Cocaine and Amphetamine Use Disorders

111

can be tapered over several weeks on an outpatient basis, with careful monitoring and patient-physician communication. Patients who abuse a sedative-hypnotic should be stabilized on an oral, long-acting barbiturate, such as phenobarbital, or benzodiazepine, such as chlorazepate (Tranxene). After stabilization, the dose is tapered. Optimally, the initial period of withdrawal should occur in the hospital. This approach allows supervision of the patient in case of intoxication or severe withdrawal symptoms, such as seizure, and prevents the patient from using other drugs or alcohol during withdrawal. Use of valproic acid or carbamazepine may allow a more rapid taper without fear of withdrawal seizures, and open trials appear promising. Hospitalization is not always possible, and sometimes benzodiazepine detoxification is accomplished on an outpatient basis with strict monitoring. Patients must be well-motivated or have strong contingent consequences; they should be seen on a daily basis and receive medication daily. Whenever possible, avoid using the abused substance for the taper, because craving and other conditioned behaviors may create difficulties.
BIBLIOGRAPHY
1. Pages KP, Ries RK: Use of anticonvulsants in benzodiazepine withdrawal. Am J Addict 7(3):198-204, 1998. 2. Perry PJ, Alexander B: Sedativehypnotic dependence: Patient stabilization, tolerance testing, and withdrawal. Drug Intell Clin Pharm 20532-537, 1986. 3. Seivewnght N, Dougal W: Withdrawal symptoms from high dose benzodiazepines in poly drug abusers. Drug Alcohol Depend 32: 15-23, 1993.

23. COCAINE AND AMPHETAMINE USE DISORDERS

JaneA. Kennedy, D . 0
1. Who uses cocaine and amphetamine? Cocaine use in the United States has escalated dramatically since the early 1970s, when about 5 million had tried the drug at least once-in the late 1980s, about 40 million had tried it. Cocaine typically is used by persons aged 18-30. In the 1990s, indicators suggested a drop in cocaine use among casual, recreational users, but sustained or increased prevalence among hard-core users. Amphetamine use is highest among 18-25 year olds; in some parts of the country it is strongly associated with motorcycle gang members. Since tightened regulation of prescription amphetamine in the late 1970s, only about 25% of abused amphetamine is prescription drug; the other 75% is illicitly manufactured. 2. Do cocaine and amphetamine have the same effect? In recent years attention has focused on cocaine dependence, because its use is more widespread than use of amphetamines. Both drugs, however, increase the central action of dopamine and both the central and peripheral action of norepinephrine. In theory, they should be quite similar in effect, but most users have a distinct preference for either cocaine or amphetamine. Both drugs are quite reinforcing. Animals will self-administer stimulants continuously until they die, forsaking food and water and suffering repeated seizures and exhaustion; for many humans, similar effects have been seen.
3. What forms are available? What are the routes of administration? Amphetamine is available in oral prescription medication as dextroamphetamine and methamphetamine; it also is manufactured illicitly as powder or crystallized (ice) methamphetamine. Cocaine hydrochloride is obtainable pharmaceutically for use as a local anesthetic; it is available illicitly in either powder or crystallized (rock or crack) forms.

I12

Cocaine and Amphetamine Use Disorders

Cocaine and amphetamine are snorted, injected, and smoked; amphetamines also may be taken orally. Crack is the smokable form of cocaine, and ice is the smokable form of amphetamine. Smoking is the most rapid route of delivery to the brain and thus the most reinforcing; however, dependence can occur with all routes of administration. A stimulant and a depressant injected together, most frequently cocaine and heroin, is called a speedball.

4. Do stimulants have approved medical uses? Cocaine hydrochloride is used as a local anesthetic; use of amphetamines such as dexedrine or methylphenidate has been limited to treatment of attention deficit hyperactivity disorder, narcolepsy, and resistant depression. 5. What are the signs and symptoms of stimulant intoxication? The most common signs and symptoms are enlarged pupils, tachycardia, hypertension, and hyperreflexia. The user feels euphoric, energetic, talkative, alert, and grandiose, with decreased appetite and need for sleep. Some people, however, feel anxious, agitated, tense, and dysphoric. Still others feel calmed, slowed down, and focused. Stomach cramps, nausea, vomiting, and diarrhea may occur. Many users clench and grind their teeth. Higher doses and more chronic use frequently lead to psychosis, usually with a paranoid quality. Reactions may range from tweaking, a sense of hypervigilance and fearfulness (small noises may be interpreted as police outside the door), to overt psychosis with auditory and visual hallucinations, ideas of reference, and full-blown delusions. Stimulants often induce stereotypic behaviors such as repetitive counting or cleaning, prolonged sexual activity, or picking at the skin (cocaine bugs) due to formication (a sensation of insects crawling on the skin).

6. What is the duration of effect from cocaine and amphetamine? Cocaines rapid, short-lived rush of 15-20 minutes contrasts with the sustained effect of amphetamine, which may last for hours. The high associated with ice (smokable amphetamine) may last up to 48 hours and can be associated with prolonged psychosis and aggression.
7. Does tolerance occur? Tolerance occurs to euphoria, wakefulness, anorexia, and possibly to convulsant and cardiovascular effects. Users may increase frequency of dosing intervals and quantities as they try to reproduce the euphoria.

8. Discuss the complications of stimulant use. Sympathomimetic responses include decreased gastrointestinal motility, bladder stimulation resulting in painful urination, tachycardia with tachyarrhythmias, hypertension (hypotension also has been reported), and fever. Increased stimulation of the central nervous system may cause seizure. Other complications include cardiac ischemia, coronary artery constriction with angina or myocardial infarction, stroke, and cardiac or respiratory arrest. Cerebral and renal vasculitis are more common with amphetamines. Although psychosis usually clears within days of stopping stimulant use, in some instances the psychosis persists, or the user develops a sustained sensitivity to its recurrence, even with small doses of amphetamine or cocaine. Panic disorder also may be precipitated by cocaine and persist even after use is discontinued. Bipolar patients may become manic with use of stimulants. Other complications depend on route of administration. Intravenous use is associated with transmission of the human immunodeficiency virus (HIV), hepatitis, and endocarditis. Nosebleeds, nasal septum imtation or perforation, and sinusitis may result from nasal insufflation, and pulmonary complications such as cough, bronchitis, and pneumothorax may result from smoking. In addition, marked weight loss and malnutrition may occur during a run, when many users go for days without eating. Use of sedatives to help with insomnia and crashing may create a secondary drug dependence. Sexual promiscuity, due either to increased sexual interest or to exchanging sex for money or drugs, may put the user at high risk for sexually transmitted diseases, especially HIV infection.

Cocaine and Amphetamine Use Disorders

I13

9. What happens with overdose?

Death may occur from seizures, severe fever, cerebrovascular hemorrhage, or cardiovascular arrest. Treatment of overdose is supportive; seizures respond to diazepam, and psychosis may require antipsychotic medication.

10. Is there a stimulant withdrawal syndrome?

Many users experience only fatigue and exhaustion, and sleep for 12-24 hours. For others, dysphoria may be severe and associated with suicidal ideation. Increased appetite, insomnia, vivid dreams, and psychomotor retardation or agitation also may be seen. Some users experience protracted depression, which may respond to antidepressants. Treatment of withdrawal, especially the re-emergence of craving for the drug, has been attempted with the use of dopamine agonists such as bromocriptine or amantadine. Open studies looked promising, but controlled trials have reported marginal results or have not supported their efficacy. Similarly, amino acid precursors of catecholamines have not proved to be useful.

11. What are the effects of stimulant use in pregnancy? Vasoconstrictive properties of stimulants lead to decreased blood flow to the placenta and thus decreased oxygen delivery to the fetus. At the very least, infants have low birth weights; children also have been reported to have central nervous system hyperactivity in the first year of life, with irritability, jumpiness, hyperreflexia, and decreased attention spans. The incidence of abruptio placentae, premature delivery, sudden infant death syndrome, and cerebral hemorrhage is increased. Lower IQ levels were found in 4-year-old children exposed to amphetamines in utero. 12. What are the pharmacologic treatments of cocaine dependence? Multiple medications have been tried without success; open trials frequently appear promising, but controlled studies show no efficacy. Desipramine, which appeared to increase abstinence from cocaine in controlled trials, has not shown the same effectiveness in repeat studies. Carbamazepine also appeared promising in open trials but did not hold up under randomized, controlled conditions. Buproprion, fluoxetine, flupenthixol, imipramine, levodopdcarbidopa, maprotiline, and trazodone also have been tried without effect. Buprenorphine, an opiate agonist-antagonist, was found to decrease cocaine use in methadone maintenance patients, but a controlled study did not replicate this finding. A cocaine vaccine, administration of an enzyme that metabolizes cocaine, and catalytic antibodies are currently being investigated.

13. What other treatments are useful for cocaine addiction? The most successful approach has been behavioral contracting with positive reinforcement for negative urine screens. Compared with patients randomized to 12-step group treatment, retention was significantly better (58% vs. 11%), as was abstinence (42% vs. 5%).2 More frequent contact (at least twice weekly) has been associated with improved outcome, and Kang et al. showed that once weekly therapy was ineffective, whether it was group, family, or individual psychotherapy.
BIBLIOGRAPHY
1. Delaney-Black V, Roumell N, Shankaran S, Bedard M: Maternal cocaine use and infant outcomes [abstract]. Pediatr Res 25:242A, 1990. 2. Higgins ST, Budney AJ, Bickel WK, Foerg FE, Donham R, Badger MS: Incentives improve outcome in outpatient behavioral treatment of cocaine dependence. Arch Gen Psychiatry 5 1568-576, 1994. 3. Higgins ST, Katz JL: Cocaine Abuse: Behavior, Pharmacology, and Clinical Applications. San Diego, Academic Press, 1998. 4. Kang S-Y, Kleinman PH, Woody GE, et al: Outcomes for cocaine abusers after once-a-week psychosocial therapy. Am J Psychiatry 148:63G635, 1991. 5. Weddington WW, Brown BS, Haertzen CA, et al: Comparison of amantadine and desipramine combined with psychotherapy for treatment of cocaine dependence. Am J Drug Alcohol Abuse 17:137-152, 1991,