AUTHOR AND EDITOR INFORMATION

Section 1 of 9  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Follow-up
• Miscellaneous
• References

INTRODUCTION

Section 2 of 9  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Follow-up
• Miscellaneous
• References

Background

The world is facing an epidemic of cocaine use by adolescents and young adults from all socioeconomic backgrounds. Epidemiologic data suggest that cocaine use is a serious public health problem because it is highly addictive and is associated with a variety of neurological complications (see Complications).

Cocaine, a natural alkaloid, is extracted from leaves of an Andean shrub, Erythroxylon coca. Coca leaves were used by the native populations to alleviate the rigors of high altitude and to diminish fatigue. Although cocaine was extracted in pure form from coca in 1860, Europeans became aware of its potential medical complications only after Sigmund Freud's Über Coca was published in 1884. It was described by Freud as a wonder drug that could cure depressed mood and alcohol dependence. It is used as an ophthalmic and spinal anesthetic.

An important factor in the most recent epidemic of cocaine use was the popularization in the late 1980s of the smoked form, known as crack or rock. It was called crack supposedly because of the sound made by crystals of cocaine popping when heated or rock because of its appearance.

Cocaine remains the primary nonalcoholic drug of abuse. It has been sold on the streets for many years as a water-soluble hydrochloride (HCl) salt for nasal insufflation (snorting) or intravenous injection. It may be injected subcutaneously or intramuscularly, but this route rarely is used because vasoconstriction slows absorption and the drug thus is less likely to result in a "rush."

Cocaine can be smoked only when it is altered to form cocaine base (ie, free base). Smoking of the base (ie, "free basing") results in an almost instantaneous "high" due to rapid absorption through the large pulmonary surface area and swift penetration into the brain. Smoking of cocaine base has increased in many cities throughout the world. Although the nasal route and smoking of the base currently are in vogue, cocaine can be absorbed readily from any mucous membrane. Irrespective of route of administration, it causes neurological complications (see Complications).

Pathophysiology

The most important pharmacological actions of cocaine are blocking the initiation or conduction of the action potential following local application to a nerve and stimulating the CNS.

The local anesthetic effect of cocaine is due to a direct membrane effect. Cocaine blocks the initiation and conduction of electrical impulses within nerve cells (ie, anesthetic effect) by preventing the rapid increase in cell-membrane permeability to sodium ions during depolarization. Its systemic effects on the nervous system probably are mediated by alterations in synaptic transmissions. The most noticeable systemic activity of cocaine is stimulation of the CNS by altering the uptake and metabolism of norepinephrine, dopamine, serotonin, and acetylcholine.

By blocking presynaptic reuptake of the neurotransmitters norepinephrine and dopamine, cocaine increases the quantity of neurotransmitters at the postsynaptic receptor sites. The resultant activation of the sympathetic nervous system produces an acute rise in arterial pressure, tachycardia, and a predisposition to ventricular arrhythmias and seizures. Sympathetic activation also may result in mydriasis, hyperglycemia, and hyperthermia. The effects of cocaine on dopaminergic neuronal systems may be involved in producing euphoria and addiction.

In the short term, cocaine appears to stimulate dopaminergic neurotransmission by blocking the reuptake of dopamine. However, evidence suggests that, with long-term use, the nerve terminals may be depleted of dopamine. Dopamine depletion has been theorized to contribute to the dysphoria that develops during withdrawal from cocaine and the subsequent craving for more of the drug. In this way, alterations in dopamine neurotransmission may be responsible for the development of compulsive use patterns. With higher doses and regular use, other neurotransmitter systems (eg, serotonin) probably are involved, directly or indirectly, in mediating CNS toxicity. With regular use, moreover, neuroadaptive mechanisms result in development of tolerance, reverse tolerance (ie, behavioral sensitization), and dependence.

Frequency

United States

Cocaine use in the United States has reached epidemic proportions. In the second half of the last century, cocaine consumption in North America rose rapidly; by the late 1980s, 30 million people were cocaine users and 6 million were cocaine addicts. In the United States, 5 million people take cocaine regularly, and every day approximately 5000 people try cocaine for the first time. Estimates in the 1990s suggested that 30-40 million Americans have some experience with cocaine and that 1 of every 2 persons aged 25-30 years has used the drug. The incidence of neurological complications is not known.

International

The figures for the consumption of cocaine have risen progressively in all Central American countries, Europe, and parts of Asia. Worldwide, hundreds of millions of people are believed to use cocaine.

Mortality/Morbidity

• Neuropsychiatric complications occur in approximately 40% of cocaine users (see Complications). Headaches occur in approximately 3.5% and convulsions in approximately 3.5% of cocaine users. A relative risk of 49.4% was found for cocaine use less than 6 hours before stroke onset and a relative risk of 6.5% for drug use of unknown interval before stroke onset when compared with controls matched for sex, age, and year of discharge. Ischemic and hemorrhagic strokes are equally likely after alkaloid cocaine use, whereas cocaine HCl use is more likely (approximately 80% of the time) to cause hemorrhagic stroke; approximately half the intracranial hemorrhages occurring after cocaine use are from ruptured cerebral saccular aneurysms or vascular malformations.
• Acute effects of cocaine include decreased food intake, increased activity, effusiveness, and diminished fatigue. Repetitive motor activity is observed with higher doses. Overdose can result in convulsions, hyperthermia, coma, and death. A dose-dependent increase in heart rate and blood pressure can occur. Regular cocaine use interferes with sleep and suppresses rapid eye movement (REM) sleep. In addition, cocaine can lower seizure threshold.
• Tolerance and dependence: Some, but not all, of the central effects (eg, euphoria, anorexia, hyperthermia) reveal tolerance. Tolerance may lead to the escalation of dose required to produce the same CNS effect.

Race

• Despite evidence of a recent overall decline in cocaine use, cocaine-related health and criminal justice problems are increasing. A change in the pattern of cocaine use, from relatively innocuous intermittent recreational use of cocaine HCl powder among the affluent to heavy smoking of crack cocaine among poor and criminal segments of the population in the inner cities has been noted. Examination of cocaine abusers revealed deficiencies in interpersonal, financial, physical, and vocational faculties. Crack cocaine users are at high risk for HIV, with high-frequency crack users increasingly engaging in HIV-related sexual risk behaviors. Studies conducted in East Harlem, NY, reported 33% of crack users to be female; 91% of the population using cocaine were African American or Hispanic.
• Interview data collected from the National Household Surveys on Drug Abuse (NHSDA) from 1979-1994 showed that an estimated 23% of US residents have tried cocaine. Among those who eventually abused the drug, the vast majority made the transition from first trial to regular use within 1 year. Males were more likely than females to try cocaine but were not more likely than females to progress to actual abuse.

Sex

• The typical cocaine user is a young man with a higher-than-average income. Many users are professionals in positions of authority that entail a high level of responsibility.
• The highest prevalence rates of cocaine use in the United States are among young white men aged 18-25 years residing in the west and the northeast.
• Young-adult cocaine users are likely to consume the drug occasionally and to use alcohol or marijuana more frequently than cocaine. Use of marijuana and cocaine in combination is not unusual.

Age

• In the United States, the use of cocaine is most prevalent among younger people; however, the number of younger people using cocaine generally has declined, while the number of older individuals using cocaine has increased.
• According to the NHSDA, the rate of cocaine use in 1998 was highest among Americans aged 18-25 years. Nineteen percent of the respondents in this age group had used cocaine within the prior year, and one third of these persons reported that they had used cocaine during the previous month.

CLINICAL

Section 3 of 9  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Follow-up
• Miscellaneous
• References

History

• Acute effects of cocaine
• • Decreased food intake
  • Increased activity
  • Effusiveness
  • Diminished fatigue
• Long-term cocaine use
• • Interferes with sleep
  • Can lower seizure threshold
• Overdose of cocaine
• • Convulsions
  • Hyperthermia
  • Coma
• Neuropsychiatric complications: Psychiatric disturbances include depression, suicidal ideation, paranoia, kleptomania, violent antisocial behavior, catatonia, and auditory or visual hallucinations. Cocaine use may lead to impulsivity, resulting in sexually risky behavior and increasing the risk of becoming infected with HIV.
• Headache is a relatively frequent symptom (3.5%) in cocaine users. Headaches occur in 11% of cocaine paste smokers.
• Convulsions
• • Convulsions occur in about 3% of cocaine users. Convulsions caused by cocaine can be generalized or partial, simple or complex. The majority of seizures are single, generalized, induced by intravenous or crack cocaine, and not associated with any lasting neurological deficits. Most focal, multiple, or induced seizures caused by nasal insufflation of cocaine are associated with an acute intracerebral complication or concurrent use of other drugs.
  • Generally, seizures caused by cocaine use are associated with cerebral lesions or with interictal EEG abnormalities.
  • All routes of administration are associated with seizures, and seizures can be induced in some persons by small quantities of cocaine. Once intoxication has passed, these individuals do not require long-term anticonvulsant therapy.
  • Although most cocaine-induced seizures are benign and self-limiting, seizures may be due to other more severe complications, such as infarction and intracranial hemorrhage.
• Cocaine can cause acute renal failure resulting from rhabdomyolysis or vasospasm.

Physical

A dose-dependent increase in heart rate and blood pressure can occur.

DIFFERENTIALS

Section 4 of 9  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Follow-up
• Miscellaneous
• References

Other Problems to be Considered

Adrenergic crisis due to amphetamine overdose and thyroid storm (occasionally may mimic acute cocaine intoxication)
Carotid disease and stroke

WORKUP

Section 5 of 9  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Follow-up
• Miscellaneous
• References

Lab Studies

• Lab tests should be ordered on the basis of patient presentation. Indications for ordering labs are as follows:
• • Diagnosis of cocaine use
    • Urine drug screen: Qualitative drug screens usually test for the inactive cocaine metabolite, benzoylecgonine, which may be present for as long as 36 hours after a single use. Metabolites can be demonstrated in the urine within 5 minutes after intravenous administration. With long-term use, urine metabolites may be detected for as long as 3 weeks after discontinuation of the drug. Urine drug screen in the neonate also can be used to detect possible in utero exposure to cocaine. The persistence of benzoylecgonine, which can be detected in the neonate's urine for as long as 4 days, is due to slow metabolism, probably related to immaturity or relative deficiency of plasma cholinesterases in the newborn.
    • Serum level of cocaine: This can be determined but has not been found to be useful clinically because of the rapid metabolism and short half-life of the drug.
  • Diagnosis of neurological complications: Tests used for diagnosing neurological complications include antinuclear antibody (ANA), creatine kinase (CK), CT scan, brain MRI, magnetic resonance angiography (MRA) of neck and intracranial vessels, 4-vessel angiogram, echocardiogram (transthoracic, transesophageal), positron emission tomography (PET), and single-photon emission computed tomography (SPECT).
  • CK: Urine should be evaluated routinely for the presence of myoglobin. Of patients with cocaine-induced rhabdomyolysis, 75% have a positive urine dipstick result for the orthotolidine reaction for heme, 67% yield positive findings for urine protein, and many manifest microscopic hematuria.

Imaging Studies

• CT scan of brain: Focal neurological deficits or alterations in mental status are indications for performing CT scan of the brain. With long-term cocaine use, significant cerebral atrophy, enlarged lateral ventricles, and widened sylvian fissures may be seen. CT scan also reveals intracerebral hemorrhage.
• MRI of brain: MRI of newborns exposed to cocaine in utero may reveal evidence of cortical infarction, major congenital malformations, and mainly midline CNS abnormalities. Prenatal cocaine exposure reveals subtle microstructural changes on diffusion tensor imaging, suggesting less mature development of frontal white matter pathways.
• MRA of brain and intracranial vessels: MRA is indicated in patients with ischemic stroke or subarachnoid hemorrhage. MRA may show evidence of vasculitis or aneurysm; venous phase may show evidence of venous thrombosis.
• Four-vessel angiogram: This study is indicated in patients with a history of cocaine abuse and presenting with intracerebral hemorrhage, especially subarachnoid hemorrhage. Angiogram may show underlying vascular abnormalities. Berry aneurysms of the circle of Willis are a common finding. Arteriovenous (AV) malformations or tumor may be seen as well. Rarely, superior sagittal sinus thrombosis with hemorrhagic venous infarction, dural AV fistula, rupture of multiple mycotic aneurysms, and large-vessel thrombosis have been described. Angiographic beading can be seen in patients with vasculitis.
• Neuroradiological study of newborns born to mothers who had used cocaine during pregnancy may reveal periventricular leukomalacia or holoprosencephaly. Evidence of intracerebral, intraventricular or subarachnoid hemorrhage may be observed. Sonography, CT scan, and MRI revealed cortical infarcts and midline congenital malformations in 15% of infants exposed to cocaine in utero.

Other Tests

• ECG: Perform ECG if patient has chest pain.
• EEG: Perform EEG in patients with seizures and a history of cocaine use. Habitual cocaine use can be associated with diffuse slowing on EEG. Focal abnormalities in the form of spikes or slowing can be seen in patients with focal seizures or intracerebral complications.
• Transthoracic and transesophageal echocardiogram: Perform transthoracic and transesophageal echocardiogram in patients with embolic stroke caused by cocaine use. These studies may show evidence of vegetations in patients with infective endocarditis.
• PET and SPECT: These studies are indicated in long-term cocaine users presenting with neuropsychiatric manifestations. Cerebral blood flow is reduced in habitual cocaine abusers, and abnormalities are most marked in the prefrontal cortex. Some investigators using PET have found reduced glucose metabolism over the entire cerebral cortex, thalamus, and midbrain. SPECT with iodine-123 isopropyl iodoamphetamine (IMP) revealed irregularly reduced cerebral perfusion even among asymptomatic social cocaine users who had normal findings on CT scans. In cocaine-dependent polydrug users (many of whom also used opioids and/or ethanol), some authors have found abnormal cerebral perfusion that primarily involved parietal, temporal, frontal, and basal ganglia.

TREATMENT

Section 6 of 9  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Follow-up
• Miscellaneous
• References

Medical Care

• Acute intoxication requires hospitalization for detoxification and management of acute neurovascular complications.
• For long-term management, drug-dependence programs can be effective in decreasing drug use by behavioral interventions. Cognitive behavioral therapy can be effective in decreasing craving for the drug.
• No pharmacotherapies have been approved for cocaine addiction. Some drugs have been tested with promising results. Disulfiram, amantadine, tiagabine, topiramate, and baclofen are some drugs that have been reported to be of possible benefit in cocaine addiction. Counseling plus buprenorphine-naloxone maintenance therapy has been reported to be successful for opioid dependence. A recent double-blinded, placebo-controlled trial of modafinil for cocaine dependence showed that modafinil improved clinical outcomes when combined with psychosocial treatment for cocaine dependence. The psychotropic analgesic nitrous oxide has been reported in one blinded trial to be effective for the treatment of acute cocaine withdrawal.
• Patients require follow-up for neurological complications.

FOLLOW-UP

Section 7 of 9  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Follow-up
• Miscellaneous
• References

Complications

• Neuropsychiatric complications
• • Neuropsychiatric complications occur in about 40% of cocaine users. Psychiatric disturbances include depression, suicidal ideation, paranoia, kleptomania, violent antisocial behavior, catatonia, and auditory or visual hallucinations. Hallucinations occurring with cocaine intoxication can be simple or complex, affecting various sensory categories (eg, visual, auditory, cutaneous, visceral, cenesthesic), and may be associated with delusions of persecution.
  • A moderate proportion of addicts develop panic attacks, which are different from primary panic attacks in that cocaine users frequently have psychosensory symptoms, infrequent agoraphobia, hypersensitivity to caffeine, untoward responses to antidepressants, partial improvement with alprazolam, and marked recovery with clonazepam or carbamazepine.
  • Cocaine panic attacks can be explained in terms of limbic-neuronal hyperexcitability.
  • Suspicious and paranoid attitudes can easily be aroused experimentally by cocaine use. The paranoid symptoms are more severe and develop more rapidly with continuous use of cocaine.
• Convulsions
• • Convulsions occur in about 3% of cocaine users. Convulsions caused by cocaine can be generalized or partial, simple or complex. The majority of seizures are single, generalized, induced by intravenous or crack cocaine, and not associated with any lasting neurological deficits. Most focal, multiple, or induced seizures caused by nasal insufflation of cocaine are associated with an acute intracerebral complication or concurrent use of other drugs.
  • The mechanism of cocaine-induced seizures is thought to be related to the local anesthetic action of the drug. Like lidocaine, cocaine lowers the seizure threshold and can block nerve cell conduction. Generally, seizures caused by cocaine use are associated with cerebral lesions or with interictal EEG abnormalities.
  • Seizures are one of the few complications of cocaine use in which a direct relationship with dose has been shown.
  • All routes of administration are associated with seizures, and seizures can be induced in some persons by small quantities of cocaine. Once intoxication has passed, these individuals do not require long-term anticonvulsant therapy.
  • Although most cocaine-induced seizures are benign and self-limiting, seizures may be due to other more severe complications, such as infarction and intracranial hemorrhage.
• Cerebrovascular disorders
• • Cerebrovascular disorders may be secondary to arterial or venous etiology. Arterial complications include either ischemic or hemorrhagic strokes.
  • Hemorrhagic manifestations may be intraparenchymal or subarachnoid hemorrhage. Hemorrhage occurs about twice as frequently as ischemia. When neurological signs are present, imaging studies show findings associated with neurological abnormalities in nearly 80% of cases.
  • Ischemic manifestations of cocaine are postulated to be secondary to vasospasm or vasculitis or due to the procoagulant effect of the drug, which enhances platelet aggregation by depletion of arachidonic acid and thromboxane.
  • With intravenous use of cocaine, ischemic stroke may be cardioembolic–a complication of endocarditis. Complications include anterior spinal artery syndrome, lateral bulbar syndrome, and transient ischemic attacks.
  • Rarely, inhalation of cocaine also can lead to subarachnoid hemorrhage. An extensive infarct of the middle cerebral artery can occur after smoking free-base cocaine or cocaine paste.
  • Hemorrhages can be subcortical, pontine, or subarachnoid and may be associated with malformations, tumors, or aneurysms.
  • Cocaine-induced stroke in patients with underlying vascular malformations is thought to be due to the transient elevation of blood pressure that occurs after cocaine ingestion.
  • Hemorrhage may occur within seconds of cocaine use or may lag cocaine use by as long as 12 hours. In many cases, however, it occurs within a few minutes. This corresponds well with the known transient period of increased systolic blood pressure seen in these patients.
  • Although most cocaine-induced strokes occur in patients younger than 50 years, age and hypertension are regarded as risk factors for cocaine-induced stroke. Alkaloid cocaine probably is associated more commonly with ischemic and hemorrhagic accidents than other forms of cocaine. Impurities of street cocaine, such as talc or sugar, may embolize to the brain after intravenous injection.
  • Subarachnoid hemorrhages primarily occur in patients with underlying vascular malformations. Berry aneurysms of the circle of Willis are a common finding; AV malformations or tumors may be seen as well.
  • Ruptures of multiple mycotic aneurysms and large-vessel thromboses have been described. Venous complications include superior sagittal sinus thrombosis with hemorrhagic venous infarction, ie, dural AV fistula.
• Movement disorders
• • One single cocaine inhalation in patients with Tourette syndrome can worsen the clinical picture considerably, possibly reflecting the intrinsic receptor hypersensitivity to dopaminergic transmission in the CNS.
  • Opsoclonus and myoclonus also are seen after cocaine inhalation.
  • Cocaine addicts can develop marked dystonic reactions during the withdrawal phase. These attacks subside quickly with administration of diphenhydramine HCl. The dystonia probably is precipitated by the functional dopamine deficiency in these patients.
• Muscular disorders
• • In regions of the world with warm climates, cocaine-intoxicated patients in emergency rooms may show rhabdomyolysis. These patients have blood CK values exceeding 12,000 U/L. More than one third of these patients develop severe kidney insufficiency with hypotension, hyperpyrexia, disseminated intravascular coagulation, hepatic dysfunction, and CK values greater than 30,000 U/L. Dialysis is indicated in such patients.
  • The pathogenesis of rhabdomyolysis remains obscure and speculative.
  • Probably because of dopamine depletion, administration of neuroleptics in agitated long-term cocaine users can worsen the clinical picture and cause development of malignant hyperthermia. These patients should be treated with a dopaminergic agonist (eg, bromocriptine) and not with neuroleptics.
• Secondary complications
• • Cocaine-induced arterial thrombosis may occur in patients with a recent history of cocaine abuse. This presents as acute limb ischemia without an identifiable cardiovascular risk factor. Prompt angiography with operative or endovascular intervention should be performed.
  • The effects of cocaine on other organ systems may lead to CNS complications.
  • Cocaine may lead to myocardial infarction, cardiac arrhythmias, and respiratory arrest; any of these complications could lead to cerebral hypoperfusion or cerebral embolization of blood products.
• Spinal cord involvement: Infarction of the spinal cord due to anterior spinal artery involvement leading to quadriplegia has been reported as a complication following acute cocaine intoxication.
• Pregnancy and newborns
• • Women using cocaine have higher numbers of spontaneous abortions, premature births, placental abruption, and placenta previa than nonusers. Babies born to these mothers exhibit significant depression in behavior and response to stimuli. Newborn babies may develop cerebral infarcts. Intrauterine fetal growth may be retarded; microcephaly, small-for-date birth weights, convulsions, infarcts, cerebral hemorrhages, hypertonicity, motor restlessness, and absence of saccadic movements on oculovestibular stimuli are more common than in newborns of mothers who do not use the drug.
  • Congenital malformations are postulated to result from fetal ischemia during the first trimester, and occlusive stroke is a consequence of ischemia during the third trimester.
  • Respiratory anomalies in newborns are more noticeable during sleep. Severe respiratory difficulty syndromes and failures of the awakening mechanism have been documented. Sonography, CT scan, and MRI revealed cortical infarcts and midline congenital malformations in 15% of infants born to mothers who used cocaine.
  • Prenatal exposure to cocaine is related to aggressive behavior at age 5 years.

Patient Education

• For excellent patient education resources, visit eMedicine's Substance Abuse Center. Also, see eMedicine's patient education articles Drug Dependence and Abuse and Substance Abuse.

MISCELLANEOUS

Section 8 of 9  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Follow-up
• Miscellaneous
• References

Medical/Legal Pitfalls

• Based on recommendations of the stroke study by the National Institute of Neurological Disorders and Stroke (NINDS), thrombolysis with intravenous tissue plasminogen activator (t-PA) is not contraindicated in patients with cocaine-induced stroke. However, on account of the risk of intracerebral hemorrhage as well as diverse nature of etiopathogenesis of cocaine-induced ischemic stroke, treating physicians are asked to exert caution in using t-PA in patients with cocaine-induced stroke.

REFERENCES

Section 9 of 9

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Follow-up
• Miscellaneous
• References

• Bendersky M, Bennett D, Lewis M. Aggression at Age 5 as a Function of Prenatal Exposure to Cocaine, Gender, and Environmental Risk. J Pediatr Psychol. Apr 12 2005;[Medline].
• Brown E, Prager J, Lee HY, Ramsey RG. CNS complications of cocaine abuse: prevalence, pathophysiology, and neuroradiology. AJR Am J Roentgenol. Jul 1992;159(1):137-47. [Medline].
• Brust JC. Clinical, radiological, and pathological aspects of cerebrovascular disease associated with drug abuse. Stroke. Dec 1993;24(12 Suppl):I129-33; discussion I134-5. [Medline].
• Chasnoff IJ, Bussey ME, Savich R, Stack CM. Perinatal cerebral infarction and maternal cocaine use. J Pediatr. Mar 1986;108(3):456-9. [Medline].
• Dackis CA, Kampman KM, Lynch KG, et al. A double-blind, placebo-controlled trial of modafinil for cocaine dependence. Neuropsychopharmacology. Jan 2005;30(1):205-11. [Medline].
• Fiellin DA, Pantalon MV, Chawarski MC, et al. Counseling plus buprenorphine-naloxone maintenance therapy for opioid dependence. N Engl J Med. Jul 27 2006;355(4):365-74. [Medline].
• Gillman MA, Lichtigfeld FJ, Harker N. Psychotropic analgesic nitrous oxide for acute cocaine withdrawal in man. 1: Int J Neurosci. 2006;116(7):847-57. [Medline].
• Green RM, Kelly KM, Gabrielsen T, et al. Multiple intracerebral hemorrhages after smoking "crack" cocaine. Stroke. Jun 1990;21(6):957-62. [Medline].
• Hayaki J, Anderson B, Stein M. Sexual risk behaviors among substance users: relationship to impulsivity. Psychol Addict Behav. 2006;20(3):328-32. [Medline].
• Jacobs IG, Roszler MH, Kelly JK, et al. Cocaine abuse: neurovascular complications. Radiology. Jan 1989;170(1 Pt 1):223-7. [Medline].
• Kaku DA, Lowenstein DH. Emergence of recreational drug abuse as a major risk factor for stroke in young adults. Ann Intern Med. Dec 1 1990;113(11):821-7. [Medline].
• Kaye BR, Fainstat M. Cerebral vasculitis associated with cocaine abuse. JAMA. Oct 16 1987;258(15):2104-6. [Medline].
• Killam AL. Cardiovascular and thrombosis pathology associated with cocaine use. Hematol Oncol Clin North Am. Dec 1993;7(6):1143-51. [Medline].
• Klonoff DC, Andrews BT, Obana WG. Stroke associated with cocaine use. Arch Neurol. Sep 1989;46(9):989-93. [Medline].
• Krendel DA, Ditter SM, Frankel MR, Ross WK. Biopsy-proven cerebral vasculitis associated with cocaine abuse. Neurology. Jul 1990;40(7):1092-4. [Medline].
• Levine SR, Brust JC, Futrell N, et al. A comparative study of the cerebrovascular complications of cocaine: alkaloidal versus hydrochloride--a review. Neurology. Aug 1991;41(8):1173-7. [Medline].
• Mody CK, Miller BL, McIntyre HB, et al. Neurologic complications of cocaine abuse. Neurology. Aug 1988;38(8):1189-93. [Medline].
• Nalls G, Disher A, Daryabagi J, et al. Subcortical cerebral hemorrhages associated with cocaine abuse: CT and MR findings. J Comput Assist Tomogr. Jan-Feb 1989;13(1):1-5. [Medline].
• Nolte KB, Brass LM, Fletterick CF. Intracranial hemorrhage associated with cocaine abuse: a prospective autopsy study. Neurology. May 1996;46(5):1291-6. [Medline].
• Oyelese Y, Ananth CV. Placental abruption. Obstet Gynecol. 2006;108(4):1005-16.
• Pascual-Leone A, Dhuna A, Altafullah I, Anderson DC. Cocaine-induced seizures. Neurology. Mar 1990;40(3 Pt 1):404-7. [Medline].
• Rivero M, Karlic A, Navaneethan SD, Singh S. Possible cocaine-induced acute renal failure without rhabdomyolysis. J Nephrol. Jan-Feb;. 2006;19(1):108-10. [Medline].
• Rohsenow DJ, Monti PM, Martin RA, et al. Motivational enhancement and coping skills training for cocaine abusers: effects on substance use outcomes. Addiction. Jul 2004;99(7):862-74. [Medline].
• Roth ME, Carroll ME. Sex differences in the escalation of intravenous cocaine intake following long- or short-access to cocaine self-administration. Pharmacol Biochem Behav. Jun 2004;78(2):199-207. [Medline].
• Sanchez-Ramos JR. Psychostimulants. Neurol Clin. Aug 1993;11(3):535-53. [Medline].
• Sen S, Silliman SL, Braitman LE. Vascular risk factors in cocaine users with stroke. J Stroke Cerebrovasc Dis. 1999;8(4):254-258.
• Sloan MA, Kittner SJ, Rigamonti D, Price TR. Occurrence of stroke associated with use/abuse of drugs. Neurology. Sep 1991;41(9):1358-64. [Medline].
• Sofuoglu M, Kosten TR. Novel approaches to the treatment of cocaine addiction. CNS Drugs. 2005;19(1):13-25. [Medline].
• Tumeh SS, Nagel JS, English RJ, Holman BL. Cerebral abnormalities in cocaine abusers: demonstration by SPECT perfusion brain scintigraphy. Work in progress. Radiology. Sep 1990;176(3):821-4. [Medline].
• Warner TD, Behnke M, Eyler FD, et al. Diffusion tensor imaging of frontal white matter and executive functioning in cocaine-exposed children. Pediatrics. 2006;118(5):2014-24. [Medline].
• Zhou W, Lin PH, Bush RL, et al. Acute arterial thrombosis associated with cocaine abuse. J Vasc Surg. Aug 2004;40(2):291-5. [Medline].

Article Last Updated: Feb 21, 2007