.

Summary

Class: Naturally occurring gut hormone; sincalide is the synthetic sulfated 8-amino-acid C-terminal fragment (CCK-8), which carries essentially all of the biological activity
Mechanism: Released by duodenal I cells after a fatty or protein-rich meal; contracts the gallbladder, drives pancreatic enzyme secretion, slows stomach emptying and signals fullness to the brain via the vagus nerve
Routes studied: Intravenous bolus or infusion (approved); intravenous infusion in appetite research; intranasal and oral analogues investigated
Half-life: Native CCK circulates for only ~2–3 minutes; sincalide's gallbladder effect peaks 5–15 minutes after a bolus
Storage: Lyophilised vials at room temperature (25 °C); reconstituted solution discarded after 8 h, diluted solution after 1 h
Regulatory status: FDA-approved (Kinevac and generic sincalide, US); Health Canada; limited availability elsewhere †

Doses are as reported in studies or by the community — never recommendations.

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

Two receptors. CCK1 (formerly CCK-A), found on gallbladder smooth muscle, pancreatic acinar cells and vagal afferent nerves; and CCK2 (CCK-B), found mainly in the brain and on gastric parietal cells, which also binds gastrin.

Digestion. CCK1 activation contracts the gallbladder, relaxes the sphincter of Oddi, releases pancreatic enzymes and slows gastric emptying — coordinating the arrival of bile and enzymes with food.

Satiety. CCK released after a meal activates CCK1 receptors on vagal nerve endings in the gut wall, which relay to the brainstem (nucleus of the solitary tract) and hypothalamus, ending the meal earlier. This is a short-term "stop eating now" signal rather than a long-term body-weight regulator; animals compensate by eating more meals.

Brain. CCK2 receptors are involved in anxiety and panic. The 4-amino-acid fragment CCK-4 reliably provokes panic attacks in volunteers and is used as an experimental panic model.

CCK released by the duodenum in response to fat and protein. Three answers at once: the gallbladder contracts and sends bile, the pancreas releases digestive enzymes, and a signal reaches the brainstem that contributes to feeling full.Schematic — not to scale

3What the research shows

Gallbladder imaging and biliary dyskinesia

Sincalide-stimulated cholescintigraphy is the standard test for functional gallbladder disorder; a 60-minute infusion (0.02 µg/kg) gives the most reproducible ejection fraction, with <38% commonly taken as abnormal (Ziessman 2001 and 2010, J Nucl Med; SNMMI consensus 2010). Whether a low ejection fraction predicts benefit from cholecystectomy remains debated. [7]

Pancreatic function and barium transit

Label indications supported by decades of clinical use; evidence is older and largely descriptive rather than from modern .

Satiety in humans

Intravenous CCK-8 or CCK-33 infusions reduce meal size by roughly 15–30% in lean and obese volunteers (Kissileff 1981, Am J Clin Nutr; Lieverse 1995, Gut), and a CCK1 antagonist (loxiglumide) increases food intake (Beglinger 2001, Am J Physiol), confirming that endogenous CCK contributes to satiety. The effect is short-lived, requires near-nauseating doses for a large effect, and chronic dosing in animals produces compensation. Oral CCK1 (e.g. GI181771X) failed to produce weight loss in a 24-week trial (Jordan 2008, Clin Pharmacol Ther). CCK agonism survives today mainly as a component in multi-hormone obesity combinations under early study. [3][4][5][6]

Graded A (as a challenge model)

Panic and anxiety (CCK-4)

CCK-4 injection induces panic in most panic-disorder patients and many healthy volunteers (Bradwejn 1990, Can J Psychiatry; de Montigny 1989, Arch Gen Psychiatry). CCK2 antagonists did not prove useful as anxiolytics in trials. [8]

Satiety and gut function in animals

Extensive rodent work since Gibbs 1973 (J Comp Physiol Psychol); CCK1-receptor-deficient OLETF rats become obese, mostly through larger meals. [2]

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.

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11Page history

30 Oct 2026Profile published — awaiting medical review

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