Substance Abuse Course #3175 or #175

About the Authors

Peggy M. Goulding, Ph.D., received a doctoral degree in educational psychology from the University of Texas at Austin and completed a post-doctoral program in clinical neuropsychology at the University of Houston. She has over twenty years of professional experience in a variety of settings, including_ private industry; hospitals; rehabilitation facilities; nursing homes; and public and private schools. A former faculty member in neurology at the Saint Louis University School of Medicine, she has also taught at the University of Houston, University of Missouri, and Maryville University.

Shelda L. Shank, RN, BSN, PHN completed her Baccalaureate Degree in Nursing and public health certificate at Azusa Pacific University, and is a member of the International Association of Forensic Nurses (IAFN). She is the Nurse Supervisor of the Instructional Systems Development section of the National Center of Continuing Education. In this capacity, she is responsible for directing the activities of this department, selecting qualified, credentialed authors for the courses offered by the National Center as well as advising staff of required course design and criteria. Ms. Shank has over 15 years of extensive experience in publishing courses in continuing education for health care professionals with the National Center.

Purpose and Goals

The goal of the course is to provide nurses and other health care providers with a comprehensive overview of the drugs of abuse that are most commonly used in the United States today. Emphasis is on short-term and long-term effects of the drugs, as well as treatment strategies and principles for prevention.

Instructional Objectives

1. Define and differentiate among drug use, drug abuse, and drug addiction.

2. Name the characteristic signs of drug abuse.

3. Recall the anatomy and neurophysiology of pleasure and its role in drug use.

4. Identify some commonly abused drugs and their characteristic short term and long term effects.

5. List the medical complications associated with various drugs of abuse.

6. Recognize the specific physiological effects of various classes of drugs of abuse.

7. Outline issues and concerns specific to the abuse of prescription medications.

8. List procedures for management of drug overdose.

9. Summarize current approaches to treatment of drug abuse and addiction.

10. Evaluate the efficacy of current strategies for prevention of drug abuse.

Introduction

Recreational drugs have been around for centuries, but drug abuse has never been so widespread. Marijuana was listed as an agent for achieving euphoria in a Chinese medical compendium traditionally dated from 2737 B.C. As far back as 2000 B.C., the Greeks used opium and the Aztecs incorporated hallucinogens into their religious rituals. Andean Indians chewed the leaves of the coca plant to decrease hunger and increase their stamina for work. Witches in the Middle Ages brewed potent concoctions, and New World merchants peddled a little opium along with their rum and slaves. Civil War soldiers were among the first addicts to prescription drugs, as their battlefield pains were dulled by laudanum.

Then along came cocaine and heroin, recommended for every malady from headaches to skin rashes. Cocaine was first extracted from coca in the 19^th century, and it was hailed as a miracle drug, prescribed for everything from exhaustion to depression, and widely available in patent medicines. Heroin, first produced in 1874, was sold by traveling salesmen and through mail order catalogs; it was thought to be useful as a cure for respiratory illnesses and for relieving morphine withdrawal. Eventually, the addictive potential of these "harmless cure-alls" was recognized: they were shunned by mainstream society and their use driven underground.

The use of marijuana as an intoxicant was commonplace from the 1850s to the 1930s, and was reinforced by use among migrant workers from Mexico. The Federal government conducted a campaign in the 1930s to discourage its use. The message of a 1936 movie, "Reefer Madness," was that "smoking the killer weed was a direct road to hell, suicide, or at least insanity," and marijuana use came to be regarded as a gateway to addiction to more powerful and dangerous drugs.

Drugs remained on the fringes of society into the 1950s, when the "beat generation" bent their minds with hallucinogens and enhanced their worldly perceptions with pot. By the 1960s, youth rebellion was in full swing, while the hippies of "Hair" and the anti-heroes of "Easy Rider" romanticized the drug culture. Recreational use of drugs was the "in" thing, an activity shared by young people with a common point of view. Following this era, drug use continued to gain in social acceptance, as people thought they could experiment with a wide range of street drugs but not become addicted. Use of the old standbys was on the rise, even as more and more use of amphetamines, inhalants, and designer drugs was recorded. A second epidemic in cocaine use began in the United States in the 1970s and peaked in the mid- to late-1980s; again the drug was at first considered relatively harmless. Even middle class America began to use this chic drug in the workplace: it was seen as a quick pick-me-up, a little "perkier" than coffee. "Crack," a new and inexpensive form of freebase cocaine with magnified effects, hit the markets in the 1980s and soon was widespread in poorer neighborhoods. By the late 1990s the cocaine and crack epidemic had subsided somewhat, however, as heroin regained popularity among illicit drug users. A growing group of new middle-class heroin users emerged in the 1990s as a potent powdered heroin became available. Throughout this period, marijuana retained its role as the gateway to other drug use. After over a decade of decreasing use, marijuana smoking began an upward trend once more in the early 1990s, especially among teenagers, but by the end of the decade this upswing had leveled off well below former peaks of use.

Despite increased public outcry and an intensification of the government's war on drugs, it appears that drug abuse will -remain a significant public health concern for the foreseeable future. In this course we will outline the neuroanatomy and neurophysiology of drug use, abuse, and addiction; review the most common classes of drugs of abuse; and summarize current approaches to treatment and -prevention.

Use, Abuse and Dependence

These long-lasting changes are a major component of the addiction itself. It is as though there is a figurative “switch” in the brain that “flips” at some point during an individual’s drug use.

Most experts in addiction medicine differentiate use, abuse, and dependence or addiction, and they are often seen as representing a continuum of severity in assessing a person's drug problem. Substance use is simply the ingestion of a chemically active agent such as a prescription or illicit drug, alcohol or tobacco. Substance abuse suggests a maladaptive pattern of substance use leading to significant difficulties in meeting major role obligations at home, work, or school; use in situations in which it is physically hazardous (such as driving); or continued use despite related social and interpersonal problems, or legal problems. Dependence implies a cluster of cognitive, behavioral, and physical symptoms which indicate that the individual continues to use the substance despite the presence of significant substance-related problems. The person develops a tolerance for the substance and requires progressively larger amounts to elicit the effects desired. Also, the person will experience physical and psychological signs and symptoms of withdrawal if the substance is not used. Addiction typically refers to a compulsive and maladaptive dependence on the substance, resulting in adverse psychological, physical, economic, social, and legal ramifications.

Neurobiology in Brief

The brain consists of several large regions, each responsible for specific activities vital for living. (Figure 1) The cerebral cortex, which is divided into right and left hemispheres, encompasses about two-thirds of the brain mass and lies over and around most of the remaining structures of the brain. It is the most highly developed part of the human brain and is responsible for thinking, perceiving, and producing and understanding language. The cerebral cortex can be divided into areas with each having a specific function, such as vision, hearing, touch, movement, or smell. Other areas are critical for thinking and reasoning. Although many functions, such as touch, are found in both the right and left cerebral hemispheres, some functions are found predominantly in only one hemisphere. For example, in most people, language abilities are localized in the left hemisphere. Even so, the cortex most often acts as a unit in processing for complex tasks, and dysfunction in any one area can affect the operation of the brain as a whole.

The brainstem is the part of the brain that connects the brain and the spinal cord. It controls basic functions such as heart rate, respiration, appetite and sleep. The cerebellum, a prominent structure located above the brainstem, coordinates the brain's processes for skilled repetitive movements and for maintaining balance and posture. It has also been implicated in higher level cognitive functions that require complex motor activities.

The diencephalon, which is also located beneath the cerebral hemispheres, contains the thalamus and hypothalamus. The thalamus is involved in sensory perception and regulation of motor functions (i.e., movement). It connects areas of the cerebral cortex that are involved in sensory perception and motor control with other parts of the brain and spinal cord that also have a role in sensation and movement. The hypothalamus is a very small but important component of the diencephalon. It plays a major role in regulating hormone production, body temperature, and many other vital activities.

On top of the brainstem and buried under the cortex, there is a set of more primitive brain structures called the limbic system. The limbic system structures are involved in many of our emotions and motivations, particularly those that are related to survival, such as fear, anger, and the pleasure derived from activities like eating and sex. Two large limbic system structures called the amygdala and hippocampus are also involved in memory. One of the reasons that drugs of abuse can exert such powerful control over our behavior is that they act directly on the more primitive brainstem and limbic structures, which can override the cortex in controlling our behavior. In effect, they eliminate the most human part of our brain from its role in behavior control.

The brain is made up of billions of nerve cells, each containing three important parts: a central cell body; short fibers called dendrites that receive messages from other neurons and relay them to the cell body; and an axon, a long single fiber that transmits messages from the cell body to the dendrites of other neurons, or to body tissues such as muscles. Although most neurons contain all three parts, there is much diversity in the shapes and sizes of neurons as well as their axons and dendrites.

The transfer of a message from the axon of one nerve cell to the dendrites of another is known as neurotransmission. Although axons and dendrites are located extremely close to each other, the transmission of a message from an axon to a dendrite does not occur through direct contact. Instead, communication between nerve cells occurs mainly through the release of chemical substances into the space, or synapse, between the axon and dendrites. When neurons communicate, a message, traveling as an electrical impulse, moves down an axon and toward the synapse. There it triggers the release of molecules called neurotransmitters from the axon into the synapse. The neurotransmitters then diffuse across the synapse and bind to special receptor molecules located within the cell membranes of the dendrites of the adjacent nerve cell. This, in turn, stimulates or inhibits an electrical response in the receiving neuron's dendrites.

There are many different types of neurotransmitters, each of which has a precise role to play in the functioning of the brain. Generally, each neurotransmitter can only bind to a very specific matching receptor. Therefore, when a neurotransmitter couples to a receptor, it is like fitting a key into a lock. This coupling then starts a whole cascade of events at both the surface of the dendrite of the receiving nerve cell and inside the cell. In this manner, the message carried by the neurotransmitter is received and processed by the receiving nerve cell. Once this has occurred, the neurotransmitter is inactivated by being either broken down by an enzyme or reabsorbed back into the nerve cell that released it. The reabsorption (also known as re-uptake) requires the action of transporter molecules, which reside in the cell membranes of the axons that release the neurotransmitters. They pick up specific neurotransmitters from the synapse and carry them back across the cell membrane and into the axon. The neurotransmitters are then available for reuse.

Pleasure is a very powerful biological force for survival. Life-sustaining activities, such as eating, activate a circuit of specialized nerve cells devoted to producing and regulating pleasure. One important set of these nerve cells, which uses a chemical neurotransmitter called dopamine, sits at the very top of the brainstem in the ventral tegmental area (VTA). These dopamine-containing neurons relay messages about pleasure through their nerve fibers to nerve cells in a limbic system structure called the nucleus accumbens. Still other fibers reach to a related part of the frontal region of the cerebral cortex. So, the pleasure circuit, which is known as the mesolimbic dopamine system, spans the -survival-oriented brainstem, the emotion-oriented limbic system, and the frontal cerebral cortex.

All drugs that are addicting can activate the brain's pleasure circuit. Drug addiction is a biological, pathological process that alters the way in which the pleasure center, as well as other parts of the brain, functions. Almost all drugs that change the way the brain works do so by affecting chemical neurotransmission. Some drugs, like heroin and LSD, mimic the effects of a natural neurotransmitter. Others, like PCP, block receptors and thereby prevent neuronal messages from getting through. Still others, like cocaine, interfere with the molecules that are responsible for transporting neurotransmitters back into the neurons that released them. (Figure 2) Finally, some drugs, such as methamphetamine, act by causing neurotransmitters to be released in greater amounts than normal.

Prolonged drug use changes the brain in fundamental and long-lasting ways. These long-lasting changes are a major component of the addiction itself. It is as though there is a figurative "switch" in the brain that "flips" at some point during an individual's drug use. The point at which this "flip" occurs varies from individual to individual, but the effect of this change is the transformation of a drug abuser to a drug addict.

Marijuana

The rate of current marijuana use among youths was 8.2% in 2002 and 7.9% in 2003. There was a significant decline in lifetime marijuana use among youths, from 20.6% in 2002 to 19.6% in 2003.

Marijuana has assumed a unique place in our culture and is looked upon benignly by some and with horror by others. Many people smoke marijuana now and then, perhaps combining it with alcohol to "mellow out,' and that is the extent of their drug use. For others, however, especially teenagers, marijuana is a major gateway experience into the drug world.

Marijuana is made from the dried leaves and flowers of the Indian hemp plant, cannabis sativa. It has been cultivated worldwide and used as a drug for centuries. The potency of marijuana depends on the method of preparation, with hashish and ganja much more powerful than the unprocessed form. Although cannabinoids are usually smoked, they can also be eaten, drunk as tea or, rarely, injected intravenously. The active ingredient of marijuana, delta-9-tetrahydrocannabinol (THC), binds to and activates specific neuroreceptors, called cannabinoid receptors, located throughout the brain in areas that control memory, thought, concentration, time and depth perception, and coordinated movement. THC generally affects these functions negatively, by decreasing the activity of the neurons in each area. Marijuana has been shown to stimulate the dopamine pathway from the ventral tegmental area to the nucleus accumbens, within the pleasure center of the brain, leading to feelings of euphoria, relaxation, and heightened sensation. The THC content of marijuana is currently higher than that of the marijuana used in past decades. Many potential adverse effects that were reported may be understated when compared with the effects of current street preparations.

Peak plasma levels of THC are normally achieved within 10 minutes of smoking marijuana, and intoxication lasts approximately two to three hours. Because of its high lipid solubility, THC accumulates in fatty tissues, leading to its long half-life and related effects. For example, the disruptive effect that marijuana has on coordination may last for more than 24 hours, which is far beyond the period of subjective intoxication.

Many investigations using animals and some studies of humans suggest that reproductive abnormalities may occur with the use of marijuana. Maternal exposure to marijuana during pregnancy may reduce the size of the fetus and the birth weight. A 10-fold increase in the risk of nonlymphoblastic leukemia in children whose mothers used marijuana before or during gestation has also been reported.

Some patients with pre-existing medical conditions who use marijuana may be at particular risk. For example, although THC acutely increases the respiratory rate and the diameter of bronchial airways, chronic use of -marijuana results in epithelial damage to the trachea and major bronchi, and decreased airway diameter. Marijuana smoke does not contain nicotine but does have a significantly higher tar content than cigarettes; it contains many carcinogens and, unlike most cigarettes, is smoked unfiltered.

A serious but often neglected adverse effect of marijuana is the risk of infection: chronic use of marijuana may lead to impairment of important pulmonary defenses. Also, marijuana can be contaminated with microorganisms such as aspergillus and salmonella, as well as fecal matter. The risk of infection may be of particular concern in patients who have HIV or AIDS, or other compromise of the immune system.

For many years, it has been known that THC acts on cannabinoid receptors in the brain. It was hypothesized that since the normal brain has these receptors, there must also be a substance produced by the brain itself that acts on these receptors. Finally, in 1992, after years of research, scientists discovered a substance produced by the brain that activates the THC receptors and has many of the same physiological effects as THC. The scientists named the substance ananda-mide, from a Sanskrit word meaning 'bliss'. The discovery of anandamide opened whole new avenues of research. It now appears that anandamide and dopamine act in opposite ways to control movements in an area of the brain called the dorsal striatum. Dopamine stimulates movements by acting in this area, and anandamide normally inhibits the action of dopamine.

The discovery of anandamide may lead to a greater understanding of certain health problems and ultimately to more effective treatments. It may be particularly useful in treating diseases related to imbalances of dopamine in the brain, including Parkinson's disease. When made synthetically and given orally, THC can be used to treat nausea associated with chemotherapy and stimulate appetite in AIDS wasting syndrome. It may also be useful for other conditions, including glaucoma. Now that the brain's own THC-like substance has been identified, researchers may soon be able to uncover the mechanisms underlying the therapeutic effects of THC, leading to the development of more effective and safer treatments for a variety of conditions.

Treatment

Identifying patients with a marijuana-related disorder can be difficult, because abuse and associated problems commonly develop slowly. Often, patients do not recognize that they have a problem; if they do, they are perhaps more likely to continue their drug use while intensifying their efforts to hide it from family, physicians and other authority figures. Although marijuana abuse in adolescents and young adults is of particular concern, it should not be overlooked in other patient groups. For example, persons with certain psychiatric disorders (such as bipolar disorder and post-traumatic stress disorder), those who are under severe emotional distress, and those who have chronic pain might be at increased risk. Ultimately, patients who need treatment will be identified through direct disclosure of marijuana-related problems by the patient, a positive urine drug screen, or identification by legal, school or employment authorities.

Researchers at the U.S. -National Institute on Drug Abuse (NIDA) have discovered a way to block the effects of THC on the cannabinoid receptors, thus minimizing the high experienced by marijuana users (Figure 4). The selective cannabinoid CB1 receptor antagonist, rimonabant, chemically blocks the receptors and thus eliminates the intoxication associated with smoking marijuana. Subjects given the highest dose of rimonabant (90 mg) reported a 45.6% reduction in how "high" they felt compared with the control group. The -treatment group also had a 59% smaller increase in heart rate, one of the primary physical effects of marijuana. Lead researcher Dr. Marilyn Huestis of NIDA said the findings help point the way toward possible treatment for people addicted to marijuana. "It's certainly an issue that is still a little controversial," she said. "But there's been some beautiful work showing that marijuana is addictive, and that a number of people who utilize the drug on a chronic basis have developed -dependence and have a very_ difficult time stopping taking the drug." By blocking the brain's cannabinoid receptors, rimonabant may also prove useful in treating obesity, cigarette smoking, and diseases such as schizophrenia, and improving memory.

Cocaine

Among users of cocaine in the year 2002, 25.2 % (1.5 million) were classified with dependence on or abuse of cocaine.

Cocaine, a powerfully addictive stimulant, is one of the oldest known drugs. The pure chemical, cocaine hydrochloride, has been an abused substance for more than 100 years; and coca leaves, the source of cocaine, have been ingested for thousands of years. Cocaine was labeled the drug of the 1980s and '90s, because of its extensive popularity and use during this period. There are basically two chemical forms of cocaine: the hydrochloride salt and the "freebase." The hydrochloride salt, or powdered form of cocaine, dissolves in water and, when abused, can be taken intravenously or inhaled. Freebase refers to a compound that has not been neutralized by an acid to make the hydrochloride salt. The freebase form of cocaine is smokeable.

Cocaine is generally sold on the street as a fine, white, crystalline powder, known as "coke," "C," "snow," "flake," or "blow." Street dealers generally dilute it with such inert substances as cornstarch, talcum powder, or sugar, or with such active drugs as procaine (a chemically-related local anesthetic) or with such other stimulants as amphetamines.

Crack (or rock) is the street name given to the freebase form of cocaine that has been processed from the powdered cocaine hydrochloride form to small clumps of smokable substance. Crack cocaine is processed with ammonia or baking soda and water, and heated to remove the hydrochloride. The term "crack" refers to the crackling sound heard when the mixture is smoked. Because crack is smoked, the user experiences a high in less than 10 seconds. This rather immediate euphoric effect is one of the reasons that crack has become enormously popular; another reason is that crack is inexpensive both to produce and to buy.

The principal routes of cocaine administration are oral, intranasal, intravenous, and inhalation. The slang terms for these routes are, respectively, "chewing," "snorting," "mainlining," "injecting," and "smoking" (including freebase and crack cocaine). Snorting is the process of inhaling cocaine powder through the nostrils, where it is absorbed into the bloodstream through the nasal tissues. Injecting releases the drug directly into the bloodstream, and heightens the intensity of its effects. Smoking involves the inhalation of cocaine vapor or smoke into the lungs, where absorption into the bloodstream is as rapid as by injection. The drug can also be rubbed onto mucous tissues. Some users combine cocaine powder or crack with heroin in a "speedball."

Cocaine use ranges from occasional use to repeated or compulsive use, with a variety of patterns between these extremes. There is no safe way to use cocaine. Any route of administration can lead to absorption of toxic amounts of cocaine, leading to acute cardiovascular or cerebrovascular emergencies that could result in sudden death. Repeated cocaine use by any route of administration can produce addiction and other adverse health consequences.

Cocaine acts on the pleasure circuit within the brain to prevent reabsorption of the neurotransmitter dopamine after its release from nerve cells. Normally, the neurons that are part of the pleasure circuit release dopamine, which then crosses the synapse to stimulate another neuron in the pleasure circuit. Once this has been accomplished, the dopamine is picked up by a transporter molecule and carried back into the original neuron. However, because cocaine binds to the dopamine transporter molecule, it prevents the reabsorption of dopamine. This causes a buildup of dopamine in the synapse, which results in strong feelings of pleasure and even euphoria. The excess dopamine that accumulates in the synapse causes the neurons that have dopamine receptors to decrease the number of receptors they make. This is called down regulation. When cocaine is no longer taken and dopamine levels return to their normal (i.e., lower) concentration, the smaller number of dopamine receptors that are available for the neurotransmitter to bind to is insufficient to fully activate nerve cells. This results in a drug "craving," which compels the addict to get the level of dopamine back up by taking cocaine. Cocaine also binds to the transporters for other neurotransmitters, including serotonin and norepinephrine, and blocks their re-uptake. Scientists are still unsure of the effects of cocaine's interaction with these other neurotransmitters.

Cocaine has also been found to specifically affect the prefrontal cortex and amygdala, which are involved in aspects of memory and emotional learning. Researchers believe that a neural network involving these brain regions reacts to environmental cues and activates drug-related memories, and this in turn triggers biochemical changes that result in cocaine craving.

Cocaine's effects appear almost immediately after a single dose, and disappear within a few minutes to hours. If taken in small amounts (100 mg or less), cocaine typically makes the user feel euphoric, sociable, and mentally alert, especially to the sensations of sight, sound, and touch. It can also temporarily decrease the need for food and sleep. Some users say that the drug helps them to perform certain physical and intellectual tasks more quickly, while others experience the opposite effect.

The duration of cocaine's immediate effects depends upon the route of administration. The faster the absorption, the more intense the high, and the shorter the duration of action. The high from snorting, for example, is relatively slow in onset, and may last 15 to 30 minutes, while that from smoking may last only 5 to 10 minutes.

Short-term physiological effects of cocaine include constricted blood vessels; dilated pupils; and increased temperature, heart rate, and blood pressure. Large amounts (several hundred milligrams or more) intensify the user's high, but may also lead to bizarre, erratic, and violent behavior. These users may experience tremors, vertigo, muscle twitches, paranoia, or, with repeated doses, a toxic reaction closely resembling amphetamine poisoning. Some users of cocaine report feelings of restlessness, irritability, and anxiety. In rare instances, sudden death can occur on the first use of cocaine or unexpectedly thereafter, perhaps the result of cardiac arrest or seizures followed by respiratory arrest.

Long-term use may lead to tolerance, and many addicts report that they eventually are unable to achieve as much pleasure as they did from their first experience. Some users will repeatedly increase their doses in an attempt to intensify and prolong the euphoric effects. While tolerance can occur, users can also become more sensitive to the drug's anesthetic and convulsant effects, without increasing the dose taken; this may explain some of the deaths that occur after apparently low doses of cocaine. Binge use of cocaine, during which the drug is taken repeatedly and at increasingly high doses, leads to a state of increasing irritability, restlessness, and paranoia. This may result in a full-blown paranoid psychosis, in which the individual loses touch with reality and experiences auditory hallucinations.

Cocaine use has been associated with severe medical complications, including cardiovascular effects such as disturbances in heart rhythm and heart attacks; increased blood pressure and body temperature; chest pain and respiratory failure; neurological effects, including seizure, headaches, strokes, and coma; and gastrointestinal complications, including abdominal pain and nausea. Because cocaine has a tendency to decrease food intake, many chronic cocaine users can experience significant weight loss and malnourishment. Research has also revealed a potentially dangerous interaction between cocaine and alcohol. Taken in combination, the two drugs are converted by the body to cocaethylene. Cocaethylene has a longer duration of action in the brain and is more toxic than either drug alone. While more research needs to be done, it is noteworthy that the mixture of cocaine and alcohol is the most common two-drug combination that results in drug-related death.

Different routes of cocaine administration can produce different adverse effects. Regularly snorting cocaine, for example, can lead to loss of sense of smell, nosebleeds, problems with swallowing, hoarseness, and an overall irritation of the nasal septum, which can in turn lead to a chronically inflamed, runny nose. Ingested cocaine can cause severe bowel gangrene, due to reduced blood flow.

Persons who inject cocaine have puncture marks and "tracks," most commonly in their forearms. Intravenous cocaine users may experience an allergic reaction to the drug or to some additive, resulting, in the most severe cases, in death. Cocaine abusers, especially those who inject, are at increased risk for contracting such infectious diseases as HIV/AIDS and hepatitis. Research has also shown that drug use can interfere with judgment about risk-taking behaviors, and can potentially lead to reduced precautions about having sex, the sharing of needles and injection paraphernalia, and the trading of sex for drugs, by both men and women.

The full extent of the effects of prenatal drug exposure on a child is not completely known, but many scientific studies have documented that babies born to mothers who abuse cocaine during pregnancy are often prematurely delivered, have low birth weights and smaller head circumferences, and are often shorter in length. In fact, "crack babies," or babies born to mothers who used cocaine while pregnant, were written off by many a decade ago as a lost generation. They were predicted to suffer from severe, irreversible brain damage, resulting in reduced intelligence and social skills. It was later found that this was a gross exaggeration. Most crack-exposed babies appear to recover fairly well. However, the fact that most of these children appear normal should not be over-interpreted as a positive sign. Using more sophisticated technologies, scientists are now finding that exposure to cocaine during fetal development may lead to subtle, but significant deficits later, especially with behaviors that are crucial to success in the classroom, such as blocking out distractions and concentrating for long periods of time.

Treatment

The majority of individuals seeking treatment for cocaine addiction smoke crack, and are likely to be poly-drug users as well. The widespread abuse of cocaine has stimulated extensive efforts to develop treatment programs for this type of drug abuse. Cocaine abuse and addiction is a complex problem involving apparently permanent biological changes in the brain as well as a myriad of social, familial, and environmental factors. Therefore, treatment of cocaine addiction is complex, and must address a variety of problems. Like any good treatment plan, cocaine treatment strategies need to assess the psychobiological, social, and pharmacological aspects of the patient's drug abuse.

Amphetamines

Amphetamines are potentially addictive drugs that belong to the class of drugs known as stimulants, along with cocaine, caffeine, and others. The amphetamines were first synthesized in the 1920s for use as decongestants and later discovered to be helpful in treating narcolepsy, a rare disorder that causes an uncontrollable desire to sleep. They were effective medications for appetite control, and were good hangover cures as well. Because of their stimulating effects, they became widely sought by students, housewives, athletes, military personnel, truck drivers, and anyone who needed a boost to reduce fatigue, prolong wakefulness, or just get through a bad day. Initially sold over the counter and in inhalers, they were eventually highly regulated with prescriptions required for their use; this in turn led to increased illegal manufacturing of the drug. Amphetamine and its variants, methamphetamine and dextroamphetamine, are so similar in their effects that lab analysis may be the only way to differentiate among them; methamphetamine, however, has more pronounced effects on the central nervous system.

Methamphetamine is commonly known as "speed," "meth," and "chalk" or, in its smokeable form, as "ice," "crystal," "crank," or "glass." It is a white, odorless, bitter-tasting crystalline powder that easily dissolves in water or alcohol. Like amphetamine, it causes increased activity, decreased appetite, and a general sense of well-being. The effects of methamphetamine can last 6 to 8 hours or more. After the initial "rush," there is typically a state of high agitation that in some individuals can lead to violent behavior.

Methamphetamine can be made easily in clandestine settings with relatively inexpensive over-the-counter ingredients; many such as drain cleaner, battery acid, and antifreeze are extremely dangerous. The rapid proliferation of so-called "basement" laboratories for the production of methamphetamine has led to a widespread problem in many communities in the U.S. Methamphetamine abuse has long been reported as the dominant drug problem in portions of Southern California, but has become a substantial drug problem in other sections of the West and Southwest as well and continues to spread to other areas of the country, including both rural and urban sections of the South and Midwest. Its use was traditionally associated with white, male, blue-collar workers, but it is being used by ever more diverse population groups that change over time and differ by geographic area.

Methamphetamine comes in many forms and can be smoked, snorted, orally ingested, or injected._ The drug alters moods in different ways, depending on how it is taken. Immediately after smoking the drug or injecting it intravenously, the user experiences an intense rush or "flash" that lasts only a few minutes and is described as extremely pleasurable. Snorting or oral ingestion produces euphoria - a high but not an intense rush. Snorting produces effects within 3 to 5 minutes, and oral ingestion produces effects within 15 to 20 minutes.

As with similar stimulants, methamphetamine most often is used in a "binge and crash" pattern. Because tolerance for methamphetamine occurs within minutes - meaning that the pleasurable effects disappear even before the drug concentration in the blood falls significantly - users try to maintain the high by binging on the drug. In the 1980s, "ice," a smokeable form of methamphetamine, came into use. Ice is a large, usually clear crystal of high purity that is smoked in a glass pipe like crack cocaine. The smoke is odorless, leaves a residue that can be re-smoked, and produces effects that may continue for 12 hours or more.

Methamphetamine acts on the pleasure circuit in the brain by altering the levels of certain neurotransmitters present in the synapse. Methamphetamine is chemically similar to dopamine and another neurotransmitter, norepinephrine. It produces its effects by causing dopamine and norepinephrine to be released into the synapse in several areas of the brain, including the nucleus accumbens, prefrontal cortex, and the striatum, a brain area involved in movement. Specifically, methamphetamine enters nerve terminals by passing directly through nerve cell membranes. It is also carried into the nerve terminals by transporter molecules that normally carry dopamine or norepinephrine from the synapse back into the nerve terminal. Once in the nerve terminal, methamphetamine enters dopamine and norepinephrine containing vesicles and causes the release of these neurotransmitters. Enzymes in the cell normally break down excess dopamine and norepinephrine, but methamphetamine blocks this process. The excess neurotransmitters are then carried by transporter molecules out of the neuron and into the synapse. Once in the synapse, the significantly higher than normal concentration of dopamine causes feelings of pleasure and euphoria. The excess norepinephrine may be responsible for the alertness and anti-fatigue effects of methamphetamine.

Long-term methamphetamine abuse results in many damaging effects, including addiction. Addiction is a chronic, relapsing disease, characterized by compulsive drug-seeking and drug use, which is accompanied by functional and molecular changes in the brain. In addition to being addicted to methamphetamine, chronic methamphetamine abusers exhibit symptoms that can include anxiety, confusion, and insomnia. They also can display a number of psychotic features, including paranoia, auditory and visual hallucinations, mood disturbances, and delusions (for example, the sensation of insects creeping on the skin, called "formication"). The paranoia can result in homicidal as well as suicidal thoughts, and out-of-control rages that can be coupled with extremely violent behavior.

As with similar stimulants, methamphetamine most often is used in a “binge and crash” pattern.

With chronic use, tolerance for methamphetamine can develop. In an effort to intensify the desired effects, users may take higher doses of the drug, take it more frequently, or change their method of drug intake. In some cases, abusers forego food and sleep while indulging in a form of binging known as a "run," injecting as much as a gram of the drug every 2 to 3 hours over several days until the user runs out of the drug or is too disorganized to continue. Although there are no physical manifestations of a withdrawal syndrome when methamphetamine use is stopped, there are several symptoms that occur when a chronic user stops taking the drug. These include depression, anxiety, fatigue, paranoia, aggression, and an intense craving for the drug.

Methamphetamine can also affect the brain in other ways, causing cerebral edema, brain hemorrhage, and hallucinations. Moreover, some of the effects of methamphetamine on the brain appear to be long lasting and even permanent. Recent research has shown that even three years after chronic methamphetamine users have discontinued use of the drug, there remains a reduction in their ability to transport dopamine back into neurons. Researchers have reported that as many as 50 percent of the dopamine-producing cells in the brain can be damaged after prolonged exposure to relatively low levels of methamphetamine. This is highly significant because dopamine has a major role in many brain functions, including experiences of pleasure, mood, and movement. In these same studies, researchers found similarities in the damage to the dopamine system of methamphetamine users to that seen in patients with Parkinson's disease. Researchers also have found that serotonin-containing nerve cells may be damaged even more extensively. Whether this toxicity is related to the psychosis seen in some long-term methamphetamine abusers is still an open question.

Methamphetamine can cause a variety of cardiovascular problems. These include rapid heart rate, irregular heartbeat, increased blood pressure, and irreversible, stroke-like damage to the small blood vessels of the brain. Hyperthermia and convulsions occur with methamphetamine overdose, and if not treated immediately can result in death.

Chronic methamphetamine abuse can result in inflammation of the heart lining, and among users who inject the drug, damaged blood vessels and skin abscesses. Methamphetamine abusers also can have episodes of violent behavior, paranoia, anxiety, confusion, and insomnia. Heavy users also show progressive social and occupational deterioration. Psychotic symptoms can sometimes persist for months or years after use has ceased.

A common method of illegal methamphetamine production uses lead acetate as a reagent; therefore, production errors may result in methamphetamine contaminated with lead. There have been documented cases of acute lead poisoning in intravenous methamphetamine abusers.

Fetal exposure to methamphetamine also is a significant problem in the United States. At present, research indicates that methamphetamine abuse during pregnancy may result in prenatal complications, increased rates of premature delivery, and altered neonatal behavioral patterns, such as abnormal reflexes and extreme irritability. Methamphetamine abuse during pregnancy may also be linked to congenital deformities.

Treatment

There are some established protocols that emergency room physicians use to treat individuals who have had a methamphetamine overdose. Because hyperthermia and convulsions are common and often fatal complications of such overdoses, emergency room treatment focuses on the immediate physical symptoms. Overdose patients are cooled off in ice baths, and anticonvulsant drugs may also be administered. Acute methamphetamine intoxication can often be handled by observation in a safe, quiet environment. In cases of extreme excitement or panic, treatment with antianxiety agents such as benzodiazepines has been helpful, and in cases of methamphetamine-induced psychoses, short-term use of neuroleptics has proven successful.

At this time the most effective treatments for methamphetamine addiction are cognitive behavioral interventions. These approaches are designed to help modify the patient's thinking, expectancies, and behaviors, and to increase skills in coping with various life stressors. Methamphetamine recovery support groups also appear to be effective adjuncts to behavioral interventions that can lead to long-term drug-free recovery. There are currently no particular pharmacological treatments for dependence on amphetamine or amphetamine-like drugs such as methamphetamine. The current pharmacological approach is borrowed from experience with treatment of cocaine dependence. Unfortunately, this approach has not met with much success since no single agent has proven efficacious in controlled clinical studies. Antidepressant medications can be helpful in combating the depressive symptoms frequently seen in newly abstinent methamphetamine users.

Abuse of Medications
for ADHD

The medications used for treatment of ADHD are primarily stimulants. While these drugs are safe and effective when used properly, they have a high potential for abuse; like other stimulants, they can lead to marked tolerance and psychological dependence, and can cause medical problems leading to serious illness or even death.

The most well known of the ADHD medications is methylphenidate (MPH, Ritalin, and the sustained release preparations Concerta and Metadate). A mild central nervous stimulant, its mechanism of action is not entirely understood. However, it appears to activate the arousal systems in the brainstem and cortex to produce its stimulant effects. While MPH appears to target the same neuroreceptors as cocaine, it does not affect all the same components of the pleasure circuit throughout the brain.

MPH can be abused orally, or tablets can be crushed and either snorted or dissolved in water and injected. The pattern of abuse is characterized by an escalation in dose, frequent episodes of binge use followed by severe depression, and an overpowering desire to continue the use of this drug despite serious, adverse medical and social consequences. Typical of other CNS stimulants, high doses of MPH often produce agitation, tremors, euphoria, tachycardia, palpitations, and hypertension. Psychotic episodes, paranoid delusions, hallucinations, and bizarre behavioral characteristics similar to amphetamine-like toxic effects have been associated with MPH abuse.

Unlike amphetamine, methamphetamine, and cocaine, where illicit manufacturing and smuggling into the United States account for the vast majority of available drugs for abuse, pharmaceutical products diverted from legitimate channels are the only sources of MPH. It is important to note that many schools have more MPH stored for daytime dosing of students than is available in some pharmacies, and many families have supplies stored in kitchen or bathroom cabinets.

Information from DEA case files and state law enforcement services indicates that MPH is sought after by a wide range of individuals, from adolescents to street addicts. Even though the lack of clandestine production, regulatory controls, and predominant use in the treatment of ADHD in children have historically limited the illegal use of this drug, non-prescription use is on the rise. Recent reports of MPH misuse/abuse among adolescents and young adults are particularly disturbing, since this group has the freest access to this drug. Reports from numerous states and local municipalities indicate that adolescents are giving and selling their MPH medication to friends and classmates. Anecdotal reports from students and faculty on college campuses indicate that MPH is being used as a study aid in the same manner that amphetamine was used on campuses in the 1960s. Ritalin abuse is increasingly observed among elementary students, and newspaper reports suggest that it is "as easy to get as candy."

Since its approval for treatment of ADHD in 1996, Adderall, a mixture of four -amphetamine salts, has become one of the most widely prescribed medications in the United States. It, too, has marked abuse -potential.

Heroin and the Opiates

Opiates are powerful drugs derived from the poppy plant that have been used for centuries to relieve pain. They include opium, heroin, morphine, and codeine. Even centuries after their discovery, opiates are still the most effective pain relievers. Although heroin has no medicinal use, the other opiates, such as morphine and codeine, are used to relieve pain related to illnesses (for example, cancer) and medical and dental procedures. When used as directed by a physician, opiates are safe and generally do not produce addiction. But opiates also possess very strong reinforcing properties and can quickly trigger addiction when used improperly.

The brain produces endorphins that activate opioid receptors located throughout the brain and body. Research indicates that endorphins are involved in many functions, including respiration, nausea, vomiting, pain modulation, and hormonal regulation. Two important effects produced by the naturally occurring endorphins and opiate drugs alike are pleasure (or reward) and pain relief.

Like cocaine and other abused drugs, opiates activate the brain's reward system. Because of its chemical structure, heroin penetrates the brain more quickly than other opiates, which is probably why many addicts prefer heroin. When a person injects, sniffs, or orally ingests heroin, the drug travels through the bloodstream, across the blood brain barrier, and into the brain. Once in the brain, heroin is rapidly converted to morphine, which then activates opiate receptors located throughout the brain, including the ventral tegmental area, nucleus accumbens and cerebral cortex within the reward system. Research suggests that stimulation of opioid receptors by morphine results in feelings of
reward and activates the pleasure circuit by causing greater amounts of dopamine to be released within the nucleus accumbens. This excessive release of dopamine and overstimulation of the reward system can lead to addiction.

Opiates also act directly on the respiratory center in the brainstem causing a slowdown in activity, resulting in a decrease in respiratory rate. Excessive amounts of an opiate, like heroin, can cause the respiratory centers to shut down breathing altogether. When someone overdoses on heroin, it is the action of heroin in the brainstem respiratory centers that can cause the person to stop breathing and die.

Heroin, the most abused and rapidly acting of the opiates, is an illegal, highly addictive drug. It is processed from morphine, the naturally occurring substance extracted from the seedpod of certain varieties of poppy plants. It is typically sold as a white or brownish powder or as the black sticky substance known on the streets as "black tar heroin." Although purer heroin is becoming more common, most street heroin is "cut" with other drugs or with substances such as sugar, starch, powdered milk, or quinine. Street heroin can also be cut with strychnine or other poisons. Because heroin abusers do not know the actual strength of the drug or its true contents, they are at risk of overdose or death. Heroin also poses special problems because of the transmission of HIV and other diseases that can occur from sharing needles or other injection equipment.

The Drug and Alcohol Services Information System (DASIS) reported in its December 2004 issue about changes in how heroin was used over the last decade. Data on substance abuse treatment provide a way to monitor changes in the way heroin has been used over the past 10 years. As suggested in an earlier report, these data support the conclusion that heroin inhalation was a new and growing problem among young adults in the early 1990s.

Between 1992 and 2002, inhalation increased as the route of administration from 20 to 33 % of primary heroin admissions, while injection decreased from 77 to 62 %. Heroin use continues to trend upward, especially among younger populations. It is often used in combination with cocaine, either concurrently or sequentially.

The racial/ethnic composition of heroin injection and inhalation admissions has also changed. The proportion of Whites increased among both heroin inhalation and injection admissions by 6 and 10 % respectively. Over the same time period, the percentage of heroin injection users who were Black declined by 7 %. And the statistics for inhalation remained about the same.

_Heroin is usually injected, sniffed/snorted, or smoked. This causes an intense euphoria, or rush, that lasts only briefly and is followed by a few hours of relaxed contentment. A typical heroin abuser may inject up to four times a day. Intravenous injection provides the greatest intensity and most rapid onset of euphoria (7 to 8 seconds), while intramuscular injection produces a relatively slow onset of euphoria (5 to 8 minutes). When heroin is sniffed or smoked, peak effects are usually felt within 10 to 15 minutes. The intensity of the rush is a function of how much drug is taken and how rapidly the drug enters the brain and binds to the natural opioid receptors. With heroin, the rush is usually accompanied by a warm flushing of the skin, dry mouth, and a heavy feeling in the extremities, and may be accompanied by nausea, vomiting, and severe itching. Although smoking and sniffing heroin do not produce a "rush" as quickly or as intensely as intravenous injection, NIDA researchers have confirmed that all three forms of heroin use are addictive.

Injection continues to be the predominant method of heroin use among addicted users seeking treatment; however, researchers have observed a shift in heroin use patterns, from injection to sniffing and smoking. In fact, sniffing/snorting heroin is now the most widely reported means of taking heroin among users admitted for drug treatment in Newark, Chicago, and New York. With the shift in heroin abuse patterns comes an even more diverse group of users. Users over 30 years of age continue to be one of the largest user groups in most national data. However, younger and more affluent and discriminating users across the country are being lured by high-purity heroin, at a lower cost, that can be sniffed or smoked instead of injected.

One of the most detrimental long-term effects of heroin is addiction itself, characterized by compulsive drug seeking and use, and by neurochemical and molecular changes in the brain. Heroin also produces profound degrees of tolerance and physical dependence. As with abusers of any addictive drug, heroin abusers gradually spend more and more time and energy obtaining and using the drug. Once they are addicted, the heroin abusers' primary purpose in life becomes seeking and using drugs. Heroin literally changes their brains into drug-seeking machines.

Physical dependence develops with higher doses of the drug. With physical dependence, the body adapts to the presence of the drug and withdrawal symptoms occur if use is reduced abruptly. Withdrawal may occur within a few hours after the last time the drug is taken. Symptoms of withdrawal include restlessness, muscle and bone pain, insomnia, diarrhea, vomiting, cold flashes with goose bumps ("cold turkey"), and leg movements. Major withdrawal symptoms peak between 24 and 48 hours after the last dose of heroin and subside after about a week. However, some people have shown persistent withdrawal signs for many months. Heroin withdrawal is never fatal to otherwise healthy adults, but it can cause death to the fetus of a pregnant addict.

Physical dependence and the emergence of withdrawal symptoms were once believed to be the key features of heroin addiction. It is now known, however, that craving and relapse can occur weeks and months after withdrawal symptoms are long gone. Interestingly, patients with chronic pain who need opiates to function (sometimes over extended periods) have few if any problems forgoing opiates after their pain is resolved by other means. This may be because the patient in pain is simply seeking relief of pain and not the rush sought by the addict.

Medical consequences of chronic heroin abuse include scarred and/or collapsed veins, bacterial infections of the blood vessels and heart valves, abscesses (boils) and other soft-tissue infections, and liver or kidney disease. Lung complications (including various types of pneumonia and tuberculosis) may result from the poor health condition of the abuser as well as from heroin's depressant effects on respiration. Many of the additives in street heroin may include substances that do not readily dissolve, thus clogging the blood vessels that lead to the lungs, liver, kidneys, or brain, and causing infection or even death of small patches of cells in vital organs. Immune reactions to these or other contaminants can cause arthritis or other rheumatologic problems. Of course, sharing of injection equipment or fluids can lead to some of the most severe consequences of heroin abuse: infections with hepatitis B and C, HIV, and a host of other blood-borne viruses, which drug abusers can then pass on to their sexual partners and children.

Treatment

A variety of effective treatments are available for heroin addiction. Treatment tends to be more effective when heroin abuse is identified early, and detoxification is the first step. The treatments that follow vary depending on the individual, but methadone, a synthetic opiate that blocks the effects of heroin and eliminates withdrawal symptoms, has a proven record of success. Other pharmaceutical approaches, like LAAM (levo-alpha-acetylmethadol) and buprenorphine, and many behavioral therapies also are used for treating heroin addiction.

Detoxification

The primary objective of detoxification is to relieve withdrawal symptoms while patients adjust to a drug-free state. Not in itself a treatment for addiction, detoxification is a useful step only when it leads into long-term treatment that is either drug-free (residential or outpatient) or uses medications as part of the treatment. The best documented drug-free treatments are the therapeutic community residential programs lasting at least 3 to 6 months.

Methadone programs

Methadone treatment has been used effectively and safely to treat opioid addiction for more than 30 years. Properly prescribed methadone is not intoxicating or sedating, and its effects do not interfere with ordinary activities such as driving a car. The medication is taken orally, once a day, and it suppresses narcotic withdrawal for 24 to 36 hours. Patients on methadone remain able to perceive pain and have emotional reactions. Most important, methadone relieves the craving associated with heroin addiction; craving is a major reason for relapse. Among methadone patients, it has been found that normal street doses of heroin are ineffective at producing euphoria, thus making the use of heroin more easily extinguishable.

Also, methadone is medically safe even when used continuously for 10 years or more. Combined with behavioral therapies or counseling and other supportive services, methadone enables patients to stop using heroin (and other opiates) and return to more stable and productive lives. Methadone dosages must be carefully monitored in patients who are receiving antiviral therapy for HIV infection, however, to avoid potential medication interactions.

Levo-alpha-acetylmethadol (Laam ) And Other Medications

_LAAM, like methadone, is a synthetic opiate that can be used to treat heroin addiction. LAAM can block the effects of heroin for up to 72 hours with minimal side effects when taken orally. In 1993 the Food and Drug Administration approved the use of LAAM for treating patients addicted to heroin. Its long duration of action permits dosing just three times per week, thereby eliminating the need for daily dosing and take-home doses for weekends. LAAM is increasingly available in clinics that already dispense methadone.

Naloxone (Narcan) and naltrexone (Trexan) are medications that also block the effects of morphine, heroin, and other opiates. As opiate antagonists, they are especially useful as antidotes. Naltrexone has long-lasting effects, ranging from 1 to 3 days, depending on the dose. Naltrexone blocks the pleasurable effects of heroin and is useful in treating some highly motivated individuals. Naltrexone has also been found to be successful in preventing relapse by former opiate addicts released from prison on parole.

Another medication buprenorphine is a recent addition to the array of medications now available for treating addiction to heroin. Buprenorphine/naloxone (Suboxone) is a combination drug product formulated to minimize abuse. Buprenorphine is an attractive treatment for heroin addiction because, compared with other medications, such as methadone, it causes weaker opiate effects and is less likely to cause overdose problems. Buprenorphine also produces a lower level of physical dependence, so patients who discontinue the medication generally have fewer withdrawal symptoms than do those who stop taking methadone. Other medications with potential for treating heroin overdose/addiction are currently under investigation by NIDA.

Behavioral therapies

Although behavioral and pharmacologic treatments can be extremely useful when employed alone, integrating both types of treatments will ultimately be most effective. There are many behavioral treatments available for heroin addiction in both residential and outpatient settings: the important task is to match the treatment approach to the particular needs of the patient. Contingency management therapy, for example, uses a voucher-based system, where patients earn points based on negative drug tests that they can exchange for items that encourage healthy living. Cognitive-behavioral interventions are designed to help modify the patient's thinking, expectations, and behaviors and to increase skills in coping with various life stressors. Both behavioral and pharmacological treatments help to restore a degree of normalcy to brain function and behavior, with increased employment rates and lower risk of HIV and other diseases and criminal behavior.

Opioid Analogs and Relatives

Drug analogs are chemical compounds that are similar to other drugs in their effects but differ slightly in their chemical structure. Some analogs are produced by pharmaceutical companies for legitimate medical reasons. Other analogs, sometimes referred to as "designer" drugs, can be produced in illegal laboratories and are often more dangerous and potent than the original drug. Two of the most commonly known opioid analogs are fentanyl and meperidine (Demerol).

Fentanyl was introduced under the brand name "Sublimaze" in 1968 by a Belgian pharmaceutical company as a synthetic narcotic to be used as an analgesic in surgical procedures because of its minimal effects on the heart. Soon thereafter, an analog version called China White began to appear: users ended up in emergency rooms with classic overdose symptoms that responded to opiate antagonists like Narcan, but there were no traces of opiates in their symptoms. Fentanyl is particularly dangerous because it is 50 times more potent than heroin and can rapidly stop respiration. This is not a problem during surgical procedures because machines are used to help patients breathe. On the street, however, users have been found dead with the needle used to inject the drug still in their arms.

A particularly tragic story is associated with attempts to -create an effective analog of Demerol for street use. The substance, called MPTP after its molecular components, turned out to be a potent neurotoxin, producing a serious and irreversible Parkinson's-like syndrome in -users. Despite all treatment -efforts, most of those affected remain unable to move or speak.

A semisynthetic narcotic, oxycodone (Percodan), has been widely used for years, often in combination with aspirin or acetaminophen. Synthesized from thebaine, an opium derivative, it is more potent than codeine and has a higher dependence potential. Street use was limited due to its tendency to make the user's ears ring. Recently, a time-release version of the venerable Percodan was introduced; OxyContin, as it is called, was widely heralded as a significant improvement over available palliative medications, because its time-release mechanism afforded significant, sustained relief for people in severe pain. It has been prescribed primarily for patients diagnosed with terminal cancer, recovering from major surgery, or suffering from debilitating migraine headaches.

Unfortunately, street users of the drug, attracted to its euphoric high that is similar to that of heroin, have created an epidemic of OxyContin abuse. The pills are crushed into powder to overcome the sustained release; the drug is then snorted or diluted and injected into the user's veins. Dosage control is thus minimal, and hundreds of people have died from overdose. Beginning in 2002, new items about the use of OxyContin and Vicoden were added to the National Institute on Drug Abuse (NIDA) survey. Specifics revealed in 2003, approximately 2.8 million people aged 12+ had used OxyContin nonmedically at least once in their lifetime. An estimated 415,000 Americans received treatment for pain reliever abuse in the past year. Considering the addictive potential of oxycodone and hydrocodone, these are disturbingly high rates of use. (NIDA InfoFacts, 2005)

Hallucinogens

Hallucinogens are drugs that cause hallucinations - altered states of perception and profound distortions of reality. They can cause users to hear voices, see images, and feel sensations that do not exist; they also can produce rapid, intense emotional swings. Hallucinogenic drugs have played a role in human life for thousands of years. Cultures from the tropics to the arctic have used plants to induce states of detachment from reality and to precipitate "visions" thought to provide mystical insight. Historically, hallucinogenic plants were used largely for social and religious ritual, and their availability was limited by the climate and soil conditions they require. After the development of LSD, a synthetic compound that can be manufactured anywhere, abuse of hallucinogens became more widespread, and from the 1960s it increased dramatically. All LSD manufactured in this country is intended for illegal use, since LSD has no accepted medical use in the United States.

Hallucinogens include natural substances, such as mescaline and psilocybin that come from plants (cactus and mushrooms, respectively), and chemically manufactured ones, such as LSD and MDMA (ecstasy). LSD is manufactured from lysergic acid, which is found in ergot, a fungus that grows on rye and other grains. MDMA is a synthetic mind-altering drug with hallucinogenic properties. Although not a true hallucinogen in the pharmacological sense, PCP causes many of the same effects as hallucinogens and so is often included with this group of drugs.

Hallucinogens disrupt the interaction of nerve cells and the neurotransmitter serotonin. Distributed throughout the brain and spinal cord, the serotonin system is involved in the control of behavioral, perceptual, and regulatory systems, including mood, hunger, body temperature, sexual behavior, muscle control, and sensory perception. Researchers are not certain that brain chemistry permanently changes from hallucinogen use, but some people who use them appear to develop chronic mental disorders. PCP and MDMA are both addicting, whereas LSD, psilocybin, and mescaline are not.

LSD

LSD (an abbreviation of the German words for "lysergic acid diethylamide") is the drug most commonly identified with the term "hallucinogen" and the most widely used in this class of drugs. LSD, also familiar as "acid," is a clear or white, odorless, water-soluble material synthesized from lysergic acid, a compound derived from a rye fungus. LSD is the most potent mood- and perception-altering drug known: oral doses as small as 30 micrograms can produce effects that last 6 to 12 hours.

LSD is initially produced in crystalline form. The pure crystal can then be crushed to powder and mixed with binding agents to produce tablets known as "microdots" or thin squares of gelatin called "window panes"; more commonly, it is dissolved, diluted, and applied to paper or other materials. The most common form of LSD is called "blotter acid" - sheets of paper soaked in LSD and perforated into 1/4-inch square individual dosage units. Variations in manufacturing and the presence of contaminants can produce LSD in colors ranging from clear or white, in its purest form, to tan or even black. Even uncontaminated LSD begins to degrade and discolor soon after it is manufactured, and drug distributors often apply LSD to colored paper, making it difficult for a buyer to determine the drug's purity or age.

LSD's effects typically begin within 30 to 90 minutes after ingestion and may last as long as 12 hours. Users refer to LSD and other hallucinogenic experiences as "trips" and to the acute adverse experiences as "bad trips;" the drug's effects are unpredictable and may vary with the amount ingested and the user's personality, mood, expectations, and surroundings. Users of LSD may experience some physiological effects, such as increased blood pressure and heart rate, dizziness, loss of appetite, dry mouth, sweating, nausea, numbness, and tremors; but the drug's major effects are emotional and sensory. The user's emotions may shift rapidly through a range from fear to euphoria, with transitions so rapid that the user may seem to experience several emotions simultaneously.

LSD also has dramatic effects on the senses. Colors, smells, sounds, and other sensations seem highly intensified. In some cases, sensory perceptions may blend in a phenomenon known as synesthesia, in which a person seems to hear or feel colors and see sounds. Hallucinations distort or transform shapes and movements, and they may give rise to a perception that time is moving very slowly or that the user's body is changing shape. On some "trips", users experience sensations that are enjoyable and mentally stimulating and that produce a sense of heightened understanding. Bad trips, however, include terrifying thoughts and nightmarish feelings of anxiety and despair that include fears of insanity, death, or losing control.

Street Names for Hallucinogens and Dissociative Drugs

LSD

acid

blotter

dots

microdot

pane

paper acid

sugar

sugar cubes

trip

window glass

window pane

Zen

Ketamine

bump

cat Valium

green

honey oil

jet

K

purple

Special K

special la coke

super acid

super C

vitamin K

PCP

angel

angel dust

boat

dummy dust

love boat

peace

supergrass

zombie

Datura

nightshade

angeltrumpet

CIA drug

jimsonweed

LSD users quickly develop a high degree of tolerance for the drug's effects: after repeated use, they need increasingly larger doses to produce similar effects. LSD use also produces tolerance for other hallucinogenic drugs such as psilocybin and mescaline, but not for drugs such as marijuana, amphetamines, and PCP, which do not act directly on the same serotonin receptors affected by LSD. Tolerance for LSD is lost if the user stops taking the drug for several days, and there is no evidence that LSD produces physical withdrawal symptoms when chronic use is stopped.

Long-term effects of LSD use can include persistent psychosis and hallucinogen persisting perception disorder (HPPD), more commonly referred to as "flashbacks." The causes of these -effects, which in some users occur after a single experience with the drug, are not known. The acute effects of LSD can be described as drug-induced psychosis: a distortion or disorganization of a person's capacity to recognize reality, think rationally, or communicate with others. Some LSD users experience devastating psychological effects that persist after the trip has ended, however, producing a long-lasting psychotic-like state. LSD-induced persistent psychosis may include dramatic mood swings from mania to profound depression, vivid visual disturbances, and hallucinations. These effects may last for years and can affect people who have no history or other symptoms of psychological disorder.

Other former LSD users report experiences known colloquially as "flashbacks" and called "HPPD" by physicians. These episodes are spontaneous, repeated, sometimes continuous recurrences of some of the sensory distortions originally produced by LSD. The experience may include hallucinations, but it most commonly consists of visual disturbances such as seeing false motion on the edges of the field of vision, bright or colored flashes, and halos or trails attached to moving objects. This condition is typically persistent and in some cases remains unchanged for years after individuals have stopped using the drug. Because HPPD symptoms may be mistaken for those of other neurological disorders such as stroke or brain tumors, sufferers may consult a variety of clinicians before the disorder is accurately diagnosed. There is no established treatment for HPPD, although some antidepressant drugs may reduce the symptoms. Psychotherapy may help patients adjust to the confusion associated with visual distraction and to minimize the fear, expressed by some, that they are suffering from ongoing brain damage or psychiatric disorder.

The precise mechanism by which LSD alters perceptions is still unclear. Evidence from laboratory studies suggests that LSD, like the hallucinogenic plants, binds to and activates certain groups of serotonin receptors designated the 5-HT₂ receptors. Normally, serotonin binds to and activates its receptors and then is taken back up into the neuron that released it. In contrast, LSD binds very tightly to the serotonin receptor, causing a greater than normal activation of the receptor. LSD's effects are most prominent in two brain regions: the cerebral cortex, an area involved in mood, cognition, and perception; and the locus ceruleus, which receives sensory signals from all areas of the body and has been described as the brain's "novelty detector" for important external stimuli.

PCP and Other Dissociative Drugs

PCP (phencyclidine), developed in the 1950s as an intravenous surgical anesthetic, is classified as a dissociative drug rather than a true hallucinogen: its sedative and anesthetic effects are trance-like, and patients experience a feeling of being "out of body" and detached from their environment. At low to moderate doses, PCP causes altered perception of body image, but rarely produces visual hallucinations. PCP can also create effects that mimic the primary symptoms of schizophrenia, such as delusions and mental turmoil.

PCP was used in veterinary medicine but was never approved for human use because of problems that arose during clinical studies, including delirium and extreme agitation experienced by patients emerging from anesthesia. Over the years PCP has developed a reputation as a dynamite drug, for its ability to transform an otherwise docile person into a raging maniac, explosive and extremely dangerous. In a study of 1000 episodes of PCP intoxication, unpredictable outbursts leading to shootings, stabbings, grotesque murders, and self-inflicted injuries occurred in 35% of the cases. Another 32% of the users displayed bizarre behaviors, including wandering about nude in public, lying down in the middle of a busy street, or driving 10 mph on the freeway.

During the 1960s, PCP in pill form became widely abused, but the surge in illicit use receded rapidly as users became dissatisfied with the long delay between taking the drug and feeling its effects, and with the unpredictable and often violent behavior associated with its use. Powdered PCP - known as "ozone," "rocket fuel," "love boat," "hog," "embalming fluid," or "superweed" - appeared in the 1970s. In powdered form, the drug is sprinkled on marijuana, tobacco, or parsley, then smoked, and the onset of effects is rapid. Users sometimes ingest PCP by snorting the powder. Normally a white crystalline powder, PCP is sometimes colored with water-soluble or alcohol-soluble dyes.

When snorted or smoked, PCP rapidly passes to the brain to disrupt the functioning of sites known as NMDA (N-methyl-D-aspartate) receptor complexes, which are receptors for the neurotransmitter glutamate. Glutamate receptors play a major role in the perception of pain; in cognition, including learning and memory; and in emotion. In the brain, PCP also alters the actions of dopamine, a neurotransmitter responsible for the euphoria and "rush" associated with many abused drugs. PCP's effects are unpredictable. Typically, they are felt within minutes of ingestion and last for several hours, but some users report feeling the drug's effects for days. One drug-taking episode may produce feelings of detachment from reality, including distortions of space, time, and body image; another may produce hallucinations, panic, and fear. Some users report feelings of invulnerability and exaggerated strength. PCP users may become severely disoriented, violent, or suicidal.

At low PCP doses (5 mg or less), physical effects include shallow, rapid breathing, increased blood pressure and heart rate, and elevated temperature. Doses of 10 mg or more can cause dangerous changes in blood pressure, heart rate, and respiration, often accompanied by nausea, blurred vision, dizziness, and decreased awareness of pain. Muscle contractions may cause uncoordinated movements and bizarre postures. When severe, the muscle contractions can result in bone fracture or in kidney damage or failure as a consequence of muscle cells breaking down. Very high doses of PCP can cause convulsions, coma, hyperthermia, and death. Repeated use of PCP can result in addiction, and recent research suggests that repeated or prolonged use of PCP can cause withdrawal syndrome when drug use is stopped. Symptoms such as memory loss, speech problems, and depression may persist for as long as a year after a chronic user stops taking PCP.

Ketamine ("K," "Special K," "cat Valium") is another dissociative anesthetic. It was developed in 1963 to replace PCP and is currently manufactured as an injectable liquid to be used in human anesthesia and veterinary medicine. Much of the ketamine sold on the street has been diverted from veterinarians' offices. In illicit use ketamine is generally evaporated to form a powder that is snorted, smoked with marijuana or tobacco products, or compressed into pills. In some cities (Boston, New Orleans, and Minneapolis/St. Paul, for example), ketamine is reportedly being injected intramuscularly.

Ketamine's chemical structure and mechanism of action are similar to those of PCP, and its effects are similar, but ketamine is much less potent than PCP with effects of much shorter duration. Users report sensations ranging from a pleasant feeling of floating to being separated from their bodies. Some ketamine experiences involve a terrifying feeling of almost complete sensory detachment that is likened to a near-death experience. These experiences, similar to a "bad trip" on LSD, are called the "K-hole." Low-dose intoxication from ketamine results in impaired attention, learning ability, and memory. At higher doses, ketamine can cause delirium, amnesia, impaired motor function, high blood pressure, depression, and potentially fatal respiratory problems.

Ketamine is odorless and tasteless, so it can be added to beverages without being detected, and it induces amnesia. Because of these properties, the drug is sometimes given to unsuspecting victims and used in the commission of sexual assaults referred to as "drug rape."

Dextromethorphan (sometimes called "DXM" or "robo") is a cough-suppressing ingredient in a variety of over-the-counter cold and cough medications. Like PCP and ketamine, dextromethorphan acts as an NMDA receptor antagonist. The most common source of abused dextromethorphan is "extra-strength" cough syrup, which typically contains 3 milligrams of the drug per milliliter of syrup. At the doses recommended for treating coughs (1/6 to 1/3 ounce of medication, containing 15 mg to 30 mg dextro-methorphan), the drug is safe and effective. At much higher doses (4 or more ounces), dextromethorphan produces dissociative effects similar to those of PCP and ketamine. The effects vary with dose, and dextromethorphan users describe a set of distinct dose-dependent "plateaus" ranging from a mild stimulant effect with distorted visual perceptions at low (approximately 2-ounce) doses to a sense of complete dissociation from one's body at doses of 10 ounces or more. The effects typically last for 6 hours. Over-the-counter medications that contain dextromethorphan often contain antihistamine and decongestant ingredients as well, and high doses of these mixtures can seriously increase risks associated with dextromethorphan abuse.

Club Drugs

"Club drugs" is a collective term for some very dangerous substances that are increasingly popular among young adults who attend all-night dance parties called raves or trances, dance clubs, and bars. Included in the term are a wide variety of drugs with a wide variety of sources, pharmacological agents, and potential contaminants, making it difficult to predict toxicity, symptoms, and consequences of use. In this category along with methamphetamine and the hallucinogens LSD and ketamine, are MDMA, the CNS depressant GHB, and the benzodiazepine Rohypnol.

MDMA (Ecstasy) is a synthetic, psychoactive drug with both stimulant and hallucinogenic properties. Other street names for MDMA include Adam, XTC, hug, beans, and love drug. MDMA was first synthesized and patented in 1914 by Merck, a German drug company, for use as an appetite suppressant but was never marketed. In the 1970s, the drug was given to psychotherapy patients because it helped them open up and talk about their feelings. This practice was stopped in 1986 when animal studies showed that Ecstasy could cause brain damage. Ecstasy gained national attention during the 1980s when it was touted as the new LSD, and now is widely considered the drug of choice at club parties. In a survey taken in 2003, 4.5% of 12th graders, 3% of 10th graders and 2.1% of 8th graders reported that they had used MDMA at least once within the year.

MDMA is usually taken orally in tablet or capsule form. Its effects last approximately 3 to 6 hours, though confusion, depression, sleep problems, anxiety, and paranoia have been reported to occur weeks after the drug is taken. MDMA can produce a significant increase in heart rate and blood pressure and a sense of alertness like that associated with amphetamine use. The stimulant effects of MDMA, which enable users to dance for extended periods, may also lead to dehydration, hypertension, and heart or kidney failure.

Users report that Ecstasy lowers their inhibitions and relaxes them. MDMA is also said to increase awareness and feelings of pleasure and to give people energy. Unlike the drug LSD, low doses of MDMA do not cause people to hallucinate. However, some people report side effects after taking MDMA such as headaches, chills, eye twitching, jaw clenching, blurred vision and nausea. MDMA can cause confusion, hallucinations, depression, sleep problems, drug craving, severe anxiety, and paranoia. In addition, in high doses it can cause a sharp increase in body temperature (malignant hyperthermia) leading to muscle breakdown and kidney and cardiovascular system failure.___

Recent data suggest that MDMA may be toxic to the brain. Its chemical structure (3-4 methylenedioxymetham-phetamine, "MDMA") is similar to methamphetamine, methyl-enedioxymetham-phetamine (MDA), and mescaline. Like the hallucinogens, MDMA causes serotonin to be released from neurons in greater amounts than normal. Once released, this serotonin can excessively activate serotonin receptors. Scientists have shown that MDMA causes excess dopamine to be released from dopamine-containing neurons as well. Particularly alarming is research in animals that has demonstrated that MDMA can damage and destroy serotonin containing neurons. A recent study of the brain scans of people who had used Ecstasy an average of 200 times over five years found visible brain damage, although the behavior of these people appeared normal; in fact, those who used the drug more often had more brain damage than less frequent users. Positron emission tomography (PET) demonstrated a 20-60% reduction in healthy serotonin cells in the drug users, potentially limiting their abilities to remember and to learn. Given the widespread role of serotonin as a neurotransmitter, additional studies are being conducted to gauge Ecstasy's effect on mood, memory, cognition, and behaviors such as eating and sleeping.

GHB (gamma hydroxybuty-rate) is a central nervous system depressant that can relax or sedate the body. Street names for the drug include Grievous Bodily Harm, G, Liquid Ecstasy, and Georgia Home Boy. It is usually abused either for its intoxicating/sedative/ euphoriant properties or for its growth hormone-releasing effects, which can build muscles. GHB can be produced in clear liquid, white powder, tablet, and capsule forms, and it is often used in combination with alcohol, making it even more dangerous. GHB is often manufactured in homes with recipes and ingredients found and purchased on the Internet; these ingredients are found in a number of dietary supplements available in health food stores and gymnasiums to induce sleep, build muscles, and enhance sexual performance.

The drug is used predominantly by adolescents and young adults, often when they attend nightclubs and raves. GHB's intoxicating effects begin 10 to 20 minutes after the drug is taken, and typically last up to 4 hours, depending on the dosage. At lower doses, GHB can relieve anxiety and produce relaxation; however, as the dose increases, the sedative effects may result in sleep and eventual coma or death. Overdose of GHB can occur rather quickly, and the signs are similar to those of other sedatives: drowsiness, nausea, -vomiting, headache, loss_ of conscious-ness, loss of reflexes, and impaired breathing. GHB is cleared from the body relatively quickly, so it is sometimes difficult to detect in emergency rooms and other treatment facilities. GHB has been increasingly involved in poisonings, overdoses, "date rapes," and fatalities.

Rohypnol (flunitrazepam) belongs to the class of drugs known as benzodiazepines. It is not approved for prescription use in the United States, although it is approved in Europe and is used in more than 60 countries as a treatment for insomnia, as a sedative, and as a pre-surgery anesthetic. Street names for the drug include Roofies, Rophies, Roche, and the Forget-Me Pill. It is usually taken orally, although there are reports that it can be ground up and snorted. Rohypnol is tasteless and odorless, and it dissolves easily in carbonated beverages. The sedative and toxic effects are aggravated by concurrent use of alcohol but, even without alcohol, a dose of Rohypnol as small as 1 mg can impair a victim for 8 to 12 hours.

Adverse effects associated with Rohypnol include decreased blood pressure, drowsiness, -visual disturbances, dizziness, confusion, gastrointestinal disturbances, and urinary retention. The drug can cause profound anterograde amnesia, so that individuals may not remember events they experienced while under the effects of the drug. This may be why one of the street names for Rohypnol is "the forget-me pill," and it reportedly has been used in sexual assaults.

Date Rape Drugs

According to the American Academy of Experts in Traumatic Stress, there continues to be an escalating problem of drug-assisted rape. In one survey, a total of 2003 urine samples submitted by rape treatment centers across the U.S. revealed the following about common drugs used in drug-assisted rape.

Alcohol 69%
Marijuana 18%
Cocaine 5%
GHB 3%
Flunitrazepam <1%

This increase in prevalence and incidence led to the passage of the Drug-induced Rape Prevention and Punishment Act (1996). This law provides for up to 20 years in prison and fines for anyone who intends to commit a violent crime by covertly distributing a controlled substance to an unknowing individual.

Other substances historically associated with drug-assisted rape include amphetamines, barbiturates, opiates, and chloral hydrate and alcohol--a "Mickey Finn."

Current substances now commonly used as "knockout" drugs that may render a woman incapable of resisting an attack are GHB, Rohypnol, Ketamine, and Burundanga/datura.

Datura is an anticholinergic and hallucinogenic substance made of refined scopolamine. It is used for motion sickness and an adjunct to anesthesia, producing sedation and amnesia. Onset is within 15-30 minutes, with effects lasting up to 2-3 days. Once ingested or inhaled one experiences submissive behavior, hypnosis, hallucinations and confusion. Serious side effects include an anticholinergic syndrome leading to coma, seizures and death. Treatment of over dose includes airway management and administration of physostigmine forsevere anticholinergic effects.

Inhalants

Inhalants are volatile substances that produce chemical vapors that can be inhaled to induce a psychoactive, or mind-altering, effect. Although other abused substances can be inhaled, the term "inhalants" is used to describe a variety of substances whose main common characteristic is that they are rarely, if ever, taken by any route other than inhalation. This definition encompasses a broad range of chemicals found in hundreds of different products that may have different pharmacological effects. (Figure 8) As a result, precise categorization of inhalants is difficult. One classification system lists four general categories of inhalants, volatile solvents, aerosol, gases, and nitrites,_ based on the form in which they are often found in household, industrial, and medical products.

Volatile solvents are liquids that vaporize at room temperatures. They are found in a multitude of inexpensive, easily available products used for common household and industrial purposes. These include paint thinners and removers, dry--cleaning fluids, degreasers, -gasoline, glues, correction fluids, and felt-tip marker fluids.

Aerosols are sprays that contain propellants and solvents. They include spray paints, deodorants and hair sprays, vegetable oil sprays for cooking, and fabric protector sprays.

Gases include medical anesthetics as well as gases used in household or commercial products. Medical anesthetic gases include ether, chloroform, halothane, and nitrous oxide, commonly called "laughing gas." Nitrous oxide is the most abused of these gases and can be found in whipped cream dispensers and products that boost octane levels in racing cars. Household or commercial products containing gases also include butane lighters, propane tanks, and refrigerants.

Nitrites often are considered a special class of inhalants. Unlike most other inhalants, which act directly on the central nervous system, nitrites act primarily to dilate blood vessels and relax the muscles. And while other inhalants are used to alter mood, nitrites are used primarily as sexual enhancers. Nitrites include cyclohexyl nitrite, isoamyl (amyl) nitrite, and isobutyl (butyl) -nitrite. Cyclohexyl nitrite is found in room deodorizers. Amyl -nitrite is used in certain diagnostic procedures and is prescribed to some patients for heart pain. Illegally diverted ampules of amyl nitrite are called "poppers" or "snappers" on the street. Butyl nitrite is an illegal substance that is often packaged and sold in small bottles also referred to as "poppers."

Inhalants, particularly volatile solvents, gases, and aerosols, are often among the first drugs that young children use. One national survey indicates that about 6 percent of U.S. children have tried inhalants by the time they reach fourth grade. Inhalants also are one of the few substances abused more by younger children than by older ones. Nevertheless, inhalant abuse can become chronic and extend into adulthood.

Generally, inhalant abusers will abuse any available substance. However, effects produced by individual inhalants vary, and some individuals will go out of their way to obtain their favorite inhalant. For example, in certain parts of the country, "Texas shoe-shine," a shoe-shining spray containing the chemical toluene, is a local favorite. Silver and gold spray paints, which contain more toluene than other spray colors, also are popular inhalants.

Data from national and state surveys suggests inhalant abuse reaches its peak at some point during the seventh through ninth grades. Gender differences in inhalant abuse have been identified at different points in childhood. One study indicates inhalant abuse is higher for boys than girls in grades 4 through 6, occurs at similar rates in grades 7 through 9, when overall use is highest, and becomes more prevalent again among boys in grades 10 through 12. People who abuse inhalants are found in both urban and rural settings. Research on factors contributing to inhalant abuse suggests that adverse socioeconomic conditions, rather than racial or cultural factors per se, may account for most reported racial and ethnic differences in rates of inhalant abuse. Poverty, a history of childhood abuse, poor grades, and dropping out of school all are associated with inhalant abuse.

Inhalants can be breathed in through the nose or the mouth in a variety of ways, such as:

"Sniffing" or "snorting" fumes from containers;
Spraying aerosols directly into the nose or mouth;
"Bagging" or sniffing or inhaling fumes from substances sprayed or deposited inside a plastic or paper bag;
"Huffing" from an inhalant-soaked rag stuffed in the mouth; and
Inhaling from balloons filled with nitrous oxide.

Inhaled chemicals are rapidly absorbed through the lungs into the bloodstream and quickly distributed to the brain and other organs. Within minutes of inhalation, the user experiences intoxication along with other effects similar to those produced by alcohol. Alcohol-like effects may include slurred speech, an inability to coordinate movements, euphoria, and dizziness. In addition, users may experience light-headedness, hallucinations, and delusions, such as thinking they can fly. Because intoxication lasts only a few minutes, abusers frequently seek to prolong the high by continuing to inhale repeatedly over the course of several hours, a very dangerous practice. With successive inhalations, abusers can suffer loss of consciousness and death. At the least, they will feel less inhibited and less in control. After heavy use of inhalants, abusers may feel drowsy for several hours and experience a lingering headache.

Many brain systems may be involved in the anesthetic, -intoxicating, and reinforcing -effects of different inhalants. Nearly all abused inhalants (other than nitrites) produce a pleasurable effect by depressing the CNS. Evidence from animal studies -suggests that a number of commonly abused volatile solvents and anesthetic gases have neuro-behavioral effects and mechanisms of action similar to those produced by CNS depressants, which include alcohol and medications such as sedatives and anesthetics. A recent study indicates that toluene, a solvent found in many commonly abused inhalants including airplane glue, paint sprays, and paint and nail polish removers, activates the brain's dopamine system. The dopamine system has been shown to play a role in the rewarding effects of many drugs of abuse. Nitrites, in contrast, dilate and relax blood vessels rather than acting as anesthetic agents.

The chemicals found in solvents, aerosol sprays, and gases can produce a variety of additional effects during or shortly after use. These effects are related to inhalant intoxication and may include belligerence, apathy, impaired judgment, and impaired functioning in work or social situations. Dizziness, drowsiness, slurred speech, lethargy, depressed reflexes, general muscle weakness, and stupor are other possible effects. For example, research shows that toluene can produce headache, euphoria, giddy feelings, and inability to coordinate movements. Exposure to high doses can cause confusion and delirium. Nausea and vomiting are other common side effects.

Inhaled nitrites dilate blood vessels, increase heart rate, and produce a sensation of heat and excitement that can last for several minutes. Other effects can include flush, dizziness, and headache.

A strong need to continue using inhalants has been reported among many individuals, particularly those who abuse inhalants for prolonged periods over many days. Compulsive use and a mild withdrawal syndrome can occur with long-term inhalant abuse. Additional symptoms exhibited by long-term inhalant abusers include weight loss, muscle weakness, disorientation, inattentiveness, lack of coordination, irritability, and depression.

Inhalant abusers risk an array of devastating medical consequences. Prolonged sniffing of the highly concentrated chemicals in solvents or aerosol sprays can induce irregular and rapid heart rhythms and lead to heart failure and death within minutes of a session of prolonged sniffing. This syndrome, known as "sudden sniffing death," can result from a single session of inhalant use by an otherwise healthy young person. Sudden sniffing death is particularly associated with the abuse of butane, propane, and chemicals in aerosols. Inhalant abuse also can cause death by:

Asphyxiation from repeated inhalations, which lead to high concentrations of inhaled fumes displacing the available oxygen in the lungs;
Suffocation from blocking air from entering the lungs when inhaling fumes from a plastic bag placed over the head;
Choking from inhalation of vomit after inhalant use; or
Fatal injury from accidents, including motor vehicle fatalities, suffered while intoxicated.

Both animal research and human pathological studies indicate that chronic abuse of volatile solvents such as toluene damages the protective sheath around certain nerve fibers in the brain and peripheral nervous system. This extensive destruction of nerve fibers is clinically similar to that seen with neurological diseases such as multiple sclerosis. The neurotoxic effects of prolonged inhalant abuse include damage to parts of the brain involved in controlling cognition, movement, vision, and hea