16. Substance-Related and Addictive Disorders

The Substance-Related disorders encompass 10 separate classes of drugs: alcohol; caffeine; cannabis; hallucinogens (with separate categories for phencyclidine [or similarly acting arylcyclohexylamines] and other hallucinogens); inhalants; opioids; sedatives, hypnotics, and anxiolytics; stimulants (amphetamine-type substances, cocaine, and other stimulants); tobacco; and other (or unknown) substances. These 10 classes are not fully distinct. All drugs that are taken in excess have in common direct activation of the brain reward system, which is involved in the reinforcement of behaviors and the production of memories. They produce such an intense activation of the reward system that normal activities may be neglected. Instead of achieving reward system activation through adaptive behaviors, drugs of abuse directly activate the reward pathways. The pharmacological mechanisms by which each class of drugs produces reward are different, but the drugs typically activate the system and produce feelings of pleasure, often referred to as a ''high." Furthermore, individuals with lower levels of self-control, which may reflect impairments of brain inhibitory mechanisms, may be particularly predisposed to develop substance use disorders, suggesting that the roots of substance use disorders for some persons can be seen in behaviors long before the onset of actual substance use itself.

In addition to the substance-related disorders, this chapter also includes gambling disorder, reflecting evidence that gambling behaviors activate reward systems similar to those activated by drugs of abuse and produce some behavioral symptoms that appear comparable to those produced by the substance use disorders. Other excessive behavioral patterns, such as Internet gaming, have also been described, but the research on these and other behavioral syndromes is less clear. Thus, groups of repetitive behaviors, which some term behavioral addictions, with such subcategories as "sex addiction," "exercise addiction," or "shopping addiction," are not included because at this time there is insufficient peer-reviewed evidence to establish the diagnostic criteria and course descriptions needed to identify these behaviors as mental disorders.

The substance-related disorders are divided into two groups: substance use disorders and substance-induced disorders. The following conditions may be classified as substance- induced: intoxication, withdrawal, and other substance/medication-induced mental disorders (psychotic disorders, bipolar and related disorders, depressive disorders, anxiety disorders, obsessive-compulsive and related disorders, sleep disorders, sexual dysfunctions, delirium, and neurocognitive disorders).

The current section begins with a general discussion of criteria sets for a substance use disorder, substance intoxication and withdrawal, and other substance/medicationinduced mental disorders, at least some of which are applicable across classes of substances. Reflecting some unique aspects of the 10 substance classes relevant to this chapter, the remainder of the chapter is organized by the class of substance and describes their unique aspects. To facilitate differential diagnosis, the text and criteria for the remaining substance/medication-induced mental disorders are included with disorders with which they share phenomenology (e.g., substance/medication-induced depressive disorder is in the chapter "Depressive Disorders").

16.1 Substance-Related Disorders

16.1.1 Alcohol-Related Disorders

16.1.1.1 Alcohol Use Disorder

Diagnostic Features

Alcohol use disorder is defined by a cluster of behavioral and physical symptoms, which can include withdrawal, tolerance, and craving. Alcohol withdrawal is characterized by withdrawal symptoms that develop approximately 4-12 hours after the reduction of intake following prolonged, heavy alcohol ingestion. Because withdrawal from alcohol can be unpleasant and intense, individuals may continue to consume alcohol despite adverse consequences, often to avoid or to relieve withdrawal symptoms. Some withdrawal symptoms (e.g., sleep problems) can persist at lower intensities for months and can contribute to relapse. Once a pattern of repetitive and intense use develops, individuals with alcohol use disorder may devote substantial periods of time to obtaining and consuming alcoholic beverages.

Craving for alcohol is indicated by a strong desire to drink that makes it difficult to think of anything else and that often results in the onset of drinking. School and job performance may also suffer either from the aftereffects of drinking or from actual intoxication at school or on the job; child care or household responsibilities may be neglected; and alcohol-related absences may occur from school or work. The individual may use alcohol in physically hazardous circumstances (e.g., driving an automobile, swimming, operating machinery while intoxicated). Finally, individuals with an alcohol use disorder may continue to consume alcohol despite the knowledge that continued consumption poses significant physical (e.g., blackouts, liver disease), psychological (e.g., depression), social, or interpersonal problems (e.g., violent arguments with spouse while intoxicated, child abuse).

Associated Features Supporting Diagnosis

Alcohol use disorder is often associated with problems similar to those associated with other substances (e.g., cannabis; cocaine; heroin; amphetamines; sedatives, hypnotics, or anxiolytics). Alcohol may be used to alleviate the unwanted effects of these other substances or to substitute for them when they are not available. Symptoms of conduct problems, depression, anxiety, and insomnia frequently accompany heavy drinking and sometimes precede it.

Repeated intake of high doses of alcohol can affect nearly every organ system, especially the gastrointestinal tract, cardiovascular system, and the central and peripheral nervous systems. Gastrointestinal effects include gastritis, stomach or duodenal ulcers, and, in about 15% of individuals who use alcohol heavily, liver cirrhosis and/or pancreatitis. There is also an increased rate of cancer of the esophagus, stomach, and other parts of the gastrointestinal tract. One of the most commonly associated conditions is low-grade hypertension. Cardiomyopathy and other myopathies are less common but occur at an increased rate among those who drink very heavily. These factors, along with marked increases in levels of triglycerides and low-density lipoprotein cholesterol, contribute to an elevated risk of heart disease. Peripheral neuropathy may be evidenced by muscular weakness, paresthesias, and decreased peripheral sensation. More persistent central nervous system effects include cognitive deficits, severe memory impairment, and degenerative changes in the cerebellum. These effects are related to the direct effects of alcohol or of trauma and to vitamin deficiencies (particularly of the B vitamins, including thiamine). One devastating central nervous system effect is the relatively rare alcohol-induced persisting amnestic disorder, or Wemicke-Korsakoff syndrome, in which the ability to encode new memory is severely impaired. This condition would now be described within the chapter "Neurocognitive Disorders" and would be termed a substance/medication-induced neurocognitive disorder.

Alcohol use disorder is an important contributor to suicide risk during severe intoxication and in the context of a temporary alcohol-induced depressive and bipolar disorder. There is an increased rate of suicidal behavior as well as of completed suicide among individuals with the disorder.

Prevalence

Alcohol use disorder is a common disorder. In the United States, the 12-month prevalence of alcohol use disorder is estimated to be 4.6% among 12- to 17-year-olds and 8.5% among adults age 18 years and older in the United States. Rates of the disorder are greater among adult men (12.4%) than among adult women (4.9%). Twelve-month prevalence of alcohol use disorder among adults decreases in middle age, being greatest among individuals 18- to 29-years-old (16.2%) and lowest among individuals age 65 years and older (1.5%). Twelve-month prevalence varies markedly across race/ethnic subgroups of the U.S. population. For 12- to 17-year-olds, rates are greatest among Hispanics (6.0%) and Native Americans and Alaska Natives (5.7%) relative to whites (5.0%), African Americans (1.8%), and Asian Americans and Pacific Islanders (1.6%). In contrast, among adults, the 12-month prevalence of alcohol use disorder is clearly greater among Native Americans and Alaska Natives (12.1%) than among whites (8.9%), Hispanics (7.9%), African Americans (6.9%), and Asian Americans and Pacific Islanders (4.5%).

Culture-Related Diagnostic Issues

In most cultures, alcohol is the most frequently used intoxicating substance and contributes to considerable morbidity and mortality. An estimated 3.8% of all global deaths and 4.6% of global disability-adjusted life-years are attributable to alcohol. In the United States, 80% of adults (age 18 years and older) have consumed alcohol at some time in their lives, and 65% are current drinkers (last 12 months). An estimated 3.6% of the world population (15-64 years old) has a current (12-month) alcohol use disorder, with a lower prevalence (1.1%) found in the African region, a higher rate (5.2%) found in the American region (North, South, and Central America and the Caribbean), and the highest rate (10.9%) found in the Eastern Europe region.

Polymorphisms of genes for the alcohol-metabolizing enzymes alcohol dehydrogenase and aldehyde dehydrogenase are most often seen in Asians and affect the response to alcohol. When consuming alcohol, individuals with these gene variations can experience a flushed face and palpitations, reactions that can be so severe as to limit or preclude future alcohol consumption and diminish the risk for alcohol use disorder. These gene variations are seen in as many as 40% of Japanese, Chinese, Korean, and related groups worldwide and are related to lower risks for the disorder.
Despite small variations regarding individual criterion items, the diagnostic criteria perform equally well across most race/ethnicity groups.

Gender-Related Diagnostic issues

Males have higher rates of drinking and related disorders than females. However, because females generally weigh less than males, have more fat and less water in their bodies, and metabolize less alcohol in their esophagus and stomach, they are likely to develop higher blood alcohol levels per drink than males. Females who drink heavily may also be more vulnerable than males to some of the physical consequences associated with alcohol, including liver disease.

Functional Consequences of Alcohol Use Disorder

The diagnostic features of alcohol use disorder highlight major areas of life functioning likely to be impaired. These include driving and operating machinery, school and work, interpersonal relationships and communication, and health. Alcohol-related disorders contribute to absenteeism from work, job-related accidents, and low employee productivity. Rates are elevated in homeless individuals, perhaps reflecting a downward spiral in social and occupational functioning, although most individuals with alcohol use disorder continue to live with their families and function within their jobs.

Alcohol use disorder is associated with a significant increase in the risk of accidents, violence, and suicide. It is estimated that one in five intensive care unit admissions in some urban hospitals is related to alcohol and that 40% of individuals in the United States experience an alcohol-related adverse event at some time in their lives, with alcohol accounting for up to 55% of fatal driving events. Severe alcohol use disorder, especially in individuals with antisocial personality disorder, is associated with the commission of criminal acts, including homicide. Severe problematic alcohol use also contributes to disinhibition and feelings of sadness and irritability, which contribute to suicide attempts and completed suicides.

Unanticipated alcohol withdrawal in hospitalized individuals for whom a diagnosis of alcohol use disorder has been overlooked can add to the risks and costs of hospitalization and to time spent in the hospital.

16.1.1.2 Alcohol Intoxication

Diagnostic Features

The essential feature of alcohol intoxication is the presence of clinically significant problematic behavioral or psychological changes (e.g., inappropriate sexual or aggressive behavior, mood lability, impaired judgment, impaired social or occupational functioning) that develop during, or shortly after, alcohol ingestion (Criterion B). These changes are accompanied by evidence of impaired functioning and judgment and, if intoxication is intense, can result in a life-threatening coma. The symptoms must not be attributable to another medical condition (e.g., diabetic ketoacidosis), are not a reflection of conditions such as delirium, and are not related to intoxication with other depressant drugs (e.g., benzodiazepines) (Criterion D). The levels of incoordination can interfere with driving abilities and performance of usual activities to the point of causing accidents. Evidence of alcohol use can be obtained by smelling alcohol on the individual's breath, eliciting a history from the individual or another observer, and, when needed, having the individual provide breath, blood, or urine samples for toxicology analyses.

Associated Features Supporting Diagnosis

Alcohol intoxication is sometimes associated with amnesia for the events that occurred during the course of the intoxication ("blackouts"). This phenomenon may be related to the presence of a high blood alcohol level and, perhaps, to the rapidity with which this level is reached. During even mild alcohol intoxication, different symptoms are likely to be observed at different time points. Evidence of mild intoxication with alcohol can be seen in most individuals after approximately two drinks (each standard drink is approximately 10-12 grams of ethanol and raises the blood alcohol concentration approximately 20 mg/ dL). Early in the drinking period, when blood alcohol levels are rising, symptoms often include talkativeness, a sensation of well-being, and a bright, expansive mood. Later, especially when blood alcohol levels are falling, the individual is likely to become progressively more depressed, withdrawn, and cognitively impaired. At very high blood alcohol levels (e.g., 200-300 mg/dL), an individual who has not developed tolerance for alcohol is likely to fall asleep and enter a first stage of anesthesia. Higher blood alcohol levels (e.g., in excess of 300-400 mg/dL) can cause inhibition of respiration and pulse and even death in nontolerant individuals. The duration of intoxication depends on how much alcohol was consumed over what period of time. In general, the body is able to metabolize approximately one drink per hour, so that the blood alcohol level generally decreases at a rate of 15-20 mg/dL per hour. Signs and symptoms of intoxication are likely to be more intense when the blood alcohol level is rising than when it is falling. Alcohol intoxication is an important contributor to suicidal behavior. There appears to be an increased rate of suicidal behavior, as well as of completed suicide, among persons intoxicated by alcohol.

Prevalence

The large majority of alcohol consumers are likely to have been intoxicated to some degree at some point in their lives. For example, in 2010,44% of 12th-grade students admitted to having been "drunk in the past year," with more than 70% of college students reporting the same.

Culture-Related Diagnostic issues

The major issues parallel the cultural differences regarding the use of alcohol overall. Thus, college fraternities and sororities may encourage alcohol intoxication. This condition is also frequent on certain dates of cultural significance (e.g.. New Year's Eve) and, for some subgroups, during specific events (e.g., wakes following funerals). Other subgroups encourage drinking at religious celebrations (e.g., Jewish and Catholic holidays), while still others strongly discourage all drinking or intoxication (e.g., some religious groups, such as Mormons, fundamentalist Christians, and Muslims).

Gender-Related Diagnostic Issues

Historically, in many Western societies, acceptance of drinking and drunkenness is more tolerated for males, but such gender differences may be much less prominent in recent years, especially during adolescence and young adulthoocj.

Functional Consequences of Alcoliol intoxication

Alcohol intoxication contributes to the more than 30,000 alcohol-related drinking deaths in the United States each year. In addition, intoxication with this drug contributes to huge costs associated with drunk driving, lost time from school or work, as well as interpersonal arguments and physical fights.

16.1.1.3 Alcohol Withdrawal

Diagnostic Features

The essential feature of alcohol withdrawal is the presence of a characteristic withdrawal syndrome that develops within several hours to a few days after the cessation of (or reduction in) heavy and prolonged alcohol use (Criteria A and B). The withdrawal syndrome includes two or more of the symptoms reflecting autonomic hyperactivity and anxiety listed in Criterion B, along with gastrointestinal symptoms. Withdrawal symptoms cause clinically significant distress or impairment in social, occupational, or other important areas of functioning (Criterion C). The symptoms must not be attributable to another medical condition and are not better explained by another mental disorder (e.g., generalized anxiety disorder), including intoxication or withdrawal from another substance (e.g., sedative, hypnotic, or anxiolytic withdrawal) (Criterion D). Symptoms can be relieved by administering alcohol or benzodiazepines (e.g., diazepam). The withdrawal symptoms typically begin when blood concentrations of alcohol decline sharply (i.e., within 4-12 hours) after alcohol use has been stopped or reduced. Reflecting the relatively fast metabolism of alcohol, symptoms of alcohol withdrawal usually peak in intensity during the second day of abstinence and are likely to improve markedly by the fourth or fifth day. Following acute withdrawal, however, symptoms of anxiety, insomnia, and autonomic dysfunction may persist for up to 3-6 months at lower levels of intensity. Fewer than 10% of individuals who develop alcohol withdrawal will ever develop dramatic symptoms (e.g., severe autonomic hyperactivity, tremors, alcohol withdrawal delirium). Tonic-clonic seizures occur in fewer than 3% of individuals.

Associated Features Supporting Diagnosis

Although confusion and changes in consciousness are not core criteria for alcohol withdrawal, alcohol withdrawal delirium (see "Delirium" in the chapter "Neurocognitive Disorders") may occur in the context of withdrawal. As is true for any agitated, confused state, regardless of the cause, in addition to a disturbance of consciousness and cognition, withdrawal delirium can include visual, tactile, or (rarely) auditory hallucinations (delirium tremens). When alcohol withdrawal delirium develops, it is likely that a clinically relevant medical condition may be present (e.g., liver failure, pneumonia, gastrointestinal bleeding, sequelae of head trauma, hypoglycemia, an electrolyte imbalance, postoperative status).

Prevalence

It is estimated that approximately 50% of middle-class, highly functional individuals with alcohol use disorder have ever experienced a full alcohol withdrawal syndrome. Among individuals with alcohol use disorder who are hospitalized or homeless, the rate of alcohol withdrawal may be greater than 80%. Less than 10% of individuals in withdrawal ever demonstrate alcohol withdrawal delirium or withdrawal seizures.

Functional Consequences of Alcohol Withdrawal

Symptoms of withdrawal may serve to perpetuate drinking behaviors and contribute to relapse, resulting in persistently impaired social and occupational functioning. Symptoms requiring medically supervised detoxification result in hospital utilization and loss of work productivity. Overall, the presence of withdrawal is associated with greater functional impairment and poor prognosis.

16.1.2 Caffeine-Related Disorders

16.1.2.1 Caffeine Intoxication

Diagnostic Features

Caffeine can be consumed from a number of different sources, including coffee, tea, caffeinated soda, "energy" drinks, over-the-counter analgesics and cold remedies, energy aids (e.g., drinks), weight-loss aids, and chocolate. Caffeine is also increasingly being used as an additive to vitamins and to food products. More than 85% of children and adults consume caffeine regularly. Some caffeine users display symptoms consistent with problematic use, including tolerance and withdrawal (see "Caffeine Withdrawal" later in this chapter); the data are not available at this time to determine the clinical significance of a caffeine use disorder and its prevalence. In contrast, there is evidence that caffeine withdrawal and caffeine intoxication are clinically significant and sufficiently prevalent. The essential feature of caffeine intoxication is recent consumption of caffeine and five or more signs or symptoms that develop during or shortly after caffeine use (Criteria A and B). Symptoms include restlessness, nervousness, excitement, insomnia, flushed face, diuresis, and gastrointestinal complaints, which can occur with low doses (e.g., 200 mg) in vulnerable individuals such as children, the elderly, or individuals who have not been exposed to caffeine previously. Symptoms that generally appear at levels of more than 1 g/ day include muscle twitching, rambling flow of thought and speech, tachycardia or cardiac arrhythmia, periods of inexhaustibility, and psychomotor agitation. Caffeine intoxication may not occur despite high caffeine intake because of the development of tolerance. The signs or symptoms must cause clinically significant distress or impairment in social, occupational, or other important areas of functioning (Criterion C). The signs or symptoms must not be attributable to another medical condition and are not better explained by another mental disorder (e.g., an anxiety disorder) or intoxication with another substance (Criterion D).

Associated Features Supporting Diagnosis

Mild sensory disturbances (e.g., ringing in the ears and flashes of light) may occur with high doses of caffeine. Although large doses of caffeine can increase heart rate, smaller doses can slow heart rate. Whether excess caffeine intake can cause headaches is unclear. On physical examination, agitation, restlessness, sweating, tachycardia, flushed face, and increased bowel motility may be seen. Caffeine blood levels may provide important information for diagnosis, particularly when the individual is a poor historian, although these levels are not diagnostic by themselves in view of the individual variation in response to caffeine.

Prevalence

The prevalence of caffeine intoxication in the general population is unclear. In the United States, approximately 7% of individuals in the population may experience five or more symptoms along with functional impairment consistent with a diagnosis of caffeine intoxication.

Functional Consequences of Caffeine Intoxication

Impairment from caffeine intoxication may have serious consequences, including dysfunction at work or school, social indiscretions, or failure to fulfill role obligations. Moreover, extremely high doses of caffeine can be fatal. In some cases, caffeine intoxication may precipitate a caffeine-induced disorder.

16.1.2.2 Caffeine Withdrawal

Diagnostic Features

The essential feature of caffeine withdrawal is the presence of a characteristic withdrawal syndrome that develops after the abrupt cessation of (or substantial reduction in) prolonged daily caffeine ingestion (Criterion B). The caffeine withdrawal syndrome is indicated by three or more of the following (Criterion B): headache; marked fatigue or drowsiness; dysphoric mood, depressed mood, or irritability; difficulty concentrating; and flu-hke symptoms (nausea, vomiting, or muscle pain/stiffness). The withdrawal syndrome causes clinical significant distress or impairment in social, occupational, or other important areas of functioning (Criterion C). The symptoms must not be associated with the physiological effects of another medical condition and are not better explained by another mental disorder (Criterion D).

Headache is the hallmark feature of caffeine withdrawal and may be diffuse, gradual in development, throbbing, severe, and sensitive to movement. However, other symptoms of caffeine withdrawal can occur in the absence of headache. Caffeine is the most widely used behaviorally active drug in the world and is present in many different types of beverages (e.g., coffee, tea, mate, soft drinks, energy drinks), foods, energy aids, medications, and dietary supplements. Because caffeine ingestion is often integrated into social customs and daily rituals (e.g., coffee break, tea time), some caffeine consumers may be unaware of their physical dependence on caffeine. Thus, caffeine withdrawal symptoms could be unexpected and misattributed to other causes (e.g., the flu, migraine). Furthermore, caffeine withdrawal symptoms may occur when individuals are required to abstain from foods and beverages prior to medical procedures or when a usual caffeine dose is missed because of a change in routine (e.g., during travel, weekends).

The probability and severity of caffeine withdrawal generally increase as a function of usual daily caffeine dose. However, there is large variability among individuals and within individuals across different episodes in the incidence, severity, and time course of withdrawal symptoms. Caffeine withdrawal symptoms may occur after abrupt cessation of relatively low chronic daily doses of caffeine (i.e., 100 mg).

Associated Features Supporting Diagnosis

Caffeine abstinence has been shown to be associated with impaired behavioral and cognitive performance (e.g., sustained attention). Electroencephalographic studies have shown that caffeine withdrawal symptoms are significantly associated with increases in theta power and decreases in beta-2 power. Decreased motivation to work and decreased sociability have also been reported during caffeine withdrawal. Increased analgesic use during caffeine withdrawal has been documented.

Prevalence

More than 85% of adults and children in the United States regularly consume caffeine, with adult caffeine consumers ingesting about 280 mg/day on average. The incidence and prevalence of the caffeine withdrawal syndrome in the general population are unclear. In the United States, headache may occur in approximately 50% of cases of caffeine abstinence. In attempts to permanently stop caffeine use, more than 70% of individuals may experience at least one caffeine withdrawal symptom (47% may experience headache), and 24% may experience headache plus one or more other symptoms as well as functional impairment due to withdrawal. Among individuals who abstain from caffeine for at least 24 hours but are not trying to permanently stop caffeine use, 11% may experience headache plus one or more other symptoms as well as functional impairment. Caffeine consumers can decrease the incidence of caffeine withdrawal by using caffeine daily or only infrequently (e.g., no more than 2 consecutive days). Gradual reduction in caffeine over a period of days or weeks may decrease the incidence and severity of caffeine withdrawal.

Culture-Related Diagnostic Issues

Habitual caffeine consumers who fast for religious reasons may be at increased risk for caffeine withdrawal.

Functional Consequences of Caffeine Withdrawal Disorder

Caffeine withdrawal symptoms can vary from mild to extreme, at times causing functional impairment in normal daily activities. Rates of functional impairment range from 10% to 55% (median 13%), with rates as high as 73% found among individuals who also show other problematic features of caffeine use. Examples of functional impairment include being unable to work, exercise, or care for children; staying in bed all day; missing religious services; ending a vacation early; and cancelling a social gathering. Caffeine withdrawal headaches may be described by individuals as "the worst headaches" ever experienced. Decrements in cognitive and motor performance have also been observed.

16.1.3 Cannabis-Related Disorders

16.1.3.1 Cannabis Use Disorder

Diagnostic Features

Cannabis use disorder and the other cannabis-related disorders include problems that are associated with substances derived from the cannabis plant and chemically similar synthetic compounds. Over time, this plant material has accumulated many names (e.g., weed, pot, herb, grass, reefer, mary jane, dagga, dope, bhang, skunk, boom, gangster, kif, and ganja). A concentrated extraction of the cannabis plant that is also commonly used is hashish. Cannabis is the generic and perhaps the most appropriate scientific term for the psychoactive substance(s) derived from the plant, and as such it is used in this manual to refer to all forms of cannabis-like substances, including synthetic cannabinoid compounds. Synthetic oral formulations (pill/capsules) of delta-9-tetrahydrocannabinol (delta-9- THC) are availal^le by prescription for a number of approved medical indications (e.g., for nausea and vomiting caused by chemotherapy; for anorexia and weight loss in individuals with AIDS). Other synthetic cannabinoid compounds have been manufactured and distributed for nonmedical use in the form of plant material that has been sprayed with a cannabinoid formulation (e.g., K2, Spice, JWH-018, JWH-073).

The cannabinoids have diverse effects in the brain, prominent among which are actions on CBl and CB2 cannabinoid receptors that are found throughout the central nervous system. Endogenous ligands for these receptors behave essentially like neurotransmitters. The potency of cannabis (delta-9-THC concentration) that is generally available varies greatly, ranging from 1% to approximately 15% in typical cannabis plant material and 10%-20% in hashish. During the past two decades, a steady increase in the potency of seized cannabis has been observed.
Cannabis is most commonly smoked via a variety of methods: pipes, water pipes (bongs or hookahs), cigarettes (joints or reefers), or, most recently, in the paper from hollowed out cigars (blunts). Cannabis is also sometimes ingested orally, typically by mixing it into food. More recently, devices have been developed in which cannabis is "vaporized." Vaporization involves heating the plant material to release psychoactive cannabinoids for inhalation. As with other psychoactive substances, smoking (and vaporization) typically produces more rapid onset and more intense experiences of the desired effects. Individuals who regularly use cannabis can develop all the general diagnostic features of a substance use disorder. Cannabis use disorder is commonly observed as the only substance use disorder experienced by the individual; however, it also frequently occurs concurrently with other types of substance use disorders (i.e., alcohol, cocaine, opioid). In cases for which multiple types of substances are used, many times the individual may minimize the symptoms related to cannabis, as the symptoms may be less severe or cause less harm than those directly related to the use of the other substances. Pharmacological and behavioral tolerance to most of the effects of cannabis has been reported in individuals who use cannabis persistently. Generally, tolerance is lost when cannabis use is discontinued for a significant period of time (i.e., for at least several months).

New to DSM-5 is the recognition that abrupt cessation of daily or near-daily cannabis use often results in the onset of a cannabis withdrawal syndrome. Common symptoms of withdrawal include irritability, anger or aggression, anxiety, depressed mood, restlessness, sleep difficulty, and decreased appetite or weight loss. Although typically not as severe as alcohol or opiate withdrawal, the cannabis withdrawal syndrome can cause significant distress and contribute to difficulty quitting or relapse among those trying to abstain.

Individuals with cannabis use disorder may use cannabis throughout the day over a period of months or years, and thus may spend many hours a day under the influence. Others may use less frequently, but their use causes recurrent problems related to family, school, work, or other important activities (e.g., repeated absences at work; neglect of family obligations). Periodic cannabis use and intoxication can negatively affect behavioral and cognitive functioning and thus interfere with optimal performance at work or school, or place the individual at increased physical risk when performing activities that could be physically hazardous (e.g., driving a car; playing certain sports; performing manual work activities, including operating machinery). Arguments with spouses or parents over the use of cannabis in the home, or its use in the presence of children, can adversely impact family functioning and are common features of those with cannabis use disorder. Last, individuals with cannabis use disorder may continue using despite knowledge of physical problems (e.g., chronic cough related to smoking) or psychological problems (e.g., excessive sedation or exacerbation of other mental health problems) associated with its use. Whether or not cannabis is being used for legitimate medical reasons may also affect diagnosis. When a substance is taken as indicated for a medical condition, symptoms of tolerance and withdrawal will naturally occur and should not be used as the primary criteria for determining a diagnosis of a substance use disorder. Although medical uses of cannabis remain controversial and equivocal, use for medical circumstances should be considered when a diagnosis is being made.

Associated Features Supporting Diagnosis

Individuals who regularly use cannabis often report that it is being used to cope with mood, sleep, pain, or other physiological or psychological problems, and those diagnosed with cannabis use disorder frequently do have concurrent other mental disorders. Careful assessment typically reveals reports of cannabis use contributing to exacerbation of these same symptoms, as well as other reasons for frequent use (e.g., to experience euphoria, to forget about problems, in response to anger, as an enjoyable social activity). Related to this issue, some individuals who use cannabis multiple times per day for the aforementioned reasons do not perceive themselves as (and thus do not report) spending an excessive amount of time under the influence or recovering from the effects of cannabis, despite being intoxicated on cannabis or coming down from it effects for the majority of most days. An important marker of a substance use disorder diagnosis, particularly in milder cases, is continued use despite a clear risk of negative consequences to other valued activities or relationships (e.g., school, work, sport activity, partner or parent relationship).

Because some cannabis users are motivated to minimize their amount or frequency of use, it is important to be aware of common signs and symptoms of cannabis use and intoxication so as to better assess the extent of use. As with other substances, experienced users of cannabis develop behavioral and pharmacological tolerance such that it can be difficult to detect when they are under the influence. Signs of acute and chronic use include red eyes (conjunctival injection), cannabis odor on clothing, yellowing of finger tips (from smoking joints), chronic cough, burning of incense (to hide the odor), and exaggerated craving and impulse for specific foods, sometimes at unusual times of the day or night.

Prevalence

Cannabinoids, especially cannabis, are the most widely used illicit psychoactive substances in the United States. The 12-month prevalence of cannabis use disorder (DSM-IV abuse and dependence rates combined) is approximately 3.4% among 12- to 17-year-olds and 1.5% among adults age 18 years and older. Rates of cannabis use disorder are greater among adult males (2.2%) than among adult females (0.8%) and among 12- to 17-year-old males (3.8%) than among 12- to 17-year-old females (3.0%). Twelve-month prevalence rates of cannabis use disorder among adults decrease with age, with rates highest among 18- to 29-year-olds (4.4%) and lowest among individuals age 65 years and older (0.01%). The high prevalence of cannabis use disorder likely reflects the much more widespread use of cannabis relative to other illicit drugs rather than greater addictive potential. Ethnic and racial differences in prevalence are moderate. Twelve-month prevalences of cannabis use disorder vary markedly across racial-ethnic subgroups in the United States. For 12- to 17-year-olds, rates are highest among Native American and Alaska Natives (7.1%) compared with Hispanics (4.1%), whites (3.4%), African Americans (2.7%), and Asian Americans and Pacific Islanders (0.9%). Among adults, the prevalence of cannabis use disorder is also highest among Native Americans and Alaska Natives (3.4%) relative to rates among African Americans (1.8%), whites (1.4%), Hispanics (1.2%), and Asian and Pacific Islanders (1.2%). During the past decade the prevalence of cannabis use disorder has increased among adults and adolescents. Gender differences in cannabis use disorder generally are concordant with those in other substance use disorders. Cannabis use disorder is more commonly observed in males, although the magnitude of this difference is less among adolescents.

Culture-Related Diagnostic Issues

Cannabis is probably the world's most commonly used illicit substance. Occurrence of cannabis use disorder across countries is unknown, but the prevalence rates are likely similar among developed countries. It is frequently among the first drugs of experimentation (often in the teens) of all cultural groups in the United States. Acceptance of cannabis for medical purposes varies widely across and within cultures. Cultural factors (acceptability and legal status) that might impact diagnosis relate to differential consequences across cultures for detection of use (i.e., arrest, school suspensions, or employment suspension). The general change in substance use disorder diagnostic criteria from DSM-IV to DSM-5 (i.e., removal of the recurrent substance-related legal problems criterion) mitigates this concern to some degree.

Functional Consequences of Cannabis Use Disorder

Functional consequences of cannabis use disorder are part of the diagnostic criteria. Many areas of psychosocial, cognitive, and health functioning may be compromised in relation to cannabis use disorder. Cognitive function, particularly higher executive function, appears to be compromised in cannabis users, and this relationship appears to be dose dependent (both acutely and chronically). This may contribute to increased difficulty at school or work. Cannabis use has been related to a reduction in prosocial goal-directed activity, which some have labeled an amotivational syndrome, that manifests itself in poor school performance and employment problems. These problems may be related to pervasive intoxication or recovery from the effects of intoxication. Similarly, cannabis-associated problems with social relationships are commonly reported in those with cannabis use disorder. Accidents due to engagement in potentially dangerous behaviors while under the influence (e.g., driving, sport, recreational or employment activities) are also of concern. Cannabis smoke contains high levels of carcinogenic compounds that place chronic users at risk for respiratory illnesses similar to those experienced by tobacco smokers. Chronic cannabis use may contribute to the onset or exacerbation of many other mental disorders. In particular, concern has been raised about cannabis use as a causal factor in schizophrenia and other psychotic disorders. Cannabis use can contribute to the onset of an acute psychotic episode, can exacerbate some symptoms, and can adversely affect treatment of a major psychotic \llness.

16.1.3.2 Cannabis Intoxication

Diagnostic Features

The essential feature of cannabis intoxication is the presence of clinically significant problematic behavioral or psychological changes that develop during, or shortly after, cannabis use (Criterion B). Intoxication typically begins with a ''high" feeling followed by symptoms that include euphoria with inappropriate laughter and grandiosity, sedation, lethargy, impairment in short-term memory, difficulty carrying out complex mental processes, impaired judgment, distorted sensory perceptions, impaired motor performance, and the sensation that time is passing slowly. Occasionally, anxiety (which can be severe), dysphoria, or social withdrawal occurs. These psychoactive effects are accompanied by two or more of the following signs, developing within 2 hours of cannabis use: conjunctival injection, increased appetite, dry mouth, and tachycardia (Criterion C). Intoxication develops within minutes if the cannabis is smoked but may take a few hours to develop if the cannabis is ingested orally. The effects usually last 3-4 hours, with the duration being somewhat longer when the substance is ingested orally. The magnitude of the behavioral and physiological changes depends on the dose, the method of administration, and the characteristics of the individual using the substance, such as rate of absorption, tolerance, and sensitivity to the effects of the substance. Because most cannabinoids, including delta-9-tetrahydrocannabinol (delta-9-THC), are fat soluble, the effects of cannabis or hashish may occasionally persist or reoccur for 12-24 hours because of the slow release of psychoactive substances from fatty tissue or to enterohepatic circulation.

Prevalence

The prevalence of actual episodes of cannabis intoxication in the general population is unknown. However, it is probable that most cannabis users would at some time meet criteria for cannabis intoxication. Given this, the prevalence of cannabis users and the prevalence of individuals experiencing cannabis intoxication are likely similar.

Functional Consequences of Cannabis Intoxication

Impairment from cannabis intoxication may have serious consequences, including dysfunction at work or school, social indiscretions, failure to fulfill role obligations, traffic accidents, and having unprotected sex. In rare cases, cannabis intoxication may precipitate a psychosis that may vary in duration.

16.1.3.3 Cannabis Withdrawal

Diagnostic Features

The essential feature of cannabis withdrawal is the presence of a characteristic withdrawal syndrome that develops after the cessation of or substantial reduction in heavy and prolonged cannabis use. In addition to the symptoms in Criterion B, the following may also be observed postabstinence: fatigue, yawning, difficulty concentrating, and rebound periods of increased appetite and hypersomnia that follow initial periods of loss of appetite and insomnia. For the diagnosis, withdrawal symptoms must cause clinically significant distress or impairment in social, occupational, or other important areas of functioning (Criterion C). Many cannabis users report smoking cannabis or taking other substances to help relieve withdrawal symptoms, and many report that withdrawal symptoms make quitting difficult or have contributed to relapse. The symptoms typically are not of sufficient severity to require medical attention, but medication or behavioral strategies may help alleviate symptoms and improve prognosis in those trying to quit using cannabis. Cannabis withdrawal is commonly observed in individuals seeking treatment for cannabis use as well as in heavy cannabis users who are not seeking treatment. Among individuals who have used cannabis regularly during some period of their lifetime, up to onethird report having experienced cannabis withdrawal. Among adults and adolescents enrolled in treatment or heavy cannabis users, 50%-95% report cannabis withdrawal. These findings indicate that cannabis withdrawal occurs among a substantial subset of regular cannabis users who try to quit.

Functional Consequences of Cannabis Withdrawal

Cannabis users report using cannabis to relieve withdrawal symptoms, suggesting that withdrawal might contribute to ongoing expression of cannabis use disorder. Worse outcomes may be associated with greater withdrawal. A substantial proportion of adults and adolescents in treatment for moderate to severe cannabis use disorder acknowledge moderate to severe withdrawal symptoms, and many complain that these symptoms make cessation more difficult. Cannabis users report having relapsed to cannabis use or initiating use of other drugs (e.g., tranquilizers) to provide relief from cannabis withdrawal symptoms. Last, individuals living with cannabis users observe significant withdrawal effects, suggesting that such symptoms are disruptive to daily living.

16.1.4 Hallucinogen-Related Disorders

16.1.4.1 Phencyclidine Use Disorder

Diagnostic Features

The phencyclidines (or phencyclidine-like substances) include phencyclidine (e.g., PCP, "angel dust") and less potent but similarly acting compounds such as ketamine, cyclohexamine, and dizocilpine. These substances were first developed as dissociative anesthetics in the 1950s and became street drugs in the 1960s. They produce feelings of separation from mind and body (hence "dissociative") in low doses, and at high doses, stupor and coma can result. These substances are most commonly smoked or taken orally, but they may also be snorted or injected. Although the primary psychoactive effects of PCP last for a few hours, the total elimination rate of this drug from the body typically extends 8 days or longer. The hallucinogenic effects in vulnerable individuals may last for weeks and may precipitate a persistent psychotic episode resembling schizophrenia. Ketamine has been observed to have utility in the treatment of major depressive disorder. Withdrawal symptoms have not been clearly established in humans, and therefore the withdraw^al criterion is not included in the diagnosis of phencyclidine use disorder.

Associated Features Supporting Diagnosis

Phencyclidine may be detected in urine for up to 8 days or even longer at very high doses. In addition to laboratory tests to detect its presence, characteristic symptoms resulting from intoxication v^ith phencyclidine or related substances may aid in its diagnosis. Phencyclidine is likely to produce dissociative symptoms, analgesia, nystagmus, and hypertension, with risk of hypotension and shock. Violent behavior can also occur with phencyclidine use, as intoxicated persons may believe that they are being attacked. Residual symptoms following use may resemble schizophrenia.

Prevalence

The prevalence of phencyclidine use disorder is unknown. Approximately 2.5% of the population reports having ever used phencyclidine. The proportion of users increases with age, from 0.3% of 12- to 17-year-olds, to 1.3% of 18- to 25-year-olds, to 2.9% of those age 26 years and older reporting ever using phencyclidine. There appears to have been an increase among 12th graders in both ever used (to 2.3% from 1.8%) and past-year use (to 1.3% from 1.0%) of phencyclidine. Past-year use of ketamine appears relatively stable among 12th graders (1.6%-1.7% over the past 3 years).

Cuiture-Related Diagnostic issues

Ketamine use in youths ages 16-23 years has been reported to be more common among whites (0.5%) than among other ethnic groups (range 0%-0.3%). Among individuals admitted to substance abuse treatment, those for whom phencyclidine was the primary substance were predominantly black (49%) or Hispanic (29%).

Gender-Related Diagnostic issues

Males make up about three-quarters of those with phencyclidine-related emergency room visits.

Functional Consequences of Pliencyclidine Use Disorder

In individuals with phencyclidine use disorder, there may be physical evidence of injuries from accidents, fights, and falls. Chronic use of phencyclidine may lead to deficits in memory, speech, and cognition that may last for months. Cardiovascular and neurological toxicities (e.g., seizures, dystonias, dyskinesias, catalepsy, hypothermia or hyperthermia) may result from intoxication with phencyclidine. Other consequences include intracranial hemorrhage, rhabdomyolysis, respiratory problems, and (occasionally) cardiac arrest.

16.1.4.2 Other Hallucinogen Use Disorder

Diagnostic Features

Hallucinogens comprise a diverse group of substances that, despite having different chemical structures and possibly involving different molecular mechanisms, produce similar alterations of perception, mood, and cognition in users. Hallucinogens included are phenylalkylamines (e.g., mescaline, DOM [2,5-dimethoxy-4-methylamphetamine], and MDMA [3,4-methylenedioxymethamphetamine; also called "ecstasy"]); the indoleamines, including psilocybin (i.e., psilocin) and dimethyltryptamine (DMT); and the ergolines, such as LSD (lysergic acid diethylamide) and morning glory seeds. In addition, miscellaneous other ethnobotanical compounds are classified as "hallucinogens," of which Salvia divinorum and jimsonweed are two examples. Excluded from the hallucinogen group are cannabis and its active compound, delta-9-tetrahydrocannabinol (THC) (see the section "Cannabis-Related Disorders"). These substances can have hallucinogenic effects but are diagnosed separately because of significant differences in their psychological and behavioral effects. Hallucinogens are usually taken orally, although some forms are smoked (e.g., DMT, salvia) or (rarely) taken intranasally or by injection (e.g., ecstasy). Duration of effects varies across types of hallucinogens. Some of these substances (i.e., LSD, MDMA) have a long half-life and extended duration such that users may spend hours to days using and/or recovering from the effects of these drugs. However, other hallucinogenic drugs (e.g., DMT, salvia) are short acting. Tolerance to hallucinogens develops with repeated use and has been reported to have both autonomic and psychological effects. Cross-tolerance exists between LSD and other hallucinogens (e.g., psilocybin, mescaline) but does not extend to other drug categories such as amphetamines and cannabis. MDMA/ecstasy as a hallucinogen may have distinctive effects attributable to both its hallucinogenic and its stimulant properties. Among heavy ecstasy users, continued use despite physical or psychological problems, tolerance, hazardous use, and spending a great deal of time obtaining the substance are the most commonly reported criteria—over 50% in adults and over 30% in a younger sample, while legal problems related to substance use and persistent desire/inability to quit are rarely reported. As found for other substances, diagnostic criteria for other hallucinogen use disorder are arrayed along a single continuum of severity. One of the generic criteria for substance use disorders, a clinically significant withdrawal syndrome, has not been consistently documented in humans, and therefore the diagnosis of hallucinogen withdrawal syndrome is not included in DSM-5. However, there is evidence of withdrawal from MDMA, with endorsement of two or more withdrawal symptoms observed in 59%-98% in selected samples of ecstasy users. Both psychological and physical problems have been commonly reported as withdrawal problems.

Associated Features Supporting Diagnosis

The characteristic symptom features of some of the hallucinogens can aid in diagnosis if urine or blood toxicology results are not available. For example, individuals who use LSD tend to experience visual hallucinations that can be frightening. Individuals intoxicated with hallucinogens may exhibit a temporary increase in suicidality.

Prevalence

Of all substance use disorders, other hallucinogen use disorder is one of the rarest. The 12-month prevalence is estimated to be 0.5% among 12- to 17-year-olds and 0.1% among adults age 18 and older in the United States. Rates are higher in adult males (0.2%) compared with females (0.1%), but the opposite is observed in adolescent samples ages 12-17, in which the 12-month rate is slightly higher in females (0.6%) than in males (0.4%). Rates are highest in individuals younger than 30 years, with the peak occurring in individuals ages 18-29 years (0.6%) and decreasing to virtually 0.0% among individuals age 45 and older. There are marked ethnic differences in 12-month prevalence of other hallucinogen use disorder. Among youths ages 12-17 years, 12-month prevalence is higher among Native Americans and Alaska Natives (1.2%) than among Hispanics (0.6%), whites (0.6%), African Americans (0.2%), and Asian Americans and Pacific Islanders (0.2%). Among adults, 12-month prevalence of other hallucinogen use disorder is similar for Native Americans and Alaska Natives, whites, and Hispanics (all 0.2%) but somewhat lower for Asian Americans and Pacific Islanders (0.07%) and African Americans (0.03%). Past-year prevalence is higher in clinical samples (e.g., 19% in adolescents in treatment). Among individuals currently using hallucinogens in the general population, 7.8% (adult) to 17% (adolescent) had a problematic pattern of use that met criteria for past-year other hallucinogen use disorder. Among select groups of individuals who use hallucinogens (e.g., recent heavy ecstasy use), 73.5% of adults and 77% of adolescents have a problematic pattern of use that may meet other hallucinogen use disorder criteria.

Culture-Related Diagnostic issues

Historically, hallucinogens have been used as part of established religious practices, such as the use of peyote in the Native American Church and in Mexico. Ritual use by indigenous populations of psilocybin obtained from certain types of mushrooms has occurred in South America, Mexico, and some areas in the United States, or of ayahuasca in the Santo Daime and Uniao de Vegetal sects. Regular use of peyote as part of religious rituals is not linked to neuropsychological or psychological deficits. For adults, no race or ethnicity differences for the full criteria or for any individual criterion are apparent at this time.

Gender-Related Diagnostic Issues

In adolescents, females may be less likely than males to endorse ''hazardous use," and female gender may be associated with increased odds of other hallucinogen use disorder.

Functional Consequences of Other Hallucinogen Use Disorder

There is evidence for long-term neuro toxic effects of MDMA/ecstasy use, including impairments in memory, psychological function, and neuroendocrine function; serotonin system dysfunction; and sleep disturbance; as well as adverse effects on brain microvasculature, white matter maturation, and damage to axons. Use of MDMA/ecstasy may diminish functional connectivity among brain regions.

16.1.4.3 Phencyclidine Intoxication

Diagnostic Features

Phencyclidine intoxication reflects the clinically significant behavioral changes that occur shortly after ingestion of this substance (or a pharmacologically similar substance). The most common clinical presentations of phencyclidine intoxication include disorientation, confusion without hallucinations, hallucinations or delusions, a catatonic-like syndrome, and coma of varying severity. The intoxication typically lasts for several hours but, depending on the type of clinical presentation and whether other drugs besides phencyclidine were consumed, may last for several days or longer.

Prevalence

Use of phencyclidine or related substances may be taken as an estimate of the prevalence of intoxication. Approximately 2.5% of the population reports having ever used phencyclidine. Among high school students, 2.3% of 12th graders report ever using phencyclidine, with 57% having used in the past 12 months. This represents an increase from prior to 2011. Past-year use of ketamine, which is assessed separately from other substances, has remained stable over time, with about 1.7% of 12th graders reporting use.

Functional Consequences of Phencyclidine Intoxication

Phencyclidine intoxication produces extensive cardiovascular and neurological (e.g., seizures, dystonias, dyskinesias, catalepsy, hypothermia or hyperthermia) toxicity.

16.1.4.4 Other Hallucinogen Intoxication

Diagnostic Features

Other Hallucinogen Intoxication reflects the clinically significant behavioral or psychological changes that occur shortly after ingestion of a hallucinogen. Depending on the specific hallucinogen, the intoxication may last only minutes (e.g., for salvia) or several hours or longer (e.g., for LSD [lysergic acid diethylamide] or MDMA [3,4-methylenedioxymethamphetamine]).

Prevalence

The prevalence of other hallucinogen intoxication may be estimated by use of those substances. In the United States, 1.8% of individuals age 12 years or older report using hallucinogens in the past year. Use is more prevalent among younger individuals, with 3.1% of 12- to 17-year-olds and 7.1% of 18- to 25-year-olds using hallucinogens in the past year, compared with only 0.7% of individuals age 26 years or older. Twelve-month prevalence for hallucinogen use is more common in males (2.4%) than in females (1.2%), and even more so among 18- to 25-year-olds (9.2% for males vs. 5.0% for females). In contrast, among individuals ages 12-17 years, there are no gender differences (3.1% for both genders). These figures may be used as proxy estimates for gender-related differences in the prevalence of other hallucinogen intoxication.

Suicide Risic

Other hallucinogen intoxication may lead to increased suicidality, although suicide is rare among users of hallucinogens.

Functional Consequences of Other Hallucinogen Intoxication

Other hallucinogen intoxication can have serious consequences. The perceptual disturbances and impaired judgment associated with other hallucinogen intoxication can result in injuries or fatalities from automobile crashes, physical fights, or unintentional selfinjury (e.g., attempts to "fly" from high places). Environmental factors and the personality and expectations of the individual using the hallucinogen may contribute to the nature of and severity of hallucinogen intoxication. Continued use of hallucinogens, particularly MDMA, has also been linked with neurotoxic effects.

16.1.4.5 Hallucinogen Persisting Perception Disorder

Diagnostic Features

The hallmark of hallucinogen persisting perception disorder is the reexperiencing, when the individual is sober, of the perceptual disturbances that were experienced while the individual was intoxicated with the hallucinogen (Criterion A). The symptoms may include any perceptual perturbations, but visual disturbances tend to be predominant. Typical of the abnormal visual perceptions are geometric hallucinations, false perceptions of movement in the peripheral visual fields, flashes of color, intensified colors, trails of images of moving objects (i.e., images left suspended in the path of a moving object as seen in stroboscopic photography), perceptions of entire objects, positive afterimages (i.e., a same-colored or complementary-colored "shadow" of an object remaining after removal of the object), halos around objects, or misperception of images as too large (macropsia) or too small (micropsia). Duration of the visual disturbances may be episodic or nearly continuous and must cause clinically significant distress or impairment in social, occupational, or other important areas of functioning (Criterion B). The disturbances may last for weeks, months, or years. Other explanations for the disturbances (e.g., brain lesions, preexisting psychosis, seizure disorders, migraine aura without headaches) must be ruled out (Criterion C).

Hallucinogen persisting perception disorder occurs primarily after LSD (lysergic acid diethylamide) use, but not exclusively. There does not appear to be a strong correlation between hallucinogen persisting perception disorder and number of occasions of hallucinogen use, with some instances of hallucinogen persisting perception disorder occurring in individuals with minimal exposure to hallucinogens. Some instances of hallucinogen persisting perception disorder may be triggered by use of other substances (e.g., cannabis or alcohol) or in adaptation to dark environments.

Associated Features Supporting Diagnosis

Reality testing remains intact in individuals with hallucinogen persisting perception disorder (i.e., the individual is aware that the disturbance is linked to the effect of the drug). If this is not the case, another disorder might better explain the abnormal perceptions.

Prevalence

Prevalence estimates of hallucinogen persisting perception disorder are unknown. Initial prevalence estimates of the disorder among individuals who use hallucinogens is approximately 4.2%.

Functional Consequences of Haliucinogen Persisting Perception Disorder

Although hallucinogen persisting perception disorder remains a chronic condition in some cases, many individuals with the disorder are able to suppress the disturbances and continue to function normally.

16.1.5 Inhalant-Related Disorders

16.1.5.1 Inhalant Use Disorder

Diagnostic Features

Features of inhalant use disorder include repeated use of an inhalant substance despite the individual's knowing that the substance is causing serious problems for the individual (Criterion A9). Those problems are reflected in the diagnostic criteria. Missing work or school or inability to perform t)^ical responsibilities at work or school (Criterion A5), and continued use of the inhalant substance even though it causes arguments with family or friends, fights, and other social or interpersonal problems (Criterion A6), may be seen in inhalant use disorder. Limiting family contact, work or school obligations, or recreational activities (e.g., sports, games, hobbies) may also occur (Criterion A7). Use of inhalants when driving or operating dangerous equipment (Criterion A8) is also seen. Tolerance (Criterion AlO) and mild withdrawal are each reported by about 10% of individuals who use inhalants, and a few individuals use inhalants to avoid withdrawal. However, because the withdrawal symptoms are mild, this manual neither recognizes a diagnosis of inhalant withdrawal nor counts withdrawal complaints as a diagnostic criterion for inhalant use disorder.

Associated Features Supporting Diagnosis

A diagnosis of inhalant use disorder is supported by recurring episodes of intoxication with negative results in standard drug screens (which do not detect inhalants); possession, or lingering odors, of inhalant substances; peri-oral or peri-nasal "glue-sniffer's rash"; association with other individuals known to use inhalants; membership in groups with prevalent iruialant use (e.g., some native or aboriginal communities, homeless children in street gangs); easy access to certain inhalant substances; paraphernalia possession; presence of the disorder's characteristic medical complications (e.g., brain white matter pathology, rhabdomyolysis); and the presence of multiple substance use disorders. Inhalant use and inhalant use disorder are associated with past suicide attempts, especially among adults reporting previous episodes of low mood or anhedonia.

Prevaience

About 0.4% of Americans ages 12-17 years have a pattern of use that meets criteria for inhalant use disorder in the past 12 months. Among those youths, the prevalence is highest in Native Americans and lowest in African Americans. Prevalence falls to about 0.1% among Americans ages 18-29 years, and only 0.02% w^hen all Americans 18 years or older are considered, v^ith almost no females and a preponderance of European Americans. Of course, in isolated subgroups, prevalence may differ considerably from these overall rates.

Cuiture-Related Diagnostic issues

Certain native or aboriginal communities have experienced a high prevalence of inhalant problems. Also, in some countries, groups of homeless children in street gangs have extensive inhalant use problems.

Gender-Related Diagnostic issues

Although the prevalence of inhalant use disorder is almost identical in adolescent males and females, the disorder is very rare among adult females. Functional Consequences of Inhalant Use Disorder Because of inherent toxicity, use of butane or propane is not infrequently fatal. Moreover, any inhaled volatile hydrocarbons may produce "sudden sniffing death" from cardiac arrhythmia. Fatalities may occur even on the first inhalant exposure and are not thought to be dose-related. Volatile hydrocarbon use impairs neurobehavioral function and causes various neurological, gastrointestinal, cardiovascular, and pulmonary problems. Long-term inhalant users are at increased risk for tuberculosis, HIV / AIDS, sexually transmitted diseases, depression, anxiety, bronchitis, asthma, and sinusitis. Deaths may occur from respiratory depression, arrhythmias, asphyxiation, aspiration of vomitus, or accident and injury.

16.1.5.2 Inhalant Intoxication

Diagnostic Features

Inhalant intoxication is an inhalant-related, clinically significant mental disorder that develops during, or immediately after, intended or unintended inhalation of a volatile hydrocarbon substance. Volatile hydrocarbons are toxic gases from glues, fuels, paints, and other volatile compounds. When it is possible to do so, the particular substance involved should be named (e.g., toluene intoxication). Among those who do, the intoxication clears within a few minutes to a few hours after the exposure ends. Thus, inhalant intoxication usually occurs in brief episodes that may recur.

Associated Features Supporting Diagnosis

Inhalant intoxication may be indicated by evidence of possession, or lingering odors, of inhalant substances (e.g., glue, paint thinner, gasoline, butane lighters); apparent intoxication occurring in the age range with the highest prevalence of inhalant use (12-17 years); and apparent intoxication with negative results from the standard drug screens that usually fail to identify inhalants.

Prevaience

The prevalence of actual episodes of inhalant intoxication in the general population is unknown, but it is probable that most inhalant users would at some time exhibit use that would meet criteria for inhalant intoxication disorder. Therefore, the prevalence of inhalant use and the prevalence of inhalant intoxication disorder are likely similar. In 2009 and 2010, inhalant use in the past year was reported by 0.8% of all Americans older than 12 years; the prevalence was highest in younger age groups (3.6% for individuals 12 to 17 years old, and 1.7% for individuals 18 to 25 years old).

Gender-Related Diagnostic issues

Gender differences in the prevalence of inhalant intoxication in the general population are unknown. However, if it is assumed that most inhalant users eventually experience inhalant intoxication, gender differences in the prevalence of inhalant users likely approximate those in the proportions of males and females experiencing inhalant intoxication. Regarding gender differences in the prevalence of inhalant users in the United States, 1% of males older than 12 years and 0.7% of females older than 12 years have used inhalants in the previous year, but in the younger age groups more females than males have used inhalants (e.g., among 12- to 17-year-olds, 3.6% of males and 4.2% of females).

Functional Consequences of inhalant intoxication

Use of inhaled substances in a closed container, such as a plastic bag over the head, may lead to unconsciousness, anoxia, and death. Separately, "sudden sniffing death," likely from cardiac arrhythmia or arrest, may occur with various volatile inhalants. The enhanced toxicity of certain volatile inhalants, such as butane or propane, also causes fatalities. Although inhalant intoxication itself is of short duration, it may produce persisting medical and neurological problems, especially if the intoxications are frequent.

16.1.6 Opioid-Related Disorders

16.1.6.1 Opioid Use Disorder

Diagnostic Features

Opioid use disorder includes signs and symptoms that reflect compulsive, prolonged selfadministration of opioid substances that are used for no legitimate medical purpose or, if another medical condition is present that requires opioid treatment, that are used in doses greatly in excess of the amount needed for that medical condition. (For example, an individual prescribed analgesic opioids for pain relief at adequate dosing will use significantly more than prescribed and not only because of persistent pain.) Individuals with opioid use disorder tend to develop such regular patterns of compulsive drug use that daily activities are planned around obtaining and administering opioids. Opioids are usually purchased on the illegal market but may also be obtained from physicians by falsifying or exaggerating general medical problems or by receiving simultaneous prescriptions from several physicians. Health care professionals with opioid use disorder will often obtain opioids by writing prescriptions for themselves or by diverting opioids that have been prescribed for patients or from pharmacy supplies. Most individuals with opioid use disorder have significant levels of tolerance and will experience withdrawal on abrupt discontinuation of opioid substances. Individuals with opioid use disorder often develop conditioned responses to drug-related stimuli (e.g., craving on seeing any heroin powder-like substance)— a phenomenon that occurs with most drugs that cause intense psychological changes. These responses probably contribute to relapse, are difficult to extinguish, and typically persist long after detoxification is completed.

Associated Features Supporting Diagnosis

Opioid use disoMer can be associated with a history of drug-related crimes (e.g., possession or distribution of drugs, forgery, burglary, robbery, larceny, receiving stolen goods). Among health care professionals and individuals who have ready access to controlled substances, there is often a different pattern of illegal activities involving problems with state licensing boards, professional staffs of hospitals, or other administrative agencies. Marital difficulties (including divorce), unemployment, and irregular employment are often associated with opioid use disorder at all socioeconomic levels.

Prevaience

The 12-month prevalence of opioid use disorder is approximately 0.37% among adults age 18 years and older in the community population. This may be an underestimate because of the large number of incarcerated individuals with opioid use disorders. Rates are higher in males than in females (0.49% vs. 0.26%), with the male-to-female ratio typically being 1.5:1 for opioids other than heroin (i.e., available by prescription) and 3:1 for heroin. Female adolescents may have a higher likelihood of developing opioid use disorders. The prevalence decreases with age, with the prevalence highest (0.82%) among adults age 29 years or younger, and decreasing to 0.09% among adults age 65 years and older. Among adults, the prevalence of opioid use disorder is lower among African Americans at 0.18% and overrepresented among Native Americans at 1.25%. It is close to average among whites (0.38%), Asian or Pacific Islanders (0.35%), and Hispanics (0.39%). Among individuals in the United States ages 12-17 years, the overall 12-month prevalence of opioid use disorder in the community population is approximately 1.0%, but the prevalence of heroin use disorder is less than 0.1%. By contrast, analgesic use disorder is prevalent in about 1.0% of those ages 12-17 years, speaking to the importance of opioid analgesics as a group of substances with significant health consequences. The 12-month prevalence of problem opioid use in European countries in the community population ages 15-64 years is between 0.1% and 0.8%. The average prevalence of problem opioid use in the European Union and Norway is between 0.36% and 0.44%.

Culture-Related Diagnostic Issues

Despite small variations regarding individual criterion items, opioid use disorder diagnostic criteria perform equally well across most race/ethnicity groups. Individuals from ethnic minority populations living in economically deprived areas have been overrepresented among individuals with opioid use disorder. However, over time, opioid use disorder is seen more often among white middle-class individuals, especially females, suggesting that differences in use reflect the availability of opioid drugs and that other social factors may impact prevalence. Medical personnel who have ready access to opioids may be at increased risk for opioid use disorder.

Suicide Risk

Similar to the risk generally observed for all substance use disorders, opioid use disorder is associated with a heightened risk for suicide attempts and completed suicides. Particularly notable are both accidental and deliberate opioid overdoses. Some suicide risk factors overlap with risk factors for an opioid use disorder. In addition, repeated opioid intoxication or withdrawal may be associated with severe depressions that, although temporary, can be intense enough to lead to suicide attempts and completed suicides. Available data suggest that nonfatal accidental opioid overdose (which is common) and attempted suicide are distinct clinically significant problems that should not be mistaken for each other.

Functional Consequences of Opioid Use Disorder

Opioid use is associated with a lack of mucous membrane secretions, causing dry mouth and nose. Slowing of gastrointestinal activity and a decrease in gut motility can produce severe constipation. Visual acuity may be impaired as a result of pupillary constriction with acute administration. In individuals who inject opioids, sclerosed veins ("tracks") and puncture marks on the lower portions of the upper extremities are common. Veins sometimes become so severely sclerosed that peripheral edema develops, and individuals switch to injecting in veins in the legs, neck, or groin. When these veins become unusable, individuals often inject directly into their subcutaneous tissue ("skin-popping"), resulting in cellulitis, abscesses, and circular-appearing scars from healed skin lesions. Tetanus and Clostridium botulinum infections are relatively rare but extremely serious consequences of injecting opioids, especially with contaminated needles. Infections may also occur in other organs and include bacterial endocarditis, hepatitis, and HIV infection. Hepatitis C infections, for example, may occur in up to 90% of persons who inject opioids. In addition, the prevalence of HIV infection can be high among individuals who inject drugs, a large proportion of whom are individuals with opioid use disorder. HIV infection rates have been reported to be as high as 60% among heroin users with opioid use disorder in some areas of the United States or the Russian Federation. However, the incidence may also be 10% or less in other areas, especially those where access to clean injection material and paraphernalia is facilitated.

Tuberculosis is a particularly serious problem among individuals who use drugs intravenously, especially those who are dependent on heroin; infection is usually asymptomatic and evident only by the presence of a positive tuberculin skin test. However, many cases of active tuberculosis have been found, especially among those who are infected with HIV. These individuals often have a newly acquired infection but also are likely to experience reactivation of a prior infection because of impaired immune function. Individuals who sniff heroin or other opioids into the nose ("snorting") often develop irritation of the nasal mucosa, sometimes accompanied by perforation of the nasal septum. Difficulties in sexual functioning are cormnon. Males often experience erectile dysfunction during intoxication or chronic use. Females commonly have disturbances of reproductive function and irregular menses.

In relation to infections such as cellulitis, hepatitis, HIV infection, tuberculosis, and endocarditis, opioid use disorder is associated with a mortality rate as high as 1.5%-2% per year. Death most often results from overdose, accidents, injuries, AIDS, or other general medical complications. Accidents and injuries due to violence that is associated with buying or selling drugs are common. In some areas, violence accounts for more opioid-related deaths than overdose or HIV infection. Physiological dependence on opioids may occur in about half of the infants born to females with opioid use disorder; this can produce a severe withdrawal syndrome requiring medical treatment. Although low birth weight is also seen in children of mothers with opioid use disorder, it is usually not marked and is generally not associated with serious adverse consequences.

16.1.6.2 Opioid Intoxication

Diagnostic Features

The essential feature of opioid intoxication is the presence of clinically significant problematic behavioral or psychological changes (e.g., initial euphoria followed by apathy, dysphoria, psychomotor agitation or retardation, impaired judgment) that develop during, or shortly after, opioid use (Criteria A and B). Intoxication is accompanied by pupillary constriction (unless there has been a severe overdose with consequent anoxia and pupillary dilation) and one or more of the following signs: drowsiness (described as being "on the nod"), slurred speech, and impairment in attention or memory (Criterion C); drowsiness may progress to coma. Individuals with opioid intoxication may demonstrate inattention to the environment, even to the point of ignoring potentially harmful events. The signs or symptoms must not be attributable to another medical condition and are not better explained by another mental disorder (Criterion D).

16.1.6.3 Opioid Withdrawal

Diagnostic Features

The essential feature of opioid withdrawal is the presence of a characteristic withdrawal syndrome that develops after the cessation of (or reduction in) opioid use that has been heavy and prolonged (Criterion Al). The withdrawal syndrome can also be precipitated by administration of an opioid antagonist (e.g., naloxone or naltrexone) after a period of opioid use (Criterion A2). This may also occur after administration of an opioid partial agonist such as buprenorphine to a person currently using a full opioid agonist. Opioid withdrawal is characterized by a pattern of signs and symptoms that are opposite to the acute agonist effects. The first of these are subjective and consist of complaints of anxiety, restlessness, and an "achy feeling" that is often located in the back and legs, along with irritability and increased sensitivity to pain. Three or more of the following must be present to make a diagnosis of opioid withdrawal: dysphoric mood; nausea or vomiting; muscle aches; lacrimation or rhinorrhea; pupillary dilation, piloerection, or increased sweating; diarrhea; yawning; fever; and insonmia (Criterion B). Piloerection and fever are associated with more severe withdrawal and are not often seen in routine clinical practice because individuals with opioid use disorder usually obtain substances before withdrawal becomes that far advanced. These symptoms of opioid withdrawal must cause clinically significant distress or impairment in social, occupational, or other important areas of functioning (Criterion C). The symptoms must not be attributable to another medical condition and are not better explained by another mental disorder (Criterion D). Meeting diagnostic criteria for opioid withdrawal alone is not sufficient for a diagnosis of opioid use disorder, but concurrent symptoms of craving and drug-seeking behavior are suggestive of comorbid opioid use disorder. ICD-IO-CM codes only allow a diagnosis of opioid withdrawal in the presence of comorbid moderate to severe opioid use disorder. The speed and severity of withdrawal associated with opioids depend on the half-life of the opioid used. Most individuals who are physiologically dependent on short-acting drugs such as heroin begin to have withdrawal symptoms within 6-12 hours after the last dose. Symptoms may take 2-4 days to emerge in the case of longer-acting drugs such as methadone, LAAM (L-alpha-acetylmethadol), or buprenorphine. Acute withdrawal symptoms for a short-acting opioid such as heroin usually peak within 1-3 days and gradually subside over a period of 5-7 days. Less acute withdrawal symptoms can last for weeks to months. These more chronic symptoms include anxiety, dysphoria, anhedonia, and insomnia.

Associated Features Supporting Diagnosis

Males with opioid withdrawal may experience piloerection, sweating, and spontaneous ejaculations while awake. Opioid withdrawal is distinct from opioid use disorder and does not necessarily occur in the presence of the drug-seeking behavior associated with opioid use disorder. Opioid withdrawal may occur in any individual after cessation of repeated use of an opioid, whether in the setting of medical management of pain, during opioid agonist therapy for opioid use disorder, in the context of private recreational use, or following attempts to self-treat symptoms of mental disorders with opioids.

Prevaience

Among individuals from various clinical settings, opioid withdrawal occurred in 60% of individuals who had used heroin at least once in the prior 12 months.

16.1.7 Sedative, Hypnotic, or Anxiolytic-Related Disorders

16.1.7.1 Sedative, Hypnotic, or Anxiolytic Use Disorder

Diagnostic Features

Sedative, hypnotic, or anxiolytic substances include benzodiazepines, benzodiazepinelike drugs (e.g., zolpidem, zaleplon), carbamates (e.g., glutethimide, meprobamate), barbiturates (e.g., secobarbital), and barbiturate-like hypnotics (e.g., glutethimide, methaqualone). This class of substances includes all prescription sleeping medications and almost all prescription antianxiety medications. Nonbenzodiazepine antianxiety agents (e.g., buspirone, gepirone) are not included in this class because they do not appear to be associated with significant misuse.

Like alcohol, these agents are brain depressants and can produce similar substance/ medication-induced and substance use disorders. Sedative, hypnotic, or anxiolytic substances are available both by prescription and illegally. Some individuals who obtain these substances by prescription will develop a sedative, hypnotic, or anxiolytic use disorder, while others who misuse these substances or use them for intoxication will not develop a use disorder. In particular, sedatives, hypnotics, or anxiolytics with rapid onset and/or short to intermediate lengths of action may be taken for intoxication purposes, although longer acting substances in this class may be taken for intoxication as well.

Craving (Criterion A4), either while using or during a period of abstinence, is a typical feature of sedative, hypnotic, or anxiolytic use disorder. Misuse of substances from this class may occur on its own or in conjunction with use of other substances. For example, individuals may use intoxicating doses of sedatives or benzodiazepines to "come down" from cocaine or amphetamines or use high doses of benzodiazepines in combination with methadone to "boost" its effects. Repeated absences or poor work performance, school absences, suspensions or expulsions, and neglect of children or household (Criterion A5) may be related to sedative, hypnotic, or anxiolytic use disorder, as may the continued use of the substances despite arguments with a spouse about consequences of intoxication or despite physical fights (Criterion A6). Limiting contact with family or friends, avoiding work or school, or stopping participation in hobbies, sports, or games (Criterion A7) and recurrent sedative, hypnotic, or anxiolytic use when driving an automobile or operating a machine when impaired by sedative, hypnotic, or anxiolytic use (Criterion A8) are also seen in sedative, hypnotic, or anxiolytic use disorder. Very significant levels of tolerance and withdrawal can develop to the sedative, hypnotic, or anxiolytic. There may be evidence of tolerance and withdrawal in the absence of a diagnosis of a sedative, hypnotic, or anxiolytic use disorder in an individual who has abruptly discontinued use of benzodiazepines that were taken for long periods of time at prescribed and therapeutic doses. In these cases, an additional diagnosis of sedative, hypnotic, or anxiolytic use disorder is made only if other criteria are met. That is, sedative, hypnotic, or anxiolytic medications may be prescribed for appropriate medical purposes, and depending on the dose regimen, these drugs may then produce tolerance and withdrawal. If these drugs are prescribed or recommended for appropriate medical purposes, and if they are uoed as prescribed, the resulting tolerance or withdrawal does not meet the criteria for diagnosing a substance use disorder. However, it is necessary to determine whether the drugs were appropriately prescribed and used (e.g., falsifying medical symptoms to obtain the medication; using more medication than prescribed; obtaining the medication from several doctors without informing them of the others' involvement). Given the unidimensional nature of the symptoms of sedative, hypnotic, or anxiolytic use disorder, severity is based on the number of criteria endorsed.

Associated Features Supporting Diagnosis

Sedative, hypnotic, or anxiolytic use disorder is often associated with other substance use disorders (e.g., alcohol, cannabis, opioid, stimulant use disorders). Sedatives are often used to alleviate the unwanted effects of these other substances. With repeated use of the substance, tolerance develops to the sedative effects, and a progressively higher dose is used. However, tolerance to brain stem depressant effects develops much more slowly, and as the individual takes more substance to achieve euphoria or other desired effects, there may be a sudden onset of respiratory depression and hypotension, which may result in death. Intense or repeated sedative, hypnotic, or anxiolytic intoxication may be associated with severe depression that, although temporary, can lead to suicide attempt and completed suicide.

Prevalence

The 12-month prevalences of DSM-IV sedative, hypnotic, or anxiolytic use disorder are estimated to be 0.3% among 12- to 17-year-olds and 0.2% among adults age 18 years and older. Rates of DSM-IV sedative, hypnotic, or anxiolytic use disorder are slightly greater among adult males (0.3%) than among adult females, but for 12- to 17-year-olds, the rate for females (0.4%) exceeds that for males (0.2%). The 12-month prevalence of DSM-IV sedative, hypnotic, or anxiolytic use disorder decreases as a function of age and is greatest among 18- to 29-year-olds (0.5%) and lowest among individuals 65 years and older (0.04%). Twelve-month prevalence of sedative, hypnotic, or anxiolytic use disorder varies across racial/ethnic subgroups of the U.S. population. For 12- to 17-year-olds, rates are greatest among whites (0.3%) relative to African Americans (0.2%), Hispanics (0.2%), Native Americans (0.1%), and Asian Americans and Pacific Islanders (0.1%). Among adults, 12-month prevalence is greatest among Native Americans and Alaska Natives (0.8%), with rates of approximately 0.2% among African Americans, whites, and Hispanics and 0.1% among Asian Americans and Pacific Islanders.

Culture-Related Diagnostic issues

There are marked variations in prescription patterns (and availability) of this class of substances in different countries, which may lead to variations in prevalence of sedative, hypnotic, or anxiolytic use disorders.

Gender-Related Diagnostic Issues

Females may be at higher risk than males for prescription drug misuse of sedative, hypnotic, or anxiolytic substances.

Functional Consequences of Sedative, Hypnotic, or Anxioiytic Use Disorder

The social and interpersonal consequences of sedative, hypnotic, or anxiolytic use disorder mimic those of alcohol in terms of the potential for disinhibited behavior. Accidents, interpersonal difficulties (such as arguments or fights), and interference with work or school performance are all common outcomes. Physical examination is likely to reveal evidence of a mild decrease in most aspects of autonomic nervous system functioning, including a slower pulse, a slightly decreased respiratory rate, and a slight drop in blood pressure (most likely to occur with postural changes). At high doses, sedative, hypnotic, or anxiolytic substances can be lethal, particularly when mixed with alcohol, although the lethal dosage varies considerably among the specific substances. Overdoses may be associated with a deterioration in vital signs that signals an impending medical emergency (e.g., respiratory arrest from barbiturates). There may be consequences of trauma (e.g., internal bleeding or a subdural hematoma) from accidents that occur while intoxicated. Intravenous use of these substances can result in medical complications related to the use of contaminated needles (e.g., hepatitis and HIV). Acute intoxication can result in accidental injuries and automobile accidents. For elderly individuals, even short-term use of these sedating medications at prescribed doses can be associated with an increased risk for cognitive problems and falls. The disinhibiting effects of these agents, Hke alcohol, may potentially contribute to overly aggressive behavior, with subsequent interpersonal and legal problems. Accidental or deliberate overdoses, similar to those observed for alcohol use disorder or repeated alcohol intoxication, can occur. In contrast to their wide margin of safety when used alone, benzodiazepines taken in combination with alcohol can be particularly dangerous, and accidental overdoses are reported commonly. Accidental overdoses have also been reported in individuals who deliberately misuse barbiturates and other nonbenzodiazepine sedatives (e.g., methaqualone), but since these agents are much less available than the benzodiazepines, the frequency of overdosing is low in most settings.

16.1.7.2 Sedative, Hypnotic, or Anxiolytic Intoxication

Diagnostic Features

The essential feature of sedative, hypnotic, or anxiolytic intoxication is the presence of clinically significant maladaptive behavioral or psychological changes (e.g., inappropriate sexual or aggressive behavior, mood lability, impaired judgment, impaired social or occupational functioning) that develop during, or shortly after, use of a sedative, hypnotic, or anxiolytic (Criteria A and B). As with other brain depressants, such as alcohol, these behaviors may be accompanied by slurred speech, incoordination (at levels that can interfere with driving abilities and with performing usual activities to the point of causing falls or automobile accidents), an unsteady gait, nystagmus, impairment in cognition (e.g., attentional or memory problems), and stupor or coma (Criterion C). Memory impairment is a prominent feature of sedative, hypnotic, or anxiolytic intoxication and is most often characterized by an anterograde amnesia tiiat resembles "alcoholic blackouts," which can be disturbing to the individual. The symptoms must not be attributable to another medical condition and are not better explained by another mental disorder (Criterion D). Intoxication may occur in individuals who are receiving these substances by prescription, are borrov^ing the medication from friends or relatives, or are deliberately taking the substance to achieve intoxication.

Associated Features Supporting Diagnosis

Associated features include taking more medication than prescribed, taking multiple different medications, or mixing sedative, hypnotic, or anxiolytic agents with alcohol, which can markedly increase the effects of these agents.

Prevaience

The prevalence of sedative, hypnotic, or anxiolytic intoxication in the general population is unclear. However, it is probable that most nonmedical users of sedatives, hypnotics, or anxiolytics would at some time have signs or symptoms that meet criteria for sedative, hypnotic, or anxiolytic intoxication; if so, then the prevalence of nonmedical sedative, hypnotic, or anxiolytic use in the general population may be similar to the prevalence of sedative, hypnotic, or anxiolytic intoxication. For example, tranquilizers are used nonmedically by 2.2% of Americans older than 12 years.

16.1.7.3 Sedative, Hypnotic, or Anxiolytic Withdrawal

Diagnostic Features

The essential feature of sedative, hypnotic, or anxiolytic withdrawal is the presence of a characteristic syndrome that develops after a marked decrease in or cessation of intake after several weeks or more of regular use (Criteria A and B). This withdrawal syndrome is characterized by two or more symptoms (similar to alcohol withdrawal) that include autonomic hyperactivity (e.g., increases in heart rate, respiratory rate, blood pressure, or body temperature, along with sweating); a tremor of the hands; insomnia; nausea, sometimes accompanied by vomiting; anxiety; and psychomotor agitation. A grand mal seizure may occur in perhaps as many as 20%-30% of individuals undergoing untreated withdrawal from these substances. In severe withdrawal, visual, tactile, or auditory hallucinations or illusions can occur but are usually in the context of a delirium. If the individual's reality testing is intact (i.e., he or she knows the substance is causing the hallucinations) and the illusions occur in a clear sensorium, the specifier 'Vith perceptual disturbances" can be noted. When hallucinations occur in the absence of intact reality testing, a diagnosis of substance/medication-induced psychotic disorder should be considered. The symptoms cause clinically significant distress or impairment in social, occupational, or other important areas of functioning (Criterion C). The symptoms must not be attributable to another medical condition and are not better explained by another mental disorder (e.g., alcohol withdrawal or generalized anxiety disorder) (Criterion D). Relief of withdrawal symptoms with administration of any sedative-hypnotic agent would support a diagnosis of sedative, hypnotic, or anxiolytic withdrawal.

Associated Features Supporting Diagnosis

The timing and severity of the withdrawal syndrome will differ depending on the specific substance and its pharmacokinetics and pharmacodynamics. For example, withdrawal from shorter-acting substances that are rapidly absorbed and that have no active metabolites (e.g., triazolam) can begin within hours after the substance is stopped; withdrawal from substances with long-acting metabolites (e.g., diazepam) may not begin for 1-2 days or longer. The withdrawal syndrome produced by substances in this class may be characterized by the development of a delirium that can be life-threatening. There may be evidence of tolerance and withdrawal in the absence of a diagnosis of a substance use disorder in an individual who has abruptly discontinued benzodiazepines that were taken for long periods of time at prescribed and therapeutic doses. However, ICD-IO-CM codes only allow a diagnosis of sedative, hypnotic, or anxiolytic withdrawal in the presence of comorbid moderate to severe sedative, hypnotic, or anxiolytic use disorder. The time course of the withdrawal syndrome is generally predicted by the half-life of the substance. Medications whose actions typically last about 10 hours or less (e.g., lorazepam, oxazepam, temazepam) produce withdrawal symptoms within 6-8 hours of decreasing blood levels that peak in intensity on the second day and improve markedly by the fourth or fifth day. For substances with longer half-lives (e.g., diazepam), symptoms may not develop for more than 1 week, peak in intensity during the second week, and decrease markedly during the third or fourth week. There may be additional longer-term symptoms at a much lower level of intensity that persist for several months. The longer the substance has been taken and the higher the dosages used, the more likely it is that there will be severe withdrawal. However, withdrawal has been reported with as little as 15 mg of diazepam (or its equivalent in other benzodiazepines) when taken daily for several months. Doses of approximately 40 mg of diazepam (or its equivalent) daily are more likely to produce clinically relevant withdrawal symptoms, and even higher doses (e.g., 100 mg of diazepam) are more likely to be followed by withdrawal seizures or delirium. Sedative, hypnotic, or anxiolytic withdrawal delirium is characterized by disturbances in consciousness and cognition, with visual, tactile, or auditory hallucinations. When present, sedative, hypnotic, or anxiolytic withdrawal delirium should be diagnosed instead of withdrawal.

Prevalence

The prevalence of sedative, hypnotic, or anxiolytic withdrawal is unclear.

16.1.8. Stimulant-Related Disorders

16.1.8.1 Stimulant Use Disorder

Diagnostic Features

The amphetamine and amphetamine-type stimulants include substances with a substituted- phenylethylamine structure, such as amphetamine, dextroamphetamine, and methamphetamine. Also included are those substances that are structurally different but have similar effects, such as methylphenidate. These substances are usually taken orally or intravenously, although methamphetamine is also taken by the nasal route. In addition to the synthetic amphetamine-type compounds, there are naturally occurring, plant-derived stimulants such as khat. Amphetamines and other stimulants may be obtained by prescription for the treatment of obesity, attention-deficit/hyperactivity disorder, and narcolepsy. Consequently, prescribed stimulants may be diverted into the illegal market. The effects of amphetamines and amphetamine-like drugs are similar to those of cocaine, such that the criteria for stimulant use disorder are presented here as a single disorder with the ability to specify the particular stimulant used by the individual. Cocaine may be consumed in several preparations (e.g., coca leaves, coca paste, cocaine hydrochloride, and cocaine alkaloids such as freebase and crack) that differ in potency because of varying levels of purity and speed of onset. However, in all forms of the substance, cocaine is the active ingredient. Cocaine hydrochloride powder is usually "snorted" through the nostrils or dissolved in water and injected intravenously.

Individuals exposed to amphetamine-type stimulants or cocaine can develop stimulant use disorder as rapidly as 1 week, although the onset is not always this rapid. Regardless of the route of administration, tolerance occurs with repeated use. Withdrawal symptoms, particularly hypersomnia, increased appetite, and dysphoria, can occur and can enhance craving. Most individuals with stimulant use disorder have experienced tolerance or withdrawal.

Use patterns and course are similar for disorders involving amphetamine-type stimulants and cocaine, as both substances are potent central nervous system stimulants with similar psychoactive and sympathomimetic effects. Amphetamine-type stimulants are longer acting than cocaine and thus are used fewer times per day. Usage may be chronic or episodic, with binges punctuated by brief non-use periods. Aggressive or violent behavior is common when high doses are smoked, ingested, or administered intravenously. Intense temporary anxiety resembling panic disorder or generalized anxiety disorder, as well as paranoid ideation and psychotic episodes that resemble schizophrenia, is seen with highdose use.

Withdrawal states are associated with temporary but intense depressive symptoms that can resemble a major depressive episode; the depressive symptoms usually resolve within 1 week. Tolerance to amphetamine-type stimulants develops and leads to escalation of the dose. Conversely, some users of amphetamine-type stimulants develop sensitization, characterized by enhanced effects.

Associated Features Supporting Diagnosis

When injected or smoked, stimulants typically produce an instant feeling of well-being, confidence, and euphoria. Dramatic behavioral changes can rapidly develop with stimulant use disorder. Chaotic behavior, social isolation, aggressive behavior, and sexual dysfunction can result from long-term stimulant use disorder.

Individuals with acute intoxication may present with rambling speech, headache, transient ideas of reference, and tinnitus. There may be paranoid ideation, auditory hallucinations in a clear sensorium, and tactile hallucinations, which the individual usually recognizes as drug effects. Threats or acting out of aggressive behavior may occur. Depression, suicidal ideation, irritability, anhedonia, emotional lability, or disturbances in attention and concentration commonly occur during withdrawal. Mental disturbances associated with cocaine use usually resolve hours to days after cessation of use but can persist for 1 month. Physiological changes during stimulant withdrawal are opposite to those of the intoxication phase, sometimes including bradycardia. Temporary depressive symptoms may meet symptomatic and duration criteria for major depressive episode. Histories consistent with repeated panic attacks, social anxiety disorder (social phobia)-like behavior, and generalized anxiety-like syndromes are common, as are eating disorders. One extreme instance of stimulant toxicity is stimulant-induced psychotic disorder, a disorder that resembles schizophrenia, with delusions and hallucinations. Individuals with stimulant use disorder often develop conditioned responses to drugrelated stimuli (e.g., craving on seeing any white powderlike substance). These responses contribute to relapse, are difficult to extinguish, and persist after detoxification. Depressive symptoms with suicidal ideation or behavior can occur and are generally the most serious problems seen during stimulant withdrawal.

Prevalence

Stimulant use disorder: amphetamine-type stimulants. Estimated 12-month prevalence of amphetamine-type stimulant use disorder in the United States is 0.2% among 12- to 17- year-olds and 0.2% among individuals 18 years and older. Rates are similar among adult males and females (0.2%), but among 12- to 17-year-olds, the rate for females (0.3%) is greater than that for males (0.1%). Intravenous stimulant use has a male-to-female ratio of 3:1 or 4:1, but rates are more balanced among non-injecting users, with males representing 54% of primary treatment admissions. Twelve-month prevalence is greater among 18- to 29-year-olds (0.4%) compared with 45- to 64-year-olds (0.1%). For 12- to 17-year-olds, rates are highest among whites and African Americans (0.3%) compared with Hispanics (0.1%) and Asian Americans and Pacific Islanders (0.01%), with amphetamine-type stimulant use disorder virtually absent among Native Americans. Among adults, rates are highest among Native Americans and Alaska Natives (0.6%) compared with whites (0.2%) and Hispanics (0.2%), with amphetamine-type stimulant use disorder virtually absent among African Americans and Asian Americans and Pacific Islanders. Past-year nonprescribed use of prescription stimulants occurred among 5%-9% of children through high school, with 5%-35% of college-age persons reporting past-year use.

Stimulant use disorder: cocaine. Estimated 12-month prevalence of cocaine use disorder in the United States is 0.2% among 12- to 17-year-olds and 0.3% among individuals 18 years and older. Rates are higher among males (0.4%) than among females (0.1%). Rates are highest among 18- to 29-year-olds (0.6%) and lowest among 45- to 64-year-olds (0.1%). Among adults, rates are greater among Native Americans (0.8%) compared with African Americans (0.4%), Hispanics (0.3%), whites (0.2%), and Asian Americans and Pacific Islanders (0.1%). In contrast, for 12- to 17-year-olds, rates are similar among Hispanics (0.2%), whites (0.2%), and Asian Americans and Pacific Islanders (0.2%); and lower among African Americans (0.02%); with cocaine use disorder virtually absent among Native Americans and Alaska Natives.

Culture-Related Diagnostic issues

Stimulant use-attendant disorders affect all racial/ethnic, socioeconomic, age, and gender groups. Diagnostic issues may be related to societal consequences (e.g., arrest, school suspensions, employment suspension). Despite small variations, cocaine and other stimulant use disorder diagnostic criteria perform equally across gender and race/ethnicity groups. Chronic use of cocaine impairs cardiac left ventricular function in African Americans. Approximately 66% of individuals admitted for primary methamphetamine/amphetamine- related disorders are non-Hispanic white, followed by 21% of Hispanic origin, 3% Asian and Pacific Islander, and 3% non-Hispanic black.

Functional Consequences of Stimulant Use Disorder

Various medical conditions may occur depending on the route of administration. Intranasal users often develop sinusitis, irritation, bleeding of the nasal mucosa, and a perforated nasal septum. Individuals who smoke the drugs are at increased risk for respiratory problems (e.g., coughing, bronchitis, and pneumonitis). Injectors have puncture marks and "tracks," most commonly on their forearms. Risk of HIV infection increases with frequent intravenous injections and unsafe sexual activity. Other sexually transmitted diseases, hepatitis, and tuberculosis and other lung infections are also seen. Weight loss and malnutrition are common.

Chest pain may be a common symptom during stimulant intoxication. Myocardial infarction, palpitations and arrhythmias, sudden death from respiratory or cardiac arrest, and stroke have been associated with stimulant use among young and otherwise healthy individuals. Seizures can occur with stimulant use. Pneumothorax can result from performing Valsalva-like maneuvers done to better absorb inhaled smoke. Traumatic injuries due to violent behavior are common among individuals trafficking drugs. Cocaine use is associated with irregularities in placental blood flow, abruptio placentae, premahire labor and delivery, and an increased prevalence of infants with very low birth weights. Individuals with stimulant use disorder may become involved in theft, prostitution, or drug dealing in order to acquire drugs or money for drugs.

Neurocognitive impairment is common among methamphetamine users. Oral health problems include "meth mouth" with gum disease, tooth decay, and mouth sores related to the toxic effects of smoking the drug and to bruxism while intoxicated. Adverse pulmonary effects appear to be less common for amphetamine-type stimulants because they are smoked fewer times per day. Emergency department visits are common for stimulant-related mental disorder symptoms, injury, skin infections, and dental pathology.

16.1.8.2 Stimulant Intoxication

Diagnostic Features

The essential feature of stimulant intoxication, related to amphetamine-type stimulants and cocaine, is the presence of clinically significant behavioral or psychological changes that develop during, or shortly after, use of stimulants (Criteria A and B). Auditory hallucinations may be prominent, as may paranoid ideation, and these symptoms must be distinguished from an independent psychotic disorder such as schizophrenia. Stimulant intoxication usually begins with a "high" feeling and includes one or more of the following: euphoria with enhanced vigor, gregariousness, hyperactivity, restlessness, hypervigilance, interpersonal sensitivity, talkativeness, anxiety, tension, alertness, grandiosity, stereotyped and repetitive behavior, anger, impaired judgment, and, in the case of chronic intoxication, affective blunting with fatigue or sadness and social withdrawal. These behavioral and psychological changes are accompanied by two or more of the following signs and symptoms that develop during or shortly after stimulant use: tachycardia or bradycardia; pupillary dilation; elevated or lowered blood pressure; perspiration or chills; nausea or vomiting; evidence of weight loss; psychomotor agitation or retardation; muscular weakness, respiratory depression, chest pain, or cardiac arrhythmias; and confusion, seizures, dyskinesias, dystonias, or coma (Criterion C). Intoxication, either acute or chronic, is often associated with impaired social or occupational functioning. Severe intoxication can lead to convulsions, cardiac arrhythmias, hyperpyrexia, and death. For the diagnosis of stimulant intoxication to be made, the symptoms must not be attributable to another medical condition and not better explained by another mental disorder (Criterion D). While stimulant intoxication occurs in individuals with stimulant use disorders, intoxication is not a criterion for stimulant use disorder, which is confirmed by the presence of two of the 11 diagnostic criteria for use disorder.

Associated Features Supporting Diagnosis

The magnitude and direction of the behavioral and physiological changes depend on many variables, including the dose used and the characteristics of the individual using the substance or the context (e.g., tolerance, rate of absorption, chronicity of use, context in which it is taken). Stimulant effects such as euphoria, increased pulse and blood pressure, and psychomotor activity are most commonly seen. Depressant effects such as sadness, bradycardia, decreased blood pressure, and decreased psychomotor activity are less common and generally emerge only with chronic high-dose use.

16.1.8.3 Stimulant Withdrawal

Diagnostic Features

The essential feature of stimulant withdrawal is the presence of a characteristic withdrawal syndrome that develops within a few hours to several days after the cessation of (or marked reduction in) stimulant use (generally high dose) that has been prolonged (Criterion A). The withdrawal syndrome is characterized by the development of dysphoric mood accompanied by two or more of the following physiological changes: fatigue, vivid and unpleasant dreams, insomnia or hypersomnia, increased appetite, and psychomotor retardation or agitation (Criterion B). Bradycardia is often present and is a reliable measure of stimulant withdrawal.

Anhedonia and drug craving can often be present but are not part of the diagnostic criteria. These symptoms cause clinically significant distress or impairment in social, occupational, or other important areas of functioning (Criterion C). The symptoms must not be attributable to another medical condition and are not better explained by another mental disorder (Criterion D).

Associated Features Supporting Diagnosis

Acute withdrawal symptoms ("a crash") are often seen after periods of repetitive high-dose use ("runs" or 'linges"). These periods are characterized by intense and unpleasant feelings of lassitude and depression and increased appetite, generally requiring several days of rest and recuperation. Depressive symptoms with suicidal ideation or behavior can occur and are generally the most serious problems seen during "crashing" or other forms of stimulant withdrawal. The majority of individuals with stimulant use disorder experience a withdrawal syndrome at some point, and virtually all individuals with the disorder report tolerance.

16.1.9 Tobacco-Related Disorders

16.1.9.1 Tobacco Use Disorder

Diagnostic Features

Tobacco use disorder is common among individuals who use cigarettes and smokeless tobacco daily and is uncommon among individuals who do not use tobacco daily or who use nicotine medications. Tolerance to tobacco is exemplified by the disappearance of nausea and dizziness after repeated intake and with a more intense effect of tobacco the first time it is used during the day. Cessation of tobacco use can produce a well-defined withdrawal syndrome. Many individuals with tobacco use disorder use tobacco to relieve or to avoid withdrawal symptoms (e.g., after being in a situation where use is restricted). Many individuals who use tobacco have tobacco-related physical symptoms or diseases and continue to smoke. The large majority report craving when they do not smoke for several hours. Spending excessive time using tobacco can be exemplified by chain-smoking (i.e., smoking one cigarette after another with no time between cigarettes). Because tobacco sources are readily and legally available, and because nicotine intoxication is very rare, spending a great deal of time attempting to procure tobacco or recovering from its effects is uncommon. Giving up important social, occupational, or recreational activities can occur when an individual forgoes an activity because it occurs in tobacco use-restricted areas. Use of tobacco rarely results in failure to fulfill major role obligations (e.g., interference with work, interference with home obligations), but persistent social or inteφersonal problems (e.g., having arguments with others about tobacco use, avoiding social situations because of others' disapproval of tobacco use) or use that is physically hazardous (e.g., smoking in bed, smoking around flammable chemicals) occur at an intermediate prevalence. Although these criteria are less often endorsed by tobacco users, if endorsed, they can indicate a more severe disorder.

Associated Features Supporting Diagnosis

Smoking within 30 minutes of waking, smoking daily, smoking more cigarettes per day, and waking at night to smoke are associated with tobacco use disorder. Environmental cues can evoke craving and withdrawal. Serious medical conditions, such as lung and other cancers, cardiac and pulmonary disease, perinatal problems, cough, shortness of breath, and accelerated skin aging, often occur.

Prevalence

Cigarettes are the most commonly used tobacco product, representing over 90% of tobacco/ nicotine use. In the United States, 57% of adults have never been smokers, 22% are former smokers, and 21% are current smokers. Approximately 20% of current U.S. smokers are nondaily smokers. The prevalence of smokeless tobacco use is less than 5%, and the prevalence of tobacco use in pipes and cigars is less than 1%.

DSM-IV nicotine dependence criteria can be used to estimate the prevalence of tobacco use disorder, but since they are a subset of tobacco use disorder criteria, the prevalence of tobacco use disorder will be somewhat greater. The 12-month prevalence of DSM-IV nicotine dependence in the United States is 13% among adults age 18 years and older. Rates are similar among adult males (14%) and females (12%) and decline in age from 17% among 18- to 29-year-olds to 4% among individuals age 65 years and older. The prevalence of current nicotine dependence is greater among Native American and Alaska Natives (23%) than among whites (14%) but is less among African Americans (10%), Asian Americans and Pacific Islanders (6%), and Hispanics (6%). The prevalence among current daily smokers is approximately 50%.

In many developing nations, the prevalence of smoking is much greater in males than in females, but this is not the case in developed nations. However, there often is a lag in the demographic transition such that smoking increases in females at a later time.

Culture-Related Diagnostic Issues

Cultures and subcultures vary widely in their acceptance of the use of tobacco. The prevalence of tobacco use declined in the United States from the 1960s through the 1990s, but this decrease has been less evident in African American and Hispanic populations. Also, smoking in developing countries is more prevalent than in developed nations. The degree to which these cultural differences are due to income, education, and tobacco control activities in a country is unclear. Non-Hispanic white smokers appear to be more likely to develop tobacco use disorder than are smokers. Some ethnic differences may be biologically based. African American males tend to have higher nicotine blood levels for a given number of cigarettes, and this might contribute to greater difficulty in quitting. Also, the speed of nicotine metabolism is significantly different for whites compared with African Americans and can vary by genotypes associated with ethnicities.

Functional Consequences of Tobacco Use Disorder

Medical consequences of tobacco use often begin when tobacco users are in their 40s and usually become progressively more debilitating over time. One-half of smokers who do not stop using tobacco will die early from a tobacco-related illness, and smoking-related morbidity occurs in more than one-half of tobacco users. Most medical conditions result from exposure to carbon monoxide, tars, and other non-nicotine components of tobacco. The major predictor of reversibility is duration of smoking. Secondhand smoke increases the risk of heart disease and cancer by 30%. Long-term use of nicotine medications does not appear to cause medical harm.

16.1.9.2 Tobacco Withdrawal

Diagnostic Features

Withdrawal symptoms impair the ability to stop tobacco use. The symptoms after abstinence from tobacco are in large part due to nicotine deprivation. Symptoms are much more intense among individuals who smoke cigarettes or use smokeless tobacco than among those who use nicotine medications. This difference in symptom intensity is likely due to the more rapid onset and higher levels of nicotine with cigarette smoking. Tobacco withdrawal is common among daily tobacco users who stop or reduce but can also occur among nondaily users. Typically, heart rate decreases by 5-12 beats per minute in the first few days after stopping smoking, and weight increases an average of 4-7 lb (2-3 kg) over the first year after stopping smoking. Tobacco withdrawal can produce clinically significant mood changes and functional impairment.

Associated Features Supporting Diagnosis

Craving for sweet or sugary foods and impaired performance on tasks requiring vigilance are associated with tobacco withdrawal. Abstinence can increase constipation, coughing, dizziness, dreaming/nightmares, nausea, and sore throat. Smoking increases the metabolism of many medications used to treat mental disorders; thus, cessation of smoking can increase the blood levels of these medications, and this can produce clinically significant outcomes. This effect appears to be due not to nicotine but rather to other compounds in tobacco.

Prevalence

Approximately 50% of tobacco users who quit for 2 or more days will have symptoms that meet criteria for tobacco withdrawal. The most commonly endorsed signs and symptoms are anxiety, irritability, and difficulty concentrating. The least commonly endorsed symptoms are depression and insomnia.

Functional Consequences of Tobacco Withdrawal

Abstinence from cigarettes can cause clinically significant distress. Withdrawal impairs the ability to stop or control tobacco use. Whether tobacco withdrawal can prompt a new mental disorder or recurrence of a mental disorder is debatable, but if this occurs, it would be in a small minority of tobacco users.

16.1.10 Other (or Unknown) Substance-Related Disorders

16.1.10.1 Other (or Unknown) Substance Use Disorder

Diagnostic Features

The diagnostic dass other (or unknown) substance use and related disorders comprises substance-related disorders unrelated to alcohol; caffeine; cannabis; hallucinogens (phencyclidine and others); inhalants; opioids; sedative, hypnotics, or anxiolytics; stimulants (including amphetamine and cocaine); or tobacco. Such substances include anabolic steroids; nonsteroidal anti-inflammatory drugs; cortisol; antiparkinsonian medications; antihistamines; nitrous oxide; amyl-, butyl-, or isobutyl-nitrites; betel nut, which is chewed in many cultures to produce mild euphoria and a floating sensation; kava (from a South Pacific pepper plant), which produces sedation, incoordination, weight loss, mild hepatitis, and lung abnormalities; or cathinones (including khat plant agents and synthetic chemical derivatives) that produce stimulant effects. Unknown substance-related disorders are associated with unidentified substances, such as intoxications in which the individual cannot identify the ingested drug, or substance use disorders involving either new, black market drugs not yet identified or familiar drugs illegally sold under false names. Other (or unknown) substance use disorder is a mental disorder in which repeated use of an other or unknown substance typically continues, despite the individual's knowing that the substance is causing serious problems for the individual. Those problems are reflected in the diagnostic criteria. When the substance is known, it should be reflected in the name of the disorder upon coding (e.g., nitrous oxide use disorder).

Associated Features Supporting Diagnosis

A diagnosis of other (or unknown) substance use disorder is supported by the individual's statement that the substance involved is not among the nine classes listed in this chapter; by recurring episodes of intoxication with negative results in standard drug screens (which may not detect new or rarely used substances); or by the presence of symptoms characteristic of an unidentified substance that has newly appeared in the individual's community.
Because of increased access to nitrous oxide ("laughing gas"), membership in certain populations is associated with diagnosis of nitrous oxide use disorder. The role of this gas as an anesthetic agent leads to misuse by some medical and dental professionals. Its use as a propellant for commercial products (e.g., whipped cream dispensers) contributes to misuse by food service workers. With recent widespread availability of the substance in "whippet" cartridges for use in home whipped cream dispensers, nitrous oxide misuse by adolescents and young adults is significant, especially among those who also inhale volatile hydrocarbons. Some continuously using individuals, inhaling from as many as 240 whippets per day, may present with serious medical complications and mental conditions, including myeloneuropathy, spinal cord subacute combined degeneration, peripheral neuropathy, and psychosis. These conditions are also associated with a diagnosis of nitrous oxide use disorder.

Use of amyl-, butyl-, and isobutyl nitrite gases has been observed among homosexual men and some adolescents, especially those with conduct disorder. Membership in these populations may be associated with a diagnosis of amyl-, butyl-, or isobutyl-nitrite use disorder. However, it has not been determined that these substances produce a substance use disorder. Despite tolerance, these gases may not alter behavior through central effects, and they may be used only for their peripheral effects.

Substance use disorders generally are associated with elevated risks of suicide, but there is no evidence of unique risk factors for suicide with other (or unknown) substance use disorder.

Prevaience

Based on extremely limited data, the prevalence of other (or unknown) substance use disorder is likely lower than that of use disorders involving the nine substance classes in this chapter.

Cuiture-Related Diagnostic issues

Certain cultures may be associated with other (or unknown) substance use disorders involving specific indigenous substances within the cultural region, such as betel nut.

16.1.10.2 Other (or Unknown) Substance Intoxication

Diagnostic Features

Other (or unknown) substance intoxication is a clinically significant mental disorder that develops during, or immediately after, use of either a) a substance not elsewhere addressed in this chapter (i.e., alcohol; caffeine; cannabis; phencyclidine and other hallucinogens; inhalants; opioids; sedatives, hypnotics, or anxiolytics; stimulants; or tobacco) or b) an unknown substance. If the substance is known, it should be reflected in the name of the disorder upon coding.

Application of the diagnostic criteria for other (or unknown) substance intoxication is very challenging. Criterion A requires development of a reversible "substance-specific syndrome," but if the substance is unknown, that syndrome usually will be unknown. To resolve this conflict, clinicians may ask the individual or obtain collateral history as to whether the individual has experienced a similar episode after using substances with the same "street" name or from the same source. Similarly, hospital emergency departments sometimes recognize over a few days numerous presentations of a severe, unfamiliar intoxication syndrome from a newly available, previously unknown substance. Because of the great variety of intoxicating substances. Criterion B can provide only broad examples of signs and symptoms from some intoxications, with no threshold for the number of symptoms required for a diagnosis; clinical judgment guides those decisions. Criterion C requires ruling out other medical conditions, mental disorders, or intoxications.

Prevalence

The prevalence of other (or unknown) substance intoxication is unknown. Functional Consequences of Other (or Unknown) Substance Intoxication Impairment from intoxication with any substance may have serious consequences, including dysfunction at work, social indiscretions, problems in interpersonal relationships, failure to fulfill role obligations, traffic accidents, fighting, high-risk behaviors (i.e., having unprotected sex), and substance or medication overdose. The pattern of consequences will vary with the particular substance.

16.1.10.3 Other (or Unknown) Substance Withdrawal

Diagnostic Features

Other (or unknown) substance withdrawal is a clinically significant mental disorder that develops during, or within a few hours to days after, reducing or terminating dosing with a substance (Criteria A and B). Although recent dose reduction or termination usually is clear in the history, other diagnostic procedures are very challenging if the drug is unknown. Criterion B requires development of a "substance-specific syndrome" (i.e., the individual's signs and symptoms must correspond with the known withdrawal syndrome for the recently stopped drug)—a requirement that rarely can be met with an unknown substance. Consequently, clinical judgment must guide such decisions when information is this limited. Criterion D requires ruling out other medical conditions, mental disorders, or withdrawals from familiar substances. When the substance is known, it should be reflected in the name of the disorder upon coding (e.g., betel nut withdrawal).

Prevaience

The prevalence of other (or unknown) substance withdrawal is unknown.

Cuiture-Related Diagnostic issues

Culture-related issues in diagnosis will vary with the particular substance.

Functional Consequences of Other (or Unknown) Substance Withdrawal

Withdrawal from any substance may have serious consequences, including physical signs and symptoms (e.g., malaise, vital sign changes, abdominal distress, headache), intense drug craving, anxiety, depression, agitation, psychotic symptoms, or cognitive impairments. These consequences may lead to problems such as dysfunction at work, problems in interpersonal relationships, failure to fulfill role obligations, traffic accidents, fighting, highrisk behavior (e.g., having unprotected sex), suicide attempts, and substance or medication overdose. The pattern of consequences will vary with the particular substance.

16.2. Non-Substance-Related Disorders

16.2.1 Gambling Disorder

Diagnostic Features

Gambling involves risking something of value in the hopes of obtaining something of greater value. In many cultures, individuals gamble on games and events, and most do so without experiencing problems. However, some individuals develop substantial impairment related to their gambling behaviors. The essential feature of gambling disorder is persistent and recurrent maladaptive gambling behavior that disrupts personal, family, and/or vocational pursuits (Criterion A). Gambling disorder is defined as a cluster of four or more of the symptoms listed in Criterion A occurring at any time in the same 12-month period.

A pattern of "chasing one's losses" may develop, with an urgent need to keep gambling (often with the placing of larger bets or the taking of greater risks) to undo a loss or series of losses. The individual may abandon his or her gambling strategy and try to win back losses all at once. Although many gamblers may "chase" for short periods of time, it is the frequent, and often long-term, "chase" that is characteristic of gambling disorder (Criterion A6). Individuals may lie to family members, therapists, or others to conceal the extent of involvement with gambling; these instances of deceit may also include, but are not limited to, covering up illegal behaviors such as forgery, fraud, theft, or embezzlement to obtain money with which to gamble (Criterion A7). Individuals may also engage in "bailout" behavior, turning to family or others for help with a desperate financial situation that w,as caused by gambling (Criterion A9).

Associated Features Supporting Diagnosis

Distortions in thinking (e.g., denial, superstitions, a sense of power and control over the outcome of chance events, overconfidence) may be present in individuals with gambling disorder. Many individuals with gambling disorder believe that money is both the cause of and the solution to their problems. Some individuals with gambling disorder are impulsive, competitive, energetic, restless, and easily bored; they may be overly concerned with the approval of others and may be generous to the point of extravagance when winning. Other individuals with gambling disorder are depressed and lonely, and they may gamble when feeling helpless, guilty, or depressed. Up to half of individuals in treatment for gambling disorder have suicidal ideation, and about 17% have attempted suicide.

Prevaience

The past-year prevalence rate of gambling disorder is about 0.2%-0.3% in the general population. In the general population, the lifetime prevalence rate is about 0.4%-1.0%. For females, the lifetime prevalence rate of gambling disorder is about 0.2%, and for males it is about 0.6%. The lifetime prevalence of pathological gambling among African Americans is about 0.9%, among whites about 0.4%, and among Hispanics about 0.3%.

Risk and Prognostic Factors

Temperamental. Gambling that begins in childhood or early adolescence is associated with increased rates of gambling disorder. Gambling disorder also appears to aggregate with antisocial personality disorder, depressive and bipolar disorders, and other substance use disorders, particularly with alcohol disorders.

Genetic and physiological. Gambling disorder can aggregate in families, and this effect appears to relate to both environmental and genetic factors. Gambling problems are more frequent in monozygotic than in dizygotic twins. Gambling disorder is also more prevalent among first-degree relatives of individuals with moderate to severe alcohol use disorder than among the general population.

Course modifiers. Many individuals, including adolescents and young adults, are likely to resolve their problems with gambling disorder over time, although a strong predictor of future gambling problems is prior gambling problems.

Culture-Related Diagnostic issues

Individuals from specific cultures and races/ethnicities are more likely to participate in some types of gambling activities than others (e.g., pai gow, cockfights, blackjack, horse racing). Prevalence rates of gambling disorder are higher among African Americans than among European Americans, with rates for Hispanic Americans similar to those of European Americans. Indigenous populations have high prevalence rates of gambling disorder.

Gender-Related Diagnostic issues

Males develop gambling disorder at higher rates than females, although this gender gap may be narrowing. Males tend to wager on different forms of gambling than females, with cards, sports, and horse race gambling more prevalent among males, and slot machine and bingo gambling more common among females.

Functional Consequences of Gambling Disorder

Areas of psychosocial, health, and mental health functioning may be adversely affected by gambling disorder. Specifically, individuals with gambling disorder may, because of their involvement with gambling, jeopardize or lose important relationships with family members or friends. Such problems may occur from repeatedly lying to others to cover up the extent of gambling or from requesting money that is used for gambling or to pay off gambling debts. Employment or educational activities may likewise be adversely impacted by gambling disorder; absenteeism or poor work or school performance can occur with gambling disorder, as individuals may gamble during work or school hours or be preoccupied with gambling or its adverse consequence when they should be working or studying. Individuals with gambling disorder have poor general health and utilize medical services at high rates.