Neurologic Effects of Cocaine

Updated: Nov 12, 2019
Author: Pinky Agarwal, MD; Chief Editor: Stephen A Berman, MD, PhD, MBA 



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 implications only after Sigmund Freud's Über Coca was published in 1884.[1] 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 is available as a free base, which is white to light brown in color depending on impurities, and as cocaine hydrochloride salt, which is a white powder. Cocaine hydrochloride is water-soluble and can be used for nasal insufflation (snorting) or may be injected subcutaneously or intramuscularly, but this route is rarely used because vasoconstriction slows absorption and the drug thus is less likely to result in a "rush."

The crystalline free-base form of cocaine is water insoluble and hence is volatilized and smoked.[2] Smoking of the base (ie, "free basing") results in an almost instantaneous "high" owing 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 are currently in vogue, cocaine can be absorbed readily from any mucous membrane. Irrespective of route of administration, it causes neurological complications (see Complications). In South American countries, cocaine is often smoked in coca paste form, which behaves more like free cocaine than like a cocaine sulfate salt.[3]

A more recent disturbing trend in cocaine use has been the increasing availability of levamisole-laced cocaine. Levamisole is an antihelminth currently approved for use for veterinary purposes. It had been previously used as an immune modulator in rheumatoid arthritis and pediatric nephrotic syndrome, but, owing to the potential to cause agranulocytosis, it has been withdrawn from human use. The exact reasons for lacing of cocaine with levamisole are not entirely clear, but it appears to potentiate the psychoactive effects of cocaine. Of all cocaine entering United States, 69% is laced with levamisole. Serious and severe adverse effects have been reported with this combination (see Complications).[4]


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.



According to the National Survey on Drug Use and Health (NSDUH), cocaine use has remained relatively stable since 2009. In 2014, there were an estimated 1.5 million current (past-month) cocaine users aged 12 years or older (0.6 percent of the population). Adults aged 18 to 25 years have a higher rate of current cocaine use than any other age group, with 1.4% of young adults reporting past-month cocaine use.[5]

The 2015 Monitoring the Future survey, which annually surveys teen attitudes and drug use, reports a significant decline in 30-day prevalence of powder cocaine use among 8th, 10th, and 12th graders from peak use in the late 1990s. In 2014, 1.1% of 12th graders and only 0.8% of 10th and half a percent of 8th graders reported using cocaine in the past month.[6]


Neuropsychiatric complications occur in approximately 40% of cocaine users (see Complications). Headaches occur in approximately 3% and convulsions in approximately 3% 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.[7]

Acute cocaine use has also been associated with a higher risk of aneurysmal rerupture in aneurysmal subarachnoid hemorrhage, and the adjusted odds of in-hospital mortality was 2.9 times higher among cocaine users versus nonusers with aneurysmal subarachnoid hemorrhage.[8]

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 may ensue. 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.


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. Cocaine abusers suffer from poor health, poverty, employment difficulties, and poor interpersonal relationships. Crack cocaine users are at high risk for HIV, with high-frequency crack users increasingly engaging in HIV-related sexual risk behaviors. In a sample of 303 African-American HIV-positive individuals who used cocaine, 72% reported having sex during the last binge with an average of 3.1 partners.[9]

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.


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.

Cocaine is commonly used as a club drug among gay and bisexual men.[10]


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.

Patient Education

For excellent patient education resources, see eMedicineHealth's patient education articles Drug Dependence and Abuse and Substance Abuse.




Acute effects 

Acute effects of cocaine use include the following:

  • Decreased food intake

  • Increased activity

  • Effusiveness

  • Diminished fatigue

Long-term use

Long-term use of cocaine interferes with sleep, can lower seizure threshold, and lead to palatal perforation. 

Overdose of cocaine

Signs of a cocaine overdose include the following:

  • 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 occur in about 1-40% of cocaine users.[11] 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.

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.

Renal failure

Cocaine can cause acute renal failure resulting from rhabdomyolysis or vasospasm.


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


Neuropsychiatric complications

Neuropsychiatric complications occur in about 40% of cocaine users. Psychiatric disturbances include depression, suicidal ideation, paranoia, kleptomania, violent antisocial behavior, intimate partner violence, 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 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 seizures associated with cocaine intoxication has not been fully elucidated. Recent reports emphasize on the interaction of cocaine with GABAergic and glutamatergic systems.[12]

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.


While heroin-associated leukoencephalopathy is well recognized, leukoencephalopathy has also been noted with cocaine use. Clinical presentation may vary from cognitive dysfunction to focal neurologic deficits. Imaging may show extensive confluent white matter signal changes best appreciated on FLAIR images of the brain, with no contrast enhancement of lesions and a lack of involvement of brainstem or cerebellum as opposed to heroin-associated leukoencephalopathy. Treatment is mainly supportive; occasionally steroids and CoeQ have been used with equivocal results.[13]

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.[14]

The effects of cocaine on other organ systems may lead to CNS complications.

Cocaine use 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.

Systemic complications from levamisole-laced cocaine

Levamisole-laced cocaine has been associated with dermatological, systemic, and hematological manifestations. Dermatological manifestations include painful hemorrhagic bullae over the face, cheeks, and helix, as well as retiform purpura on the lower extremities. Pathologically, a vasculitic and pseudovasculitic picture has been noted. Other systemic manifestations include arthralgias, flulike symptoms, leukopenia, and thrombocytopenia with positive antineutrophil antibody, antineutrophil cytoplasmic antibody, and antiproteinase-3 antibodies. Antihuman elastase antibodies are specific and sensitive for levamisole-associated vasculitis.[15]

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.


Cocaine use is associated with cardiac ischemia, myocarditis, cardiomyopathy, and arrhythmias. Chest pain is a common complication of cocaine use.[16]  Reports of acute myocardial infarction vary from 1-31%.[17]  Cocaine causes increased myocardial oxygen demand, coronary vasoconstriction, platelet aggregation, and in situ thrombus formation, which can lead to acute myocardial infarction in patients with normal coronary arteries.[18]  A study by Chang et al that examined acute coronary syndromes reported no increased likelihood of development of coronary disease in cocaine users.[19]


Cocaine use is associated with vasculitides, infectious complications, and numerous dermatologic conditions. It has been associated with formication (ie, tactile hallucinations of insects crawling underneath the skin), which leads to delusions of parasitosis.

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.





Laboratory Studies

Lab tests should be ordered on the basis of patient presentation. Indications for ordering labs are as follows:

Diagnosis of cocaine use

See the list below:

  • 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.

  • Detection: Zinc sulphate and zinc supplements may interfere with detection of cocaine analogues.[20]

  • 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).

Creatine kinase 

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

See the list below:

  • 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.[21] Fast fluid-attenuated inversion-recovery (FLAIR) images may also show diffuse white matter changes as seen in toxic leukoencephalopathies.

  • 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

See the list below:

  • 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 may provide additional information 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.[22]

  • Ophthalmoscopic examinations and fundus photography of the retinas of cocaine addicts have revealed increased retinal arterial branching angle and venular caliber.[23]



Medical Care

Acute intoxication requires hospitalization for detoxification and management of acute neurovascular complications.

Treatment of complications from levamisole-laced cocaine is supportive, with immediate cessation of cocaine and levamisole use. Steroids have been used in some patients, without clear evidence of significant benefits. Patients with extensive skin involvement require care in specialized burn units with a multidisciplinary surgical team involvement.[4]

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. A systematic review found that contingency management, a behavioral therapy modeled after operant conditioning, appeared to help improve cocaine abstinence and was synergistic to pharmacotherapy when used along with standard cognitive behavioral therapy and other psychotherapies.[24]

No pharmacotherapies have been approved for cocaine addiction; but 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. Disulfiram has been noted to have a paradoxical effect at lower doses, and, hence, weight-based dosing has been suggested.[25] Other drugs that have shown potential benefits in small studies include varenicline and galantamine.

Nepicastat, a selective dopamine beta hydroxylase analogous to disulfiram, is being studied in a multicenter, double-blind, placebo-controlled trial for cocaine dependance.

Counseling plus buprenorphine-naloxone maintenance therapy has been reported to be successful for opioid dependence

A 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.

In one trial, both quetiapine and risperidone reduced drug cravings from cocaine.[26] Clonidine may also help lower stress induced by cocaine craving and subsequent relapse.[27]

A recent randomized, double-blind, placebo controlled trial comparing treatment with bupropion and placebo in combination with standard cognitive behavioral therapy found no statistical difference in bupropion relative to placebo.[28]

Patients require follow-up for neurological complications.

Use of beta-blockers in cocaine-induced chest pain is a controversial issue.[29] The American Heart Association (AHA) published a scientific statement on management of cocaine-associated chest pain and myocardial infarction in 2008 which recommends avoiding use of beta blockers which may exacerbate vasospasm.[30]

Martell et al conducted a phase IIb randomized, double-blind, placebo-controlled trial to evaluate the immunogenicity, safety, and efficacy of a cocaine vaccine in cocaine-dependent and opioid-dependent individuals. Of the 115 patients recruited, 94 (82%) completed the trial. Participants were administered 5 vaccinations with placebo or succinylnorcocaine over 12 weeks. Within the vaccine group, those with serum IgG anticocaine antibody levels ≥43 mcg/mL had significantly more cocaine-free urine samples than those with serum levels < 43 mcg/mL and those who received placebo. Reduction of cocaine use by 50% was significantly greater if a high IgG level was achieved (53% of participants) compared with a low IgG level (23% of participants) (P =.048).[31]