Contributor disclosures are reviewed for conflicts of interest by the editorial group. When found, these are addressed by vetting through a multi-level review process, and through requirements for references to be provided to support the content. Appropriately referenced content is required of all authors and must conform to UpToDate standards of evidence.
INTRODUCTION — Cocaine is a tropane ester alkaloid found in leaves of the Erythroxylum coca plant, a bush that grows in the Andes Mountain region of South America . Cocaine use can lead to addiction and adverse physical effects, such as stroke and cardiac arrest.
Cocaine is classified as a Schedule II medication under the Controlled Substances Act in the United States. Cocaine hydrochloride is still legally available in the United States as a 4 or 10 percent solution for use as a local or topical anesthetic, although it has largely been replaced in clinical practice by synthetic local anesthetics .
The DSM-IV-TR psychiatric diagnoses cocaine abuse and cocaine dependence were replaced by one diagnosis, cocaine use disorder, in DSM-5 . Although the crosswalk between DSM-IV and DSM-5 disorders is imprecise, cocaine dependence is approximately comparable to cocaine use disorder, moderate to severe subtype, while cocaine abuse is similar to the mild subtype .
This topic addresses the epidemiology, pharmacology, clinical effects, and diagnosis of cocaine use disorder in adults. Acute intoxication from cocaine use, specific cardiovascular and pulmonary complications related to cocaine, and treatment of stimulant use disorder are discussed separately. (See "Cocaine: Acute intoxication" and "Pulmonary complications of cocaine abuse" and "Evaluation and management of the cardiovascular complications of cocaine abuse" and "Pharmacotherapy for stimulant use disorders in adults" and "Psychosocial interventions for stimulant use disorder in adults".)
EPIDEMIOLOGY — Cocaine is used by an estimated 18.2 million people worldwide, about 0.4 percent of the global population age 15 to 64 years . Use is most prevalent in North America (5.1 million people, 1.6 percent of population older than 14 years) and Central and South America (4.4 million people, 1.5 percent) and in Western and Central Europe (3.5 million people, 1.1 percent). Current use (3.4 percent in 2013) in the United Kingdom and Spain now exceeds population rates in the United States , which have declined by almost one-quarter over the past 15 years . Common street names used in the United States for cocaine are shown in a table (table 1).
There is less cocaine use in West and Central Africa, East and Southeast Asia, and Eastern and Southeastern Europe, with little use elsewhere in the world . This pattern may be due to supply rather than demand factors, because of the difficulty in obtaining cocaine from its only source in South America and the ready availability of alternative synthetic stimulants such as amphetamines  or synthetic cathinones (“bath salts”).
Most cocaine use is by urban men age 15 to 35 years. About 3 percent of current users in the United States are adolescents 12 to 17 years old . Cocaine use has declined almost fourfold among this age group in the past decade, while declining about one-quarter in the overall population.
Less than one-fifth (18.6 percent) of the 4.8 million United States residents estimated to use cocaine in 2015 met DSM-IV diagnostic criteria for cocaine abuse or dependence (cocaine use disorder in DSM-5) . Six-hundred and fifteen thousand cocaine users received specialty treatment for their cocaine use or associated medical problems in 2015 .
Cocaine is the illegal drug most often associated with visits to Untied States hospital emergency departments. In 2011, it was involved in an estimated 40.3 percent of illicit drug-related emergency department visits (about 505,000 visits), versus about 36 percent (456,000 visits) for marijuana and about 20.6 percent (258,000 visits) for heroin . Nearly one-quarter of emergency room visits by patients seeking medical assistance for withdrawal (“detoxification”) involved cocaine use; 6.3 percent of emergency room visits for suicide attempts involved cocaine use.
Patterns of use — Cocaine is used in a variety of patterns [10,11]. The typical "binge" involves short periods of heavy use (eg, payday or weekends) separated by longer periods of little or no use. Others may use for an extended period until their finances are exhausted or access to cocaine is interrupted. A small number of users may be self-medicating an underlying neuropsychiatric disorder, such as attention deficit hyperactivity disorder (ADHD) , excessive daytime sleepiness , Parkinsonism , or cluster headaches . Most cocaine users living in the community do not use very frequently. More than half (58 percent) of past-year users used less than 12 times in the year; only 22 percent used at least 50 times .
Risk factors — While cocaine use occurs in all sociodemographic groups, it is not equally distributed among the United States population. The highest prevalence of use is among unemployed men in their 20s with no more than a high school education who live in urban areas.
Cocaine use is highly associated with use of other legal and illegal substances and with psychiatric disorders. Cigarette smokers and heavy alcohol drinkers are 10 and 20 times more likely, respectively, than non-users to also use cocaine . Concurrent use of cocaine and alcohol produces a new compound, cocaethylene, which is pharmacologically active (see 'Metabolism' below).
Cocaine users are at high risk for developing a cocaine use disorder. Community-based interview surveys suggest that up to one in six persons who use cocaine will develop dependence by DSM-IV-TR criteria . Heavier users and users who take the drug intravenously or by smoking are more likely to develop dependence than lighter users or intranasal and oral users [18-20]. The greater abuse potential of intravenous or smoked cocaine is attributed to the faster rate of drug delivery to the brain (within 10 seconds), and faster onset of psychological effects [21,22]. This faster onset is associated with a more intense pleasurable response (the so-called "rate hypothesis" of psychoactive drug action) . Oral use of the coca leaf is not typically associated with significant adverse consequences .
The environment (including family, religious, and social factors) has the strongest influence on initial cocaine use . Studies of drug use by pairs of fraternal (dizygotic) and identical (monozygotic) twins suggested a significant genetic influence on the risk of developing cocaine abuse or dependence after use has begun. Several promising candidate genes have been identified, including those for cholinergic nicotinic and cannabinoid CB1 receptors, but no specific gene has been clearly linked with cocaine addiction .
Co-occurring conditions — Many cocaine users use other substances either to enhance the "high" (eg, simultaneous use of opiates ["speedballing"]) or to ameliorate adverse effects of intoxication or withdrawal (eg, use of alcohol, cannabis, or benzodiazepines). Current cocaine users are twice as likely as non-users to have symptoms of depressive or anxiety disorders .
MECHANISM OF ACTION — Cocaine enhances monoamine neurotransmitter (dopamine, norepinephrine, and serotonin) activity in the central and peripheral nervous systems by blocking the presynaptic reuptake pumps (transporters) for these neurotransmitters [28,29]. Cocaine's positive psychological effects and abuse liability are considered to be due to its enhancement of brain dopamine activity, especially in the so-called corticomesolimbic dopamine reward circuit. Cocaine addiction has been conceptualized as a disease of the brain's dopamine reward system .
Cocaine is unique among stimulant drugs in having a second action of blocking voltage-gated membrane sodium ion channels. This action accounts for its local anesthetic effect, and may contribute to cardiac arrhythmias. (See "Evaluation and management of the cardiovascular complications of cocaine abuse".)
PHARMACOLOGY — Illegal cocaine comes in two forms: base (alkaloid, as in coca leaves) and salt [31,32]. Both forms consist of the same cocaine molecule and exert the same pharmacological actions once they reach the brain or other target organ. They differ in physical properties, which allow different routes of administration.
Cocaine base ("crack," "freebase") can be smoked because it has a relatively low melting point (98ºC) and vaporizes before substantial pyrolytic destruction has occurred. Cocaine base is difficult to dissolve for injection because it is relatively insoluble in water.
Cocaine salt, in contrast, cannot be efficiently smoked because it melts at 195ºC, with substantial breakdown of the cocaine molecule before vaporization. Cocaine salt is readily injected or insufflated ("snorted") through the nose; it is highly water soluble, making it easy to dissolve for injection purposes and facilitating absorption across mucus membranes.
The average purity of seized cocaine samples in the United States is around 50 percent . Common adulterants include both inert fillers that resemble cocaine in appearance (such as dextrose, lactose, mannitol, or starch) and active chemicals that may mimic the local anesthetic effect of cocaine (such as benzocaine, lidocaine, or procaine) or provide some psychoactive effect (such as ephedrine, amphetamine, caffeine, or PCP) . Street cocaine also may contain contaminants from the preparation process (such as benzene, acetone, or sodium bicarbonate). An increasingly common cocaine adulterant is the veterinary anti-helminthic agent levamisole . Cocaine adulterated with levamisole is associated with serious side effects, including leucopenia, agranulocytosis, and cutaneous vasculitis.
Absorption — Cocaine is readily absorbed through the mucous membranes of the nose and mouth, and from the genitourinary, gastrointestinal, and respiratory tracts. Passive absorption may occur through intact skin or by inhalation of second-hand cocaine smoke [36-38]. Such passive exposure can cause adverse effects in infants [39,40].
Distribution — Cocaine is rapidly taken up into most body organs, including the heart, kidney, adrenal glands, and liver . Cocaine (and its hydrolytic metabolites) appears in blood, urine, hair , sweat , saliva , and breast milk [45,46]. It crosses the placenta to appear in meconium . Analysis of these tissues and fluids is used for drug detection in workplace, legal, and treatment settings .
Onset of action — The onset of action for cocaine depends on the route of administration. Intravenous and inhaled (smoked) administration results in onset of action within seconds. Intranasal and gastrointestinal administration result in slower onsets of 20 to 30 minutes and up to 90 minutes, respectively.
Duration of action — The effects of intravenous or inhaled cocaine administration typically last 15 to 30 minutes; effects of intranasal and gastrointestinal administration are about one and three hours, respectively.
Metabolism — Cocaine is 95 percent metabolized by hydrolysis of its ester bonds to benzoylecgonine (by carboxyesterases in the liver) and to ecgonine methylester (by butyrylcholinesterase in the liver, plasma, brain, lung, and other tissues) [49-51]. The remaining 5 percent is N-demethylated to norcocaine by the liver cytochrome P450 microsomal enzyme system. The hydrolytic metabolites appear to be largely inactive. Norcocaine has some pharmacological actions similar to those of cocaine, and is hepatotoxic .
Smoked cocaine produces an additional series of pyrolysis products, the chief of which are anhydroecgonine methylester and noranhydroecgonine methylester [50,53].
Cocaine used together with alcohol leads to formation of a new compound, cocaethylene, by transesterification . Cocaethylene has pharmacological actions similar to, but less potent than, those of cocaine, and has a longer half-life [54,55]. Formation of cocaethylene may contribute to more severe or longer lasting toxic effects of cocaine when it is used along with alcohol.
Elimination — Cocaine is largely eliminated in the urine . Benzoylecgonine is the metabolite found in highest concentration in urine. It is this metabolite, rather than the parent drug cocaine, that is measured in urine drug tests for cocaine (see 'Screening' below).
Acute intoxication — Typical cocaine doses are 12 to 15 g orally (coca leaf), 20 to 100 mg intranasally, 10 to 50 mg intravenously, and 50 to 200 mg smoked. The intended effects include increased energy, alertness, and sociability; elation or euphoria; and decreased fatigue, need for sleep, and appetite [56-58]. The intense pleasurable feeling has been described as a "total body orgasm" .
There is wide variability in the acute response to cocaine and poor correlation between cocaine plasma concentrations and toxic effects [56,59]. Fatal cases of cocaine intoxication may present with 100-fold differences in plasma cocaine concentration .
Unintended adverse effects occur with increasing dose, duration of use, or a more efficient route of administration (eg, intravenous or smoked versus intranasal). These effects include dysphoric mood (anxiety, irritability), panic attacks, suspiciousness, paranoia, grandiosity, impaired judgment, and psychotic symptoms such as delusions and hallucinations. Up to one-quarter of non-treatment-seeking cocaine users may experience anxiety, depression, sleep disturbance, or weight loss (due to appetite suppression and changes in fat regulation) [60,61]. Concurrent behavioral effects include restlessness, agitation, tremor, dyskinesia, and repetitive or stereotyped behaviors such as picking at the skin or foraging for drugs ("punding," "hung-up activity") . Associated physiological effects include tachycardia, pupil dilation, diaphoresis, and nausea, reflecting stimulation of the sympathetic nervous system.
Cocaine-associated psychotic symptoms (paranoia, delusions, hallucinations) are reported by up to 80 percent of individuals with a cocaine use disorder [63,64]. These symptoms may somewhat resemble those due to acute schizophrenia . Cocaine-associated psychosis may differ from acute schizophrenic psychosis in being marked by less thought disorder and bizarre delusions and fewer negative symptoms such as alogia and inattention . Hallucinations may be auditory, visual, or tactile, but the last two are much more common with cocaine use than with schizophrenia [63,66]. Tactile hallucinations are especially typical of stimulant-associated psychosis and include the sensation of something (eg, insects) crawling under the skin (“formication,” “cocaine bugs”).
The presentation and treatment of cocaine intoxication is discussed in greater detail separately (see "Cocaine: Acute intoxication").
Chronic use — Chronic cocaine use can result in either of two distinct pharmacological adaptations: sensitization (increased drug response) or tolerance (decreased drug response) [67,68]. In animal studies, sensitization results from low-dose, intermittent exposure, while tolerance results from frequent, high-dose, or long-term exposure.
The factors that determine sensitization and tolerance in humans, however, are not well understood. Sensitization to the cardiovascular effects of oral cocaine, but not to its psychological effects, has been demonstrated in laboratory studies . Tolerance to the psychological, cardiovascular, and neuroendocrine effects of cocaine develops after several doses [70,71]. Tolerance to cardiovascular effects may develop more quickly and completely than does tolerance to psychological effects [71,72]. This rapid tolerance presumably allows binge users to take large cumulative doses of cocaine.
Chronic cocaine use is associated with cognitive impairment affecting visuo-motor performance, attention, verbal memory, and risk-reward decision-making . These impairments persist for at least several weeks of abstinence.
Cocaine use is associated with suicidal ideation and suicide attempts [74,75]. The extent to which suicide is a direct consequence of use, rather than an associated sociodemographic or psychological factor, remains unclear [76,77]. Factors associated with increased risk of suicidality among cocaine users include depression, severe cocaine withdrawal, comorbid alcohol or opioid dependence, history of childhood trauma, and family history of suicidality [78,79].
Chronic cocaine use by any route of administration is associated with increased risk of infection, especially viral hepatitis  and HIV , and of risky sexual behavior (such as unprotected sex) .
Chronic cocaine use does not appear to increase the risk of general anesthesia, as long as the patient has normal cardiovascular parameters at the time of surgery .
Withdrawal symptoms — Cessation of heavy chronic cocaine use results in a withdrawal syndrome that has prominent psychological features, but is rarely medically serious [84-86]. Symptoms include depression, anxiety, fatigue, difficulty concentrating, decreased ability to experience pleasure (anhedonia), increased cocaine craving, increased appetite, increased sleep, and increased dreaming (due to increased REM sleep). An initial period of intense symptoms (commonly termed the "crash") may occur, including psychomotor retardation and severe depression with suicidal ideation. However, most users experience milder symptoms that resolve within one to two weeks without treatment.
Physical signs of cocaine withdrawal are usually minor and rarely require treatment. These include nonspecific musculoskeletal pain, tremors, chills, and involuntary motor movement . The first week of stimulant withdrawal has been associated with myocardial ischemia , possibly due to coronary vasospasm.
EFFECTS ON SPECIFIC ORGAN SYSTEMS
Central nervous system
●Seizure – Evidence regarding an association between cocaine use and seizures is mixed:
•A 2016 prospective observational study of 1134 patients hospitalized for aneurysmal subarachnoid hemorrhage found that cocaine use within 72 hours of the event was associated with seizures during the hospitalization (odds ratio 2.06, 95% CI 1.330-3.175) after controlling for age, clinical grade, presence of intracranial hemorrhage, and location of aneurysm .
•An earlier 2013 systematic review of 22 cross-sectional studies and one case-control study found no good-quality evidence of an association between cocaine use and seizures .
•Case reports and case series have reported an association between cocaine use (including first-time use) and seizures in persons without a seizure history. The seizures were described as usually single, generalized tonic-clonic seizures occurring within 90 minutes of cocaine use [91-93].
•Cocaine euphoria is associated with transient increases in EEG activity followed by longer-lasting increases in activity .
●Stroke – Cerebral vasoconstriction, cerebrovascular disease, and hemorrhagic and ischemic stroke are increased in cocaine users, even in patients with no other risk factors [91-93,95,96]. A systematic review of seven case-control studies and two cross-sectional studies found a positive association between cocaine use and both hemorrhagic and ischemic stroke (adjusted odds ratios of 2 to 6 ).
A population-based case-control study of 1090 cocaine users and 1154 controls found an increased risk of stroke with cocaine use in the prior 24 hours (adjusted odds ratio 5.7, 95% CI 1.7-19.7, adjusted for current alcohol and tobacco use and hypertension) . Etiologic mechanisms include tachycardia and increased blood pressure from sympathetic activation, vasoconstriction, vasospasm, and intravascular thrombosis due to increased platelet aggregation .
●Brain abnormalities – MRI, SPECT, and PET imaging in chronic cocaine users demonstrate structural and functional brain abnormalities: cerebral gray matter atrophy and decreased glucose metabolism in the frontal and temporal lobes, small cerebral perfusion defects, increased creatine concentration in parietal white matter (suggesting abnormal energy metabolism), and decreased D2 dopamine receptors in the striatum [99-101]. An autopsy study using melanin immunoreactivity found cocaine users to have 16 percent fewer midbrain dopamine neurons than non-using subjects . Impairment of behavioral inhibition in cocaine users has been associated with reduced activity in the anterior cingulate and prefrontal cortices .
●Movement disorders – Cocaine use is associated with a variety of movement disorders, including stereotyped behaviors, acute dystonic reactions, choreoathetosis and akathisia (so-called "crack dancers"), buccolingual dyskinesias ("twisted mouth" or "boca torcida"), and exacerbation of Tourette's syndrome and tardive dyskinesia [56,91,103]. Cocaine users are at increased risk of acute dystonic reactions from neuroleptic (antipsychotic) medications .
Cardiovascular system — Cardiopulmonary symptoms are the most frequent complaints in cocaine users who seek medical help, with chest pain being the most frequent symptom . Cocaine acutely increases heart rate, blood pressure, and systemic vascular resistance by increasing adrenergic activity in the heart, and indirectly via the CNS [105,106]. The increased myocardial oxygen demand, coupled with decreased coronary blood flow from vasospasm and vasoconstriction, can cause acute myocardial infarction (AMI), even in young persons without atherosclerosis.
Cocaine use is a factor in about one-quarter of nonfatal heart attacks in persons younger than 45 years . Cocaine is not necessarily associated with a more serious outcome of AMI. As an example, a prospective cohort study of 1003 adult inpatients following an AMI with S-T segment elevation (STEMI) found no difference between 58 subjects with cocaine-associated STEMI and 945 subjects with non-cocaine-associated STEMI in subsequent death (hazard ratio 1.46, 95% CI 0.49-4.37) or death or hospital readmission (hazard ratio 1.14, 95% CI 0.74-1.76) . The median follow-up period was 2.7 years.
Cocaine use is associated with supraventricular and ventricular cardiac arrhythmias, S-T segment elevation (often asymptomatic), and sudden death [112-114]. Chronic use is associated with left ventricular hypertrophy and dysfunction, cardiomyopathy, myocardial fibrosis, and myocarditis . (See "Evaluation and management of the cardiovascular complications of cocaine abuse".)
Respiratory system — The effects of cocaine on the respiratory system depend on the route of administration. Intranasal cocaine use ("snorting") may cause chronic rhinitis, perforation of the nasal septum, oropharyngeal ulcers, and osteolytic sinusitis, due to vasoconstriction and resulting ischemic necrosis [91,103]. Anosmia is rare.
Smoked (“crack”) cocaine produces acute respiratory symptoms in up to half of users, including productive cough, shortness of breath, wheezing, chest pain, and hemoptysis , and is a factor in up to one-third of young adult cases of acute asthma exacerbation seen in hospital emergency departments . Rarer pulmonary complications of smoked cocaine use include pulmonary edema, pulmonary hemorrhage, pneumothorax, pneumomediastinum, and thermal airway injury [116,118]. These effects are due to a combination of direct damage to the alveolar-capillary membrane by cocaine or inhaled microparticles, damage to the pulmonary vascular bed from vasoconstriction, interstitial disease, and/or toxicity from adulterants such as levamisole .
Chronic cocaine smokers generally have normal spirometry tests, but may have increased alveolar epithelial permeability and moderately decreased pulmonary diffusion capacity, even when asymptomatic. “Crack lung” refers to an acute pulmonary syndrome, associated with smoked cocaine use, whose pathophysiology and optimum treatment remain unclear [116,118]. It is associated with fever, hypoxemia, hemoptysis, respiratory failure, and diffuse alveolar infiltrates (usually eosinophil-rich). (See "Pulmonary complications of cocaine abuse".)
Gastrointestinal system — Cocaine use by any route of administration reduces salivary secretions (xerostomia)  and causes bruxism . Cocaine reduces gastric motility and delays gastric emptying . Cocaine-induced vasoconstriction and ischemia may result in gastrointestinal ulceration, infarction, perforation, and ischemic colitis [91,103]. Cocaine-associated ulcers are distributed primarily in the greater curvature and prepyloric region of the stomach, pyloric canal, but, similar to peptic ulcers, also occur in the first portion of the duodenum.
Liver — Cocaine users may have mild, transient elevation in transaminases , but there is no direct evidence that cocaine is hepatotoxic in humans. As an example, a prospective cohort study of 573 patients coinfected with HIV and hepatitis C virus, who were followed from 2003 to 2013 and lacked significant baseline liver fibrosis, found no association between progression to significant fibrosis and lifetime cocaine use (hazard ratio 0.96, 95% CI 0.58-1.57) or prior-six-month cocaine use (hazard ratio 0.88, 95% CI 0.63-1.25), after adjustment for age, sex, duration of hepatitis C infection, and alcohol and other drug use .
Cocaine does cause liver damage in rodents; however, the responsible hepatotoxins are oxidative metabolites such as norcocaine, which are very minor metabolites in humans (see 'Metabolism' above). Liver abnormalities in cocaine users can almost always be accounted for by viral hepatitis from injection drug use, alcoholic liver disease, concurrent rhabdomyolysis , use of other hepatotoxic drugs (such as MDMA [“ecstasy”]), or other consequences of a drug-using lifestyle. Concurrent alcohol intake may sensitize hepatocytes to damage by cocaine, as well as generating the hepatotoxic metabolite cocaethylene .
Kidneys — Cocaine use can impair kidney function by a variety of mechanisms . Cocaine-induced rhabdomyolysis is a significant cause of acute renal failure  (see "Drug-induced myopathies" and "Clinical features and diagnosis of heme pigment-induced acute kidney injury").
Cocaine use by hypertensive patients enhances their decline in kidney function  and the progression from hypertensive nephrosclerosis to end-stage renal disease . While cocaine promotes atherosclerosis in renal vessels, cocaine-induced renal infarction is relatively rare .
Endocrine — Acute cocaine use activates the hypothalamic-pituitary-adrenal (HPA) axis, increasing levels of epinephrine, corticotropin-releasing hormone (CRH), ACTH, cortisol, and luteinizing hormone, and decreasing plasma prolactin levels [103,128,129]. Chronic cocaine users, however, usually have normal plasma levels of prolactin, testosterone, cortisol, luteinizing hormone, and thyroid hormones.
Skin — Cocaine use is associated with a variety of pseudovasculitic lesions that may mimic rheumatologic syndromes such as Wegener's granulomatosis, necrotizing vasculitis, and Henoch-Schönlein purpura (IgA vasculitis) . Use of cocaine contaminated with levamisole (an anti-helminthic now approved in the United States only for veterinary use) has been associated with cutaneous vasculitis or vasculopathy (picture 1) [131,132]. (See "Evaluation of adults with cutaneous lesions of vasculitis", section on 'Etiology' and "Evaluation of adults with cutaneous lesions of vasculitis", section on 'Evaluation for vasculitis due to levamisole-contaminated cocaine'.)
Sexual dysfunction — Although cocaine is often considered an aphrodisiac, it actually may impair sexual function, especially with chronic use, and may cause delayed or inhibited ejaculation in men [133-135].
Reproductive, fetal, and neonatal health — Cocaine may cause irregular menses in women [134,135].
Topical cocaine is classified as pregnancy category C (risk cannot be ruled out because human studies are lacking) by the US Food and Drug Administration. Maternal cocaine use has been associated with vaginal bleeding, abruptio placenta, placenta previa, premature rupture of membranes, premature birth, decreased head circumference, low birth weight, and autonomic instability [136,137]. However, it is unclear to what extent these adverse effects are due to prenatal (in utero) cocaine exposure, rather than to other factors in the cocaine-using lifestyle, such as concomitant drug use (including alcohol, nicotine, and opiates), poor nutrition, and lack of prenatal care. Rodent and monkey studies, in which these confounding factors are excluded, show few direct adverse effects of prenatal exposure to cocaine .
The long-term effects of prenatal exposure to cocaine are also unclear . Well-controlled, prospective studies of children born to cocaine-using mothers have not confirmed most earlier concerns regarding long-term cognitive impairment and behavioral problems.
Cocaine appears in breast milk and may cause irritability, sleep disturbance, and tremors in the nursing infant [45,46].
ASSESSMENT — Initial assessment of the cocaine-abusing patient addresses the following areas .
•Use of all psychoactive substances (not just cocaine), including illegal, prescription, and over-the-counter as well as duration, quantity, frequency, route of administration, and effects for each substance used
•Prior treatment, if any
•Psychiatry history, including relationship of any psychiatric symptoms to substance use or withdrawal
•Social and developmental history, especially current social network
•Insight into condition
•Motivation and preferences for treatment
•Memory, short- and long-term
•Presence of thought disorder, eg, delusions, hallucinations
•Mood and affect
•Heart, lungs, abdomen, extremities, skin
•Stigmata of cocaine use, eg, skins lesions from injection, perforated nasal septum from insufflation (“snorting”)
•Blood or urine drug testing
•Complete blood count (CBC)
•Blood chemistries, including liver tests
•Blood-borne and sexually transmitted diseases, eg, HIV, syphilis, hepatitis B and C
Goals of the initial psychiatric assessment are to:
●Determine the severity of the addiction problem
●Identify concurrent substance use (alcohol, opiates, or cannabis)
●Diagnose co-occurring psychiatric or medical disorders
●Identify strengths (eg, employment, supportive social network)
●Identify weaknesses (criminal behavior, poor social skills)
●Evaluate motivation for treatment
●Discuss treatment preferences
Screening — Screening for cocaine use can be performed with brief self-report instruments or by drug testing. (See "Screening for unhealthy use of alcohol and other drugs in primary care", section on 'Unhealthy use of other drugs' and "Screening for unhealthy use of alcohol and other drugs in primary care".)
Patient self-report — Patient self-report via questions or instruments provide an economical and efficient means of cocaine screening, and are typically used in high-volume clinical settings such as a primary care practice or emergency department. Several studies suggest that self-reports of cocaine and other illegal substance use can be fairly accurate, as long as there are no adverse consequences (such as criminal charges) for acknowledging use .
Systematic review has identified several cocaine-use screening instruments, comprised of one to three questions, with good (though varying) sensitivity and reliability . Based on simplicity of use and favorable test performance characteristics, we favor the use of the three-question Tobacco, Alcohol, Prescription Medication, and Other Substance Use screening instrument :
●“In the past three months, did you use cocaine, crack, or methamphetamine (crystal meth)?” If yes,
●“Did you use at least once a week or more often?” If yes,
●“Has anyone expressed concern about your use?”
In a study of 2000 adult patients consecutively recruited from the waiting areas of five primary care clinics, a “yes” answer to the first question had a sensitivity of 0.68 (95% CI 0.59-0.77) and specificity of 0.99 (95% CI 0.98-0.99) for identifying problem stimulant use (based on at least one positive item on the Composite International Diagnostic Interview [CIDI]). Two “yes” answers had a sensitivity of 0.57 (95% CI 0.47-0.67) and specificity of 0.99 (95% CI 0.99-1.00) for identifying stimulant use disorder (based on at least two positive items on CIDI).
Drug testing — Drug testing detects cocaine use, but is not diagnostic of a cocaine use disorder, which implies adverse consequences from use. Conversely, a negative drug screen may only indicate lack of recent use. Cocaine and its metabolites can be measured in urine, blood, oral fluid, sweat, and hair [48,144]. The window of detection is shorter for cocaine than for its major metabolite, benzoylecgonine, and varies with the sensitivity of the assay method.
Urine testing (which measures benzoylecgonine, not cocaine), including rapid point-of-care methods, is common in clinical settings because the sample can be collected non-invasively. It has a detection window of about two to three days after cocaine use, but may be positive up to two weeks after chronic heavy use [145,146].
Blood testing has a detection window of 12 hours for cocaine and 48 hours for benzoylecgonine. It is rarely used outside the setting of acute intoxication. Actual blood cocaine concentrations have little correlation with acute symptoms of cocaine intoxication in the emergency department setting .
Oral fluid testing has a detection window similar to that of blood, with the advantage of non-invasive collection and better patient acceptability . Sweat testing (via patches worn on the skin) has a detection window of several weeks, but is useful only for prospective evaluation (ie, monitoring future drug intake). Results may be influenced by location of the skin patch and environmental exposure to cocaine .
Hair testing has the longest detection window (potentially years), but valid results require careful technique, and some questions remain unresolved. Results may be influenced by hair location, racial/ethnic differences in hair composition, prior hair treatments, and environmental exposure to cocaine . Cocaine continues to be incorporated into hair for a few months after last use .
A variety of relatively inexpensive commercial assays are available for testing of urine and oral fluid, including disposable kits that allow on-site testing with results available within minutes. Results from such screening tests should be confirmed by a standard laboratory assay, especially in legal or workplace settings.
DIAGNOSIS — The diagnosis of cocaine use disorder is made on the basis of history, obtained primarily from the patient and from collateral sources (eg, family, friends, and medical records) when available.
Diagnoses of cocaine abuse and cocaine dependence in DSM-IV-TR were replaced by the single diagnosis, cocaine use disorder, in DSM-5 . DSM-5 diagnostic criteria for cocaine use disorder are described below.
DSM-5 criteria — A problematic pattern of cocaine use leading to clinically significant impairment or distress, as manifested by two or more of the following within a 12-month period:
●Cocaine is often taken in larger amounts or over a longer period than was intended
●There is a persistent desire or unsuccessful efforts to cut down or control cocaine use
●A great deal of time is spent in activities necessary to obtain cocaine, use cocaine, or recover from its effects
●Craving, or a strong desire or urge to use cocaine
●Recurrent cocaine use resulting in a failure to fulfill major role obligations at work, school, or home
●Continued cocaine use despite having persistent or recurrent social or interpersonal problems caused or exacerbated by the effects of cocaine
●Important social, occupational, or recreational activities are given up or reduced because of cocaine use
●Recurrent cocaine use in situations in which it is physically hazardous
●Continued cocaine use despite knowledge of having a persistent or recurrent physical or psychological problem that is likely to have been caused or exacerbated by cocaine
Specifiers for the diagnosis include:
●In early remission – After full criteria for cocaine use disorder were previously met, none of the criteria for cocaine use disorder have been met (with the exception of craving) for at least three months but less than 12 months
●In sustained remission – After full criteria for cocaine use disorder were previously met, none of the criteria for cocaine use disorder have been met (with the exception of craving) during a period of 12 months or longer
●In a controlled environment – If the individual is in an environment where access to cocaine is restricted
The severity of cocaine use disorder at the time of diagnosis can be specified as a subtype based on the number of symptoms present:
●Mild: Two to three symptoms
●Moderate: Four to five symptoms
●Severe: Six or more symptoms
Most clinical trials of treatments for cocaine use were conducted in samples limited to patients with cocaine dependence (DSM-IV-TR or earlier criteria). Applying trial results to patients diagnosed with DSM-5 cocaine use disorder is imprecise; the most closely comparable patients are those with cocaine use disorder, moderate to severe subtype . Cocaine abuse is similar to the mild subtype of cocaine use disorder. (See "Pharmacotherapy for stimulant use disorders in adults" and "Psychosocial interventions for stimulant use disorder in adults".)
INFORMATION FOR PATIENTS — UpToDate offers two types of patient education materials, “The Basics” and “Beyond the Basics.” The Basics patient education pieces are written in plain language, at the 5th to 6th grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are written at the 10th to 12th grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon.
Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on “patient info” and the keyword(s) of interest.)
●Basics topic (see "Patient education: Cocaine use disorder (The Basics)")
SUMMARY AND RECOMMENDATIONS
●Cocaine use is most prevalent in North and South America, and increasingly in Western Europe, especially among urban men aged 15 to 35 years. It is the illegal drug most often associated with emergency department visits in the United States. (See 'Introduction' above.)
●Up to one in six persons who use cocaine will develop dependence (DSM-IV-TR criteria) or moderate to severe cocaine use disorder (DSM-5 criteria); abuse liability is greater with intravenous and smoked cocaine, compared to intranasal and oral use. Cocaine base has a low melting point and can be smoked; cocaine salt is water soluble and can be injected or absorbed across mucous membranes. (See 'Risk factors' above and 'Pharmacology' above.)
●Cocaine is largely metabolized to inactive hydrolytic products in the liver and plasma. Use of alcohol with cocaine produces a new metabolite, cocaethylene, which has actions similar to cocaine but a longer half-life. Concurrent alcohol use with cocaine may cause more severe and longer lasting toxic effects. (See 'Metabolism' above.)
●Drug testing detects the metabolite benzoylecgonine, which is usually detectable two to four days after the last cocaine use, although this can be up to 14 days after heavy, prolonged use. (See 'Elimination' above.)
●Cocaine use increases energy and alertness, can produce euphoria, and decreases appetite and need for sleep. Adverse effects may include anxiety, irritability, paranoia, delusions, and hallucinations. These may be accompanied by tachycardia, diaphoresis, nausea, and pupil dilatation. There is poor correlation between cocaine plasma concentrations and toxicity. (See 'Acute intoxication' above.)
●Withdrawal symptoms from chronic cocaine use are predominantly psychological: depression, anxiety, anhedonia, cocaine craving, and increased sleep. Most symptoms are self limited and resolve within one to two weeks. (See 'Withdrawal symptoms' above.)
●Effects of cocaine on specific organ systems are (see 'Effects on specific organ systems' above):
•CNS: seizures, stroke, movement disorders
•Cardiovascular: myocardial infarction, arrhythmia, cardiomyopathy, myocarditis
•Respiratory: rhinitis and septal perforation (with intranasal use) cough, wheeze, chest pain (with smoked use)
•GI: xerostomia, gastric ulcers, ischemic colitis
●Diagnoses of cocaine abuse and cocaine dependence in DSM-IV-TR were replaced by the single diagnosis, cocaine use disorder, in DSM-5. (See 'Diagnosis' above.)
- Karch, SB. A Brief History of Cocaine, 2nd ed, CRC Press, Boca Raton, FL 2006.
- Harper SJ, Jones NS. Cocaine: what role does it have in current ENT practice? A review of the current literature. J Laryngol Otol 2006; 120:808.
- American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5), American Psychiatric Association, Arlington, VA 2013.
- Compton WM, Dawson DA, Goldstein RB, Grant BF. Crosswalk between DSM-IV dependence and DSM-5 substance use disorders for opioids, cannabis, cocaine and alcohol. Drug Alcohol Depend 2013; 132:387.
- World Drug Report 2016. Report no. E.16.XI.7, United Nations Office on Drugs and Crime, Vienna, Austria 2016.
- European Monitoring Centre for Drugs and Drug Addiction. Table GPS-29 http://www.emcdda.europa.eu/data/stats2015#displayTable:GPS-29 (Accessed on July 27, 2015).
- Degenhardt L, Chiu WT, Sampson N, et al. Toward a global view of alcohol, tobacco, cannabis, and cocaine use: findings from the WHO World Mental Health Surveys. PLoS Med 2008; 5:e141.
- Center for Behavioral Health Statistics and Quality. 2015 National Survey on Drug Use and Health: Detailed Tables. Substance Abuse and Mental Health Services Administration, Rockville 2016.
- Substance Abuse and Mental Health Services Administration. Drug Abuse Warning Network, 2011: National Estimates of Drug-related Emergency Department Visits. HHS Publication No. (SMA) 13-4760 DAWN Series D-39. Rockville, MD: Substance Abuse and Mental Health Services Administration, 2013.
- Levin FR, Hess JM, Gorelick DA, et al. Patterns of cocaine use among cocaine-dependent outpatients. Am J Addict 1993; 2:109.
- Myers MG, Rohsenow DJ, Monti PM, Dey A. Patterns of cocaine use among individuals in substance abuse treatment. Am J Drug Alcohol Abuse 1995; 21:223.
- Mariani JJ, Khantzian EJ, Levin FR. The self-medication hypothesis and psychostimulant treatment of cocaine dependence: an update. Am J Addict 2014; 23:189.
- Marzullo P, Menegatti M, Guzzaloni G, et al. Cocaine abuse and sleep apnea in severe obesity. J Addict Med 2013; 7:294.
- Di Rocco A, Nasser S, Werner P. Inhaled cocaine used to relieve "off" periods in patients with Parkinson disease and unpredictable motor fluctuations: a report of 2 cases. J Clin Psychopharmacol 2006; 26:689.
- Di Lorenzo C, Coppola G, Di Lorenzo G, et al. The use of illicit drugs as self-medication in the treatment of cluster headache: Results from an Italian online survey. Cephalalgia 2016; 36:194.
- Results from the 2013 National Survey on Drug Use and Health: Summary of National Findings, NSDUH Series H-48, HHS Publication No. (SMA) 14-4863, Office of Applied Studies, Substance Abuse and Mental Health Services Administration, Rockville, MD 2014.
- Anthony JC, Warner LA, Kessler RC. Comparative epidemiology of dependence on tobacco, alcohol, controlled substances, and inhalants: Basic findings from the National Comorbidity Survey. Experimental and Clinical Psychopharmacology 1994; 23:244.
- Gorelick DA. Progression of dependence in male cocaine addicts. Am J Drug Alcohol Abuse 1992; 18:13.
- Gossop M, Griffiths P, Powis B, Strang J. Cocaine: patterns of use, route of administration, and severity of dependence. Br J Psychiatry 1994; 164:660.
- Woody GE, Cottler LB, Cacciola J. Severity of dependence: data from the DSM-IV field trials. Addiction 1993; 88:1573.
- Gorelick DA. The rate hypothesis and agonist substitution approaches to cocaine abuse treatment. Adv Pharmacol 1998; 42:995.
- Volkow ND, Fowler JS, Wang GJ. Imaging studies on the role of dopamine in cocaine reinforcement and addiction in humans. J Psychopharmacol 1999; 13:337.
- Nelson RA, Boyd SJ, Ziegelstein RC, et al. Effect of rate of administration on subjective and physiological effects of intravenous cocaine in humans. Drug Alcohol Depend 2006; 82:19.
- Montoya ID, Chilcoat HD. Epidemiology of coca derivatives use in the Andean region: a tale of five countries. Subst Use Misuse 1996; 31:1227.
- Kendler KS, Myers J, Prescott CA. Specificity of genetic and environmental risk factors for symptoms of cannabis, cocaine, alcohol, caffeine, and nicotine dependence. Arch Gen Psychiatry 2007; 64:1313.
- Bühler KM, Giné E, Echeverry-Alzate V, et al. Common single nucleotide variants underlying drug addiction: more than a decade of research. Addict Biol 2015; 20:845.
- Kandel DB, Huang FY, Davies M. Comorbidity between patterns of substance use dependence and psychiatric syndromes. Drug Alcohol Depend 2001; 64:233.
- Rothman RB, Baumann MH, Dersch CM, et al. Amphetamine-type central nervous system stimulants release norepinephrine more potently than they release dopamine and serotonin. Synapse 2001; 39:32.
- Howell LL, Kimmel HL. Monoamine transporters and psychostimulant addiction. Biochem Pharmacol 2008; 75:196.
- Dackis CA, O'Brien CP. Cocaine dependence: a disease of the brain's reward centers. J Subst Abuse Treat 2001; 21:111.
- Hatsukami DK, Fischman MW. Crack cocaine and cocaine hydrochloride. Are the differences myth or reality? JAMA 1996; 276:1580.
- Karch, SB. The Pathology of Drug Abuse, 2nd ed, CRC Press, Boca Raton, FL 1996.
- Cunningham JK, Callaghan RC, Liu LM. US federal cocaine essential ('precursor') chemical regulation impacts on US cocaine availability: an intervention time-series analysis with temporal replication. Addiction 2015; 110:805.
- Broséus J, Gentile N, Esseiva P. The cutting of cocaine and heroin: A critical review. Forensic Sci Int 2016; 262:73.
- Roberts JA, Chévez-Barrios P. Levamisole-Induced Vasculitis: A Characteristic Cutaneous Vasculitis Associated With Levamisole-Adulterated Cocaine. Arch Pathol Lab Med 2015; 139:1058.
- Cone EJ, Yousefnejad D, Hillsgrove MJ, et al. Passive inhalation of cocaine. J Anal Toxicol 1995; 19:399.
- Kavanagh KT, Maijub AG, Brown JR. Passive exposure to cocaine in medical personnel and its effect on urine drug screening tests. Otolaryngol Head Neck Surg 1992; 107:363.
- Le SD, Taylor RW, Vidal D, et al. Occupational exposure to cocaine involving crime lab personnel. J Forensic Sci 1992; 37:959.
- Mott SH, Packer RJ, Soldin SJ. Neurologic manifestations of cocaine exposure in childhood. Pediatrics 1994; 93:557.
- Mirchandani HG, Mirchandani IH, Hellman F, et al. Passive inhalation of free-base cocaine ('crack') smoke by infants. Arch Pathol Lab Med 1991; 115:494.
- Fowler JS, Volkow ND, Wang GJ, et al. [(11)]Cocaine: PET studies of cocaine pharmacokinetics, dopamine transporter availability and dopamine transporter occupancy. Nucl Med Biol 2001; 28:561.
- Musshoff F, Driever F, Lachenmeier K, et al. Results of hair analyses for drugs of abuse and comparison with self-reports and urine tests. Forensic Sci Int 2006; 156:118.
- Follador MJ, Yonamine M, de Moraes Moreau RL, Silva OA. Detection of cocaine and cocaethylene in sweat by solid-phase microextraction and gas chromatography/mass spectrometry. J Chromatogr B Analyt Technol Biomed Life Sci 2004; 811:37.
- Pil K, Verstraete A. Current developments in drug testing in oral fluid. Ther Drug Monit 2008; 30:196.
- American Academy of Pediatrics Committee on Drugs. Transfer of drugs and other chemicals into human milk. Pediatrics 2001; 108:776.
- Nice FJ, Snyder JL, Kotansky BC. Breastfeeding and over-the-counter medications. J Hum Lact 2000; 16:319.
- Ostrea EM Jr. Testing for exposure to illicit drugs and other agents in the neonate: a review of laboratory methods and the role of meconium analysis. Curr Probl Pediatr 1999; 29:37.
- Caplan YH, Goldberger BA. Alternative specimens for workplace drug testing. J Anal Toxicol 2001; 25:396.
- Cone EJ. Pharmacokinetics and pharmacodynamics of cocaine. J Anal Toxicol 1995; 19:459.
- Jenkins, AJ, Cone, EJ. Pharmacokinetics: drug absorption, distribution, and elimination. In: Drug Abuse Handbook, Karch, SB, (Ed), CRC Press, Boca Raton, FL 1998. p. 151.
- Warner A, Norman AB. Mechanisms of cocaine hydrolysis and metabolism in vitro and in vivo: a clarification. Ther Drug Monit 2000; 22:266.
- Gorelick, DA. Pharmacokinetic approaches to treatment of drug addiction. Expert Review of Clinical Pharmacology 2008; 1:277.
- Cone EJ, Tsadik A, Oyler J, Darwin WD. Cocaine metabolism and urinary excretion after different routes of administration. Ther Drug Monit 1998; 20:556.
- Pennings EJ, Leccese AP, Wolff FA. Effects of concurrent use of alcohol and cocaine. Addiction 2002; 97:773.
- Baker J, Jatlow P, Pade P, et al. Acute cocaine responses following cocaethylene infusion. Am J Drug Alcohol Abuse 2007; 33:619.
- Angrist, B. Clinical effects of central nervous system stimulants: A selective update. In: Brain Reward Systems and Abuse, Engel, J, Oreland, L, Ingvar, DH, et al (Eds). Raven Press, New York 1987. p. 109-27.
- Baselt, RC. Drug Effects on Psychomotor Performance. Biomedical Publications, Foster City, CA 2001.
- Fischman, MW, Foltin, RW. Cocaine self-administration research: implications for rational pharmacotherapy. In: Behavior, Pharmacology, and Clinical Applications, Higgins, ST, Katz, JL (Eds). Cocaine Abuse Academic Press, San Diego, CA 1998. p. 181-207.
- Blaho K, Logan B, Winbery S, et al. Blood cocaine and metabolite concentrations, clinical findings, and outcome of patients presenting to an ED. Am J Emerg Med 2000; 18:593.
- Williamson S, Gossop M, Powis B, et al. Adverse effects of stimulant drugs in a community sample of drug users. Drug Alcohol Depend 1997; 44:87.
- Ersche KD, Stochl J, Woodward JM, Fletcher PC. The skinny on cocaine: insights into eating behavior and body weight in cocaine-dependent men. Appetite 2013; 71:75.
- Rosse RB, Fay-McCarthy M, Collins JP Jr, et al. Transient compulsive foraging behavior associated with crack cocaine use. Am J Psychiatry 1993; 150:155.
- Smith MJ, Thirthalli J, Abdallah AB, et al. Prevalence of psychotic symptoms in substance users: a comparison across substances. Compr Psychiatry 2009; 50:245.
- Roncero C, Ros-Cucurull E, Daigre C, Casas M. Prevalence and risk factors of psychotic symptoms in cocaine-dependent patients. Actas Esp Psiquiatr 2012; 40:187.
- Harris D, Batki SL. Stimulant psychosis: symptom profile and acute clinical course. Am J Addict 2000; 9:28.
- Caton CL, Drake RE, Hasin DS, et al. Differences between early-phase primary psychotic disorders with concurrent substance use and substance-induced psychoses. Arch Gen Psychiatry 2005; 62:137.
- Koob GF. Drug addiction: the yin and yang of hedonic homeostasis. Neuron 1996; 16:893.
- Schenk S, Partridge B. Sensitization and tolerance in psychostimulant self-administration. Pharmacol Biochem Behav 1997; 57:543.
- Kollins SH, Rush CR. Sensitization to the cardiovascular but not subject-rated effects of oral cocaine in humans. Biol Psychiatry 2002; 51:143.
- Mendelson JH, Sholar M, Mello NK, et al. Cocaine tolerance: behavioral, cardiovascular, and neuroendocrine function in men. Neuropsychopharmacology 1998; 18:263.
- Ward AS, Haney M, Fischman MW, Foltin RW. Binge cocaine self-administration in humans: intravenous cocaine. Psychopharmacology (Berl) 1997; 132:375.
- Perez-Reyes M, White WR, McDonald SA, et al. Clinical effects of daily methamphetamine administration. Clin Neuropharmacol 1991; 14:352.
- Rogers RD, Robbins TW. Investigating the neurocognitive deficits associated with chronic drug misuse. Curr Opin Neurobiol 2001; 11:250.
- Friedman AS, Terras A, Zhu W, McCallum J. Depression, negative self-image, and suicidal attempts as effects of substance use and substance dependence. J Addict Dis 2004; 23:55.
- Marzuk PM, Tardiff K, Leon AC, et al. Prevalence of cocaine use among residents of New York City who committed suicide during a one-year period. Am J Psychiatry 1992; 149:371.
- Wilcox HC, Conner KR, Caine ED. Association of alcohol and drug use disorders and completed suicide: an empirical review of cohort studies. Drug Alcohol Depend 2004; 76 Suppl:S11.
- Wines JD Jr, Saitz R, Horton NJ, et al. Suicidal behavior, drug use and depressive symptoms after detoxification: a 2-year prospective study. Drug Alcohol Depend 2004; 76 Suppl:S21.
- Roy A. Characteristics of cocaine-dependent patients who attempt suicide. Am J Psychiatry 2001; 158:1215.
- Sofuoglu M, Dudish-Poulsen S, Brown SB, Hatsukami DK. Association of cocaine withdrawal symptoms with more severe dependence and enhanced subjective response to cocaine. Drug Alcohol Depend 2003; 69:273.
- Karmochkine M, Carrat F, Dos Santos O, et al. A case-control study of risk factors for hepatitis C infection in patients with unexplained routes of infection. J Viral Hepat 2006; 13:775.
- Friedman H, Pross S, Klein TW. Addictive drugs and their relationship with infectious diseases. FEMS Immunol Med Microbiol 2006; 47:330.
- Meade CS, Bevilacqua LA, Moore ED, et al. Concurrent substance abuse is associated with sexual risk behavior among adults seeking treatment for prescription opioid dependence. Am J Addict 2014; 23:27.
- Hill GE, Ogunnaike BO, Johnson ER. General anaesthesia for the cocaine abusing patient. Is it safe? Br J Anaesth 2006; 97:654.
- Coffey SF, Dansky BS, Carrigan MH, Brady KT. Acute and protracted cocaine abstinence in an outpatient population: a prospective study of mood, sleep and withdrawal symptoms. Drug Alcohol Depend 2000; 59:277.
- Cottler LB, Shillington AM, Compton WM 3rd, et al. Subjective reports of withdrawal among cocaine users: recommendations for DSM-IV. Drug Alcohol Depend 1993; 33:97.
- Lago JA, Kosten TR. Stimulant withdrawal. Addiction 1994; 89:1477.
- Khantzian EJ, McKenna GJ. Acute toxic and withdrawal reactions associated with drug use and abuse. Ann Intern Med 1979; 90:361.
- Nademanee K, Gorelick DA, Josephson MA, et al. Myocardial ischemia during cocaine withdrawal. Ann Intern Med 1989; 111:876.
- Chang TR, Kowalski RG, Carhuapoma JR, et al. Cocaine use as an independent predictor of seizures after aneurysmal subarachnoid hemorrhage. J Neurosurg 2016; 124:730.
- Sordo L, Indave BI, Degenhardt L, et al. A systematic review of evidence on the association between cocaine use and seizures. Drug Alcohol Depend 2013; 133:795.
- Boghdadi MS, Henning RJ. Cocaine: pathophysiology and clinical toxicology. Heart Lung 1997; 26:466.
- Brust JC. Acute neurologic complications of drug and alcohol abuse. Neurol Clin 1998; 16:503.
- Neiman J, Haapaniemi HM, Hillbom M. Neurological complications of drug abuse: pathophysiological mechanisms. Eur J Neurol 2000; 7:595.
- Reid MS, Flammino F, Howard B, et al. Topographic imaging of quantitative EEG in response to smoked cocaine self-administration in humans. Neuropsychopharmacology 2006; 31:872.
- Treadwell SD, Robinson TG. Cocaine use and stroke. Postgrad Med J 2007; 83:389.
- Westover AN, McBride S, Haley RW. Stroke in young adults who abuse amphetamines or cocaine: a population-based study of hospitalized patients. Arch Gen Psychiatry 2007; 64:495.
- Sordo L, Indave BI, Barrio G, et al. Cocaine use and risk of stroke: a systematic review. Drug Alcohol Depend 2014; 142:1.
- Cheng YC, Ryan KA, Qadwai SA, et al. Cocaine Use and Risk of Ischemic Stroke in Young Adults. Stroke 2016; 47:918.
- Rojas R, Riascos R, Vargas D, et al. Neuroimaging in drug and substance abuse part I: cocaine, cannabis, and ecstasy. Top Magn Reson Imaging 2005; 16:231.
- Mena JC, Cuellar H, Vargas D, Riascos R. PET and SPECT in drug and substance abuse. Top Magn Reson Imaging 2005; 16:253.
- Magalhaes AC. Functional magnetic resonance and spectroscopy in drug and substance abuse. Top Magn Reson Imaging 2005; 16:247.
- Little KY, Ramssen E, Welchko R, et al. Decreased brain dopamine cell numbers in human cocaine users. Psychiatry Res 2009; 168:173.
- Warner EA. Cocaine abuse. Ann Intern Med 1993; 119:226.
- van Harten PN, van Trier JC, Horwitz EH, et al. Cocaine as a risk factor for neuroleptic-induced acute dystonia. J Clin Psychiatry 1998; 59:128.
- McCord J, Jneid H, Hollander JE, et al. Management of cocaine-associated chest pain and myocardial infarction: a scientific statement from the American Heart Association Acute Cardiac Care Committee of the Council on Clinical Cardiology. Circulation 2008; 117:1897.
- Phillips K, Luk A, Soor GS, et al. Cocaine cardiotoxicity: a review of the pathophysiology, pathology, and treatment options. Am J Cardiovasc Drugs 2009; 9:177.
- Qureshi AI, Suri MF, Guterman LR, Hopkins LN. Cocaine use and the likelihood of nonfatal myocardial infarction and stroke: data from the Third National Health and Nutrition Examination Survey. Circulation 2001; 103:502.
- Shitole SG, Srinivas Y, Alapati V, et al. Clinical profile, acute care, and middle-term outcome of cocaine-associated ST-segment elevation myocardial infarction in an inner-city community. Am J Cardiol 2016; 117:1224.
- Brecklin CS, Gopaniuk-Folga A, Kravetz T, et al. Prevalence of hypertension in chronic cocaine users. Am J Hypertens 1998; 11:1279.
- Vupputuri S, Batuman V, Muntner P, et al. The risk for mild kidney function decline associated with illicit drug use among hypertensive men. Am J Kidney Dis 2004; 43:629.
- Norris KC, Thornhill-Joynes M, Robinson C, et al. Cocaine use, hypertension, and end-stage renal disease. Am J Kidney Dis 2001; 38:523.
- Lange RA, Hillis LD. Cardiovascular complications of cocaine use. N Engl J Med 2001; 345:351.
- Ghuran A, Nolan J. Recreational drug misuse: issues for the cardiologist. Heart 2000; 83:627.
- Ramirez FD, Femenía F, Simpson CS, et al. Electrocardiographic findings associated with cocaine use in humans: a systematic review. Expert Rev Cardiovasc Ther 2012; 10:105.
- Maceira AM, Ripoll C, Cosin-Sales J, et al. Long term effects of cocaine on the heart assessed by cardiovascular magnetic resonance at 3T. J Cardiovasc Magn Reson 2014; 16:26.
- Tseng W, Sutter ME, Albertson TE. Stimulants and the lung : review of literature. Clin Rev Allergy Immunol 2014; 46:82.
- Caponnetto P, Auditore R, Russo C, et al. "Dangerous relationships": asthma and substance abuse. J Addict Dis 2013; 32:158.
- de Almeida RR, de Souza LS, Mançano AD, et al. High-resolution computed tomographic findings of cocaine-induced pulmonary disease: a state of the art review. Lung 2014; 192:225.
- Pawlik E, Mahler H, Hartung B, et al. Drug-related death: adulterants from cocaine preparations in lung tissue and blood. Forensic Sci Int 2015; 249:294.
- Antoniazzi RP, Sari AR, Casarin M, et al. Association between crack cocaine use and reduced salivary flow. Braz Oral Res 2017; 31:e42.
- Fung EY, Giannini PJ. Implications of drug dependence on dental patient management. Gen Dent 2010; 58:236.
- Pateria P, de Boer B, MacQuillan G. Liver abnormalities in drug and substance abusers. Best Pract Res Clin Gastroenterol 2013; 27:577.
- Martel-Laferrière V, Nitulescu R, Cox J, et al. Cocaine/crack use is not associated with fibrosis progression measured by AST-to-Platelet Ratio Index in HIV-HCV co-infected patients: a cohort study. BMC Infect Dis 2017; 17:80.
- Ponsoda X, Bort R, Jover R, et al. Increased toxicity of cocaine on human hepatocytes induced by ethanol: role of GSH. Biochem Pharmacol 1999; 58:1579.
- Pendergraft WF 3rd, Herlitz LC, Thornley-Brown D, et al. Nephrotoxic effects of common and emerging drugs of abuse. Clin J Am Soc Nephrol 2014; 9:1996.
- Fernandez WG, Hung O, Bruno GR, et al. Factors predictive of acute renal failure and need for hemodialysis among ED patients with rhabdomyolysis. Am J Emerg Med 2005; 23:1.
- Bemanian S, Motallebi M, Nosrati SM. Cocaine-induced renal infarction: report of a case and review of the literature. BMC Nephrol 2005; 6:10.
- Mello NK, Mendelson JH. Cocaine's effects on neuroendocrine systems: clinical and preclinical studies. Pharmacol Biochem Behav 1997; 57:571.
- Warner EA, Greene GS, Buchsbaum MS, et al. Diabetic ketoacidosis associated with cocaine use. Arch Intern Med 1998; 158:1799.
- Bhinder SK, Majithia V. Cocaine use and its rheumatic manifestations: a case report and discussion. Clin Rheumatol 2007; 26:1192.
- Gross RL, Brucker J, Bahce-Altuntas A, et al. A novel cutaneous vasculitis syndrome induced by levamisole-contaminated cocaine. Clin Rheumatol 2011; 30:1385.
- Chung C, Tumeh PC, Birnbaum R, et al. Characteristic purpura of the ears, vasculitis, and neutropenia--a potential public health epidemic associated with levamisole-adulterated cocaine. J Am Acad Dermatol 2011; 65:722.
- Macdonald PT, Waldorf D, Reinarman C, Murphy S. Heavy cocaine use and sexual behavior. J Drug Issues 1988; 18:437.
- Palha AP, Esteves M. Drugs of abuse and sexual functioning. Adv Psychosom Med 2008; 29:131.
- Carey JC. Pharmacological effects on sexual function. Obstet Gynecol Clin North Am 2006; 33:599.
- Chiriboga CA. Fetal alcohol and drug effects. Neurologist 2003; 9:267.
- Kuczkowski KM. The effects of drug abuse on pregnancy. Curr Opin Obstet Gynecol 2007; 19:578.
- Schama, KF, Howell, LL, Byrd, LD. Prenatal exposure to cocaine. In: Cocaine Abuse: Behavior, Pharmacology, and Clinical Applications, Higgins, ST, Katz, JL, (Eds), Academic Press, San Diego, CA 1998. p. 159-79.
- Williams JH, Ross L. Consequences of prenatal toxin exposure for mental health in children and adolescents: a systematic review. Eur Child Adolesc Psychiatry 2007; 16:243.
- Rawson, RA (ed). Treatment for Stimulant Use Disorders (TIPS #33). Center for Substance Abuse Treatment, Rockville, MD 1999.
- Hjorthøj CR, Hjorthøj AR, Nordentoft M. Validity of Timeline Follow-Back for self-reported use of cannabis and other illicit substances--systematic review and meta-analysis. Addict Behav 2012; 37:225.
- Newton AS, Gokiert R, Mabood N, et al. Instruments to detect alcohol and other drug misuse in the emergency department: a systematic review. Pediatrics 2011; 128:e180.
- McNeely J, Wu LT, Subramaniam G, et al. Performance of the Tobacco, Alcohol, Prescription Medication, and Other Substance Use (TAPS) Tool for Substance Use Screening in Primary Care Patients. Ann Intern Med 2016; 165:690.
- Verstraete AG. Detection times of drugs of abuse in blood, urine, and oral fluid. Ther Drug Monit 2004; 26:200.
- Preston KL, Epstein DH, Cone EJ, et al. Urinary elimination of cocaine metabolites in chronic cocaine users during cessation. J Anal Toxicol 2002; 26:393.
- Cone EJ, Weddington WW Jr. Prolonged occurrence of cocaine in human saliva and urine after chronic use. J Anal Toxicol 1989; 13:65.
- Uemura N, Nath RP, Harkey MR, et al. Cocaine levels in sweat collection patches vary by location of patch placement and decline over time. J Anal Toxicol 2004; 28:253.
- Gambelunghe C, Rossi R, Ferranti C, et al. Hair analysis by GC/MS/MS to verify abuse of drugs. J Appl Toxicol 2005; 25:205.
- Felli M, Martello S, Marsili R, Chiarotti M. Disappearance of cocaine from human hair after abstinence. Forensic Sci Int 2005; 154:96.