Excerpt from Cocaine-Related Psychiatric Disorders

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Background

Cocaine is a naturally occurring alkaloid found within the leaves of a shrub, Erythroxylon coca. The earliest reported use of cocaine dates back to times when the ancient inhabitants of Peru used the leaves for religious ceremonies. Cocaine was first isolated from the coca leaf in 1859. Its first use as a local anesthetic was reported in 1884. In the late 19th century, Sigmund Freud proposed cocaine for the treatment of depression, cachexia, and asthma. It later became prescribed for almost any illness and could be found in numerous tonics. In 1885, John Styth Pemberton registered a cocaine-containing drink in the United States. This drink was later named Coca-Cola. In 1914, the Harrison Narcotics Act banned all nonprescription use of cocaine. Finally, in 1970, the Controlled Substances Act prohibited the possession of cocaine in the United States, except for limited medical uses.

Cocaine may be abused through a number of different routes. The most widespread routes of administration include inhaling (snorting), subcutaneous injection (skin popping), intravenous injection (shooting-up), and smoking (freebasing or smoking crack). Because of poor absorption and significant first-pass metabolism, cocaine is rarely ingested.

Cocaine abuse is associated with numerous detrimental health effects. All organ systems can be adversely affected by its use. Cocaine-related psychiatric disorders have been well-documented in the literature. Ten cocaine-induced psychiatric disorders are described in the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision (DSM-IV-TR)¹. These cocaine-induced disorders include the following:

• Cocaine intoxication
• Cocaine withdrawal
• Cocaine intoxication delirium
• Cocaine-induced psychotic disorder with delusions
• Cocaine-induced psychotic disorder with hallucinations
• Cocaine-induced mood disorder
• Cocaine-induced anxiety disorder
• Cocaine-induced sexual dysfunction
• Cocaine-induced sleep disorder
• Cocaine-related disorder not otherwise specified

For related information, see Medscape's CME course, The Dark Side of Drug Addiction.

Pathophysiology

The time to peak effects of cocaine depends on the dose and route of administration. When cocaine is injected intravenously or crack is smoked, the onset of action is within seconds and peak effects occur within 5 minutes. When snorted, the onset of action of cocaine is within the first 5 minutes and its effects typically peak within 30 minutes. Cocaine can be absorbed across any mucosal surface, including the respiratory, gastrointestinal, and genitourinary tracts.

Two major routes account for cocaine's metabolism: (1) enzymatic metabolism by both liver esterases and plasma cholinesterase to ecgonine methyl ester and (2) nonenzymatic degradation to benzoylecgonine. The half-life of cocaine is 30-90 minutes. The metabolites ecgonine methyl ester and benzoylecgonine are excreted in the urine. Drug screens detect the presence of benzoylecgonine, which may be present in the urine for 2-3 days, depending on the dose and chronicity of usage. Rare cases of benzoylecgonine detection in the urine for 22 days following cocaine use have been reported.

Cocaine has a number of pharmacologic effects on the human body. Neuronal fast sodium channel blockade produces a local anesthetic effect that continues to be used in medicine today. During myocardial fast sodium channel blockade, cocaine blocks fast cardiac sodium channels, which results in type I antidysrhythmic activity. This may lead to prolongation of the QRS complex and contribute to the induction of the dysrhythmias associated with cocaine use.

Blockade of catecholamine reuptake (ie, norepinephrine, dopamine, and serotonin reuptake blockade) occurs in both the central and peripheral nervous systems. Blockade of reuptake of norepinephrine leads to the sympathomimetic syndrome associated with cocaine use. This syndrome consists of tachycardia, hypertension, tachypnea, mydriasis, diaphoresis, and agitation. Inhibition of dopamine reuptake in the CNS synapses, such as in the nucleus accumbens, contributes to the euphoria associated with cocaine. Norepinephrine release augments norepinephrine reuptake blockade effects.

Frequency

United States

The following statistics are from the 2005 National Survey on Drug Use & Health (NSDUH) for the age group 12 years and older.²

• Approximately 33.7 million Americans have tried cocaine at least once in their lifetimes, representing 13.8% of the 12 years and older population.
• Approximately 5.5 million (2.3%) used cocaine in the past year and 2.4 million (1%) used cocaine in the past month. 
• The incidence of cocaine use generally rose throughout the 1970s to a peak in 1980 (1.7 million new users) and subsequently declined until 1991 (0.7 million new users). Cocaine initiation steadily increased during the 1990s, reaching 1.2 million in 2001.
• Within the past 12 months of the time the survey was taken, 872,000 persons used cocaine for the first time. That is a statistically significant reduction from 2002 when there were more than 1 million past-year cocaine initiates.

International

Cocaine continues to be a major drug of abuse internationally. In Mexico, for example, patients in drug abuse treatment programs in 16 cities report cocaine as the primary drug of choice.

Mortality/Morbidity

The Drug Abuse Warning Network (DAWN) reports drug-related deaths. For 2003, 122 jurisdictions in 35 metropolitan areas and 6 states submitted mortality data to DAWN.

• In drug misuse deaths, cocaine was among the top 5 drugs in 28 of the 32 metropolitan areas and in all of the 6 states.
• On average, cocaine alone or in combination with other drugs was reported in 39% of drug misuse deaths.
• The etiologies of some of the deaths associated with cocaine abuse include cardiac dysrhythmias, myocardial infarctions, intractable seizures, strokes, and aortic dissection.

Race

• In the 2005 Youth Risk Behavior Survey, Hispanic and white students  were significantly more likely than African American students to report lifetime cocaine use (12.2% and 7.7%, respectively, vs 2.3%).
• The 1999 Drug Abuse Warning Network data reported cocaine as an agent in 59%, 36%, and 35% of drug-related emergency department visits among African Americans, Hispanics, and whites, respectively.

Sex

In the 2005 National Youth Risk Behavior Survey, 8.4% of males and 6.8% of females had used cocaine at least once in 2005. According to DAWN, males are disproportionately represented among deaths related to drug misuse or abuse. After adjusting for population size, the rate of drug misuse deaths per 1,000,000 population for males was 2.4 that for females.

Age

Among students surveyed as part of the 2006 Monitoring the Future study, 3.4% of eighth graders, 4.8% of tenth graders, and 8.5% of twelfth graders reported lifetime use of cocaine. Approximately 8.8% of college students and 14.3% of young adults (aged 19-28) surveyed in 2005 reported lifetime use of cocaine.

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