Neurologic Effects of Cocaine

Neurologic Effects of Cocaine

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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.

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. 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. More than 5 million Americans use cocaine regularly via insufflation (snorting/sniffing), inhalation (smoking), and injection. [5] The incidence of neurological complications is not known.


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.

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. [6]

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. [7]

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. [8]

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. [9]

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.

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Pinky Agarwal, MD Clinical Associate Professor, Department of Neurology, University of Washington School of Medicine; Attending Neurologist, Medical Director, Booth Gardner Parkinson’s Care Center

Pinky Agarwal, MD is a member of the following medical societies: American Academy of Neurology, International Parkinson and Movement Disorder Society

Disclosure: Nothing to disclose.

Sindhu R Srivatsal, MD, MPH Fellow in Movement Disorders, Department of Neurology, University of Washington School of Medicine; Acting Instructor, Veterans Affairs Puget Sound Healthcare Systems

Sindhu R Srivatsal, MD, MPH is a member of the following medical societies: American Academy of Neurology, International Parkinson and Movement Disorder Society, Washington State Neurological Society

Disclosure: Nothing to disclose.

Souvik Sen, MD, MPH, MS, FAHA Professor and Chair, Department of Neurology, University of South Carolina School of Medicine

Souvik Sen, MD, MPH, MS, FAHA is a member of the following medical societies: American Academy of Neurology, Association for Patient-Oriented Research, American Heart Association

Disclosure: Nothing to disclose.

Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Received salary from Medscape for employment. for: Medscape.

Stephen A Berman, MD, PhD, MBA Professor of Neurology, University of Central Florida College of Medicine

Stephen A Berman, MD, PhD, MBA is a member of the following medical societies: Alpha Omega Alpha, American Academy of Neurology, Phi Beta Kappa

Disclosure: Nothing to disclose.

Edward L Hogan, MD Professor, Department of Neurology, Medical College of Georgia; Emeritus Professor and Chair, Department of Neurology, Medical University of South Carolina

Edward L Hogan, MD is a member of the following medical societies: Alpha Omega Alpha, Society for Neuroscience, American Society for Biochemistry and Molecular Biology, American Academy of Neurology, American Neurological Association, Phi Beta Kappa, Sigma Xi, Southern Clinical Neurological Society

Disclosure: Nothing to disclose.

Neurologic Effects of Cocaine

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