Drug Addiction

Abuse

The percent of persons with cocaine dependence or abuse decreased between 2006 and 2011 from 0.7 to 0.3 %. In 2011, the number of persons with cocaine dependence or abuse was roughly 821,000. Despite the downward trend, cocaine, after alcohol, remained the leading substance of abuse related to frequent ED contacts, general hospital admissions, family violence, and other social problems. Cocaine use resulted in 40% of all illicit drug-related ED visits in 2011. Even individuals with normal psychological profiles are vulnerable to compulsive cocaine use. Acute use leads to intense euphoria that is often associated with increased sexual desire and with improved sexual function. These rewards are often followed by a moderate-to-severe post–cocaine use depression that stimulates a strong incentive for further cocaine use. These responses are primarily mediated by disruptions of synaptic dopamine. The initial cocaine response is a function of elevated dopamine generated by blockade of the dopamine reuptake transporter (DAT) and the inhibition of the reuptake of synaptic dopamine. Chronic cocaine use leads to down-regulation of dopamine receptors and ultimately to depletion of synaptic dopamine, which is thought to be the cause of post–cocaine use depression ( Figure 16-5 ). Like other stimulants, cocaine also disrupts the synthesis and reuptake of serotonin. Other receptors affected include norepinephrine, N -methyl- d -aspartate (NMDA), gamma-aminobutyric acid (GABA), and opioid receptors. Plasma cholinesterases rapidly convert cocaine into benzoylecognine (BE), an inactive metabolite that can be detected in the urine for 3 days. When alcohol is taken in conjunction with cocaine, liver esterases produce cocaethylene, an active metabolite that has a longer half-life (2–4-hours) and is more cardiotoxic than cocaine. The combination of cocaine and marijuana also produces more intense euphoria, higher plasma levels, and more cardiotoxicity than does cocaine alone.

The signs and the symptoms of acute cocaine intoxication are similar to those of amphetamine abuse. Typical complaints associated with intoxication include anorexia, insomnia, anxiety, hyperactivity, and rapid speech and thought processes (“speeding”). Signs of adrenergic hyperactivity (such as hyperreflexia, tachycardia, diaphoresis, and dilated pupils responsive to light) may also be seen. More severe symptoms (e.g., hyperpyrexia, hypertension, cocaine-induced vasospastic events [e.g., stroke or myocardial infarction]) are relatively rare among users, but are fairly common in those seen in hospital EDs. Patients may also manifest stereotyped movements of the mouth, face, or extremities. Snorting the drug may produce rhinitis or sinusitis and, rarely, perforations of the nasal septum. Free-basing (inhalation of cocaine alkaloid vapors) may produce bronchitis. Grand mal seizures are another infrequent complication. Patients also describe “snowlights” (i.e., flashes of light usually seen at the periphery of the visual field). Crack is a highly addictive free-base form of cocaine that is sold in crystals and can be smoked.

The most serious psychiatric problem associated with chronic cocaine use is a cocaine-induced psychosis (manifest by visual and auditory hallucinations and paranoid delusions often associated with violent behavior). Tactile hallucinations (called “coke bugs”) involve the perception that something is crawling under the skin. A cocaine psychosis may be indistinguishable from an amphetamine psychosis, but it usually does not last as long. High doses of stimulants can also cause a state of excitation and mental confusion known as “stimulant delirium.”

Management

Cocaine abuse became common among affluent young people in the early to mid-1980s, but with the availability of packaged smokable cocaine, or crack, in low-cost doses, all classes and racial groups have become potential users. Occasional cocaine use does not require specific treatment except in the case of a life-threatening overdose. Most potentially lethal doses are metabolized within 1 hour. In the interim, intubation and assisted breathing with oxygen may be necessary. Stroke has been reported, and death can be caused by ventricular fibrillation or myocardial infarction. The cardiac status should therefore be monitored closely. High doses of benzodiazepines are recommended for management of stimulant-induced delirium and agitation. Neuroleptics should be avoided because of the risk of potentially fatal hyperthermia. Intravenous (IV) diazepam should be used to control convulsions.

Chronic cocaine use produces tolerance, severe psychological dependency, and physiological dependence (marked by irritability, anhedonia, low mood, insomnia or hypersomnia, and anxiety). Dependent users typically follow a cyclical pattern of 2 or 3 days of heavy binge use, followed by a withdrawal “crash.” Use is resumed again in 3 to 4 days, depending on the availability of cash and the drug. A gradual reduction in use of the drug is almost never possible. Detoxification is accomplished by the abrupt cessation of all cocaine use, usually through restricted access (e.g., a loss of funds or contacts, or incarceration). Symptoms of withdrawal begin to resolve within 7 days; the value of medication treatment for withdrawal symptoms has yet to be confirmed. Drugs that enhance CNS catecholamine function may reduce craving, although they are of limited clinical benefit and they have not been proven effective in double-blind placebo-controlled trials. There is some indication that amantadine (an indirect dopamine agonist) and propranolol may be helpful to individuals with severe withdrawal symptoms. The major complication of withdrawal is a severe depression with suicidal ideation. If this occurs, the patient typically requires psychiatric hospitalization. The need for inpatient care may be time-limited, since suicidal ideation usually clears promptly with the cessation of cocaine use. A less severe anhedonic state may persist for 2 to 3 months and is thought to reflect a more persistent state of dopamine depletion.

For the cocaine addict, the compulsion to use is overwhelming. For this reason, a hospitalized, cocaine-dependent patient should be monitored closely and should have a drug screen performed after behavioral change, particularly after departures from the floor or receiving visitors. Urine should be examined for cocaine metabolites and, preferably, for all drugs of abuse.

Once compulsive cocaine use has begun, it is almost impossible for the user to return to a pattern of occasional, controlled use. Such individuals are also likely to develop problems with alcohol and other drugs. For that reason, the goal of treatment should be abstinence from cocaine and all other drugs. All cocaine abusers should be referred for individual or group counseling, and participation in 12-step self-help programs should be strongly recommended. Manual-guided cognitive-behavioral therapy (CBT) has been efficacious in the treatment of cocaine dependence. Twelve-step facilitation and CBT appear to be helpful, particularly in individuals with more severe dependence and in those with co-morbid disorders. Family members or significant others should be referred separately to Al-Anon because they will gain insights that may help them eliminate systemic support for the patient's drug use. There is no Food and Drug Administration (FDA)–approved pharmacotherapy for cocaine dependence. Trials with desipramine, fluoxetine, bupropion, amantadine, and carbamazepine have had inconsistent results. Positive responses have been reported in trials with topiramate, baclofen, and modafinil, but these drugs require further investigation. Several trials with disulfiram have shown benefit, with reduced craving and use, and a reported increase in the aversive effects of cocaine should the patient relapse. These reactions are thought to be mediated by the inhibitory effect of disulfiram on dopamine beta-hydroxylase. This action will elevate depleted plasma dopamine levels in chronic users and will produce abnormally high dopamine levels if cocaine is ingested; this results in a dysphoric experience for most users.

Abuse

In 2011, roughly 970,000 persons ≥ 12 years were active non-medical users of prescription stimulants. Between 2004 and 2011, prescription CNS stimulants led to a striking 307% increase in ED visits. Among these agents, the ADHD drug amphetamine-dextroamphetamine (e.g., Adderall ^® ) showed a 650% increase during that period.

Illicitly-produced methamphetamine fueled an epidemic of abuse on the West Coast and in much of the Midwest in the 1990s. Since then, the number of methamphetamine abusers had declined as a result of stricter federal controls on the production and distribution of certain medications.

The primary action of these drugs is an increase in synaptic dopamine via the release of dopamine into the synapse; methamphetamine also blocks the DAT. This produces a dopamine “high” that is both more intense and longer lasting than results from cocaine, lasting anywhere from 8 to 24 hours. Methamphetamine, invented for military use by the Japanese in World War I, is currently a schedule II drug, that can be taken orally (“speed”), taken anally, smoked (“crystal”), snorted, or injected. It has been approved for the treatment of ADHD and obesity. Long-term use of amphetamines can cause cognitive impairment (including dulled awareness, decreased intellectual capacity, memory impairment, and motor retardation). Positive positron emission tomography (PET) scans show loss of DAT in the caudate and the putamen, and magnetic resonance imaging (MRI) studies show decreased perfusion in the putaman and the frontal cortex as well as loss of volume in both the amygdala and the hippocampus. Routine medical evaluation may uncover the most common type of amphetamine abuse seen in clinical settings (involving use of amphetamines to control obesity and that later led to chronic amphetamine abuse). Amphetamine abusers quickly develop tolerance and may use 100 mg each day in an unsuccessful effort to control weight. This type of amphetamine abuse can be treated by abruptly discontinuing the drug or by gradually tapering the dose. In either case, the patient should be given a more appropriate program for weight control.

A more serious problem involves the patient who develops a severe psychological dependence on amphetamines and who may have the same symptoms seen in younger street-drug users and abusers. Illicit amphetamine and methamphetamine (speed) use accounted for 12.8 % of all illicit-drug-use-related ED visits in 2011.

The signs and symptoms of acute amphetamine intoxication are similar to those of cocaine abuse. Long-term effects include depression, brain dysfunction, and weight loss. In addition, either with acute or chronic amphetamine intoxication a paranoid psychosis without delirium can develop. Although typically seen in young people who use IV methamphetamine hydrochloride, paranoia can also occur in chronic users of dextroamphetamine or other amphetamines. A paranoid psychosis may also occur with or without other manifestations of amphetamine intoxication. The absence of disorientation distinguishes this condition from most other toxic psychoses. This syndrome is clinically indistinguishable from an acute schizophrenic episode of the paranoid type, and the correct diagnosis is often made in retrospect, based on a history of amphetamine use and a urine test that is positive for amphetamines. Use of haloperidol or low-dose atypical antipsychotics is often effective in the acute management of this type of substance-induced psychosis.

Other distinctive features of chronic stimulant abuse include dental problems (e.g., caries, missing teeth, bleeding and infected gums), muscle cramps (related to dehydration and low levels of magnesium and potassium), constipation (due to dehydration), nasal perforations, and excoriated skin lesions (speed bumps) ( Figure 16-6 ). The urine may have a stale smell due to ammonia constituents used in the illicit manufacture of methamphetamine.

Treatment

Amphetamines can be withdrawn abruptly. If the intoxication is mild, the patient's agitation can be handled by reassurance alone. The patient can be “talked down,” much as one might handle an adverse d -lysergic acid diethylamide (LSD) reaction. If sedation is necessary, benzodiazepines are the drugs of choice. Phenothiazines should be avoided because they may heighten dysphoria and increase the patient's agitation. Hypertension will usually respond to sedation with benzodiazepines. When severe hypertension arises, phentolamine is recommended for vasodilation. Beta- or mixed alpha- and beta-adrenergic blockers (such as propranolol or labetalol) are to be avoided because they may exacerbate stimulant-induced cardiovascular toxicity.

Most signs of intoxication clear in 2 to 4 days. The major problem is management of depression upon discontinuation of amphetamine use. In mild cases, this depression can be manifest by lethargy, as well as by the temptation to use amphetamines for energy. In more serious cases, the patient may become suicidal and require inpatient psychiatric treatment. The efficacy of antidepressants in such cases has not been adequately documented. Even with support and psychotherapy, most patients experience symptoms of depression for 3 to 6 months following the cessation of chronic amphetamine abuse. CBT has been helpful, but it may need to be adapted to allow for the cognitive impairment associated with long-term methamphetamine use.