Adolescent Health Care: A Practical Guide

Chapter 71

Psychoactive Substances of Abuse Used by Adolescents

Sharon Levy

Alan D. Woolf

Misuse of drugs, chemicals, plants and herbs, mushrooms, and other agents continues to be a major cause of mortality and morbidity in adolescents and young adults. According to the 2005 Youth Risk Behavior Survey, nationwide 25.4% of high school students were offered, sold, or given an illegal drug on school property (CDC, 2006). Although overall the proportion of teens who report use of illicit drugs during 2006 has dropped from a peak in the 1990, still almost 50% of high school 12th graders admit to experimenting with an illicit drug, such as cocaine, marijuana, amphetamines, hallucinogens, narcotics, and tranquilizers (Johnston et al., 2007). Furthermore, according to the same survey, the use of prescription medications (including opioid narcotics, benzodiazepines, and stimulants) has risen since the mid to late 1990s, and teenagers report that it is easy to obtain a prescription from a physician (Friedman, 2006). Many teens describe their use of these drugs as for practical effect rather than intoxication, and believe this type of use is “safe” (Friedman, 2006). However, as with all substances of abuse, adolescents are vulnerable to the direct toxic effects of these drugs and chemicals, and also risk long-term addictions, with consequential collateral injury from the effects of their substance abuse on family and social relationships and its detrimental effects on work or school performance. The comorbidities of substance abuse can include lowered self-esteem, lack of motivation, depression, suicidal ideation, and delinquency. Physical trauma can result from motor vehicle accidents and other risk-taking behaviors and poor judgment. Sexual disinhibition and memory loss can result in rape, unplanned pregnancy, and/or sexually transmitted diseases. Some substance-abusing youth will face arrest for infractions of the law, including such offenses as theft, assault, prostitution, or drug possession and/or distribution. The loss of a productive life can follow from the long-term adverse effects of drugs on learning, behavior, personality, vocational choices, and psychosocial adjustment.

In this chapter, we review the clinical toxicology and management of the effects of psychoactive substances of abuse other than alcohol and tobacco. Younger adolescents may experiment first with easily obtained “gateway” drugs such as alcohol, tobacco, marijuana, and over-the-counter cold remedies and inhalants. The complex interplay of genetic, psychological, and family and social factors may underlie whether they later exhibit addictive behaviors and move on to include illicit agents such as the opiates or cocaine. Newer categories of substance abuse include over-the-counter cough and cold and weight loss preparations, herbal remedies and “natural” dietary supplements, and anabolic steroids. The advent of the Internet has provided young people with access to a lot of inaccurate information from the plethora of Web sites portraying substance abuse as a safe and acceptable lifestyle (Boyer et al., 2000). The assessment of such patients by health care providers is complicated by sometimes inaccurate or deliberately misleading histories of substance use, such that the actual substances implicated are unknown. Adolescents may use several drugs and chemicals concurrently, so that the consequent toxic effects may not be those classically associated with one class of substances.



Marijuana is the most widely abused illicit drug in the United States, with >90.8 million adults (42.9%) aged 18 or older admitting marijuana use at least once in their lifetime (SAMHSA, 2005). Among marijuana users, 2.1% reported initiation of its use before age 12 years, 52.7% between ages 12 and 17, and 45.2% at age 18 or older (SAMHSA, 2005). Data from the Monitoring the Future survey suggests that lifetime marijuana use among 12th grade high school students has declined recently from a peak of 49.7% in 1999 to the current prevalence of 42.3% in 2006 (Johnstone et al., 2007). Corresponding figures for lifetime marijuana use in 2006 among 8th graders was 15.7%, and 31.8% for 10th graders. Rates for annual marijuana use in 2006 were 11.7% for 8th graders, 25.2% for 10th graders, and 31.5% for high school seniors (Johnston et al., 2007).

The 2005 Youth Risk Behavior Survey results suggest that the lifetime prevalence of marijuana use among high school students is higher among males (40.9%) than females (35.9%) (CDC, 2006). Lifetime marijuana use was also higher among Hispanic (42.6%) and black (42.6%) students than whites (38%). During the 30 days before the survey, 20.2% of high school students reported that they had used marijuana. Almost one tenth (8.7%) of students nationwide had tried marijuana for the first time before 13 years of age, and 4.5% of students had used marijuana on school property one or more times in the previous 30 days (CDC, 2006).


TABLE 71.1
Common Preparations of Cannabis

Cannabis Preparations

Description of Preparations


Chopped up leaves and stems rolled into cigarettes and smoked


Cigar sized marijuana cigarette


Similar to tobacco pipes, marijuana leaves are placed in the bowl and smoked through a stem

Bong (water pipe)

The bowl of the water pipe is placed below a chamber filled with water, and the marijuana smoke passes through the water, cooling it and removing nonpsychoactive substances, before it is inhaled


This preparation is the strongest form of marijuana; it is composed of a pure resin derived from the leaves and flowers of the female plant and is usually pressed into a “brick” and smoked


Marijuana is sometimes baked into cookies or brownies and ingested orally

Because marijuana is so readily available and perhaps not as stigmatized as other substances, it often serves as the introduction of an adolescent to illicit drug use. Marijuana has negative effects on both physical and psychological health and is associated with the development of tolerance, dependence, and a withdrawal syndrome. Regular marijuana use can have adverse effects on learning, with possible psychological and cognitive impairment, and it also affects job performance, driving skills and judgment, social and family relations, and other activities of everyday life. Marijuana use can predict an individual's tendency toward the use and abuse of other substances. One prospective study of 250 addicted individuals, discharged from a detoxification facility, found that continued marijuana use predicted their risk of relapse for cocaine, alcohol, and heroin use (Aharonovich et al., 2005).

Medical Use

There is still significant debate over the medicinal value of marijuana. The active ingredient, delta-9-tetrahydrocannabinol 9-tetrahydrocannabinol (THC), has been synthesized and is available in capsule form known as dronabinol (Marinol). Dronabinol has been considered as a second-line agent for use in the treatment of anorexia associated with weight loss in patients with the acquired immunodeficiency syndrome (AIDS) or for nausea and vomiting associated with chemotherapy. It has also been proposed for the treatment of other conditions such as glaucoma and epilepsy and to help decrease tremors, ataxia, and spasticity in patients with multiple sclerosis.

Preparation and Dose

Marijuana is derived from the resinous oil of the flowering tops and leaves of the plant, Cannabis sativa. Although the oil contains >60 cannabinoids the major psychoactive ingredient appears to be THC. The content of THC is highest in the flowering tops and declines in leaves, stems, and seeds. Marijuana joints obtained mainly from the flowering tops and leaves usually have a THC content of 0.5% to 5%, and hashish, which consists of dried cannabis resin and compressed flowers, contains 2% to 20%. Hashish oil may contain 15% to 30% THC.

In the 1960s, the average potency of marijuana was 0.1% to 0.5% THC. Recent analysis shows that today most marijuana averages 4% to 5% THC. Samples of sinsemilla, a marijuana species cultivated to obtain high THC levels, average 7% to 9% but have tested as high as 14%. This increase in potency may be a factor in an increase in reports of side effects.

Routes of Administration and Street Names

Marijuana is usually smoked but may be eaten, brewed in tea, or ingested in pill form. Table 71.1 describes the most common forms and vernacular used by adolescents. Street names include weed, pot, Mary Jane, Acapulco gold, bud, grass, and dope.

Physiology and Metabolism

Two endogenous cannabinoid receptors have been found, CB1 (found mainly in the brain) and CB2 (found only in peripheral tissues, especially in the immune system). Endogenous cannabinoids, anandamide and 2AG, are part of the cannabinoid neurotransmission system in the brain. It appears that cannabinoids may have a natural role in pain modulation, control of movement, cognition, and memory. Marijuana stimulates the dopamine pathway from the ventral tegmental area to the nucleus accumbens. This is believed to be the reward center of the brain. Receptors are most prevalent in the cerebral cortex, hippocampus, basal ganglia, and cerebellum. The location of these receptors helps explain the cognition, motor coordination, memory, and mood changes produced by marijuana.

THC is metabolized primarily in the liver through the cytochrome P-450 system. Peak plasma levels of THC are reached within approximately 10 minutes of smoking marijuana; effects last 2 to 3 hours. Smoked marijuana has 5 to 10 times the bioavailability of the ingested drug. THC is lipid soluble and accumulates in fat stores. Changes in activity or diet that mobilize fat may cause sudden increases in levels of cannabinoids detected in urine. Because marijuana has a long half-life and persists in body tissues, the effects on nerve function may persist after the immediate effects have disappeared.

Cannabinoid metabolites are carried by the enterohepatic circulation to the intestinal lumen and excreted in the feces (65%) or are carried through the renal circulation and excreted in the urine (35%). Carboxy and hydroxy cannabinoids are the major metabolites detected in urine drug screening tests. The cannabinoid metabolites may be


detected for 3 to 10 days in the occasional user and for 1 to 2 months in chronic users (see Table 71.2).

TABLE 71.2
Cannabinoid Physiology




Metabolism and Excretion

(Pertwee, 1997).

·   CB1–brain

·   CB2–peripheral tissue

Stimulates the dopamine pathway from the ventral tegmental area to the nucleus accumbens

Lipid soluble; accumulates in fat stores

Cytochrome P-450 system

·   65% excreted in feces

·   35% in urine

Drug Interactions

Marijuana may enhance sedation when used with alcohol, diazepam, antihistamines, phenothiazines, barbiturates, or narcotics, and it may enhance stimulation when used with cocaine or amphetamines. Marijuana is antagonistic to the effects of phenytoin, propranolol, and insulin.

Effects of Intoxication

  1. Low to moderate doses of marijuana: Produce euphoria, time distortion, increased talking, and auditory and visual enhancements or distortions which users find to be pleasant.
  2. Acute intoxication: Produces an increased heart rate, erythema of the conjunctivae, dry mouth and throat, dilated pupils, and impaired learning and cognitive functions. As acute effects wear off, marijuana users often have increased appetite and feel sleepy.
  3. High doses: High doses of marijuana may produce mood fluctuations, depersonalization, and hallucinations.
  4. Toxic reactions: Includes anxiety, panic, organic brain syndrome, psychoses, delusions, hallucinations, and paranoia. Marijuana may produce seizures in epileptic individuals or psychotic episodes in schizophrenic individuals. Marijuana use has also been associated with the precipitation of psychotic episodes in patients not previously diagnosed with schizophrenia. In some cases, these episodes do not resolve with discontinuation of marijuana use.

Adverse Effects

  1. Central nervous system: Acute effectsinclude the psychological effects described above, many of which are pleasurable, although some may be disturbing and/or disabling.
  2. Psychomotor and reaction times: Marijuana causes a decrease in both psychomotor functions and reaction times, thereby presenting a dangerous risk for the adolescent who drives after getting high (Wilson et al., 1994). Impairments of selective attention, on-task behaviors, and ability to focus and concentrate are notable and possibly related both to frequency and duration of cannabis use (Soliwij et al., 1991; Solowij et al., 1995). Specific functions related to driving skills that are impaired include tracking (the ability to follow a moving object and to control the position of a car in relation to the highway), signal detection (the ability to quickly notice and respond to lights or other unpredictable stimuli), glare recovery time (the ability to see clearly after exposure to bright lights such as headlights). The impairment of these driving skills, in conjunction with marijuana-induced decreased judgment, impaired time and distance estimation, and impaired motor performance, make driving under the influence of marijuana dangerous (DuPont, 1985). There is good evidence that marijuana causes lingering effects on memory and coordination. Striking changes in the ability of pilots to operate a landing simulator persisted 24 hours after exposure to cannabis, during which time the pilots reported no awareness of marijuana after effects (Leirer et al., 1991).
  3. Behavioral problems and neurocognition: Because heavy drug users may already have underlying behavioral problems and may already be depressed, alienated, or bored, it is difficult to distinguish whether marijuana is the cause or the behaviors are preexistent. However, studies have suggested that regular heavy use of marijuana may lead to long-term adverse neurocognitive effects. Pope et al. (1996) studied the neuropsychological residual effects of heavy cannabis use among 65 college students versus 64 control students reporting only “light” use. The results suggested a “drug residue” effect on attention and other executive functions, psychomotor tasks, and short-term memory in heavy users. Pope et al. (1995) also reported that marijuana use may lead to permanent impairment of cognitive function and behavior. Chronic buildup of cannabinoids may affect executive functions such as focus, attention, and ability to filter out irrelevant information or compromise and may impair memory, learning ability, and perception.
  4. Chronic heavy marijuana use may lead to a state of passive withdrawal from usual work and recreational activities known as the amotivational syndrome. Schwartz (1987)identified seven components that define this syndrome:
  • Loss of interest, general apathy, and passivity
  • Loss of desire to work consistently and loss of productivity, accompanied by a lack of concern about the poor work performance
  • Loss of energy, and tiredness
  • Moodiness, sullenness, and inability to handle frustration
  • Impairment in concentration and inability to process new material



  • Slovenly habits and appearance
  • A lifestyle revolving around procurement and use of marijuana and other drugs
  1. Pulmonary and cardiovascular: Marijuanasmoking results in a substantially greater respiratory burden of carbon monoxide and tar than does cigarette smoking (Wu et al., 1988).
  2. Effects on pulmonary function: Heavy marijuana smokers who do not smoke tobacco have functional impairment of airway conductance (Tashkin et al., 1993), and, just as with tobacco, chronic marijuana smoking leads to bronchoconstriction, cellular inflammation and damage, and bronchitis with cough, increased sputum production, and wheezing (Gil et al., 1995; Fligiel et al., 1997). Human studies demonstrate a decrease in forced expiratory volume in 1 second (FEV1), a decrease in maximal midexpiratory flow rate (MMFR), and an increase in airway resistance. Sherman et al. (1991) found that in contrast to tobacco smokers pulmonary alveolar macrophages of marijuana-only smokers do not produce increased amounts of oxidants, as compared with macrophages of nonsmoking subjects.
  3. Cellular damage: Metaplastic cellular changes have been observed in dogs and humans (Tashkin, 1999). A link between chronic exposure to marijuana smoke and lung cancer in humans has been postulated (Ferguson et al., 1989).
  4. Cardiac effects: Marijuana use leads to an increase in sympathetic tone and a decrease in parasympathetic activity, producing tachycardia, increased myocardial oxygen consumption, and increased cardiac output. In patients with underlying cardiac disease, such effects may induce ischemic chest pain and myocardial infarction (MI) (Mittleman et al., 2001). Vagal stimulation coupled with sympathetic discharge may also produce electrophysiological pathology such as atrial tachyarrhythmias or atrial flutter in some individuals (Fisher et al., 2005).
  5. Endocrine and immune function effects: Immune function may be suppressed with heavy doses of THC (Trisler et al., 1994). Chronic administration of high doses of THC in animals lowers testosterone secretion; impairs sperm production, motility, and viability; and alters the menstrual cycle. It is unclear if these effects occur in humans.


  1. Acute overdose and emergency treatment: Marijuana use in large doses can cause delirium, nausea, vomiting, dizziness, and anxiety in some individuals. It can be contaminated with diarrhea-causing infectious agents such as Salmonellaspecies. Marijuana purchased on the street is sometimes mixed with other drugs, which also may cause toxicity. The health care provider should look for symptoms and signs of the toxicities of ethanol, opiates, stimulants, or other substances in addition to marijuana, as the patient may be unaware or choose not to disclose which other chemicals may also be involved in the overdose. Toxicological screening of the blood and urine may be helpful, because THC is distributed into fatty tissues and may subsequently be detectable for days in heavy users.
  2. Withdrawal syndrome: A mild withdrawal syndrome from cannabis has been described. Some regular marijuana users develop restlessness, irritability, mild agitation, insomnia, nausea, cramping, and sleep electroencephalographic disturbances on cessation (Crowley et al., 1998).
  3. Medical management of addiction: Treatment of marijuana use in the adolescent involves differentiation between experimental or occasional use and the abuse of marijuana. After initially experimenting with marijuana, many adolescents do not use it again or use it very infrequently. However, when counseling families physicians should point out the negative effects of marijuana use in teenagers. Deterioration in school performance, family and social problems, accidents, and legal difficulties suggest the need for intervention and treatment. Frequent marijuana use can interfere with the cognitive, emotional, and social development of adolescents. Research has shown that frequent marijuana use in young girls increases their risk of developing anxiety and depression as compared with peers (Patton et al., 2002). Problems associated with marijuana use accrue slowly and can be quite insidious; many teenagers who meet criteria for marijuana abuse or dependence do not identify marijuana use as connected with other problems in their lives. These teens may be quite ambivalent towards changing their marijuana use. Chapter 73 discusses office-based management in more detail.



More than 5.9 million Americans aged 12 or older (2.5%) have used cocaine in the last year, with males predominating 2:1 over females as abusers of the drug (SAMHSA, 2005). However, lifetime use of cocaine among U.S. high school students has declined notably since prevalence rates as high as 17.3% were observed in the epidemic of the mid-1980s (Johnston et al., 2005). By 1999 only 4.7% of 8th graders, 7.7% of 10th graders, and 9.8% of high school seniors reported that they had ever used the drug (Johnston et al., 2005). Since then reports of cocaine use have mostly continued to decline. Comparable rates in 2006 were down to 3.4%, 4.8%, and 8.5% respectively (up from 8.0% in 2005). The number of 12th grade students reporting regular cocaine use on an annual basis has remained relatively stable at 5.7%, with 2.5% admitting cocaine use within the preceding 30 days (Johnston et al., 2007).

Lifetime prevalence of crack cocaine use has also declined since rates as high as 5.4% among high school seniors were recorded in 1987. In 2006, the lifetime prevalence of crack cocaine use was reported to be 2.3% among 8th graders, 2.2% among 10th graders, and 3.5% among 12th graders (Johnston et al., 2007). The reader is cautioned that the Monitoring the Future survey data only reflects reports from high school students, and almost certainly underestimates the prevalence of cocaine use among higher risk groups of adolescents, such as school dropouts, delinquents, and homeless youth.

Data from the 2005 Youth Risk Behavior Survey (CDC, 2006) indicated that 7.6% of students had used some form of cocaine during their lifetime. The prevalence of use was higher among Hispanic (12.2%) and white (7.7%)


than black (2.3%) students. Lifetime cocaine use was much higher among white and Hispanic women (7.7% and 9.4%, respectively) than black women (1.2%). This was also true for white and Hispanic males (7.8% and 14.9%, respectively) who reported higher lifetime cocaine use rates than blacks (3.4%).

Medical Use

Cocaine is used medically to provide local anesthesia in surgical repairs. It provides hemostasis in the operative field by the vasoconstriction of mucous membranes, and is often used topically in otolaryngological, plastic surgical, and emergency medical procedures.

Preparation and Dose

  1. Cocaine: Cocaine (benzoylmethylecgonine, molecular weight 339.81, C17H21NO4) is a stimulant made from an alkaloid contained in the leaves of the coca bush, Erythroxylon coca,first used by the Inca people 3,000 years ago. The cocaine commonly available is actually the hydrochloride salt, which is 89% cocaine by weight. Most cocaine is “cut” by adding an inexpensive substance with similar appearance (white granular or crystalline powder) such as mannitol, lactose, or cornstarch. The “cocaine” sold on the street is actually part cocaine and part an adulterant, and costs $20 to $200/g. Nasal insufflation is often the preferred route of exposure, although local vasoconstriction may delay the onset of effects and prolong the duration of action. Users form the powder into lines approximately in. wide and 2 in. long, each containing approximately 10 to 35 mg cocaine, and then snort the powder through a rolled piece of paper or dollar bill. The cocaine “high” associated with nasal insufflation lasts approximately 60 to 90 minutes.
  2. Freebase: Freebase (molecular weight 303.86) refers to cocaine without the hydrochloride. The melting point of freebase is much lower than cocaine hydrochloride, so that it can be smoked without destroying its potency. The old method of making freebase involved mixing cocaine with an alkaline solution and adding a solvent such as ether. The solution would separate into two layers, with the top layer containing freebase cocaine dissolved in the solvent. The solvent would then be evaporated, leaving relatively pure cocaine crystals. This method of preparing freebase is dangerous because of the flammability of the solvents.
  3. Crack: Alternatively, “crack” involves converting cocaine hydrochloride to a freebase by an extraction with the use of baking soda, heat, and water. The term crackis thought to derive from either the crackling sound the rocks generate as they burn or the shattered appearance of the freebase cocaine when the precipitated layer is dropped to make many small pieces. Because this method is safe, simple, and inexpensive compared with making freebase cocaine with ether, the use of crack spread rapidly in the United States beginning in the mid-1980s. Dealers prefer to sell crack because of its high addiction potential, low cost, and ease of handling. Each vial sold typically contains one or more small, cream-colored chunks resembling rock salt at about $20 to $125/g; a single “rock” can be purchased for as little as $5. It is usually smoked with marijuana in a joint, in a cigarette or cigar, or in a crack pipe. Crack is also sold in larger pieces called “slabs,” which resemble a stick of chewing gum. The “high” associated with crack smoking lasts approximately 20 minutes.

Routes of Administration and Street Names

Cocaine is most often insufflated, but may be injected intravenously, ingested orally, or the freebase preparations can be smoked. Inhalation, smoking, and ingestion all result in 20% to 40% absorption. Street names include—coke, Bernice, blow, bump, C, candy, Charlie, flake, nose candy, rock, toot, base, snow, crack, and gold dust. Cocaine may also be used in combination with other drugs, as described in Table 71.3.

TABLE 71.3
Street Names & Colloquial Terms Used for Common Combinations of Cocaine with Other Drugs

LSD, lysergic acid diethylamide.

Speedball, birdie powder, dynamite, foo-foo stuff, joy powder, junk, lace, leaf

Heroin and cocaine
The term was synonymous with intravenous use but now can refer to administration of any opiate with cocaine in close temporal proximity by any route


Cocaine and marijuana, smoked

Space base

Cocaine and phencyclidine (PCP), smoked

Caviar or champagne

Rock or crack cocaine and marijuana, smoked

Jim Jones

Marijuana cigarette laced with cocaine and dipped in PCP


Cocaine sprinkled on a bowl of marijuana


 Other names for this combination include banano, blunt, bush, coca puff, hooter, and woolas

Space basing

Rock or crack cocaine with PCP and tobacco


Rock or crack cocaine with PCP and tobacco, smoked


Cocaine combined with LSD

C and M

Cocaine combined with morphine

Snow seals or turkey

Cocaine and amphetamines



Physiology and Metabolism

Cocaine has three different effects on the central nervous system (CNS):

  1. Stimulation of D1and D2 presynaptic dopamine receptors, causing the release of dopamine (primarily), serotonin, and norepinephrine into the synaptic cleft
  2. Blockade of neurotransmitter reuptake, causing synaptic entrapment and leaving an excess of neurotransmitters in the synapse
  3. Increase in the sensitivity of the postsynaptic receptor sites

TABLE 71.4
Cocaine physiology




Metabolism and Excretion

D1 and D2dopamine receptors

·   Release of dopamine, epinephrine, norepinephrine, and serotonin

·   Blockade of neurotransmitter reuptake

·   Increase sensitivity of postsynaptic receptor sites

Plasma and extracellular fluid

·   Hepatic esterases (80%) and plasma cholinesterase to form benzoylecgonine and ecgonine methyl ester

·   Hepatic-N-demethylation to form norcocaine

The dopamine reuptake transporter controls the level of the neurotransmitter in the synapse by carrying dopamine back into nerve terminals. Because cocaine effectively blocks this transporter, dopamine levels remain high in the synapse, affecting adjacent neurons and perpetuating the classic “high” associated with the drug. Because neurotransmitter reuptake is blocked, depletion eventually occurs as entrapped neurotransmitters are broken down by enzymes. This leaves the user feeling dysphoric, with feelings of irritability, restlessness, and depression. This downside can be so intense that it leads to repeated use to overcome the dysphoric feeling. The study of the neurochemical pathways underlying these neuroadaptations is facilitating new approaches to treatment, such as N-methyl-aspartateN-Methyl-D-aspartate (NMDA) receptor antagonists that block both dopaminergic and reinforcing effects.

Cocaine also blocks neuronal reuptake of norepinephrine and stimulates the release of epinephrine, leading to what has been described as an “adrenergic storm” stimulating the neurological, respiratory, and cardiovascular systems. Cocaine is similar to methamphetamine in that both drugs achieve their reinforcing effects through profound stimulation of the mesolimbic/mesocortical dopaminergic neuronal system, which consists of the ventral tegmental area, nucleus accumbens, ventral pallidum, and medial prefrontal cortex. Repeated exposure results in either sensitization or tolerance depending on dose and pattern of use. Intake of either drug causes neuroadaptation, a process that explains many of the disease aspects of addiction. Sensitization is mediated by the D1 and D2 dopamine receptors.

Cocaine is metabolized enzymatically to the inactive metabolite, ecgonine methyl ester, primarily by hepatic esterases and, to a lesser degree, by plasma cholinesterase. Nonenzymatic formation of benzoylecgonine is mediated by hydrolysis. Between 5% and 10% of cocaine is metabolized by cytochrome P-450 mediated N-demethylation into norcocaine, the only active metabolite. Pharmacologically, norcocaine has greater vasoconstrictive and neurological activity than cocaine. Progesterone increases hepatic-N-demethylation, resulting in increased formation of norcocaine. Because of this, women may be more sensitive than men to the cardiotoxic effects of cocaine.

Any medical condition that decreases hepatic perfusion, such as hypotension or low cardiac output, results in increased cocaine levels. Plasma cholinesterase activity is lower in pregnant women, fetuses, infants, and patients with liver disease. Plasma cholinesterase can also be low as a result of genetic or nutritional causes. In these patients, extreme reactions or sudden death can occur after seemingly small doses of cocaine. See Table 71.4 for physiology of cocaine.

Effects of Intoxication

Cocaine has several potent pharmacological actions. It is a stimulant of the central and peripheral nervous systems; it has local anesthetic activity; and it is a vasoconstrictor. The CNS stimulation produces an intense euphoric “rush” (feelings of extreme pleasure, power, strength, and excitement) and “high” (increased alertness, confidence, and a general sense of well-being) upon ingestion when smoked, or injected intravenously. Inhaled cocaine generally produces the high without the rush.

Symptoms of cocaine intoxication include a hyper-alert state, increased talking, restlessness, elevated temperature, anorexia, nausea, vomiting, dry mouth, dilated pupils, sweating, dizziness, hyperreflective reflexes, tachycardia, hypertension, and arrhythmias (see “Adverse Effects” section). People “coming down” from cocaine experience dysphoria, depression, sadness, crying spells, suicidal ideation, apathy, inability to concentrate, delusions, anorexia, insomnia, and paranoia.

Adverse Effects

  1. Psychiatric: Toxic psychosis, hallucinations, delirium, formication, body image changes, agitation, anxiety, and irritability.
  2. Neurological: Seizures, paresthesias, hyperactive reflexes, tremor, pinprick analgesia, facial grimaces, headache, cerebral hemorrhage, cerebral infractions, cerebral vasculitis, and coma.



  1. Skin: Excoriations, rashes, and secondary skin infections.
  2. Cardiovascular
  3. Acute: Vasoconstriction, increased myocardial oxygen demand, tachycardia, angina, arrhythmias, chest pain, aortic dissection, hypertension, stroke, MI, and cardiovascular collapse (Mouhaffel et al., 1995; Hollander et al., 1995; Lange et al., 2001). Dysrhythmias and conduction disturbances associated with cocaine use range from sinus tachycardia or bradycardia to bundle branch block or a Brugada pattern, complete heart block, idioventricular rhythms, Torsades de pointes, ventricular tachycardia or fibrillation, or sudden asystole (Lange et al., 2001).
  4. Subacute: In a study of 102 intravenous drug users, an increased rate of bacterial endocarditis was found in those who also routinely used cocaine (Chambers et al., 1987).
  5. Chronic: Accelerated atherosclerosis and thrombosis, endocarditis, myocarditis, cardiomyopathy, coronary artery aneurysms (Willens et al., 1994; Kloner et al., 2003).
  6. Gastrointestinal: Acute ischemia, gastropyloric ulcers, perforation of the small and large bowel, colitis, and hepatocellular necrosis.
  7. Respiratory: Pneumothorax, pneumomediastinum, pneumopericardium, pulmonary edema, pulmonary hemorrhage, tracheobronchitis, and respiratory failure.
  8. Musculoskeletal: Rhabdomyolysis was associated with cocaine use in 39 patients, of whom 13 had associated renal failure (Roth et al., 1988). Six patients in this series, who had associated disseminated intravascular coagulation (DIC), died.
  9. Obstetric: Low birth weight, prematurity, microcephaly, and placental abruption.

Acute Overdose and Treatment

Cocaine is short-acting drug; treatment of acute intoxication is not usually necessary. In some patients, acute cocaine use may result in lethal cardiovascular or respiratory collapse. The pathogenesis of these cardiovascular complications has not been fully elucidated, but it may be related to the combination of sympathomimetic and membrane anesthetic effects of cocaine. Treatment of acute overdose is similar to other cardiovascular and respiratory emergencies.

  1. Initial management: The primary response in managing cocaine overdose is to support respiratory and cardiovascular functions, monitor vital signs and cardiac rhythm, and establish intravenous access. Cocaine is detectable in urine for up to 72 to 96 hours postexposure; whereas blood levels may fall below detectable thresholds as soon as 60 to 90 minutes after use. A “toxic screen” of the blood and urine may also reveal opiates or other sedative-hypnotics used simultaneously. Electrocardiogram (ECG) monitoring, cardiac isoenzymes, and a chest x-ray are other useful studies in cocaine poisoning. Blood creatine kinase and renal function tests may be necessary in patients suspected of having significant rhabdomyolysis.
  2. Removal of residual cocaine: All residual cocaine should be removed from the patient's nostrils. If ingestions are suspected, or if the patient is a “body packer” or “stuffer,” then activated charcoal should be administered orally or by gastric tube.
  3. Specific interventions
  4. Hypoglycemia: If the patient presents with altered mental status, a blood glucose level should be checked, and hypoglycemia treated if present.
  5. Hyperthermia: Hyperthermia can be treated with antipyretics, a cooling blanket, and iced saline lavage. Muscle paralysis with a nondepolarizing agent may be necessary to reduce muscle contractions contributing to the hyperthermia.
  6. Seizures: Seizures can be treated with benzodiazepines or other standard anticonvulsants.
  7. Arrhythmias: Ventricular dysrhythmias may require an antiarrhythmic agent such as lidocaine; whereas supraventricular arrhythmias may respond to therapy with calcium channel blockers. Cardioversion may be necessary in some patients.
  8. Chest pain: Cocaine-associated chest pain should be treated with nitroglycerin and benzodiazepines. Creatinine kinase (CK and CK-MB fractions) may be elevated after cocaine ingestion even in patients without M One prospective study of 302 patients with cocaine-associated chest pain found that those without an evolving clinical picture of ischemia or cardiovascular complications during the initial 9 to 12 hours of observation and monitoring in the emergency department were unlikely to develop life-threatening complications in the subsequent 30-day period (Weber et al., 2003). Thrombolysis should be considered if the symptoms and signs of toxicity, an ECG, and cardiac enzymes are consistent with acute MI.
  9. Hypertensive crisis: Hypertensive crisis can precipitate cerebrovascular hemorrhage and must be treated emergently. Blood pressure elevations may be the result of direct CNS stimulation (treated with benzodiazepines), or peripheral α-agonist effects (treated with either vasodilators [e.g., nifedipine, nitroglycerin, nitroprusside] or an α-adrenergic antagonist such as phentolamine).
  10. Agitation and psychosis: Acutely intoxicated patients should be approached in a subdued manner, with soft voice and slow movements. Agitation and psychosis should be treated with haloperidol or droperidol; chlorpromazine should be avoided because of the possibility of a severe drop in blood pressure, provocation of arrhythmias or seizures, or anticholinergic crisis. Flumazenil should be avoided for fear of unmasking seizure activity.
  11. Body stuffer syndrome: Overdose has occurred after leakage or rupture of small bags of cocaine swallowed by an individual while running from law authorities; this type of overdose has been called “body stuffer syndrome” and is associated with hypertension, tachycardia, seizures, and other signs of toxicity (Sporer et al., 1997). People attempting to smuggle cocaine or heroin into the United States from overseas will sometimes swallow 30 to 40 sealed condoms or latex gloves filled with drug and then use purgatives to retrieve the drug after their entry into the country (McCarron et al., 1983). Termed “body packers,” these individuals know the catastrophic consequences should one of the bags burst and so they take the time to seal them (unlike the body stuffers, who are much more likely to become symptomatic from hastily wrapped and swallowed drugs). Several cases of acute hepatotoxic effects and hepatocellular necrosis from cocaine use have also been reported (Gourgoutis et al., 1994).



Chronic Use

Cocaine is irritating to the mucosa, skin and airways, and chronic use is associated with erosion of dental enamel, gingival ulceration, keratitis, chronic rhinitis, perforated nasal septum, midline granuloma, altered olfaction, optic neuropathy, osteolytic sinusitis, burns, and skin infarction. People addicted to cocaine also frequently experience anorexia, weight loss sexual dysfunction, and hyperprolactinemia.

Tolerance and Withdrawal

Because of cocaine's powerful euphoric effects and its short half-life, repeated use leads to rapid development of tolerance; addicts can progress from small doses to large daily quantities in a short period. No tolerance to the cardiovascular side effects is developed.

Symptoms of cocaine abstinence or withdrawal include depression, anhedonia, irritability, aches and pains, restless but protracted sleep, tremors, nausea, weakness, intense cravings for more cocaine, slow comprehension, suicidal ideation, lethargy, and hunger. There is currently no widely accepted treatment for cocaine withdrawal. Although many uncontrolled studies have been reported in the literature, and some drugs look promising in early trials, no drug has been proven effective in controlled studies. Relapse rates are very high in cocaine-addicted patients who attempt abstinence.


When alcohol is used with cocaine, a third substance, cocaethylene, is formed in the liver (Randall, 1992; Jatlow, 1993; Rose, 1994). The half-life of cocaethylene is 2 hours, compared with 38 minutes for cocaine. Cocaethylene increases the toxicity of cocaine, particularly on the heart. It is also able to block dopamine reuptake, thereby extending the period of intoxication and toxicity. When alcohol is ingested and metabolized along with cocaine, the risk of sudden cardiac death is increased 25 times. In animal models cocaethylene is more likely to cause seizure activity. A recent study (Bolla et al., 2000) showed that neurobehavioral performance was significantly worse in those individuals who combined alcohol and cocaine use, and these effects persisted even after 4 weeks of abstinence.

Betel Nut

Though betel nut is unknown to most Western physicians, it is chewed on a daily basis by 15% of the world's population (600 million people). It is chewed alone or, more commonly, in a “quid.” The quid consists of betel nut, catechu gum (produced from the sap of the Malaysian acacia tree), and calcium hydroxide paste (produced by burning limestone, reef coral, or shells) wrapped in betel leaf. This combination is placed in the lateral gingival pocket, and the strongly alkaline saliva-generated calcium hydroxide solution activates enzymes in the catechu gum, releasing eugenol (betel oil) from the betel leaf. Eugenol contains two psychoactive phenols, betel-phenol and chavicol, and an alkaloid stimulant called cadinenethat has cocaine-like properties. Betel nut releases arecoline, a volatile cholinergic alkaloid and CNS stimulant. Tobacco is frequently added to the quid.

More than 4% of the U.S. population is of Asian or Pacific Island descent, and the use of betel nut (with or without tobacco) is culturally accepted in these communities. Most youth in these communities have experimented with this substance by adolescence. Dependence occurs rapidly, and if the individual leaves the community, transition to tobacco products is common. Knowledge of traditional cultural practices is key to diagnosis.

Amphetamine (Amphetamine, Methamphetamine, Methylphenidate, Khat)


On the basis of the 2003 National Survey on Drug Use and Health, 20.8 million Americans aged 12 or older (8.8% of the population) had used prescription-type stimulants nonmedically at least once in their lifetime, and an estimated 378,000 persons met the criteria for dependence or abuse within the last year (SAMHSA, 2005). Lifetime use of methamphetamine was reported by 12.3 million; prescription diet pills by 8.7 million; Ritalin or methylphenidate by 4.2 million; and Dexedrine by 2.6 million. Continuing surveillance suggests that methamphetamine use is on the rise. In 2004, the National Survey on Drug Use and Youth estimated that 1.4 million persons aged 12 and older (0.6% of the population) had used methamphetamine within the last year, with 600,000 reporting its use within the last month (SAMHSA, 2005). The average age of first users increased from 18.9 years in 2002, to 20.4 years in 2003, and to 22.1 years in 2004.

The 2006 Monitoring the Future survey of almost 50,000 American high school students (Johnston et al., 2007) documented the continued gradual decline in the lifetime use of amphetamines over the last 10 years from a peak of 13.5% of 8th graders, 17.7% of 10th graders, and 15.3% of 12th graders in 1996 to the current prevalence rates of 7.3%, 11.2% and 12.4% respectively in 2006. Corresponding figures for methamphetamine use among high school students have also dropped to 2.7% of 8th graders, 3.2% of 10th graders, and 4.4% of high school seniors, since lifetime usage rates for this particular drug were first introduced into the survey in 1999 at 4.5%, 7.3%, and 8.2% for the three classes of students, respectively. Separate tallies are also kept for the crystalline form of methamphetamine known as “ice.” In 2006, 3.4% of 12th graders reported experimenting with “ice” at least once in their lifetime (Johnston et al., 2007). A second source of information, the 2005 Youth Risk Behavior Survey, reported that 6.2% of students had used methamphetamines one or more times in their lifetime (CDC, 2006).

Such figures should be approached with caution. As suggested with other illicit drugs, the school-based survey likely underestimates use by the total population of adolescents, which includes dropouts, the homeless, working youth, and others. It may also undercount misuse of methylphenidate and other drugs which, although structurally similar to amphetamines, may not be recognized by students as within the amphetamine class of drugs and therefore not reported by them.



Medical Use

Amphetamines have been used as a weight loss aid, although efficacy is questionable. Other uses include treatment of narcolepsy and attention-deficit hyperactivity disorder (ADHD). The recent increase in the diagnosis and medical management of ADHD has increased the availability of amphetamines to adolescents, who may misuse their own prescriptions by taking a higher dose than prescribed, or distribute pills to peers who may misuse them either as study aids or for intoxication. Appropriate treatment of adolescents with ADHD has been shown to decrease the risk of illicit substance use, but must be carefully supervised. Longer-acting medications may have lower addiction potential than short-acting ones.

Preparation and Dose

The term “amphetamine” refers to a class of drugs containing an amphetamine base, available either in prescription form (such as amphetamine, dextroamphetamine, amphetamine sulfate), or illicitly manufactured (mainly in the form of methamphetamine). Amphetamines are CNS stimulants. Methamphetamine has a stronger effect on the CNS than other forms of amphetamine. Methylphenidate is a nonamphetamine stimulant with similar action available in prescription form.

Amphetamine and methamphetamine differ structurally in that a methyl group attaches to the terminal nitrogen to form methamphetamine. Methamphetamine can be produced in clandestine “labs” beginning with ephedrine or pseudoephedrine that can be isolated from over-the-counter cold preparations. Synthesis is relatively easy, and illicit production occurs in home kitchens, workshops, recreational vehicles, and rural cabins. The federal government and some states have enacted laws decreasing the availability of necessary precursor chemicals. Many of these agents can still be obtained in neighboring states or countries.

The methamphetamine produced by ephedrine reduction is a lipid-soluble pure base form that is fairly volatile and can evaporate if left exposed to room air. This product is converted to the water-soluble form, methamphetamine HCl salt. Illicitly synthesized methamphetamine may be contaminated by organic or inorganic impurities. Poisoning from heavy metals (e.g., lead, mercury) or from solvents used in the synthesis process has been reported. Exposures to carcinogenic materials have been noted. Street methamphetamine may be mixed with many drugs, including cocaine. Studies show that 8% to 20% of street-available stimulants contain both drugs. In a report on cocaine intoxication, 7% of patients sought medical help because of the concurrent use of cocaine and amphetamines.

The production process described here results in a high yield of D-methamphetamine, which is cortically more active than the L-isomer (the active ingredient in Vicks Inhaler). Methamphetamine HCl is much more versatile than the hydrochloride salt of cocaine. It has high bioavailability in the salt form by any route of administration, such as snorting, smoking, ingesting by mouth, or passing across other mucous membranes such as the vaginal mucosa. “Ice” consists of pure crystals of D-methamphetamine. There is no difference between smoking street speed and smoking ice.

There are areas in the western and southwestern United States where methamphetamine is the predominant stimulant of abuse. Look-alikes containing combinations of caffeine, ephedrine, and phenylpropanolamine are particularly dangerous. A much larger dose is necessary to achieve the same level of cortical stimulation as achieved with amphetamines. This combination has greater cardiovascular stimulation, so abuse of look-alikes puts the user at great risk for stroke, MI, or hypertensive crisis.

The maximum typically prescribed dose of amphetamine is in the range of 60 to 100 mg, but addicted patients may ingest up to 100 times the daily dose during a binge.

Routes of Administration and Street Names

Prescription amphetamines are typically ingested orally, or through nasal insufflation. Illicit methamphetamine is usually smoked. Either preparation may be ground up, heated, and injected intravenously. Smoking methamphetamine may be more potent and addictive than snorting or ingesting it; smoking produces higher concentrations of drug in the brain for a shorter period. The user places methamphetamine HCl powder, crystals, or ice into a piece of aluminum foil that has been molded into the shape of a bowl, a glass pipe, or a modified light bulb and heats it over the flame of a cigarette lighter or torch; then the volatile methamphetamine fumes are inhaled through a straw or pipe. Street names for amphetamines include A's, meth, speed, crystal, cartwheel, copilots, footballs, magnums, powder, 20–20, whites, white crosses, crank, ice, ups, dexies, bombido, bennies, black beauties, splash, crosses, and crossroads (Table 71.5).

Physiology and Metabolism

Amphetamines are CNS stimulants that work as sympathomimetic drugs. Amphetamines act on the CNS to release neurotransmitters from presynaptic neurons, directly stimulate postsynaptic catecholamine receptors, prevent reuptake of neurotransmitters (dopamine, serotonin, and norepinephrine), and act as a mild monoamine oxidase (MAO) inhibitor. Stimulation of the nucleus accumbens causes the experience of pleasure. Stimulation of the basal ganglia causes repetitive movements that may be seen in amphetamine addicts. Increased serotonin is associated with changes in sleep and appetite patterns, increased body temperature, mood changes, aggressiveness, and psychosis. See Table 71.6 for amphetamine physiology.

Effects of Intoxication

Amphetamines are CNS stimulants. Users experience increased energy, psychological euphoria, and physical well-being. These effects are nearly identical to cocaine use, but last much longer. Smoked methamphetamine results in immediate euphoria that results from rapid absorption in the lungs and deposition in the brain.

Symptoms of amphetamine intoxication include alertness, anxiety, confusion, delirium, dry mouth, tachycardia, hypertension, tachypnea, jaw clenching, bruxism (teeth grinding), reduced appetite, sweating, and psychosis. As with cocaine, depletion of neurotransmitters leads to post


use dysphoria. Deaths related to use of amphetamines have been associated with assaults, suicides, homicides, accidents, driving impairment, and maternal–fetal and infant exposures. Methamphetamine use by pregnant women has been associated with embryopathy and fetal wastage (Stewart et al., 1997).

TABLE 71.5
Chemical Names, Brand Names, and Street Names of Amphetamines

Prescription Medications


Brand Name

Street Name



Dexies, hearts, oranges




Amphetamine sulfate

Benzedrine sulfate

Hearts, peaches, footballs






Speed, crystal, meth


Illicit Methamphetamine


Street Name



Ice, crystal

Purified methamphetamine ingested by smoking



Methamphetamine and caffeine tablet which may be smoked or ingested orally



Methamphetamine and crack cocaine


Adverse Effects

  1. Psychiatric: Aggressiveness, confusion, delirium, psychosis.
  2. Neurological: Seizures, choreoathetoid movements, cerebrovascular accidents cerebral edema, cerebral vasculitis. One 20-year-old girl suffered hyperreflexia, multiple seizures, and decerebrate posturing after having stuffed bags of methamphetamine into her vagina to avoid their detection. Her serum methamphetamine and amphetamine concentrations were 3,100 ng/mL and 110 ng/mL, respectively (Kashani et al., 2004).
  3. Cardiovascular: Tachycardia, hypertension, atrial and ventricular arrhythmias, MI, cardiac ischemia, coronary artery vasospasm, necrotizing angiitis, arterial aneurysms, aortic dissections.
  4. Gastrointestinal: Ulcers, ischemic colitis, hepatocellular damage.
  5. Musculoskeletal: Muscle contractions, rhabdomyolysis. Intoxicated patients may experience rhabdomyolysis (Richards, 1999) with associated elevated levels of CK and myoglobin, and in some cases may develop secondary acute renal failure.
  6. Respiratory: Pneumomediastinum, pneumothorax, pneumo-pericardium; acute noncardiogenic pulmonary edema, pulmonary hypertension.
  7. Renal: Acute tubular necrosis.
  8. Dental: Chronic gingivitis, numerous dental caries, severe dental abscesses and necrosis known colloquially as “meth mouth.”

Overdose and Emergency Treatment

Complications of amphetamine overdose resemble those of cocaine. However, cocaine and the amphetamines are structurally dissimilar. Unlike cocaine, amphetamines do not have anesthetic effects or effects on nerve conduction.

TABLE 71.6
Amphetamine Physiology





Serotonin binding sites and monoaminergic reuptake sites

·   Release of neurotransmitters from the presynaptic neurons

·   Direct stimulation of postsynaptic catecholamine receptors

·   Reuptake blockade

·   Mild monoamine oxidase inhibitor

Crosses into the CNS with CSF levels approximately 80% of plasma levels

·   Little metabolism

·   Renal excretion, enhanced in acidic urine

As with cocaine, emergency treatment is directed toward cardiovascular and respiratory stabilization and control of seizures. Because of the ability of methamphetamine to cause significant agitation, patients who present to emergency departments for acute intoxication may require pharmacological intervention. Hyperactive or


agitated persons should be treated with droperidol or haloperidol. These are butyrophenones and dopamine-blocking agents that specifically antagonize the central behavioral effects of methamphetamine. Multiple clinical reports attest to the efficacy of droperidol and haloperidol in acute amphetamine toxicity. Patients with acute choreoathetoid syndrome associated with use of amphetamines may show rapid improvement with haloperidol. Diazepam was found to be highly effective in antagonizing the toxic effects of cocaine but not as effective against amphetamines in animal models. A study of 146 patients presenting to an emergency department with agitated, violent, or psychotic reactions due to methamphetamine showed that they responded better to droperidol than to lorazepam, with more rapid and more profound sedation (Richards et al., 1998). Both drugs produced clinically significant reductions in pulse, systolic blood pressure, respiration rate, and temperature over a 60-minute period. Avoid chlorpromazine (Thorazine) because of the possibility of a severe drop in blood pressure, anticholinergic crisis, or seizure activity. Beyond 5 to 10 mg of haloperidol or droperidol, the sedating benefit is minimal and benzodiazepines should be added.

Chronic Use

Chronic use of amphetamines can produce severe psychiatric as well as physical problems, including delusions, hallucinations, and formication, leading individuals to tear and damage their skin. Animal studies have demonstrated that high doses of amphetamines damage neuron cell endings. Some former users seem to have permanent personality changes even after long periods of abstinence from methamphetamine.

Tolerance and Withdrawal

Tolerance does occur with chronic methamphetamine use, and users will frequently escalate their dose or change the route of exposure in order to maintain effect. Symptoms of withdrawal include depression; fatigue; sleep problems; increased appetite, headaches, and drug cravings. These symptoms may begin as soon as the high ends and can last up to 7 to 10 days (McGregor et al., 2005). There is no specific medical treatment for acute amphetamine withdrawal, other than supportive care.

Cathine and Cathinone (Khat)

Cathinone is chemically similar to D-amphetamine, and cathine (D-norisoephedrine) is a milder form of cathinone (Kalix, 1994; Boyer et al., 2000). These compounds are the active ingredients in khat leaves (Catha edulis), which are used as a tea or chewed for their euphoriant and stimulant effects by persons in Africa, the Middle East, and corresponding immigrant and refugee communities in developed nations. The plant grows as a large flowering evergreen shrub or tree. If left unrefrigerated, the cathinone degrades within 48 hours, explaining the preference for fresh leaves. The U.S. Drug Enforcement Agency has classified cathinone as a schedule I narcotic, whereas cathine remains a schedule IV narcotic. Outside the United States, khat is sold by African or Arab sellers and is used within cultural norms with little evidence of abuse. Khat-induced psychosis is rare but has been described in the literature; it most commonly occurs in the context of nonculturally sanctioned polydrug abuse. Western physicians are frequently unaware of the widespread use and availability of khat in certain African and Arabian communities. Susceptible children and adolescents in these communities are at risk because khat can potentially act as a gateway substance when the protective context of culture and family are absent.

In Russia, methcathinone synthesis from ephedrine in makeshift home laboratories is widespread, and it is one of the most common drugs of abuse, after alcohol and tobacco. When ephedrine is reduced, the hydroxy group is lost and methamphetamine results. When this group is oxidized, methcathinone is produced. Clandestine laboratories producing this substance appeared in the midwestern United States in the 1990s, yet production has been limited and methcathinone has failed to achieve the abuse status of other stimulants. In Russian immigrant and refugee communities, knowledge of and experience with methcathinone may predispose at-risk individuals to seek out methamphetamine or other stimulants. In either population, abuse of khat or methcathinone or a family history of such should be suspected in the substance-abusing adolescent from a representative community.

Ecstasy (Methylenedioxymethamphetamine, [MDMA])


According to the 2003 National Survey on Drug Use and Health, approximately 2.1 million persons aged 12 and above reported ecstasy use within the last year, with virtually all of them reporting concomitant use of alcohol and 90% reporting use of other illicit drugs also (SAMHSA, 2005). Another survey, the Youth Risk Behavior Survey, reported lifetime ecstasy use rates in 6.3% of students nationwide in 2005 (CDC, 2006). This represented a drop from 11.1% in the 2001 and 2003 surveys. According to the Monitoring the Future survey, reported lifetime use of MDMA by high school students has declined slowly since the drug seemingly peaked in 2001 at rates of 5.2% of 8th graders, 8.0% of 10th graders, and 11.7% of 12th graders to the corresponding current lower rates of 2.5%, 2.8%, and 6.5% in 2006 (Johnston et al., 2007). Still such rates are comparable to the percentage of adolescents reporting use of cocaine and surpass those using crack or lysergic acid diethylamide (LSD). Methylenedioxyamphetamine (MDA) and methylenedioxy-N-ethylamphetamine (MDEA) are synthetic hallucinogens similar to MDMA that were popular in the 1960s. Currently MDMA is much more popular.

Raves and Circuit Parties

Raves are essentially all-night dance parties or mass gatherings of individuals who listen to loud, syncopated, “techno” music being “spun” by a DJ band, often in coordination with laser effects and other visual and auditory stimuli. The music at raves is usually computer generated, without vocals, and noncommercial in nature. Because alcohol is usually not available at raves, there is often no age restriction on admission. Raves are usually


held at different venues each time and may not occur as announced, to deter police surveillance. Exact locations may be released only hours before an event takes place. Most attendees are between 15 and 25 years of age, and often they are from middle socioeconomic backgrounds. Circuit parties are large-scale dance parties lasting from one to several days and primarily attended by gay and bisexual men in their thirties and forties. Circuit parties may facilitate the use of drugs such as methamphetamine which, in turn, cause disregard of normal sexual precautions and inhibitions, predisposing the participants to the transmission of diseases such as human immunodeficiency virus (HIV) (Boddiger, 2005).

Although not all attendees use drugs and alcohol is not served, drugs are used liberally and many illicit drugs are available at raves. The term club drugs was coined to describe a number of primarily synthetic drugs that are preferred by adolescent and young adult attendees at “raves,” nightclubs that stay open all night, and “circuit parties.” Drugs used at raves include ecstasy, LSD, ketamine, phencyclidine (PCP), crystal methamphetamine, gamma-hydroxybutyrate (GHB), gamma-butyrolactone (GBL), fentanyl, Rohypnol, cocaine, and marijuana. MDMA started to become more popular in the 1980s, and several features of the drug specifically shaped virtually all aspects of the rave. The intense motor restlessness and stimulation of the “stereotypic behavior” portions of the brain occur as a side effect of MDMA and are relieved by group “movement” (dancing) and “wandering” from one stage area to another. In addition, because of the hallucinogenic properties of MDMA and the predictable occurrence of “seeing tracers,” the light show or laser effects are coordinated with the music.

Medical Use

MDMA was first patented in 1912 as an appetite suppressant by a scientist working on the chemical structures found in methamphetamine. However, it was never manufactured and sold commercially, although it did resurface in the 1950s as a potential psychotherapeutic agent for psychoanalysis. However, there are no current medical uses for MDMA.

Preparation and Dose

In the early 1980s MDMA (together with MDA and MDEA) was sold legally, and was in the group of substances called designer drugs. “Designer drug” is an imprecise term that describes a synthetic substance closely related to a controlled substance and yet technically legal. Legislation has closed this loophole, but the term “designer drug” persists. “Designer drugs” have included dextromethamphetamine (MDA), MDMA (ecstasy), MDEA, and α-methylfentanyl. In 1985, MDMA was classified as a schedule I drug by the U.S. Food and Drug Administration (FDA) after reports were published of neurotoxicity in laboratory animals, making production and distribution illegal. Most pharmaceutical-grade ecstasy tablets are now produced in Europe and smuggled into the United States. The drug is sold as a tablet or capsule, often with a symbol printed on it. Tablets sold as MDMA may actually contain MDA, MDEA, or something entirely unrelated to the drug such as LSD, caffeine, pseudoephedrine, or dextromethorphan. The typical ecstasy tablet contains 0 to 100 mg of MDMA, although the concentration of MDMA may vary 70-fold or more among tablets sold. Orally ingested doses take approximately 30 minutes for onset of effect and the duration of action is 1 to 2 hours. Many users begin with a low dose (40–70 mg) and gradually add more pills until they experience the desired effect at a common dosage range of 75 to 125 mg, a practice known as “rolling.”

Routes of Administration and Street Names

MDMA can be snorted, smoked, or injected, but is usually taken orally. Street names include ecstasy, liquid “X,” Adam, “XTC,” and MDM. MDEA is referred to as Eve.

Physiology and Metabolism

MDMA causes release of stored serotonin from neuronal vesicles into the synapse. Serotonin binding to post synaptic receptors results in the effects of MDMA. Serotonin is largely broken down in the synapse by MAO, and repeated use of MDMA causes serotonin depletion, after which further doses have little or no effect. MDMA's onset of action is related to the route of administration; for the oral dose, onset usually occurs within 30 to 45 minutes and last 3 to 6 hours. Single doses of MDMA have caused nerve damage in animal studies. See Table 71.7 for MDMA physiology.

Effects of Intoxication

MDMA has both stimulant and hallucinogen effects. Users describe feelings of enhanced well-being and introspection, empathy, love, affection, and increased energy.

Adverse Effects

  1. Psychological: Confusion, depression, fatigue, sleep problems, anxiety, paranoia
  2. Neurological: Seizures, muscle spasms, bruxism, hyperthermia, sweating, syndrome of inappropriate secretion of antidiuretic hormone (SIADH), blurred vision, faintness, chills, excessive sweating, hyponatremia, serotonin syndrome (with repeated dosing). Water loading, excessive sweating and overheating, and SIADH can contribute to clinically significant hyponatremia or hyponatremic dehydration (Gomez-Balaguer et al., 2000).
  3. Musculoskeletal: Muscle rigidity, rhabdomyolysis
  4. Cardiovascular: Tachycardia, hypertension, arrhythmias, cardiovascular failure, and asystole. A 27-year-old with no history of cardiac disease claimed that he ingested tablet of MDMA with whiskey at a party. He developed chest pain 3 hours later, which was diagnosed as an acute MI with multiple thrombi visible in the right coronary artery by angiography. His plasma MDMA level was 1,100 ng/mL and his urinary MDMA level was 96,800 ng/mL, with a corresponding urinary MDA level of 13,000 ng/mL, confirming significant exposure (Lai et al., 2003).
  5. Gastrointestinal: Nausea, severe hepatic damage. Several cases of severe hepatic damage requiring liver transplantation have been described (Brauer et al., 1997; Andreu et al., 1998; Schwab et al., 1999). In a review by


Andreu et al (1998), MDMA was the second most common cause of liver injury in patients younger than 25 years. It accounted for 20% of the cases in this group of patients—36% if viral hepatitis was excluded. Full recovery occurred in all cases in 3 to 12 months.

TABLE 71.7
Methylenedioxymethamphetamine Physiology




Metabolism and Excretion

·   Serotonin 5-HT2 receptors

·   Central and peripheral catecholamine receptors

·   Release of serotonin into the synapse

·   Release of endogenous catecholamines

·   Inhibition of serotonin reuptake

·   Depletion of serotonin stores occurs with repeated dosing, after which no further effect is achieved by taking more drug

·   Few pharmacological studies have been performed in humans

·   Peak concentrations at 2 hours, half-life 8–9 hours

·   Metabolized through cytochrome P-450 isoenzyme CYP2D6 into 3,4-methylenedioxyamphetamine (MDA)

·   75% excreted in the urine as parent compound

Overdose and Emergency Treatment

The most common severe reaction to toxic MDMA ingestion is a syndrome of altered mental status, tachycardia, tachypnea, profuse sweating, and hyperthermia. This syndrome can appear similar to acute amphetamine overdose. The health care provider is cautioned that MDMA may not be detected in routine toxicological screening of the urine for amphetamines (Boyer et al., 2001).

Williams et al. (1998) reported on MDMA users who presented to an emergency room facility. The mean number of tablets taken was two. Approximately 40% had taken MDMA before, and 50% had used another illicit substance, with stimulants and cocaine being most common. The most common features found in those presenting to the emergency room were nonspecific symptoms of feeling unwell or strange; many patients had collapsed or lost consciousness. The most frequent signs were related to sympathetic overactivity and included agitation or disturbed behavior and increased temperature. Serious complications such as delirium, seizures, and profound coma were more frequent with the combination of MDMA and other substances. Teens and young adults who present late at night on weekends and have clinical manifestations of sympathetic overactivity and increased temperature (“Saturday night fever”) should be suspected of using stimulants, and MDMA in particular.

The treatment of toxic ingestions of MDMA is supportive and similar to that for amphetamine overdose, including support of airway, breathing, and circulation; assessment and treatment of cardiac arrhythmias; and monitoring of vital signs and level of consciousness. Close monitoring of vital signs, serum electrolytes and fluid balance, and urine output is required because of the possibility of SIADH-induced and/or water loading–induced hyponatremia. Hyperthermia should be treated with cooling blankets and intravenous fluids. Use of muscle relaxants, anticonvulsants, and sedatives may be indicated.

There have been reports of life-threatening toxicity and death associated with ecstasy use. The mechanisms of death appear to be related to fatal hyperthermia, DIC, rhabdomyolysis, renal failure, cardiac arrhythmias and sudden asystole, hyponatremia, and seizures (Henry et al., 1992). Other reports have also included deaths due to serotonin syndrome, DIC and hepatic failure, cerebral infarction, and cerebral hemorrhage. Mueller et al. (1998) report a 20-year-old woman who ingested two ecstasy tablets and within 4 hours presented to the emergency department cyanotic and comatose, with hyperthermia (temperature 107°F) and autonomic instability typically seen in serotonin syndrome. She went on to develop hyperkalemia, multiple seizures, hypotension, and ventricular fibrillation leading to her death 4 hours after presentation. Risky behaviors related to poor judgment induced by MDMA can also lead to accidental deaths (Dowling et al., 1997).

Chronic Use

Research links MDMA to long-term damage to areas of the brain that are critical to thought and memory. In experiments in monkeys, exposure to MDMA for 4 days caused brain damage that was evident 6 years later. Ricaurte et al. (1988) found that both serotonin and 5-hydroxyindoleacetic acid were depleted and serotonergic fibers were damaged in a dose-dependent manner in the brains of monkeys who had been administered MDMA. Curran (2000) reviewed the research on MDMA neurotoxicity in both rodents and nonhuman primates. Her conclusions were that MDMA has been shown to cause serotonergic neuronal toxicity in every animal species tested, although recovery occurred in some. Direct evidence in humans has been more difficult to demonstrate because of the problems with study methods in humans. Bolla et al. (1998) found evidence of verbal and visual memory impairment in previous MDMA users. Parrott (2000a) found that users of ecstasy had impairment of several cognitive functions, including reduced memory for new information, impaired higher executive processing, and heightened impulsivity. Kish (2000) reported that striatal levels of serotonin and hydroxyindoleacetic acid (HIAA) were depleted by 50% to 80% in the brains of chronic users of MDMA. Long-lasting impairment of the 5-hydroxytryptamine (5-HT) system has been found in past users of MDMA, which may be more prominent in females and may be reversible in some patients (Gerra et al., 2000; Reneman et al., 2001).



Withdrawal Syndrome

Ecstasy withdrawal is similar to withdrawal from stimulants; the most common symptoms include depression, anxiety, panic attacks, sleeplessness, paranoia, and delusions. Treatment is supportive. Although depressed effect may persist, there is no role for psychopharmacological management.



Opioids (opium, heroin, meperidine, OxyContin, oxycodone, fentanyl, sufentanil), especially the potent oral analgesics such as hydrocodone (Vicodin), oxycodone (OxyContin), and oxycodone plus acetaminophen (Percocet), continue to be attractive to teenagers. The prevalence of nonmedical oxycodone use increased significantly from 2002 to 2003, with an estimated 11 million Americans aged 12 and older reporting nonmedical oxycodone use at least once in their lifetime (SAMHSA, 2005). The Monitoring the Future survey of high school seniors (which changed its questionnaire in 2002 to include specific examples of these oral opiates) recorded a lifetime prevalence of use rate in 2006 of 13.4% in high school senior and an annual use rate of 9.0% for “other narcotics.” In 2006, 3.0% of 8th graders, 7.0% of 10th graders, and 9.7% of 12th graders reported experimenting with Vicodin at least once within the preceding year. Usage rates of OxyContin in the same year were 2.6%, 3.8%, and 4.3%, respectively (Johnston et al., 2007). Heroin use, which had briefly increased in popularity in the late 1990s, has since dropped to lifetime usage rates averaging 1.4% to 1.6% among high school students in the past several years, with prevalence rates of annual use averaging 0.8% to 0.9% among 10th and 12th graders (Johnston et al., 2007). However, the 2005 Youth Risk Behavior Survey reported higher values, with 2.4% of students admitting they had used heroin one or more times during their lifetime (CDC, 2006). The prevalence was higher among Hispanic (3.6%) than white (2.2%) students; and higher among males (3.3%) than females (1.4%).

Medical Use

Opioids have several legitimate medical uses; they are potent antitussives, antidiarrheals, and extremely potent pain relievers. Newer oral medications with extended half-lives are a tremendous asset in the field of pain management. Unfortunately, opioids have a high addiction potential as well, and the development of newer medications has led to increased opioid use and dependence among adolescents. In addition, synthetic narcotics, such as fentanyl, are 80 times more potent than morphine and pose an increased danger of death by overdose.

Preparation and Dose

Opium has been known and used for centuries. The term opioid refers to all drugs, natural and synthetic, with morphine-like activity, as well as antagonists that bind to opioid receptors. All opiates are derived from the opium poppy, Papaver somniferum. The plant is grown primarily in the Middle East and in the Far East. Crude opium is obtained from the seed pods of the poppy. From this crude opium, morphine, codeine, and heroin are manufactured. The average purity of heroin sold on the street is 38%, up from 18% in 1990. The increased purity allows users to snort or smoke heroin. Over the last 10 years the price of heroin has dropped significantly. The ability to use heroin without needles and the lower prices have made heroin more accessible to adolescents, and the average age at first use dropped from 23 years in 1992 to 19.8 years in 1999.

Synthetic opioid pain relievers such as oxycodone, hydrocodone, and oxymorphone are pharmaceutical products that may be diverted and sold on the street. Many teens believe that these products are safer than drugs manufactured in clandestine laboratories and their popularity has increased dramatically since 2000.

Routes of Administration and Street Names

Opioids can be ingested, insufflated nasally, smoked, or injected intravenously or subcutaneously. Most adolescents first use prescription pain medications either orally or by snorting. OxyContin was developed as a long-acting pain reliever. It is intended to be swallowed whole so as to prolong its analgesic efficacy over 8 to 12 hours. Crushing the tablet destroys this continuous release property and makes the total dose available for a rapid “rush.”

The street cost of oxycodone is approximately $1/g. Because of rapid tolerance and the need for increased doses, opioid addiction quickly becomes expensive, and users may begin using heroin which is less expensive. Opioid dependence, regardless of the chosen route of administration, creates intense addictive disease and carries a guarded prognosis. However, newer replacement therapies have been shown to reduce relapse rates substantially (Fudala, 2003), particularly when combined with supportive counseling.

Heroin available on the street is commonly mixed with sugar, talcum powder, Epsom salt, or quinine. This mixture is usually heated into a solution and injected intravenously. Other than leg and arm veins, the veins between the toes, the veins under the tongue, and the dorsal vein of the penis are often used for injection. Heroin is sometimes injected under the skin (“skin popping”) or snorted in the same manner as cocaine; the effect is less intense with any of these methods than with intravenous use. The duration of the effects of intravenously injected heroin is 3 to 6 hours.

Street names for heroin include smack, scat, junk, horse, H. Jones, shit, hard stuff, brown, chiva, do-jee, estuffa, hombre, mud, polvo, and stofa. Oxycodone is referred to as OC's, oxy, or percs; hydrocodone is referred to as vics.

Physiology and Metabolism

There are three opioid receptors in humans—µ, κ, and δ; these have been further classified into µ1 and µ2; δ1 and δ2; and κ1, κ2, and κ3. The µ receptor is the major opioid receptor in the brain and responsible for the majority of neurological effects, including euphoria and pain relief. The κ receptor is found primarily in the brain stem and spinal cord and contributes to pain relief and sedation. The δ receptors are located in the limbic system and are believed to be responsible for affective and emotional changes associated with opioid use.

Morphine is only partially lipid soluble and crosses the blood–brain barrier slowly. By contrast, heroin is very lipid


soluble and crosses the blood–brain barrier quickly, but does not bind to opioid receptors. Heroin is metabolized to morphine within the CNS, which is the active drug. The main effect of heroin is to create a rush of morphine in the CNS. See Table 71.8 for opioid physiology.

TABLE 71.8
Opioid Physiology




Metabolism and Excretion

µ, κ, and δ Opioid receptors (primarily µ).

Stimulation of opioid receptors produces euphoria, pain relief, and other effects

·   Morphine—low lipid solubility, crosses blood–brain barrier slowly

·   Heroin—high lipid solubility, crosses blood–brain barrier quickly and then is metabolized, creating a “morphine rush”

·   Metabolized by the liver (N-demethylation, N-dealkylation, O-dealkylation, conjugation and hydrolysis)

·   Primarily excreted in the urine (90%)

Naloxone (Narcan) is a synthetic opioid antagonist. It binds to the opioid receptor with greater affinity than other opioids, and as such it is a useful treatment for overdose. However, naloxone will precipitate sudden withdrawal in patients who have used an opioid. Buprenorphine is a new synthetic opioid partial agonist that has been approved for use as replacement therapy for opioid addiction. It has intermediate avidity for the opioid receptor, between naloxone and other opioids (see Chapter 74 for further information on use of buprenorphine as replacement medication).

Effects of Intoxication

Opioids produce analgesia and, in high doses, euphoria. Symptoms of intoxication include anxiety, slow comprehension, euphoria, floating feeling, flushing, hypotonia, pinpoint pupils, skin picking, sleepiness, poor appetite, and constipation.

Adverse Effects

  1. Psychiatric: Sedation, apathy, dysphoria, psychomotor agitation or retardation, impaired judgment, delirium, stupor.
  2. Neurological: Diminished reflexes, miosis, pinprick analgesia, ataxia, hypothermia, hypotonia, coma.
  3. Cardiovascular: Circulatory collapse, hypotension, hypothermia, peripheral vein thrombosis, phlebitis.
  4. Respiratory: Blocked cough reflex, bradypnea, respiratory failure, pulmonary edema.
  5. Gastrointestinal: Constipation.
  6. Skin: Rashes, allergic reactions, secondary bacterial infections, abscesses, cellulites.
  7. Obstetric: Low birth weight, neonatal withdrawal, and respiratory compromise.

Overdose and Emergency Treatment

Opioid overdose results in respiratory depression or failure, and circulatory collapse. Treatment begins with support of respiratory and circulatory function, protection of the airway to prevent aspiration, and treatment of hypoglycemia if present. Patients should receive naloxone (0.4–2 mg) intravenously every 5 minutes until response occurs or up to a maximum of 10 mg. Usually, if there is no response after three intravenous doses, this indicates that the individual has not taken an opioid overdose. Repeated doses may be needed in 2 to 3 hours as the naloxone wears off. Naloxone lasts for approximately 1 or 2 hours, whereas the effects of most opioids last 3 to 6 hours, and that of methadone lasts 24 to 36 hours; necessitating close observation during the treatment for opioid overdose. Resedation and respiratory failure may recur as the effects of naloxone wear off. Naloxone does not reverse hypotension that is caused by opiate-induced histamine release.

Chronic Use

Problems related to chronic use of opioids are primarily related to impurities present in the drugs taken, complications of injection or insufflation, and behaviors associated with addiction, such as prostitution, lying, and stealing. Frequent complications include:

  1. Skin: Abscesses and cellulitis caused by injecting infectious organisms directly into the skin.
  2. Vascular: Arteritis and thrombosis of the pulmonary vessels, lung abscesses with resulting pulmonary fibrosis and pulmonary hypertension endocarditis, and secondary septic emboli, osteomyelitis, septic arthritis tetanus, HIV, and hepatitis C from injecting infectious organisms directly into a vein.
  3. Hepatitis and glomerulonephritis from injecting foreign material (talc, sugar) into a vein.
  4. Respiratory: Recurrent aspiration pneumonia from respiratory suppression and blocking of the cough reflex, pulmonary edema, and arrhythmias caused by quinine.
  5. Myositis ossificans: Extraosseous metaplasia of muscle caused by needle manipulation.

Tolerance and Withdrawal

Tolerance, dependence, and addiction occur very quickly, and patients must increase dose and frequency constantly to avoid withdrawal symptoms. Opioid withdrawal presents with flu-like symptoms which can be extremely unpleasant, but are not life threatening in otherwise healthy


individuals. Symptoms include anxiety, irritability, yawning, restlessness, sleep disturbances, muscle aches, chills and sweating, piloerection, hyperthermia, lacrimation and nasal secretions, abdominal cramps with vomiting and diarrhea, paresthesias, tremors, mydriasis, hypertension, and tachycardia. The Clinical Opiate Withdrawal Scale (COWS) (Table 71.9) was developed to quantify the symptoms of opioid withdrawal and may be useful clinically to help time the induction with buprenorphine (Wesson et al., 2003).

TABLE 71.9
Clinical Opiate Withdrawal Scale (COWS)

5–12 = mild; 13–24 = moderate; 25–36 = moderately severe; 36+ = severe withdrawal.

Resting pulse rate: (record beats per minute)

Runny nose or tearing: Not accounted for by cold symptoms or allergies

Measured after patient has been sitting or lying for 1 minute

0 Not present

0 Pulse rate 80 or below

1 Nasal stuffiness or unusually moist eyes

1 Pulse rate 81–100

2 Nose running or tearing

2 Pulse rate 101–120

4 Nose constantly running or tears streaming down cheeks

4 Pulse rate greater than 120


Gastrointestinal (GI) upset: Over last hour

Sweating: Over past hour not accounted for by room temperature or patient activity

0 No GI Symptoms

0 No report of chills or flushing

1 Stomach cramps

1 Subjective report of chills or flushing

2 Nausea or loose stool

2 Flushed or observable moistness on face

3 Vomiting or diarrhea

3 Beads of sweat on brow or face

5 Multiple episodes of diarrhea or vomiting

4 Sweat streaming off face

Tremor: observation of outstretched hands

Restlessness: Observation during assessment

0 No tremor

0 Able to sit still

1 Tremor can be felt, but not observed

1 Reports difficulty sitting still, but is able to do so

2 Slight tremor observable

3 Frequent shifting or extraneous movements of legs/arms

4 Gross tremor or muscle twitching

5 Unable to sit still for more than a few seconds

Yawning: Observation during assessment

Pupil size:

0 No yawning

0 Pupils pinned or normal size for room light

1 Yawning once or twice during assessment

1 Pupils possibly larger than normal for room light

2 Yawning three or more times during assessment

2 Pupils moderately dilated

4 Yawning several times/minute

5 Pupils so dilated that only the rim of the iris is visible

Anxiety or irritability

Bone or joint aches: If patient was having pain previously, only the additional component attributed to opiates withdrawal is scored

0 None

0 Not present

1 Patient reports increasing irritability or anxiousness

1 Mild diffuse discomfort

2 Patient obviously irritable/anxious

2 Patient reports severe diffuse aching of joints/muscles

4 Patient so irritable or anxious that participation in the assessment is difficult

4 Patient is rubbing joints or muscles and is unable to sit still because of discomfort

Gooseflesh skin


0 Skin is smooth


3 Piloerection of skin can be felt or hairs standing up on arms


5 Prominent piloerection



Treatment for opioid withdrawal is supportive, and includes symptomatic treatment of aches and pains with nonsteroidal anti-inflammatory medications, abdominal cramping with dicyclomine (Bentyl), and reassurance. Clonidine may also be helpful. Withdrawal can also be managed with buprenorphine (see Chapter 74).

Medical Management of Addiction

Methadone and buprenorphine are two medications that can be used as replacement therapy for opioid-dependent patients. Each of these medications has been shown to reduce the relapse rate in patients seeking treatment (see Chapter 74).



Nonnarcotic Central Nervous System Depressants

The CNS depressants include the barbiturates such as benzodiazepines; nonbarbiturate hypnotic drugs such as glutethimide (Doriden) and methaqualone (Quaalude), GHB, flunitrazepam (Rohypnol), and major tranquilizers (phenothiazines); and carbamates such as meprobamate (Equanil and Miltown). Physical symptoms of sedative–hypnotic intoxication include slurred speech, incoordination, unsteady gait, nystagmus, decreased reflexes, impaired attention or memory, and stupor or coma; psychiatric symptoms of intoxication include inappropriate behavior, mood lability, impaired judgment, impaired social functioning, and impaired occupational functioning.



Nonmedical use of barbiturate tranquilizers continues to be a problem among adolescents. The 2006 Monitoring the Future study recorded an increased in lifetime use of barbiturates among high school seniors from 8.8% in 2003 to 10.2% in 2006, while annual use rates also rose from 6% to 6.6% (Johnston et al., 2007).

Medical Uses

Barbiturates are used as sleep aides, as a sedative–hypnotic anesthesia, as an anticonvulsant, for reduction of intracranial pressure and cerebral ischemia after head trauma, for poststroke management, and for preinduction of anesthesia. Their medical use has decreased over the past decade as they have been replaced by benzodiazepines for several indications.

Preparation and Dose

Barbiturates are sedative/hypnotic drugs derived from barbituric acid. More than 50 types of pills containing barbiturates are available in the United States. The most frequently abused barbiturates are secobarbital and pentobarbital. Many of the illicit pills are made in Mexico and contain varying amounts of secobarbital.

Barbiturates are divided into ultrashort-acting (thiopental [Pentothal] and methohexital [Brevital]), short-acting (secobarbital [Seconal] and pentobarbital [Nembutal]), intermediate-acting (amobarbital [Amytal] and butabarbital [Butisol]), and long-acting types (phenobarbital [Luminal]). Ultrashort-acting barbiturates are often used for anesthesia, whereas short-acting barbiturates are used as sleeping pills. Pentobarbital, for example, has an onset of effect 60 to 90 minutes after ingestion, with peak effects occurring in 1 to 2 hours, whereas phenobarbital has steady-state half-life of approximately 80 to 90 hours in adults. Therapeutic serum concentrations of phenobarbital range from 10 to 25 mcg/mL. Approximately 75% of phenobarbital is hydroxylated in the liver, with 25% excreted unchanged in urine, whereas secobarbital and butabarbital undergo 99% hepatic metabolism with little if any urinary excretion of parent compound.

Routes of Administration and Street Names

Barbiturates are usually taken orally, although some users inject them intravenously.

Street names include reds, red devils, yellow jackets, rainbows, tooies, blue heavens, purple hearts, Mexican reds, nebbies, nimbies, bluebirds, blue devils, blues, yellows, Christmas trees, trees, barbs, beans, goofballs, and stumblers.

Physiology and Metabolism

Barbiturates are γ-aminobutyric acid (GABA) A receptor agonists. GABA is the main inhibitory neurotransmitter of the CNS. Barbiturates bind to a unique location on the GABA receptor (separate from the GABA binding site). Once bound, barbiturates have two functions. First, they enhance binding of GABA to its unique site. Secondly, they open the chloride ion channel of the GABA receptor even in the absence of GABA. These two effects together make barbiturates potent drugs with a narrow window of safety.

By enhancing GABA, barbiturates produce all degrees of CNS depression, from sedation to general anesthesia. The mesencephalic reticular activating system is particularly sensitive to barbiturates.

Barbiturates are metabolized by the liver and enhance liver metabolism, shortening the half-life of other drugs (e.g., anticoagulants, corticosteroids, phenothiazines) and reducing their clinical effectiveness. They can increase the CNS depressant effects of meperidine by increasing its active metabolites. See Table 71.10 for barbiturate physiology.

TABLE 71.10
Barbiturate Physiology




Metabolism and Excretion

GABA A agonists

Enhance GABA binding

·   Barbiturates bind to plasma proteins in varying amounts (50%–97%), and cross into the cerebrospinal fluid and the placenta to varying degrees

·   Open the chloride ion channel of the GABA receptor

·   Metabolized in the liver, may enhance metabolism of other compounds

·   Excreted by the kidney

Effects of Intoxication

Barbiturates are CNS depressants. Low doses result in mild sedation, higher doses result in hypnosis, and still higher doses result in anesthesia and possible death. Symptoms of intoxication include sleepiness, yawning, slowed comprehension, slurred speech, lateral nystagmus, anorexia, dizziness, and orthostatic hypotension. Allergic reactions including bronchospasm, urticaria, dermatitis, fever, and angioneurotic edema can be caused by barbiturates. When barbiturates are used in combination with


other depressants such as alcohol or opioids, the effects of both are potentiated and lethal overdoses can occur more easily.

Adverse Effects

  1. Fatigue
  2. Neurological: Ataxia, slowed comprehension, diplopia, dizziness, dysmetria, hypotonia, poor memory, lateral nystagmus, and slowed speech.
  3. Psychiatric: Euphoria or depressed mood, irritability, violent behavior, toxic psychosis.
  4. Skin: Cutaneous lesions and bullae.

Overdose and Emergency Treatment

Signs and symptoms of barbiturate overdose include miosis, hypotension, hypothermia, respiratory depression, and decreased gastrointestinal motility. Coma, shock, and death are possible. The presentation is indistinguishable from opiate or other sedative overdose on clinical examination. Urine toxicology can be helpful for diagnosis, but quantitative levels are not predictive of the clinical course.

Treatment of barbiturate overdose is primarily supportive, and aimed at supporting airway, breathing, and circulation. Because of the decreased gastrointestinal motility and delayed gastric emptying drug absorption can continue for a long time after ingestion. Unabsorbed toxins should be removed by gastric lavage followed by activated charcoal for recent ingestion. Absorbed toxins should be removed by alkaline diuresis or dialysis. CNS stimulants should be avoided. Ingestion of >3 g or blood level of >2 mg/dL is the lethal dose for short-acting barbiturates; ingestion of >6 to 9 g or blood level >11 to 12 mg/dL is the lethal dose for long-acting barbiturates.

Tolerance and Withdrawal

Few adolescents use barbiturates with the frequency necessary to develop dependence. However, if dependence is suspected, detoxification must be done under close medical supervision as withdrawal can be life threatening. The severity of the withdrawal syndrome parallels the strength of the drug, the dose used, and the duration of prior abuse. Withdrawal symptoms include anxiety, delirium, hallucinations, irritability, sleep disturbance, seizures, headaches, weakness, hyperactive reflexes, tremor, abdominal cramps, flushing, nausea, sweating, and increased temperature. Orthostatic hypotension may also occur. Barbiturate withdrawal is treated with replacement by phenobarbital followed by a slow taper until the patient is drug free.



Use of benzodiazepine tranquilizers by teenagers continues to be disturbingly high. The Monitoring the Future study has recently documented a slight drop-off in the lifetime prevalence rates since 2001 to 4.3%, 7.2% of 10th graders, and 10.3% of 12th graders in 2006, although this represents a slight increase since 2005 (Johnston et al., 2007). Annual use rates in 2006 were 2.6%, 5.2% and 6.6% among 8th, 10th, and 12th graders respectively. Rohypnol use has remained relatively constant at approximately 1% of high school 12th grade students, since its availability in the United States for medicinal uses was curtailed in the late 1990s.

Medical Use

Medical use of the benzodiazepines became widespread in the 1970s, and this class of drugs continues to be used clinically as anxiolytic, hypnotic, anticonvulsant, and antispasmodic medication. Benzodiazepines are also used to treat the effects of alcohol withdrawal. Initially benzodiazepines were thought to be free of negative consequences, but it is now known that they carry the risk of dependence, withdrawal, and negative side effects.

Preparation and Dose

Several thousand benzodiazepine formulations have been investigated, but only a handful have found clinical utility. Table 71.11 lists some of the more prominent members of the chemical class, and some of their major uses, although many of these drugs have overlapping clinical indications and may be used for other purposes, such as insomnia, chemical restraint, alcohol withdrawal, and so on.

Long-acting benzodiazepines include diazepam, chlordiazepoxide, clonazepam, flurazepam, and chlorazepate. Typical elimination half-lives for these longer-acting benzodiazepines range from 18 to 100 hours. Short-acting benzodiazepines include oxazepam and lorazepam, with half-lives of approximately 6 hours. Midazolam is an example of an ultra–short-acting benzodiazepine.

Benzodiazepines are sedative-hypnotic medications; many drugs of this class are produced and sold in the United States, and they are readily available on the street. Nearly all the available benzodiazepines have been abused; those that cross the blood–brain barrier more quickly have a higher abuse potential than those that cross more slowly.

TABLE 71.11
Major Pharmacological Actions of Various Benzodiazepines


Major Pharmacological Action

Diazepam, chlordiazepoxide, oxazepam, chlorazepate, lorazepam, prazepam, alprazolam, halazepam


Flurazepam, temazepam, flunitrazepam, triazolam, midazolam


Diazepam, clonazepam



Muscle relaxant

Benzodiazepines may be obtained by diverting legitimate prescriptions or by theft from pharmaceutical supplies. Diversion of flunitrazepam tablets across the Mexican border has also been reported. Abuse of benzodiazepines generally occurs within the context of another substance abuse disorder. These drugs are often used to augment the effects of another drug or prevent symptoms of withdrawal (O'brien, 2005). However, benzodiazepines are the drug of choice for a small portion of adolescents with substance abuse problems and sedative-hypnotic dependence has been described.



Routes of Administration and Street Names

Benzodiazepines are most often taken orally, although some adolescents may snort them or inject them intravenously. Street names include tranks, downers, blues, yellows, zans, blue footballs, blues, z bars, zan bars, tombstones, totem poles, quad bars, blue magoo, V, and vallies.

Physiology and Metabolism

Benzodiazepines bind to a unique site on the GABA A receptor and enhance the inhibitory effects of GABA. Like barbiturates, benzodiazepines enhance the binding of GABA to its receptor. Unlike barbiturates, however, benzodiazepines do not open the chloride ion channel of the GABA receptor in the absence of GABA. This makes benzodiazepines relatively milder in effect and safer to use than barbiturates. Variability between specific drugs regarding their water solubility and the affinity of the drug for the receptor may be one factor mediating differences among benzodiazepines in the pharmacokinetics of sedation as well as their propensity to cause amnesia.

Benzodiazepines are metabolized by the liver; different drugs in the class have different half-lives based on structural differences. The half-life is often determined by the half-life of active metabolites. Benzodiazepines can be divided into long-acting drugs such as diazepam, chlordiazepoxide, clonazepam, flurazepam, and clorazepate. Diazepam is highly lipophilic and has rapid absorption after ingestion, with an elimination half-life ranging from 18 to 100 hours. It is metabolized in the liver through a two-phased process of demethylation involving the cytochrome P-450 system, followed by glucuronidation. Shorter-acting benzodiazepines include oxazepam and lorazepam, which are metabolized directly in the liver by single-step glucuronidation and have elimination half-lives of approximately 6 hours. Ultra–short-acting agents include triazolam, temazepam, and midazolam. Benzodiazepines can cross the placenta and are excreted in breast milk.

Benzodiazepines and their metabolites may accumulate in the body, resulting in a delayed appearance of adverse reactions and continued clinical effects beyond discontinuation of the drug. Unlike the barbiturates, benzodiazepines do not induce the metabolism of other drugs. See Table 71.12 for benzodiazepine physiology.

TABLE 71.12
Benzodiazepine Physiology




Metabolism and Excretion

GABA A receptor agonists

Enhance the binding of GABA to the GABA receptor

·   Protein bound

·   Cross into the central nervous system based on their solubility and lipophilicity

·   Metabolized in the liver

·   Many active metabolites, which accounts for wide variation of half-lives

Effects of Intoxication

Benzodiazepines are CNS depressants. They produce drowsiness, dizziness, weakness, sedation, and a sense of calmness.

Adverse Effects

  1. Psychiatric: Paradoxical aggression, anxiety, delirium, agitation.
  2. Neurological: Oversedation, ataxia, memory loss, impaired psychomotor function.
  3. Cardiovascular: Mild hypotension.

Overdose and Emergency Treatment

Benzodiazepine overdose typically presents with dizziness, confusion, drowsiness or unresponsiveness, and blurred vision. Some patients may present with anxiety and agitation. Physical examination findings include nystagmus, slurred speech, ataxia, weakness or hypotonia, hypotension, and respiratory depression. Treatment for benzodiazepine overdose is primarily supportive including securing the airway, and cardiovascular and respiratory stabilization. Flumazenil is the first specific benzodiazepine receptor antagonist to become available. To treat severe benzodiazepine overdose, flumazenil is given in incremental doses over a few minutes. If a clinical effect is not seen after five doses have been given, it is unlikely that higher doses will be helpful. Patients who have overdosed on a long-acting benzodiazepine may require redosing to prevent return of symptoms.

In mixed overdoses involving tricyclic antidepressants or other seizure-causing agents, flumazenil is contraindicated. In this setting, it can cause seizure activity by removing any anticonvulsant protection conferred by the benzodiazepine. It is also contraindicated in individuals who are physically dependent on benzodiazepines. This dependence can occur rapidly and use of flumazenil can precipitate a full-blown benzodiazepine withdrawal state (agitation, tremor, flushing).

Chronic Use

Benzodiazepines have a high abuse and dependence potential. Care should be used in prescribing benzodiazepines for management of sleep or anxiety in any patient who has been diagnosed with drug problems. Benzodiazepines are contraindicated in adolescents with alcohol problems, opioid addiction, or on opioid replacement therapy.

Tolerance and Withdrawal

If benzodiazepine dependence is suspected, withdrawal must be carefully supervised. Patients who abruptly stop taking benzodiazepines can develop life-threatening, protracted seizures. Other symptoms of benzodiazepine withdrawal include anxiety, agitation, confusion, sleep disturbance, and flu-like symptoms, including fatigue, headache, muscle pain and weakness, sweating, chills, nausea, vomiting, and diarrhea.

Detoxification from benzodiazepine dependence is done by replacement with long-acting benzodiazepines followed by a taper. The taper can be accomplished either


gradually (over 2–3 months) on an outpatient basis by decreasing the dose by one sixth every 10 days or rapidly (over 10–14 days) on an inpatient basis.

“Date Rape” Drugs

Flunitrazepam, GHB, and ketamine are often colorless, tasteless, and odorless. These drugs have the reputation of being the so-called “date rape” drugs because they have been added to beverages and ingested by individuals unknowingly. They can produce both antegrade and retrograde amnesia in the victim, such that they have no memory of events surrounding their use of the drug. In 1996, federal legislation was passed that increased penalties for the use of any controlled substance to aid in sexual assault. Information and educational materials directed toward college students are available from the Rape Treatment Center at Santa Monica—UCLA Medical Center at 1-800-END-RAPE (1-800-363-7273).


Flunitrazepam (Rohypnol), a benzodiazepine, is predominantly a CNS depressant. Use of flunitrazepam began in Europe in the 1970s and appeared in the United States in the early 1990s. Street names include rophies, roofies, roach, and rope. The Monitoring the Future survey included questions on Rohypnol in 1996. In that year, 1.2% of seniors had used Rohypnol at some time; this figure rose to 3% in 1998 before falling to 1.7% in 2001. Although not measured in 12th graders since that time, use in 10th graders has declined from 1.5% in 2001 to 0.8% in 2006 after a peak in 1998 of 2%. Flunitrazepam is rapidly absorbed within 30 minutes of oral ingestion. It is a highly lipophilic drug, readily crossing the blood–brain barrier; consequently CNS depression is rapid in onset. Clinical effects are the same as those of other benzodiazepines, but with an exaggerated amnesia effect. If mixed with alcohol, it can incapacitate victims and prevent them from resisting sexual assault, hence its reputation as a “date rape” drug. Victims may also have impaired memory for the events surrounding the drug's use. This drug can be lethal when combined with alcohol and other depressants. This drug is not approved for use in the United States, and it is illegal to import flunitrazepam into the United States. Occasionally, clonazepam (Klonopin) is sold as “roofies.” Flunitrazepam may not be detected in routine laboratory screening for benzodiazepines, but specific testing can detect flunitrazepam in the urine for up to 72 hours after ingestion. Management of patients with suspected overdoses includes decontamination with oral activated charcoal and supportive care.

Gamma-Hydroxybutyrate (Precursors: 1,4 butanediol, Butyrolactone, Gamma-valerolactone)

GHB is a CNS depressant that acts through a metabolite of the inhibitory neurotransmitter GABA and can function as a neurotransmitter itself. GHB triggers the release of an opiate-like substance and can mediate sleep cycles, temperature regulation, memory, and emotional control. In some countries, GHB is used as an anesthetic and for narcolepsy. It is rapidly absorbed after ingestion. Precursors of GHB, such as 1,4 butanediol and butyrolactone, are converted to GHB by the alcohol dehydrogenase enzyme system in the liver (Quang et al., 2002; Quang et al., 2004). Therefore, sedative effects experienced after these as yet unregulated chemical precursors may be delayed by several hours, until their metabolism is complete.

The illicit use of GHB has grown in the United States, among both body builders and ravers. Body builders claim that it metabolizes fat and builds muscles. Ravers use it as a euphoriant. It has also been mentioned as one of the several “date rape” drugs. It has been sold as a strength enhancer, euphoriant, and aphrodisiac. Some of the common street names include liquid ecstasy, somatomax, scoop, Georgia Home Boy, and grievous bodily harm. The drug comes in both liquid and powder form. Before February 2000, GHB was not illegal to possess, but now it is a schedule I drug. GHB has not been sold over the counter in the United States since 1992. However, products containing precursor chemicals such as gamma butyrolactone (GBL) are used in a number of dietary supplements in health food stores and gymnasiums and are also readily available over the Internet.

Adverse effects include:

  1. Cardiorespiratory: Bradycardia, respiratory depression (particularly if used with other depressants), increased or decreased blood pressure
  2. Neurological: Hypothermia, dizziness, weakness, ataxia, vertigo, nystagmus, short-term amnesia, coma, tonic-clinic seizures
  3. Psychiatric: Confusion, sedation, aggression, impaired judgment, hallucinations
  4. Respiratory: Respiratory depression with acidosis
  5. Gastrointestinal: Vomiting
  6. Endocrine: Mild hyperglycemia
  7. Acute respiratory acidosis

Heavy doses can lead to coma and respiratory depression, which can be exacerbated by the use of alcohol. The FDA has issued a warning about GHB because the products have been linked to at least 122 serious illnesses and at least six deaths (O'Connell et al., 2000). The diagnosis of GHB toxicity may be facilitated by the recent finding of an abnormal peak in urinary organic acids (Quang et al., 2005). There is no antidote for GHB overdose; the treatment is supportive care. Withdrawal effects include insomnia, anxiety, tremors, and sweating.


Ketamine (“Special K”) is an arylcycloalkylamine chemical congener of PCP; it is similar to PCP pharmacologically, but it has a more rapid onset and is less potent. It is known as a rapid-acting dissociative anesthetic that combines sedative–hypnotic, analgesic, and amnesic effects with the maintenance of pharyngeal reflexes and respiratory function. Like PCP, ketamine is an NMDA receptor antagonist and is used as a human and veterinary anesthetic. Like PCP-induced anesthesia, it occasionally produces unpleasant emergence reactions, anxiety, dysphoria, and hallucinations. Ketamine entered the rave scene in the early 1990s as a substance of abuse and its use has been growing in the United States. Users are attracted to the “dreamy” state of mild hallucinations and “out of body” experiences induced by light ketamine anesthesia. Adverse effects include a cataleptic state, with nystagmus, excessive salivation, involuntary tongue and limb movements, and hypertonus. Laryngospasm, seizures, apnea, and respiratory arrest have all been reported on rare occasions with ketamine-induced anesthesia. Accidents are often of greater threat to the individual than toxicity secondary to the loss of physical


control. Ketamine can be used as an alternative to cocaine, and it is often snorted. The drug is also often sold in tablets similar to “ecstasy,” and users may take ketamine thinking they are using MDMA. Treatment of ketamine overdose is primarily supportive, with attention to neurological, cardiovascular, and respiratory monitoring. Airway control and ventilatory support may be necessary for some patients. Treatment of agitation related to an emergence reaction entails dim lighting, reduction of extraneous external stimuli, and administration of a benzodiazepine. For idiosyncratic dystonic reactions, intravenous diphenhydramine may be of benefit.

Glutethimide, Meprobamate, Methaqualone

Glutethimide (Doriden), meprobamate (Miltown, Meprosan), and methaqualone (Quaalude) are barbiturates similar in effect and were popularly used in the 1950s and 1960s. They are outmoded drugs and are no longer commercially available in the United States. These drugs are lipophilic, with sedative effects that can last for hours. They have high abuse potential. Tolerance and psychological and physical dependence can all occur. The effects of the drugs include a sense of euphoria, a loss of concern for self, and withdrawal from reality. Heavy use leads to intoxication, with unsteadiness, tremors, loss of memory, irritability, and delirium, and may result in coma and cardiovascular and respiratory failure. Withdrawal from these drugs is dangerous and can result in tremors, insomnia, seizures, coma, and death. Treatment includes oral decontamination with gastric lavage and activated charcoal. Hemoperfusion has been considered in the past for patients with confirmed exposures and life-threatening toxicity.

Baclofen and Muscle Relaxants

Abuse of prescription drugs such as muscle relaxants has become more common among adolescents. Muscle relaxants are diverse in chemical structure and actions; they include such drugs as baclofen, meprobamate, orphenadrine, and methocarbamol. Baclofen (Lioresal) is chemically related to the inhibitory neurotransmitter, GABA, and can induce drowsiness, coma, muscle flaccidity, cardiac dysrhythmias, and respiratory depression or sudden respiratory arrest. Baclofen and other muscle relaxants are not detected in routine toxicological screens of the blood and urine, and should be ordered specifically if an overdose is suspected. Treatment of patients who overdose on muscle relaxants includes oral decontamination with activated charcoal, close monitoring of neurological and cardiovascular status, and supportive care. Intubation and mechanical ventilation may be necessary in cases of severe poisoning. In one retrospective study, 14 teenagers took overdoses of baclofen ranging from 60 to 600 mg at a party. Nine were subsequently admitted to the critical care unit for mechanical ventilation because of respiratory failure. All survived, although the mean length of time on mechanical ventilation was 40 hours (Perry et al., 1998).



On the basis of the National Survey on Drug Use and Youth conducted in 2002 and 2003, an annual average of 718,000 (8.6%) of youths aged 12 and 13 years had used an inhalant in their lifetime; and approximately 35% of those had used other illicit drugs (SAMHSA, 2005). The 2006 Monitoring the Future survey of high school students found a lifetime prevalence of inhalant use in 16.1% of 8th graders, 13.3% of 10th graders, and 11.1% of 12th graders in 2006. There has been an upward trend in recent years among 8th graders with a small drop in 2006 (15.2% in 2002, 15.8% in 2003, 17.3% in 2004, 17.1% in 2005 and 16.1% in 2006) (Johnston et al., 2007). This trend may signal resurgence in student acceptance of inhalants as agents for experimentation. The prevalence of inhalant use within the previous year was highest again in 8th graders (9.1%), followed by 10th graders (6.5%) and 12th graders (4.5%). “Fad” use of inhalants is also common, such that misuse of butane lighters or aerosols in food products may gain short-term popularity in a particular school or town based on word-of-mouth reports among teens.


Inhalants are attractive to adolescents because of their rapid onset of action, low cost, and easy availability. They are typically used by inhaling from a plastic bag containing the substance (“bagging”) or by inhaling a cloth saturated with the substance (“huffing”). The initial effect is stimulation and excitation, which then progresses to a depressant effect on the CNS. Of the myriad products and substances abused, toluene is the most common volatile component. It is present in spray paint, airplane glues, rubber cement, cleaning fluids, inks (magic markers), and lacquer thinner.

Circumstances of Abuse

Inhalants are inexpensive, legal products that do not arouse suspicion in most homes (Table 71.13). When parents report finding fluid saturated cloths, empty spray paint cans or plastic bags in a bedroom, other paraphernalia, or unusual chemicals, they and the physician should suspect inhalant use and ask about it directly. Disinterest in school, declining grades, abandonment of usual friends and activities, secretive or oppositional behaviors, and emotional lability are all the signposts of substance abuse, including inhalant abuse.

Physiology and Metabolism

The effects of inhalants are felt within minutes of inhalation, because of the immediate absorption of the chemicals crossing the large surface area of lung alveoli into the pulmonary circulation. Their lipophilicity facilitates rapid absorption into the brain, and their pharmacology often involves anesthetic effects at the cellular level. Peak effects occur within minutes and excretion is rapid, such that the course of intoxication after one huffing event may last only 15 to 30 minutes.

Effects of Intoxication

Inhalant use results in euphoria, decreased inhibition, and decreased judgment. Symptoms of inhalant use include heavy lidded glazed eyes, slurred speech, lacrimation, rhinorrhea, salivation, and irritation of the mucus membranes.


Anesthesia is common with drowsiness, stupor or even obtundation, accompanied by respiratory depression. Users report spinning or floating sensations, with disinhibition, exhilaration, and mild delirium. Feelings of grandiosity and omnipotence impart a sense of control and dominance.

TABLE 71.13
Classes of Inhalants, Chemical Examples and Toxicity

Class of Inhalant

Product/Chemical Examples


Volatile products

Glues, gasoline, spray paints, butane, paint thinner

Cardiac arrhythmias, respiratory failure, coma, pneumothorax


Nitrous oxide

Simple asphyxia



Coma, respiratory failure


Amyl nitrate, butyl nitrate

Cardiovascular failure, coma methemoglobin

Adverse Effects

Common adverse effects associated with inhalant abuse include gastrointestinal complaints such as anorexia, vomiting, and abdominal pain associated with gastritis. Neurological effects accompanying inhalant abuse include sleepiness, headaches, dizziness, ataxia, incoordination, and diplopia. Users may have a distinctive chemical odor to their breath, hair, or clothing. Disregard of personal hygiene may result in a disheveled appearance. Defatting properties of solvents may lead to perinasal and perioral skin rashes and nosebleeds. Respiratory irritation may cause the user to develop a chronic dry cough, new onset wheezing, and shortness of breath.

Overdose of inhalants can result in life-threatening complications, such as seizures, loss of consciousness, arrhythmias, respiratory failure, or cardiopulmonary arrest (Table 71.14). In addition, specific inhalant groups are associated with unique toxicities.

TABLE 71.14
Agent-Specific Toxicities of Inhalant Chemicals

Inhalant Chemical

Agent-Specific Toxicity


Renal damage, embryopathy

Amyl and butyl nitrites

Methemoglobinemia, hypotension


Lead poisoning, benzene-induced leukemia

Carbon tetrachloride, trichloroethylene

Hepatitis, cirrhosis

Methylene chloride (Paint thinner)

Carbon monoxide poisoning

Death is not an uncommon outcome in adolescent inhalant abuse, either directly due to respiratory or cardiac toxic causes or as a result of trauma from risk-taking behaviors and poor judgment. Sudden sniffing-death syndrome has occurred after inhalation of fluorocarbons or halogenated hydrocarbons. The postulated mechanism involves sensitization of the myocardium by the solvent to the arrhythmogenic effects of epinephrine and increased sympathetic outflow, which occurs during the initial brief excitatory phase of intoxication.

Although tolerance to inhalants may develop, withdrawal symptoms do not usually occur. Inhalants are difficult or impossible to detect in drug samples. Conventional toxicology screening tests give negative results in patients with inhalant abuse.

Chronic Use

Inhalant abuse is notable for escalation in the frequency of use and in binge behaviors, due to the short duration of the “high.” Chronic effects of inhalant abuse are characterized by irreversible damage to target organs such as the brain and kidneys. Fatty brain tissues such as myelin and neuronal cell bodies are damaged or destroyed, and white matter degeneration may be evident. One recent study (Rosenberg et al., 2002) compared psychological test scores and magnetic resonance imaging (MRI) studies of 55 solvent abusers to a control group of 61 abusers of other drugs. Solvent abusers had higher rates of MRI abnormalities (44% of the 50 subjects who had an MRI) in subcortical structures including the thalamus, basal ganglia, pons, and cerebellum. Although both groups underperformed on cognitive tests compared to normal populations, solvent abusers did significantly worse than the controls on measures of working memory and executive function (e.g., planning, self-monitoring, ability to focus and concentrate). Mean verbal and performance IQ scores for solvent abusers were 82 and 87, respectively. Such formal psychological testing and imaging studies reveal results typical of a “solvent encephalopathy,” consisting of IQ loss, slow mentation, visuospatial dysfunction, faulty memory, poor insight, loss of executive function, cerebral atrophy, and subcortical dementia.


Many inhalants are so quickly metabolized and/or excreted through pulmonary or other routes that they cannot be detected by the time the patient arrives in the emergency department. Standard toxicological screening tests of the blood or urine do not include such chemicals as hydrocarbons or nitrites. However some products, such as paint thinners or glue, may leave chemical signatures behind. A 14-year-old girl who presented to the emergency department with confusion, hallucinations, and intermittent laughing and crying after inhaling glue several times daily for 5 days consecutively, had elevated


urinary hippuric acid levels indicative of heavy toluene exposure (Raikhlin-Eisenkraft et al., 2001).


Treatment is supportive, and is aimed at control of arrhythmias, and respiratory and circulatory support. Epinephrine should be avoided because it may provoke cardiac irritability in those patients who have inhaled halogenated hydrocarbons. Intubation and mechanical ventilation may be necessary in severely affected patients who present with respiratory depression and blood gas evidence of hypoxia, hypercarbia, and respiratory acidosis.

Nitrous Oxide

Also known as laughing gas, nitrous oxide (N2O) has long been abused by health care personnel. More recently there has been a resurgence of interest in it among the adolescent population. It is most commonly sold in small balloons or inhaled from whipped-cream cans, in which it is used as a propellant. Occasionally, individual users gain access to a tank of nitrous oxide. Deaths have occurred after prolonged inhalation of 100% N2O in a closed space.


Amyl, butyl, and isobutyl nitrites are examples of nitrites. They are volatile liquids abused for their vasodilatory action and subjective feeling of lightheadedness (known as the “rush”). Amyl nitrite requires a prescription and is currently indicated in cyanide poisoning to produce methemoglobin. Butyl and isobutyl nitrite are available over the counter (commonly in “head shops”) as a room deodorizer, cologne, or liquid incense.

Individuals abusing nitrites rarely seek medical attention for complications of abuse. The most common side effects are severe headache, dizziness, orthostatic hypotension, and occasionally syncope. These effects are a result of smooth muscle relaxation. Nitrites can be oxidizing agents and as such, can cause methemoglobin formation. However, clinically significant methemoglobinemia is extremely rare as a complication of nitrite abuse.


The hallucinogen class of drugs includes LSD, PCP, psilocybin, peyote, mescaline, dimethyltryptamine (DMT), morning glory seeds, serenity-tranquility-peace pill (STP), jimsonweed, dextromethorphan, MDMA, MDA, and MDEA. The term hallucinogen (“producer of hallucinations”) is actually a misnomer, because prototypical hallucinogens such as LSD, mescaline, and psilocybin at typical dosage levels do not cause hallucinations (sensory perception changes without a corresponding environmental stimulus) but rather illusions (perceptual distortion of a real environmental stimulus) or distortions of perceived reality. True hallucinations do occur with the use of volatile solvents such as gasoline. Set (the user's attitudes and expectations) and setting (the drug-taking environment) greatly influence a user's experience with this class of drugs. With the exception of the hallucinogenic amphetamines, physical withdrawal does not occur. However, long-term recrudescence of fleeting distortions and illusions, termed “flashbacks,” are not uncommon, and can occur despite abstinence from further experimentation with the drug.

Overall, the prevalence of hallucinogen use decreased in the late 1970s and early 1980s and then began a slow but definite rise in the late 1980s that continued into the 1990s until about 1997, after which rates have again fallen somewhat. Two trends emerging from the “pop culture” scene are partially responsible for the resurgence of LSD and the emergence of the use of MDMA (ecstasy), a hallucinogenic methamphetamine derivative. “Raves” “house” or “circuit” parties (see pages 916–918) involve alternative forms of rock music played in coordination with colorful, pulsating light effects and augmented by the use of LSD or MDMA. Frequently, the drugs are supplied as part of the admission price or by the organizers of the event. An extremely important fact should be remembered in regard to the current patterns of LSD use. In the 1960s, doses of up to 500 µg were not unusual. The average current dose is in the 20- to 80-µg range. Most users today describe a seemingly mild “trip” with colorful visual “tracers,” enhancement of sound, and light sensations. Psychiatric emergency services are not seeing the same level of acuteness as was seen in the 1960s. There is clearly a disregard for and underestimation of the dangers of LSD because of the lower dose. However, even at this lower dosage level, one is at risk for chronic psychiatric problems, acute physical trauma, and other consequences of risk-taking behaviors that might occur under the influence of the drug.

Types of Hallucinogens

Table 71.15 contains the subgrouping of hallucinogens based on distinctive psychoactive effects and structure–activity relationship similarities.

Lysergic Acid Diethylamide

LSD was initially developed as a circulatory stimulant, when it was incidentally found to cause hallucinations. In the 1950s, LSD was marketed under the name Delsyd as a treatment for mental illness; the military also had interest in developing the drug as an agent for “mind control.” By the mid-1960s no significant medical benefits of the drug had been found, and development stopped. Nonmedical use of LSD became illegal in 1965 and medical production of the drug ended in 1966.


The abuse of LSD peaked in the 1960s and then drifted lower during the 1970s and 1980s, reaching a low prevalence rate of use (7.2%) by high school seniors by 1986. Yet the drug then experienced somewhat of a resurgence of popularity among youth in the 1990s. By 1997 the lifetime usage rate of LSD among high school seniors, at 13.6% of students, had surpassed the rate of 11.3% recorded in 1975. However, since that time its popularity has again steadily waned, such that only 3.3% of 12th graders reported that they have ever used with LSD in 2006 (Johnston et al., 2007). Corresponding rates of use in 2006 among 8th and 10th graders were 1.6% and 2.7%, respectively.



TABLE 71.15
Types of Hallucinogens and the Psychoactive Effects They Produce


Psychoactive Effect


LSD, lysergic acid diethylamide; DMT, dimethyltryptamine; MDMA, methylenedioxymethamphetamine; MDA, methylenedioxyamphetamine; MDEA, methylenedioxy-N-ethylamphetamine; PCP, phencyclidine.


Prominent hallucinations and synesthesias with mild distortion of time and reality, impaired attention/concentration, mild disruption in ego structure

·   Indolealkylamines: LSD, psilocybin, DMT

·   Phenlyalkylamines: mescaline


Structural similarities to psychedelics (mescaline) and amphetamines; unique psychoactive characteristics include improved communication, empathy with others, and positive mood enhancement


Dissociative anesthetics

Causes anesthesia, emergence reactions, and ‘out of body’ experiences

PCP, ketamine


Mild distortion of time, impaired attention/concentration, mild mood enhancement, euphoria and feelings of well-being


Preparation and Dose

LSD is derived from an alkaloid found in rye fungus. It is made by mixing lysergic acid with diethylamide, freezing the mixture, and then extracting the resulting LSD. The procedure is not easy; therefore, much of the LSD sold on the street is either adulterated or contains no LSD.

LSD is an extremely potent drug with doses measured in micrograms. Low doses of LSD (50–75 µg) produce euphoria whereas higher doses result in typical LSD illusions or “trips.” In the 1960s the typical illicit dose of LSD was 100 to 300 µg; currently, the usual dose is 20 to 80 µg.

Routes of Administration and Street Names

The drug is commonly distributed as a soluble powder or liquid. It is usually colorless, odorless, and tasteless in its manufactured state, but it is most often colored when sold. It is sold as cylindrical tablets or gelatin squares or applied to small pieces of paper; these preparations are known on the street, respectively, as microdots, windowpanes, and blotters. LSD is also sold as decals or stickers. The drug is ingested by placing the blotter on the tongue where it is dissolved in saliva and absorbed through the mucus membranes. LSD can also be mixed in with foods or liquids for oral consumption; liquid LSD can be absorbed through the mucus membranes of the eyes. LSD cannot be smoked as it gets destroyed with heat.

Slang names for LSD include acid, beast, big D, black, blue barrels, blotters, blue cheer, boomers, brown dot, cubes, fry, microdots, orange sunshine, panes, sugar, sunshine, trips, white lightning, window panes, and yellow sunshine.

Physiology and Metabolism

LSD is rapidly absorbed from the gastrointestinal tract, with onset of action in 30 to 40 minutes. It binds to receptors throughout the CNS, including the hippocampus, corpus striatum, cerebral cortex and cerebellum. Its main effects result in the inhibition of release of serotonin, which allows increased firing of sensory neurons, as well as resulting in a nonspecific stress response and resulting autonomic changes. The increased reactivity of sensory neurons results in visual and auditory distortions, which form the basis of hallucinations. See Table 71.16 for hallucinogen physiology.

TABLE 71.16
Hallucinogen Physiology




Metabolism and Excretion

Nonspecific intracellular binding throughout the central nervous system

Inhibition of serotonin release, resulting in:

·   Increased firing of sensory neurons

·   Nonspecific stress response

Primarily protein bound

Rapidly absorbed through the gastrointestinal (GI) tract

·   Onset of action is 30–40 minutes

·   Half-life is 3 hours

Effects of Intoxication

LSD intoxication results in euphoria and sensory illusions which may give rise to hallucinations. Symptoms of intoxication include dilated pupils, conjunctival injection,


hyperthermia, tachycardia, hypertension, flushing, and tremor. The sense of being an observer is frequently reported by LSD users and distinguishes LSD psychosis from schizophrenia.

Adverse Effects

  1. Psychiatric: Visual and auditory hallucinations, synesthesias, depersonalization, loss of sense of time, loss of ego boundaries, impairment of attention, motivation and concentration, anxiety, depression, paranoia, confusion, flashbacks.
  2. Neurological: Flushing, hyperthermia, piloerection, dizziness, paresthesia, dilated pupils, blurred vision, conjunctival injection, lacrimation, hyperactive reflexes, ataxia and tremor, loss of muscle coordination and pain perception, restlessness and sleep disturbances.
  3. Cardiovascular: Hypertension and tachycardia.
  4. Gastrointestinal: Anorexia, nausea, dry mouth.

Overdose and Emergency Treatment

LSD overdose may result in grand mal seizures, circulatory collapse, coagulopathies, and coma. Treatment is supportive. LSD can be readily detected in urine by thin layer chromatography or other analytical techniques.

Some LSD users experience “bad trips,” which are negative emotional responses triggered both by the circumstances of use as well as feelings within the user. These responses terrify the user and may produce a sense of panic, fragmentation, or fear of “going crazy.” LSD users may also experience “flashbacks” or the recurrence of the LSD-induced state after the effects of the drug have worn off. Flashbacks may occur spontaneously for variable lengths of time after original drug ingestion. Concurrent use of selective serotonin reuptake inhibitor agents may induce or worsen the LSD flashback syndrome (Markel et al., 1994), possibly as a result of the similarities in serotonin receptor physiology. Important components of treatment include providing a peaceful, calm environment (darkened lights, few extraneous stimuli), and helping the patient to restore contact with reality. The health care provider should try to calm the user by talking to him or her about familiar things. The patient should be reassured that his or her unusual sensations will cease when the drug wears off. The helping individual should listen carefully to the patient and respond sympathetically. Health care providers should avoid discussing the reasons for use of the drug or personal problems during a bad trip, and medication use should be avoided if possible. It is important to monitor the cycles of lucidity and periods of intense reactions to the drug. If the cycles are frequent, then the individual is probably early in the course of experiencing effects of the drug; if the cycles are less frequent, the drug effects may have peaked.

It is important to remember that one cannot rely on the history when managing alleged use of a hallucinogen. Especially in this class of drugs, adulteration, and misrepresentation of the substance are common. In addition, in the case of a patient with clouded sensorium and fever, even with a history of ingestion of LSD, the differential diagnosis must include CNS infection, endocrine disorder, drug or alcohol withdrawal syndrome, and ingestion of an unknown toxin.

Another dilemma occurs in the situation of the combative patient with a history of hallucinogen use. Although chemical and physical restraints are discouraged, if more passive means of calming the patient have not been effective, restraints must be used to facilitate further clinical evaluation and diagnostic testing. It is essential that every health care provider become adept at using at least one sedative and one major tranquilizer. Lorazepam is probably the best suited of the benzodiazepines because it can be given intramuscularly, intravenously, or orally and is more effective than diazepam as an anticonvulsant. Haloperidol and droperidol are superior to the phenothiazines because they have fewer cardiovascular side effects such as hypotension. Droperidol has come into favor recently because of its more rapid onset of action and shorter half-life and because it is approved for intravenous use. It is also more sedating than haloperidol. A cautionary note is that the major tranquilizers can also lower the seizure threshold.

Chronic Use

Chronic adverse effects may include psychosis, depression, and personality changes. The use of a hallucinogen should be considered in the differential diagnosis of an adolescent who presents with a new onset of psychosis.

Tolerance and Withdrawal

Tolerance to LSD develops rapidly but is short lived. Some daily users of LSD describe the practice of “doubling up” (doubling the previous day's dose when using on consecutive days) to counteract tolerance. No withdrawal syndrome is described, although “flashbacks” are common and can be persistent.



The use of PCP has steadily declined from a high of 12.8% in the late 1970s to a lifetime prevalence use of only 2% to 4% through the 1990s, dropping further to only 2.2% of 12th graders in 2006 (Johnston et al., 2007). Only 0.7% of high school seniors reported using PCP within the previous 12 months in 2006.

Preparation and Dose

PCP (Sernyl) is an arylamine (1-[1-phenyl{cyclohexyl} piperidine]) introduced in the 1950s as a general anesthetic. It is structurally related to ketamine. Clinical trials revealed PCP to be an effective anesthetic, but during surgical recovery the emergence reactions to PCP were frequent and unpleasant, with excessive agitation, excitement, and disorientation. A “drowning swimmer” phenomenon, with feelings of imminent suffocation, was prominent. In 1965, the drug was discontinued as a medicinal product for human use. In the late 1960s, its use increased in San Francisco as an experimental psychedelic drug, called the “peace pill.” It was unpopular at that time because of excessive reports of bad trips. However, during the middle and late 1970s its popularity increased tremendously, and it became one of the nation's major drugs of abuse. Until 1978, the drug was still legally manufactured as Semylan for veterinary anesthesia. Dose ranges vary tremendously, from 0.1 to more than 150 mg in one survey. In addition, approximately 20% of drug samples sold as PCP contained no PCP. In terms of potency, <5 mg is considered a low dose, 5 to 10 mg a moderate dose, and >10 mg a high dose.



Routes of Administration and Street Names

PCP may be packaged as a liquid, powder, tablet, leaf mixture, or rock crystal. It can be used intravenously (average dose, 10 mg), intramuscularly, or orally (average dose, 5 mg), or it can be snorted (average dose, 5 mg) or smoked (average dose, 3 mg). Street names for PCP include angel dust, dummy dust, magic dust, peace, peace pill, rocket fuel, whack, zombie weed, and zoom.

Physiology and Metabolism

PCP is the hydrogen chloride salt of PCP. It is a dissociative anesthetic with analgesic, stimulant, depressant, and hallucinogenic properties. The pharmacology of PCP is complex and not fully understood. Its major psychiatric effects are thought to be the result of binding to the glutamate-NMDA receptors, to increase the production of dopamine and inhibit reuptake. The drug acts on the thalamus, midbrain, and sensory cortex to impair proprioception and the brain's ability to organize input. PCP is rapidly inactivated by hepatic metabolism and is excreted in the urine as monopiperidine conjugate. Because PCP is fat soluble, it has the ability to remain in the body for prolonged periods. Its urinary excretion is highly dependent on urine pH, with significantly higher excretion rates at an acidic pH. The half-life of PCP is 3 days. See Table 71.17 for phencyclidine physiology.

TABLE 71.17
Phencyclidine Physiology




Metabolism and Excretion

Glutamate-N-methyl-D-aspartate (NMDA) receptors

·   Increases the production of dopamine

·   Inhibits dopamine reuptake

Metabolites are fat soluble, although not physiologically active

·   Metabolized by the liver to monopiperidine conjugate

·   pH dependent urinary excretion

Effects of Intoxication

The clinical symptoms of PCP use vary with the dose, the route of administration, and the experience of the user. Intravenous, intramuscular, and oral routes of administration are more difficult to regulate than the smoking of PCP. In addition, inexperienced users have more side effects than experienced users do. PCP usually induces one of several clinical states (see Table 71.18 for PCP intoxication states).

TABLE 71.18
Phencyclidine Intoxication States

Acute intoxication

Delusion, disinhibition, dissociation (“out of body” experience)

Acute or prolonged delirium

Disorientation, clouded consciousness, and abnormal cognition

Schizophreniform psychosis

Hallucinations, thought disorder, and delusions


Hallucinations, elevated mood, elevated self-attitude, feelings of omnipotence

Depressive reactions

Dysphoria, social withdrawal, paranoia, isolation

PCP is the only drug of abuse that causes a characteristic vertical nystagmus. It can also cause horizontal or rotatory nystagmus. Other symptoms include ataxia, miosis with reactive pupils, hypertension, and increased deep tendon reflexes.


The diagnosis of PCP use should be suspected in all adolescents with a distorted thought process, especially when there is evidence of analgesia or nystagmus. Any individual with open-eye coma, horizontal and vertical nystagmus, hypertension, and rigidity should be considered to have taken PCP. PCP can be detected in the blood, urine, and gastrointestinal secretions; the best fluid to sample is the urine. A serum concentration of 25 to 100 ng/mL may be found in patients who are in an acute state of confusion; a level of >100 ng/mL may be found in comatose patients. The urinary concentration may vary in different clinical states. Excretion in the urine is highly pH dependent and decreases dramatically as the pH becomes alkaline.

Adverse Effects

Adverse effects associated with PCP use are dose related (Table 71.19).

Overdose and Emergency Treatment

PCP use may result in generalized motor seizures either early in the course of intoxication or delayed in appearance. Hypertension is usually mild, but there was one reported case of hypertensive cerebral hemorrhage in a 13-year-old adolescent (Eastman et al., 1975). Cogen et al (1978) reported rhabdomyolysis in patients with PCP poisoning, due to increased muscular contractions, muscle rigidity, and increased tone. Death can occur and is usually caused by injuries sustained during periods of analgesia and aggression directed at self or others. Death can also occur


as a result of convulsions and cerebral hemorrhage. One case report described an infant with abnormal behavior and abnormal facies born to a mother who used PCP (Golden et al., 1980).

TABLE 71.19
Adverse Effects of Phencyclidine by Dose

Low dose (<5 mg)


Blank stare
Horizontal and vertical nystagmus
Increased deep tendon reflexes
Decreased proprioception and sensations
Miosis or midposition, reactive pupils

Behavioral disorders:

·   Disorganized thought processes

·   Distortion of body image and of objects

·   Amnesia

·   Agitated or combative behavior

·   Unresponsive behavior

·   Disinhibition of underlying psychopathology

·   Schizophrenic reactions

·   Catalepsy, catatonia

·   Illusions

·   Anxiety, excitement

Moderate dose (5–10 mg)


Vertical and horizontal nystagmus
Midposition pupil size

Anxiety, excitement

·   Stupor or extreme agitation

·   Violent or psychotic behavior can occur

High dose (>10 mg)


Unresponsive, immobile state
Eyes that may remain open during coma
Increased deep tendon reflexes
Muscle rigidity
Decerebrate posturing

Spontaneous nystagmus
Decreased urine output
Diaphoresis and flushing

Extremely high dose (>500 mg)


Prolonged coma
Extensor (decerebrate) posturing

Hypertension or hypotension
Prolonged and fluctuating confusional state after recovery from coma

Reduction of stimuli:

When treating patients with PCP overdose, health care providers must use extreme caution. Patients are unpredictable and often have little awareness of the consequences of their behavior. Reducing the levels of light, sound, and other external stimuli can rapidly calm down a PCP user. In an emergency, covering the intoxicated patient with a blanket may be helpful. All hazards should be removed from the environment. Patients should not be touched or cornered. Restraints are not recommended; they may cause the patient to harm himself or herself in an attempt to escape. Health care providers should not attempt to talk to a patient who has recently used PCP.

Supportive care:

Treatment for PCP overdose is largely supportive. In addition to basic cardiopulmonary resuscitation, it is essential to check for signs of head, neck, back, and internal injuries, which can occur because of the behavioral effects of the drug. Unconscious victims should be placed on their side so that aspiration does not occur.


Try to avoid administering other medications, but, if necessary, intravenous diazepam or lorazepam can be used to treat seizures. Severe agitation and psychosis can be treated with haloperidol. Avoid phenothiazines and neuroleptics because of the risk of excessive orthostatic hypotension and the potential for enhancing the cholinergic imbalance. Intravenous diphenhydramine may be used for dystonias.


Recovery usually occurs within 24 hours but can take days, depending on the dose and the acidity


of the urine. During the recovery phase, an adolescent may require short-term inpatient psychiatric care to deal with paranoia, regressive behavior, and a slow phase of reintegration. With higher doses the coma can last 5 to 6 days and can be followed by a prolonged recovery period marked by behavioral disorders. Cognitive, memory, and speech disorders may last up to 1 year after the last use of PCP. Flashbacks may occur, as with LSD.


Dextromethorphan, the dextro isomer of the codeine analog, levorphanol, has a chemical structure resembling a synthetic opiate, but lacks an opiate's potent analgesic, sedative, or addicting properties. The drug's prominent antitussive properties make it a common ingredient in nonprescription cough and cold syrups, usually in amounts of 10 to 15 mg per teaspoon or per tablespoon. While the use of most hallucinogens is on the decline, the misuse of over-the-counter cold and cough medicines as an inexpensive “high” is one of the fastest growing drugs of abuse. Maximum daily doses range from 30 mg for children to 120 mg for adults. Those engaged in substance abuse may drink 8 to 16 oz of such a cough syrup in an attempt to get high. The volume of cough syrup required to get “high” has led adolescents to order the pure, highly concentrated powder from Internet sources, or to purchase high concentration dextromethorphan-containing tablets such as Coricidin products instead (Kirages et al., 2003). Street language describes the abuse of dextromethorphan as “Robing out,” “robo-copping,” “triple C,” “DXMing,” or “Dexing.” Dextromethorphan can induce euphoria, and produce dissociative effects.

Physiology and Metabolism

Dextromethorphan in high doses binds to opiate sigma receptors, which may account for some of its sedative and psychomimetic properties. The drug is metabolized by O-demethylation to an active metabolite, dextrorphan, which interacts with the same PCP receptor in NMDA neurotransmitter complex. This primary metabolism is under the control of hepatic cytochrome complex, CYP2D6, whose genetic polymorphisms may explain why some users are more susceptible to adverse effects than others (Zawertailo et al., 1998). The dug undergoes secondary conjugation in the liver to inactive glucuronide and sulfate esters, and has an elimination half-life of approximately 3.3 hours.


The actions of dextrorphan may explain dextromethorphan's PCP-like symptoms in overdose (Szekely et al., 1991). It can produce somnolence and ataxia, slurred speech, hallucinations, dysphoria, nystagmus, dystonia, tachycardia, and elevated blood pressure. Dextromethorphan also blocks presynaptic serotonin reuptake and has dopaminergic properties. Dextromethorphan may interact with other drugs, including selective serotonin reuptake inhibitors, MAO inhibitors, tricyclic antidepressants, and lithium, to produce movement disorders or the serotonin syndrome of rigidity and hyperthermia. It is also fetotoxic in animal studies.


Routine toxic screening of the blood for opiates may remain negative despite recent use of dextromethorphan. However in some cases depending on concentration, the test for PCP may be weakly positive in dextromethorphan poisoning. Treatment is supportive; the role of naloxone is not well established although there are case reports of its efficacy (Schneider et al., 1991). Health care providers should note that dextromethorphan poisonings often involve concomitant intoxications with other ingredients in over the counter cold medications such as acetaminophen, antihistamines, pseudoephedrine, and guaifenesin, for which additional medical therapies may be necessary (Schwartz, 2005). Because dextromethorphan is formulated as a hydrobromide salt, an overdose with the drug can also produce toxic effects, such as somnolence, related to bromide poisoning.


Mushrooms containing psilocybin and psilocin produce effects similar to those of the other hallucinogens. Users reportedly experience euphoria, prominent visual and auditory hallucinations and synesthesias (i.e., perceptual distortions resulting in an apparent ability to visualize sounds or hear colors). The mushrooms are ingested orally, and there is a rapid onset of effects in approximately 15 minutes. The effects peak at 90 minutes, begin to wear off in 2 to 3 hours, and disappear after approximately 5 or 6 hours. The average dose is 4 to 10 mg of psilocybin. Street names for psilocybin mushrooms include “shrooms,” mushrooms, Silly Putty, magic Mexican mushrooms, and psychedelic mushrooms. Because many other species can be confused with true psilocybe mushrooms, ingestion of misidentified, toxic non-psilocybe species can pose a special danger to users.

Jimson Weed

Jimson weed (Datura stramonium) is an annual plant found growing wild along roadways and railroad trestles in many parts of the United States, Canada, and the West Indies. Also known as locoweed, thorn apple, devil's apple, angel's trumpet and stink weed, the plant has anticholinergic and mildly hallucinogenic properties. Seed-containing pods ripen in the late summer and autumn. The toxins in the seeds, leaves and roots include tropane belladonna alkaloids such as hyoscyamine, atropine, and scopolamine, with the highest concentrations of these alkaloids present in the seeds. These chemicals act as competitive antagonists to acetylcholine at both central and peripheral parasympathetic receptor sites, with paralysis of parasympathetic innervated organs. Peripheral receptors include exocrine glands controlling sweating, salivation, and smooth and cardiac muscle cells. As tertiary amines, they also cross the blood brain barrier to cause a central anticholinergic syndrome.

Adolescents make tea from the seeds, eat the seeds themselves, or smoke cigarettes made from jimson weed. Pleasurable effects include mild euphoria and hallucinations. However these are more than offset by severe retching, abdominal pain, agitation, headaches, respiratory arrest, and coma. First-time users who experience many of the adverse effects rarely experiment with jimsonweed again. Onset of symptoms is usually within an hour or two; the delayed gastric emptying and slow intestinal motility attributable to anticholinergic effects may prolong the duration of symptoms in untreated patients for as long as several days.



Users may present to the emergency room with the dry mouth, dilated pupils, urinary retention, flushed warm dry skin, tachycardia, and hypo- or hypertension. Decontamination using oral activated charcoal is recommended. Agitated delirium is typical of the central anticholinergic syndrome and will usually resolve upon administration of a benzodiazepine sedative or the cholinergic agent, physostigmine. (Note: Physostigmine should be reserved for only the most severe poisonings and used with precautions such as ECG monitoring, because the administration of cholinergic agents can themselves induce seizures, cholinergic crisis, bradyarrhythmia or asystole). Elevated body temperature remits with the use of fans, cooling blankets, and antipyretics. Repeated retching after jimsonweed use is common and may require treatment with antiemetics; catheterization of the bladder may be necessary to treat urinary retention.

Peyote and Mescaline

Peyote is a cactus (Lophophora) that grows in the southwestern United States and in Mexico. The tops of the cactus contain numerous alkaloids, including mescaline (3,4,5-trimethoxyphenethylamine), but they are difficult to find and not readily available to the drug abuse marketplace. Most drugs sold as “mescaline” capsules contain no mescaline, but rather contain LSD, PCP, both LSD and PCP, or something else. Peyote is sold either as buttons derived from the cactus or as capsules containing ground peyote. Street names include big chief, buttons, cactus, mesc, and mescal. The usual human dose ranges from 100 to 500 mg.

Mescaline has its onset of action within 30 minutes to 2 hours after ingestion, and the effects last for 6 to 12 hours. The mescaline high is less intense and less disorienting than LSD and tends to intensify body sense (as opposed to LSD which has a stronger effect on the mind). Mescaline use is frequently accompanied by unpleasant side effects such as nausea and vomiting.

Bad trips are less severe and less frequent with mescaline than with LSD, though tolerance and dependence do occur.

Serenity-Tranquility-Peace Pill

STP (also known as the “serenity-tranquility-peace pill”) is related to mescaline but approximately 100 times more potent. Its effects are also similar to those of other hallucinogenic drugs, with the exception that with STP the incidence of unpleasant sensations is increased and the effects seem to last longer, up to 72 hours.


DMT is a natural constituent of the seeds of several plants found in the West Indies and South America. DMT is usually prepared as an orange liquid in which either tobacco, marijuana, or parsley is soaked and then smoked; it is inactive orally. This drug has effects similar to those of other hallucinogens, except that the “trip” is short, lasting only 1 to 3 hours. DMT is known on the street as the “businessman's special” or “businessman's lunch.”

Morning Glory Seeds

The seeds of some members of the bindweed family, including the morning glory (Rivea corymbosa and Ipomoea), have been used for centuries for their hallucinogenic effects. Morning glory seeds are legally available on seed racks, but, to prevent spoilage, seeds intended for planting are usually coated with dangerous chemicals such as methyl mercury. The active principal ingredient in the seeds is similar to LSD but approximately one tenth as potent. The effects of morning glory seeds are similar to those of LSD; however, there is an increase in side effects such as nausea, dizziness, and diarrhea, and there is an extremely bitter taste.


Nutmeg is extracted from the dried seed kernels of an evergreen tree found in the South Pacific Islands. This common spice is ubiquitous in household pantries, and outbreaks of its use usually follow media reports of its hallucinogenic properties. However the dried spice quickly loses its potency on the shelf. Fresh nutmeg contains terpene hydrocarbons (e.g., pinene, camphene) as well as eugenol, safrole, borneol, and several hallucinatory allylbenzene derivatives, such as myristicin and elemicin, which can be converted into hallucinogenic amphetamine and mescaline-like congeners. Abuse requires the ingestion of large quantities of freshly ground seed, because the volatile oils, comprising 8% to 15% of a nutmeg by weight, are necessary for its CNS effects. Users typically grind and swallow 3 to 10 or so nutmegs (approximately 20–80 g of powder), containing approximately 3 to 10 g of the myristicin-containing oil (Stein et al., 2001). Effects include delirium, hallucinations, and euphoria, with onset within 30 minutes or so. One 13-year old girl developed visual, auditory, and tactile hallucinations after ingesting 15 to 24 g of nutmeg and smoking marijuana; she recovered after receiving decontamination with oral activated charcoal (Sangalli et al., 2000).

The presence of an extremely potent emetic, geraniol, has discouraged widespread use. The predominant effects of nutmeg overdose are anticholinergic mydriasis, dry mouth, tachycardia, dizziness and repeated vomiting. Some patients may experience anxiety reactions with agitation and restlessness. Others may develop allergic reactions and rashes (Van den Akker et al., 1990). One 18-year-old woman developed severe anxiety, dilated pupils, dry mouth, palpitations, dizziness, tachycardia, and a “trance-like” state, but no hallucinations, 30 minutes after drinking a milk shake containing 50 g of grated nutmeg (Demetriades et al., 2005). She was rehydrated and reassured, and symptoms had resolved 16 hours after the ingestion.

Anabolic Steroids

Anabolic steroids are synthetic derivatives of testosterone (see also Chapter 18). Abusers of this class of drug exhibit tolerance, withdrawal, and psychological dependence. Treatment may require detoxification and a rehabilitation phase comparable to traditional drug treatment.



The numerous agents fit into two basic categories: the oral agents are 17α-methyl derivatives of testosterone, and the injectable agents are esters of testosterone and 19-nortestosterone. The ideal steroid would have maximal anabolic and minimal androgenic activity and a longer half-life than the parent compound, testosterone. The 17α-alkylated steroids have a half-life of 8 to 10 hours, whereas the injectable forms have half-lives in the range of 21 days. Although these agents have less androgenic activity in lower dosage ranges, this advantage is lost at higher doses. Many abusers use 10 times the usual therapeutic dose and use combinations of oral and injectable agents concurrently in 6- to 12-week cycles (“stacking”).

Prevalence and Epidemiology

Use of anabolic steroids by high school students has remained steady, with 1.6% of 8th graders, 1.8% of 10th graders, and 2.7% of 12th graders in 2006 reporting that they have experimented with steroids at least once in their life (Johnston et al., 2007). Annual prevalence of use rates in 2006 slipped to 0.9% in 8th graders (1.7% in 2000), 1.2% of 10th graders (2.2% in 2000) and 1.8% of 12th graders (2.5% in 2004). Whereas it was previously thought that only male athletes used steroids and only for strength training, and that these students did not abuse other drugs, these assumptions were shown by Durant et al. (1993; 1995) to be false. Those students using anabolic steroids were also likely to be engaging in other forms of substance abuse. These researchers analyzed the Centers for Disease Control's Youth Risk Behavior Survey of 12,272 high school students and found that males outnumbered females in steroid use 4:1, but that females also reported steroid use for increasing strength and muscle tone. Adolescent steroid users were more likely than other students to engage in injected drug use and use of other substances such as cocaine, tobacco, amphetamines, and alcohol. In the 2005 Youth Risk Behavior Survey, 4.8% of males in high school and 3.2% of females reported ever having used steroids illegally.

Adverse Effects

  1. Psychiatric: Psychosis, mania, mood swings, hyperaggressive behavior, violence. Withdrawal may be associated with depression.
  2. Cardiovascular: Decreased high density lipoprotein cholesterol, hypertension, ventricular remodeling, myocardial ischemia, sudden death.
  3. Endocrine: Premature epiphyseal closure and shortened stature, female virilization and hypogonadism, testicular atrophy, reduced libido, infertility.
  4. Other: Acne, hemolysis, enlarged prostate gland, hepatocellular carcinoma with chronic use.

Treatment of Withdrawal or Dependence

Patients exhibiting psychotic behavior or severe depression require inpatient care. Appropriate pharmacological intervention with antipsychotic, antidepressant, and anxiolytic agents may be indicated, usually for a short period. For the patient meeting DSM-IV criteria (3 of 12 listed) for substance dependence, a traditional drug treatment approach is indicated. Attending 12-step meetings and “working a program” are ideal methods to provide the adolescent with a conceptual framework to work through this problem.

Web Sites

General Monitoring the future is a large epidemiologic survey of the behaviors, attitudes and values of American secondary students, college students and adults. National Institute on Drug Abuse (NIDA), NIH. The Mind Over Matter series is designed to encourage young people in grades 5 through 9 to learn about the effects of drug abuse on the body and the brain. The types of drugs discussed include inhalants, hallucinogens, steroids, opiates, and nicotine. The series also offers a teachers' guide that provides background information and lesson plans. Information from NIDA on many drugs Information on side effects of drugs of abuse from NIDA

Specific Substances


Club Drugs



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