Abstract
Background
Cocaine is the second most widely used illicit substance worldwide and exerts potent sympathomimetic effects by inhibiting the reuptake of norepinephrine, dopamine, and serotonin. While cardiovascular and neurological complications are well recognized, gastrointestinal (GI) manifestations are increasingly reported. These arise from multifactorial mechanisms including vasospasm, endothelial dysfunction, thrombosis, ischemia, and direct mucosal toxicity, often with severe clinical consequences.
Objective
This narrative review summarizes the mechanisms, pharmacokinetics, pharmacodynamics, routes of use, and spectrum of GI complications associated with cocaine exposure, with emphasis on ischemic, ulcerative, hemorrhagic, inflammatory, fibrotic, hepatobiliary, and pancreatic sequelae; provides a differential-diagnosis and diagnostic algorithm; and critically appraises the strength of the supporting evidence and its principal confounders.
Methods
PubMed/MEDLINE, Embase, and Scopus were searched from January 1, 1987 through July 17, 2026, using the Boolean strings detailed in the Methods section. Case reports, case series, retrospective cohort/case-control studies, and systematic reviews published in English were eligible; both abstract and, where accessible, full text were screened. Reference lists of retrieved articles were hand-searched (snowballing) for additional citations.
Results
Cocaine induces GI injury through vasoconstriction, pro-thrombotic effects, microvascular dysfunction, and direct cytotoxicity. Reported complications span ischemic/vascular disease (mesenteric ischemia/infarction, colonic ischemia, ischemic/hemorrhagic colitis, vascular thrombosis), ulcerative/perforative disease (peptic ulcer disease; gastric, duodenal, small-, and large-bowel perforation), inflammatory/fibrotic disease (enteritis, enterocolitis, strictures, retroperitoneal fibrosis), hepatobiliary and pancreatic injury, splenic infarction/hematoma/rupture, and other presentations including gastric antral vascular ectasia, an inflammatory bowel disease (IBD)-mimicking phenotype, and, rarely, acalculous cholecystitis. A systematic review of 53 studies (69 patients) found broadly similar mortality and surgical rates across routes of cocaine use, and two hybrid cohort/case-control studies of cocaine-associated ischemic colitis reported substantially higher mortality and surgical intervention rates than non-cocaine-related ischemic colitis. Polysubstance use — particularly concurrent alcohol (via the metabolite cocaethylene) and tobacco — and pre-existing vascular disease are common but incompletely characterized confounders. Notably, the evidence base underlying nearly every complication described here remains dominated by single case reports and small case series rather than comparative studies, a limitation that should temper the strength of any causal inference drawn from it.
Conclusion
Cocaine use is a significant and under-recognized contributor to severe GI morbidity and mortality, with complications spanning ischemia and perforation to hepatopancreatic injury. The evidentiary foundation remains overwhelmingly derived from case reports and small series; only three comparative or aggregated studies provide quantitative risk data, two limited to ischemic colitis and one examining route of use across the wider intestinal-ischemia literature. Clinicians should maintain a high index of suspicion for cocaine-related GI disease in young patients presenting with abdominal pain or ischemic features, use the differential-diagnosis framework and algorithm proposed here to avoid diagnostic delay, and account for polysubstance use when interpreting presentations. Future research should prioritize registry-based or multicenter comparative studies to better quantify risk, outcomes, and the independent contribution of confounders.