Amphetamines and Related Disorders
Amphetamines and Related Disorders
Amphetamines and Related Disorders
Amphetamines are a group of powerful and highly addictive substances that dramatically affect the central nervous system. They induce a feeling of well-being and improve alertness, attention, and performance on various cognitive and motor tasks. Closely related are the so-called substitute amphetamines, which include MDMA, also known as ecstasy and methamphetamine. Finally, some over-the-counter drugs used as appetite suppressants also have amphetamine-like action. Amphetamine-related disorders refer to the effects of abuse, dependence, and acute intoxication stemming from inappropriate amphetamine and amphetamine-related drug usage.
Several amphetamines are currently available in the United States, including dextroamphetamine (Dexedrine) and methylphenidate (Ritalin). These Schedule II stimulants (those the U.S. Drug Enforcement Agency considers to have medical usefulness and a high potential for abuse), known to be highly addictive, require a triplicate prescription that cannot be refilled. Amphetamines are also known as sympatho-mimetics, stimulants, and psychostimulants. Methamphetamine, the most common illegally produced amphetamine, goes by the street name of “speed,” “meth,” or “chalk.” When it is smoked, it is called “ice,” “crystal,” “crank,” or “glass.” Methamphetamine is a white, odorless, bitter-tasting crystalline powder that dissolves in water or alcohol.
The leaves of the East African bush Catha edulis can be chewed for their stimulant effects. This drug, cathinone or Khat, has an effect on most of the central nervous system, in addition to providing the other properties of amphetamines. Also, manufacture of methamphetamine in illegal laboratories has increased dramatically in recent years, leading to stricter laws governing the sale of products containing ephedrine or pseudoephedrine, the primary components of this drug.
Amphetamines intended for medical use were first used in nasal decongestants and bronchial inhalers. Early in the 1900s, they were also used to treat several medical and psychiatric conditions, including attention-deficit disorders, obesity, depression, and narcolepsy (a rare condition in which individuals fall asleep at dangerous and inappropriate moments and cannot maintain normal alertness). They are still used to treat these disorders today.
In the 1970s, governmental agencies initiated restrictions increasing the difficulty of obtaining amphetamines legally through prescription. During this same time period, a drug chemically related to the amphetamines began to be produced. This so-called designer drug, best known as “ecstasy,” but also as MDMA, XTC, and Adam, has behavioral effects that combine amphetamine-like and hallucinogen-like properties.
The structure of amphetamines differs significantly from that of cocaine, even though both are stimulants with similar behavioral and physiological effects. Like cocaine, amphetamine results in an accumulation of the neurotransmitter dopamine in the prefrontal cortex. It is this excessive dopamine concentration that appears to produce the stimulation and feelings of euphoria experienced by the user. Cocaine is much more quickly metabolized and removed from the body, whereas amphetamines have a much longer duration of action. A large percentage of the drug remains unchanged in the body, leading to prolonged stimulant effects.
The handbook that mental health professionals use to diagnose mental disorders is the Diagnostic and Statistical Manual of Mental Disorders, also known as the DSM. The 2000 edition of this manual (the fourth edition, text revision, also known as DSM-IV-TR) describes four separate amphetamine-related disorders. These are:
- amphetamine dependence: Refers to chronic or episodic binges (known as “speed runs”), with brief drug-free periods of time in between use.
- amphetamine abuse: Less severe than dependence. Individuals diagnosed with amphetamine abuse have milder but nevertheless still substantial problems due to their drug usage.
- amphetamine intoxication: Refers to serious maladaptive behavioral or psychological changes that develop during, or shortly after, use of an amphetamine or related substance.
- amphetamine withdrawal: Refers to symptoms that develop within a few hours to several days after reducing or stopping heavy and prolonged amphetamine use. Withdrawal symptoms are, in general, opposite to those seen during intoxication, and include fatigue, vivid and unpleasant dreams, insomnia or hypersomnia (too much sleep), increased appetite, and agitation or slowing down.
All amphetamines are rapidly absorbed when taken orally, and even more rapidly absorbed when smoked, snorted, or injected. Tolerance develops with both standard and designer amphetamines, leading to the need for increasing doses by the user.
Amphetamines, such as dextroamphetamine, methamphetamine, and methylphenidate, produce their primary effects by causing the release of catecholamines, especially the nerve-signaling molecule or neurotransmitter dopamine, in the brain. These effects are particularly strong in areas of the brain associated with pleasure, specifically, the cerebral cortex and the limbic system, known as the “reward pathway.” The effect on this pathway is probably responsible for the addictive quality of the amphetamines.
MDMA causes the release of the neurotransmitters dopamine and serotonin and the neurohormone norepinephrine. Serotonin is responsible for producing the hallucinogenic effects of the drug.
According to the DSM-IV-TR, symptoms of heavy, chronic, or episodic use of amphetamine, known as amphetamine dependence, can be very serious. Amphetamine dependence is characterized by compulsive drug-seeking and drug use, leading to functional and molecular changes in the brain. Aggressive or violent behavior may occur, especially when high doses are ingested. Individuals may develop anxiety or paranoid ideas, also with the possibility of experiencing terrifying psychotic episodes that resemble schizophrenia, with visual or auditory hallucinations, delusions such as the sensation of insects creeping on the skin (known as “formication”), hyperactivity, hypersexuality, confusion, and incoherence. Amphetamine-induced psychosis differs from true psychosis in that despite other symptoms, the disorganized thinking that is a hallmark of schizophrenia tends to be absent. Amphetamine dependence consistently affects relationships at home, school, and/or work.
Amphetamine abuse is less serious than dependence, but can cause milder versions of the symptoms described above, as well as problems with family, school, and work. Legal problems may stem from aggressive behavior while using, or from obtaining drugs illegally. Individuals may continue to use despite the awareness that usage negatively impacts all areas of their lives.
Acute amphetamine intoxication begins with a “high” feeling that may be followed by feelings of euphoria. Users experience enhanced energy, becoming more outgoing and talkative, and more alert. Other symptoms include anxiety, tension, grandiosity, repetitive behavior, anger, fighting, and impaired judgment.
In both acute and chronic intoxication, individuals may experience dulled feelings, along with fatigue or sadness, and social withdrawal. These behavioral and psychological changes are accompanied by other signs and symptoms including increased or irregular heartbeat, dilation of the pupils, elevated or lowered blood pressure, heavy perspiring or chills, nausea and/or vomiting, motor agitation or retardation, muscle weakness, respiratory depression, chest pain, and eventually confusion, seizures, coma, or a variety of cardiovascular problems, including stroke. With amphetamine overdoses, death can result if treatment is not received immediately. Long-term abuse can lead to memory loss as well, and contributes to increased transmission of hepatitis and HIV/AIDS. Impaired social and work functioning is another hallmark of both acute and chronic intoxication.
Following amphetamine intoxication, a “crash” occurs with symptoms of anxiety, shakiness, depressed mood, lethargy, fatigue, nightmares, headache, perspiring, muscle cramps, stomach cramps, and increased appetite. Withdrawal symptoms usually peak in two to four days and are gone within one week. The most serious withdrawal symptom is depression, possibly very severe and leading to suicidal thoughts.
Use of so-called designer amphetamines, such as MDMA, leads to similar symptoms. Users also report a sense of feeling unusual closeness with other people and enhanced personal comfort. They describe seeing an increased luminescence of objects in the environment, although these hallucinogenic effects are less than those caused by other hallucinogens, such as LSD. Some psychotherapists have suggested further research into the possible use of designer amphetamines in conjunction with psychotherapy. This idea is highly controversial, however.
As with other amphetamines, use of MDMA produces cardiovascular effects of increased blood pressure, heart rate, and heart oxygen consumption. People with pre-existing heart disease are at increased risk of cardiovascular catastrophe resulting from MDMA use. MDMA is not processed and removed from the body quickly and remains active for a long period of time. As a result, toxicity may rise dramatically when users take multiple doses over brief time periods, leading to harmful reactions such as dehydration, hyperthermia, and seizures.
MDMA tablets often contain other drugs, such as ephedrine, a stimulant, and dextromethorphan, a cough suppressant with PCP-like effects at high doses. These additives increase the harmful effects of MDMA. They also appear also to have toxic effects on the brain’s serotonin system. In tests of learning and memory, people who use MDMA perform more poorly than people who do not use. Research with primates shows that MDMA can cause long-lasting brain damage. Exposure to MDMA during the period of pregnancy in which the fetal brain is developing is associated with learning deficits that last into adulthood.
Amphetamine dependence and abuse occur at all levels of society, most commonly among 18- to 30-year-olds. Intravenous use is more common among individuals from lower socioeconomic groups, and has a male-to-female ratio of three or four to one. Among people who do not use intravenously users, males and females are relatively equally divided.
Of greatest recent concern has been the rise in the use of methamphetamine, although in some areas, this increase has leveled off in recent years. The lifetime prevalence of methamphetamine abuse among U.S. students in grade 12 fell from 6.2% of respondents to 4.5% over two years in one recent government survey. However, in some metropolitan areas, including Atlanta, Denver, Honolulu, and Phoenix, use has increased, and there was a 15% increase in methamphetamine treatment admissions in St. Louis from 2004 to 2005. In some parts of Texas, this drug has replaced crack as a drug of choice. Another national survey found that 10.4 million Americans age 12 or older had tried methamphetamine at least once in their lives. The problem seems to be particularly concerning in Western states, although it is spreading quickly in the South and Midwest, being reported as the fastest-growing problem in metropolitan Atlanta in 2006.
Four classic amphetamine-related diagnostic categories are listed in the DSM-IV-TR. These are:
- amphetamine dependence
- amphetamine abuse
- amphetamine intoxication
- amphetamine withdrawal
Amphetamine dependence refers to chronic or episodic use of amphetamines, involving drug binges known as “speed runs.” These episodes are punctuated by brief, drug-free periods. Aggressive or violent behavior is associated with amphetamine dependence, particularly when high doses are ingested. Intense but temporary anxiety may occur, as well as paranoid ideas and psychotic behavior resembling schizophrenia. Increased tolerance and withdrawal symptoms are part of the diagnostic picture. Conversely, some individuals with amphetamine dependence become sensitized to the drug, experiencing increasingly greater stimulation, and other negative mental or neurological effects, even from small doses.
Amphetamine abuse, while not as serious as amphetamine dependence, can also cause multiple problems. Legal difficulties are common, in addition to increased arguments with family and friends. If tolerance or withdrawal occur, amphetamine dependence is diagnosed.
Amphetamine intoxication refers to serious behavioral or psychological changes that develop during, or shortly after, use of amphetamine. Intoxication begins with a “high” feeling, followed by euphoria, enhanced energy, talkativeness, hyperactivity, restlessness, hypervigilance indicated by an individual’s extreme sensitivity, and closely observant of everything in the environment. Other symptoms are anxiety, tension, repetitive behavior, anger, fighting, and impaired judgment. With chronic intoxication, there may be fatigue or sadness and withdrawal from others. Other signs and symptoms of intoxication are increased heart rate, dilation of the pupils, elevated or lowered blood pressure, perspiration or chills, nausea or vomiting, weight loss, cardiac irregularities, and, eventually, confusion, seizures, coma, or death.
During amphetamine withdrawal, intense symptoms of depression are typical. Additional diagnostic symptoms are fatigue, vivid and unpleasant dreams, insomnia or sleeping too much, increased appetite, and agitation.
According to the National Institute on Drug Abuse (NIDA), the most effective treatments for amphetamine addiction are cognitive-behavioral interventions. These are psychotherapeutic approaches that help individuals learn to identify and change their problematic patterns of thoughts and beliefs. As a result of changed thoughts and beliefs, feelings become more manageable and less painful. Interventions also help individuals increase their skills for coping with life’s stressors. Amphetamine recovery groups, and Narcotics Anonymous also appear to help.
No specific medications are known to exist that are helpful for treating amphetamine dependence. On occasion, antidepressant medications can help combat the depressive symptoms frequently experienced by people who are newly abstinent from amphetamine use.
Overdoses of amphetamines are treated in established ways in emergency rooms. Because hyperthermia (elevated body temperature) and convulsions are common, emergency room treatment focuses on reducing body temperature and administering anti-convulsant medications.
Acute methamphetamine intoxication is often handled by observation in a safe, quiet environment. When extreme anxiety or panic is part of the reaction, treatment with antianxiety medications may be helpful. In cases of methamphetamine-induced psychoses, short-term use of antipsychotic medications is usually successful.
According to the DSM-IV-TR, some individuals who develop abuse or dependence on amphetamines initiate use in an attempt to control their weight. Others become introduced through the illegal market. Dependence can occur very quickly when the substance is used intravenously or is smoked. The few long-term data available show a tendency for people who have been dependent on amphetamines to decrease or stop using them after 8 to 10 years. This may result from the development of adverse mental and physical effects that emerge with long-term dependence. Few data are available on the long-term course of abuse.
The NIDA reports that studies provide direct evidence that chronic use of MDMA causes brain damage in humans. Using advanced brain imaging techniques, one study found that MDMA harms neurons that release serotonin. Serotonin plays an important role in regulating memory and other mental functions.
In a related study, researchers found that people who heavily use MDMA have memory problems that persist for at least two weeks after stopping use of the drug. Both studies strongly suggest that the extent of damage is directly related to the amount of MDMA used.
Amphetamine abuse —An amphetamine problem in which the user experiences negative consequences from the use, but has not reached the point of dependence.
Amphetamine dependence —The most serious type of amphetamine problem. Amphetamine intoxication—The effects on the body that develop during or shortly after amphetamine use.
Amphetamine withdrawal —Symptoms that develop shortly after reducing or stopping heavy amphetamine use.
Amphetamines —A group of powerful and highly addictive substances that stimulate the central nervous system. Amphetamines may be prescribed for various medical conditions, but are often purchased illicitly and abused.
Catecholamine —A group of neurotransmitters synthesized from the amino acid tyrosine and released by the hypothalamic-pituitary-adrenal system in the brain in response to acute stress. The catecholamines include dopamine, serotonin, norepinephrine, and epinephrine.
Catha edulis —Leaves of an East African bush that can be chewed for their stimulant effect. Designer amphetamines—Substances close in chemical structure to classic amphetamines that provide both stimulant and hallucinogenic effects.
Dopamine —A chemical in brain tissue that serves to transmit nerve impulses (is a neurotransmitter) and helps to regulate movement and emotions. Large amounts of dopamine are released following ingestion of amphetamines.
Ecstasy —Best known of the so-called designer amphetamines, also known as MDMA. It produces both stimulant and hallucinogenic effects.
Ephedrine —An amphetamine-like substance used as a nasal decongestant.
Formication —The sensation of bugs creeping on the skin.
Hyperthermia —Elevated body temperature resulting from ingestion of amphetamines.
Methamphetamine —The most common illegally produced amphetamine.
Serotonin —A widely distributed neurotransmitter that is found in blood platelets, the lining of the digestive tract, and the brain, and that works in combination with norepinephrine. It causes very powerful contractions of smooth muscle, and is associated with mood, attention, emotions, and sleep. Low levels of serotonin are associated with depression. Large amounts of serotonin are released after ingestion of MDMA.
“Speed run” —The episodic bingeing on amphetamines.
In 1999, NIDA began a program known as the “Club Drug Initiative” in response to recent increases in abuse of MDMA and other drugs used in similar environments. This ongoing program seeks to increase awareness of the dangers of these drugs among teens, young adults, parents, and community members.
Research indicates a pervasive perception among users that MDMA is a “fun” drug with minimal risks. This myth might point to the main reason for the widespread increase in the drug’s abuse. The Club Drug Initiative seeks to make the dangers of MDMA use far better known. Evidence of the program’s initial success with this initiative might be seen in what is considered a growing perception by high school seniors that MDMA is a dangerous drug.
American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders. 4th ed., Text rev. Washington, D.C.: American Psychiatric Association, 2000.
Kaplan, Harold I., MD, and Benjamin J. Sadock, MD. Synopsis of Psychiatry: Behavioral Sciences/Clinical Psychiatry. 8th ed. Baltimore, MD: Lippincott Williams and Wilkins, 1998.
Sulzer, David, and others. “Mechanisms of Neurotransmitter Release by Amphetamines: A Review.” Progress in Neurobiology 75 (2005): 406–33.
Narcotics Anonymous (NA). P.O. Box 9999, Van Nuys, CA 91409. Telephone: (818) 780-3951.
National Institute on Drug Abuse (NIDA). U.S. Department of Health and Human Services, 5600 Fishers Lane, Rockville, MD 20857. Telephone: (301) 443-6245. <http://www.nida.nih.gov>.
NIDA. Club Drug Initiative. <http://www.clubdrugs.org>.
National Institute on Drug Abuse. NIDA Infofacts: Meth-amphetamine. 2006. <http://www.nida.nih.gov/Infofacts/methamphetamine.html>.
National Institute on Drug Abuse. NIDA Research Report. Methamphetamine Abuse and Addiction: NIH Publication No. 06-4210, Sept. 2006. <http://www.nida.nih.gov/ResearchReports/methamph/methamph.html>.
National Library of Medicine. National Institutes of Health. “Amphetamines.” Updated links to news and information. <http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202031.html>.
National Library of Medicine. National Institutes of Health. Information about prescription amphetamines. “Amphetamines, systemic.” <http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202031.html>.
National Survey on Drug Use and Health. “The NSDUH Report: Methamphetamine.” 2007. <http://oas.samhsa.gov/2k6/meth/meth.htm>.
U.S. Food and Drug Administration. “Some Cold Medicines Move Behind Counter.” FDA Consumer Magazine July-Aug. (2006). <http://www.fda.gov/fdac/features/2006/406_meth.html>.
Barbara S. Sternberg, PhD
Emily Jane Willingham, PhD