Adverse effects of cocaine


Cocaine is one of the most frequently abused illicit drugs and the adverse effects of cocaine use have been well summarized. According to the 1997 National Household Survey on Drug Abuse (NHSDA) an estimated 1.5 million Americans were current cocaine users (National Institute on Drug Abuse, 1999). Of patients presenting to the emergency department following cocaine use, cardiopulmonary, neurologic, and psychiatric presentations have been shown to be the most common. Although the overall morbidity and mortality of patients presenting with cocaine-associated complaints appears to be low, devastating effects, including death, do occur. Of New York City residents who died between 1990 and 1992 from intentional or unintentional injury, evidence of recent cocaine use was found in one-fourth of cases. Of these deaths, one-third were attributed to cocaine intoxication and two-thirds to traumatic injury. The psychiatric adverse effects of cocaine are likely contributory to trauma-related deaths.


The most significant adverse effects from cocaine use involve the cardiovascular system. In addition, many of the adverse effects in other organ systems are mediated through the effects of cocaine on the cardiovascular system. Adverse effects include myocardial infarction, dysrhythmias, cardiomyopathies, aortic dissection, and endocarditis.

Various pathophysiologic mechanisms help explain the adverse effect cocaine has on the heart. Cocaine-induced ischemia of the cardiac muscle results in the myocardial infarctions seen in cocaine users. The production of tachycardia, hypertension, accelerated atherosclerosis of the coronary arteries, and enhanced platelet aggregation from cocaine use, may contribute to ischemia. Vasospasm of the coronary arteries likely explains why, in some cases, cocaine associated myocardial infarctions occur in the absence of coronary artery disease. Cocaine-induced myocardial ischemia may precipitate dysrhythmias and in addition, the sodium-channel-blocking effect of cocaine may also contribute to conduction disturbances and dysrhythmias. Myocardial infarctions and dysrhythmias may be one of the major causes of sudden death related to cocaine use. Chronic myocardial ischemia and systemic hypertension from cocaine may also explain the reported cases of cardiomyopathy. The acute hypertension seen with cocaine use has also been implicated in the development of aortic dissections. The higher than expected incidence of endocarditis from intravenous cocaine administration suggests that by an as yet unknown mechanism, cocaine increases the likelihood of this potentially devastating condition.

Many of the most serious cardiovascular complications seem to be rare, considering the relatively common use of cocaine. However, these adverse effects occur with use of cocaine, can be life-threatening, and must be taken seriously. For example, the presence of cocaine-associated chest pain in an otherwise healthy young patient should be taken very seriously by the treating physician.


The adverse effects of cocaine on the neurologic system include all forms of stroke, convulsions, headache, and movement disorders. A retrospective study conducted by researchers at San Francisco General Hospital detailed that convulsions and focal neurological symptoms and signs were the two major presenting acute neurological complications of cocaine use. Many of these complications can be severe and result in long-term morbidity and death.

A particularly devastating neurologic effect of cocaine use is stroke. Cocaine-related strokes have mostly been reported in patients younger than fifty, an age group that otherwise has a very low incidence of strokes. All types of strokes including subarachnoid hemorrhage, intracerebral hemorrhage, and ischemic infarcts have been reported from cocaine use. In addition, all major vascular territories of the brain have been involved and all routes of cocaine administration have been implicated. Various etiologies have been postulated. The pharmacologic effect of cocaine to acutely increase blood pressure seems especially likely as an etiology resulting in hemorrhage. The rapid increase in blood pressure may rupture both normal and preexisting abnormal cerebrovasculature. Vasospasm, platelet aggregation, and vasculitis may also be contributory to both ischemic and hemorrhagic infarctions.

Generalized convulsions are another adverse effect associated with cocaine use. The local anesthetic effect of cocaine seems a likely etiology and unlike many other adverse effects of cocaine, convulsions appear to be dose related.

Various movement disorders have been associated with cocaine use. The association of choreiform movements with crack cocaine use led to the term “crack dancing”. Cocaine use may worsen preexisting movement disorders, increase the risk of acute dystonic reactions in patients taking dopamine-blocking agents, and occasionally induce an acute dystonic reaction without other contributing factors. The mechanism by which cocaine induces these effects remains unclear but is thought to be related to dopamine dysregulation.


Pulmonary symptoms are a common presenting complaint of cocaine users and a wide variety of adverse pulmonary effects of cocaine use have been reported. In contrast to the adverse effects on many other organs, the route of cocaine administration seems particularly important in producing pulmonary problems. The vast majority of adverse effects reported result from smoking cocaine either as freebase or crack. Adverse effects range from acute respiratory irritation to asthma exacerbation, pulmonary edema, eosinophilic lung disease, granulomatous lung disease, barotrauma, pulmonary hypertension, and possibly a persistent gas-exchange abnormality.

Cough, hemoptysis, and shortness of breath are common acute respiratory symptoms after smoking cocaine. Often these symptoms are not the result of significant pulmonary damage and are likely from the local irritant effect of cocaine. However, this irritant effect of cocaine has also been implicated in causing more serious pathology. Severe asthma exacerbations have been associated with cocaine smoking, and some evidence indicates the increasing incidence of death from asthma may, in part, be related to cocaine use. The fact that inhaled but not intravenous cocaine administration induces bronchoconstriction supports a local irritant effect. The irritant effect has also been implicated in the hypersensitivity-related eosinophilic lung disorder referred to as “crack lung,” which involves diffuse alveolar infiltrates associated with fever and eosinophilia. The presence of cutting agents in cocaine may also cause irritation to the lungs and result in granulomatous lung disease. Both cellulose and talc granulomas in the lung have resulted from nasal insufflation of cocaine.

Pulmonary barotrauma including pneumediastinum, pneumothorax, and pneumopericardium, have all been reported in association with cocaine inhalation. Pneumomediastinum has also been reported with cocaine insufflation. Prolonged and repeated Valsalva maneuvers performed by individuals attempting to heighten the effect of the drug are thought to induce alveolar rupture. The escaped air then can induce a pneumothorax or move to the mediastinum or, rarely, the pericardium. The fact that similar barotrauma has been reported with the use of other drugs suggests that the etiology is not the result of an intrinsic property of cocaine ().

Much still remains to be learned about the effect of cocaine on the lungs. The etiology of noncardiogenic pulmonary edema seen in association with cocaine use is unknown. The majority of cases have occurred from smoking cocaine, but one report exists of fatal pulmonary edema from intravenous administration of “free-base” cocaine. Cocaine may alter pulmonary diffusion capacity but studies are conflicting. Cocaine has also been shown to decrease the effectiveness of alveolar macrophages, but the clinical significance of this has yet to be determined.


Various psychiatric problems occur with cocaine use. Exactly what effect is observed depends on whether a patient is acutely intoxicated, in a state of withdrawal, or suffering chronic effects from the drug. The exact mechanisms by which cocaine produces such effects are unclear.

Cocaine intoxication may be complicated by poor judgment, delirium, and, in severe cases, psychosis. Psychosis from cocaine use may occur both with acute intoxication with high doses and also more insidiously with chronic use. Psychosis with acute intoxication has been noted to often be associated with violent behavior. Cocaine use in individuals with a predisposition for or preexisting psychiatric illness may certainly make an accurate diagnosis difficult.

Long thought not to occur, a tri-phasic abstinence syndrome observed in outpatients following chronic cocaine abuse has been described. Phase one of the withdrawal involves the “crash” of mood and energy following cocaine binge cessation. It is marked by dysphoria, anxiety, depression, and profound exhaustion, and may last for days. Cocaine craving is also typical. The crash is thought to reflect acute neurotransmitter depletion caused by cocaine. Following the crash, phase two, or cocaine withdrawal ensues. In contrast to the withdrawal associated with many other abused drugs, with cocaine there are no gross physiological alterations. However, significant dysphoria, anhedonia, and amotivation are noted. Memories of cocaine euphoria may prompt the individual to reuse cocaine. Finally, phase three (extinction) occurs, which may last years, in which anhedonia and further craving may prompt reuse. It must be noted that additional inpatient studies on cocaine withdrawal did not reveal distinct phases, but a gradually resolving dysphoria. It is currently thought that the characteristics of withdrawal differ from an outpatient to inpatient setting and may rest with the presence or absence of triggering cues which can prompt cravings.


Adverse effects of cocaine use on the genitourinary system are significant. Adverse effects include acute renal failure, renal infarction, and progression of chronic renal failure. In addition, various sexual dysfunctions have been described.

Cocaine-induced rhabdomyolysis (muscle breakdown) is well documented and may lead to acute renal failure. The mechanism by which cocaine induces rhabdomyolysis is unclear and may be multi-factorial. Although often associated with convulsions and hyperthermia, rhabdomyolysis associated with cocaine use has been documented without either of these conditions being present. A direct toxic effect of cocaine on skeletal muscle, increased muscular activity, and cocaine-induced vasospasm with resultant ischemia have all been suggested mechanisms. It is thought that renal damage occurs from the toxic effect of myoglobin on the renal tubules. Acute renal failure may also be the result of the severe hypertension precipitated by cocaine use. Hypertension from cocaine use may also accelerate the progression of chronic renal failure. It is not surprising that reports of renal infarction exist with cocaine use, with the pathophysiology likely similar to that associated with myocardial infarction involving accelerated atherosclerosis, vasospasm, and enhanced platelet aggregation.

At low doses, cocaine can delay ejaculation and orgasm, which combined with its euphoric effects may be used to heighten the sexual experience. However, chronic cocaine use has been associated with sexual dysfunction. Male users have difficulty maintaining erection and ejaculating. In addition, cocaine use has been associated with priapism. The mechanisms responsible for sexual dysfunction and priapism remain unclear.


Compared with the effect of cocaine use on other organ systems, there are relatively few reported adverse effects on the gastrointestinal tract. However, serious adverse effects of cocaine on the gastrointestinal tract have been observed, and include intestinal ischemia, intestinal infarction, and ulcer perforation. A particular problem with cocaine, related to the gastrointestinal tract, is the ingestion of cocaine in an effort to either hide evidence (“body sniffers”) or transport large amounts of it (“body packers”).

The occurrence of intestinal ischemia from cocaine use has been well documented and has occurred from all routes of exposure, including insufflation, intravenous injection, smoking, and ingestion. Ischemia in both the large and small intestine has been reported and has progressed to infarction and death in some cases. In many of the reported cases, the intestinal vasculature was normal on examination, suggesting vasospasm as the etiology of ischemia and infarction. In some cases, however, abnormalities have been documented in the arteries. Damage to small caliber arterioles has been observed, suggesting that the cocaine may have caused endothelial damage. Thrombosis in the major mesenteric arteries has also been demonstrated angiographically. In some cases of gastrointestinal infarction, perforation of the gastrointestinal tract has occurred. Perforations of gastric and duodenal ulcers are also known to occur in temporal relation to crack use. The mechanism for this remains unknown but may also be related to the vasoconstrictive effect of cocaine on the stomach and duodenum.

A particular problem frequently encountered is the individual who has swallowed large amounts of cocaine. This may have been done in an attempt to conceal evidence during imminent arrest, or as a means of concealment for drug smuggling. When done for drug smuggling the cocaine is often packaged in balloons or condoms. Although many people pass the packets uneventfully, rupture of one or more of the packets has caused convulsions and death.


Liver damage is a relatively uncommon reported adverse effect associated with cocaine use. However, liver damage, and in some cases liver failure, have been reported. In addition, the lifestyle of cocaine users and the intravenous route of cocaine administration may predispose users to various viral causes of hepatitis.

The mechanism for cocaine-induced liver damage is probably multi-factorial and liver damage often occurs in the setting of cocaine-induced hyperthermia and shock, which are known causes of liver injury. Furthermore, the metabolism of cocaine may lead to toxic metabolites which may be directly injurious to liver cells. The majority of cocaine is metabolized in the blood by pseudocholinesterase and in the liver by hepatic esterase to nontoxic metabolites. Within the liver, the cytochrome P450 system metabolizes the remaining cocaine through a minor pathway which produces metabolites such as norcocaine nitroxide, a free radical that may initiate liver damage.


One study from Brazil associated chronic cocaine smoking with the development of pancreatic adenocarcinoma. Further study is required to confirm this association.

Head and Neck, Nose and Throat

Head and neck complications from cocaine use are intimately related to the route of drug administration. Adverse effects include chronic rhinitis, nasal septal perforations, destructive facial processes, sinusitis, dental erosions, and thermal injuries.

Chronic nasal insufflation of cocaine may lead to various local effects to the nares. Rebound hyperemia after drug discontinuation may lead to a condition of chronic rhinitis similar to rhinitis medicamentosa. Nasal septal perforation is a well-known adverse effect of chronic cocaine insufflation that in some cases has progressed to nasal cartilage collapse and saddle-nose deformity. An even more devastating condition is an aggressive destructive facial process that may simulate Wegener’s granulomatosis, neoplasms, or chronic infections. A similar condition resulted when an individual was assaulted and had crack cocaine forcibly impacted in the nostrils. Nasal septal perforation and the more devastating conditions associated with chronic nasal insufflation all involve the progressive destruction of tissue. This is likely the result of a combination of chronic cocaine-induced vasoconstriction, irritation, and local trauma from nasal picking. Irritation from adulterants in the insufflated cocaine may also be contributory. Insufflation has also been associated with bacterial sinusitis, including an unusual case in which the causative organism was Clostridium botulinum.

Dental erosions have been reported with insufflation and with an abuser who applied cocaine topically. Rapid gingival recession has also been reported in an individual who regularly applied cocaine to his gums.

Thermal injuries from smoking both freebase and crack have resulted in burns to the upper respiratory tract and esophagus. Both the hot cocaine vapors and metal from the pipes used to smoke the cocaine have been implicated. One of the potentially life-threatening thermal injuries described is epiglottitis. In one case, passive inhalation of crack smoke in a child was implicated in thermal epiglottitis. Hot cocaine vapor has also caused loss of eyelash and eyebrow hair.


Relatively few adverse effects of cocaine use on the eyes have been reported. The adverse effects include corneal epithelial defects, preseptal cellulitis, optic neuropathy, precipitation of acute angle-closure glaucoma, opsoclonus, and impaired color vision.

Corneal epithelial defects resulting from crack smoking have led to the term “crack eye”. Multiple mechanisms postulated include a direct toxic effect of the cocaine alkaloid and a local anesthetic effect that disrupts normal blink mechanisms and causes an exposure keratopathy. In some cases, the injuries led to a secondary bacterial infection. Another infection, preseptal cellulitis, has been reported in the setting of cocaine-induced bony orbit destruction. The ability of chronic cocaine use to cause an osteolytic sinusitis leading to bilateral optic neuropathy has also been reported.

Nasal insufflation of cocaine has precipitated narrow angle-closure glaucoma. It is thought that cocaine may reach the eye by retrograde delivery via the nasolacrimal system or by inadvertent rubbing of the eye. The mydriatic (pupil-dilating) effect of cocaine appears to be a precipitating factor.

Opsoclonus, an abnormal movement disorder of the eye that involves rapid, irregular, nonrhythmic movements in horizontal and vertical directions, has been reported with cocaine use. The mechanism is unclear. Studies have also shown impaired color vision in patients recovering from cocaine use. It is postulated that cocaine interferes with the retinal dopamine system, which affects retinal neurotransmission.


Cocaine use during pregnancy is associated with various adverse effects both to the mother and fetus including an increased incidence of placental abruption, prematurity, intrauterine growth retardation, and microcephaly (small brain size). Various neurologic, cardiac, ophthalmic, and gastrointestinal defects have occurred in children who were exposed in utero to cocaine. A detailed review of the effects of cocaine on the fetus appears in site.