524 Substance-Related and Addictive Disorders
Specify the particular hallucinogen.
Specify if:
In early remission:  After full criteria for other hallucinogen use disorder were previ-
ously met, none of the criteria for other hallucinogen use disorder have been met for
at least 3 months but for less than 12 months (with the exception that Criterion A4,
“Craving, or a strong desire or urge to use the hallucinogen,” may be met).
In sustained remission:  After full criteria for other hallucinogen use disorder were
previously met, none of the criteria for other hallucinogen use disorder have been met
at any time during a period of 12 months or longer (with the exception that Criterion A4,
“Craving, or a strong desire or urge to use the hallucinogen,” may be met).
Specify if:
In a controlled environment:  This additional specifier is used if the individual is in an
environment where access to hallucinogens is restricted.
Coding based on current severity:  Note for ICD-10-CM codes: If a hallucinogen intoxication
or another hallucinogen-induced mental disorder is also present, do not use the codes below
for hallucinogen use disorder. Instead, the comorb id hallucinogen use disorder is indicated in
the 4th character of the hallucinogen-induced disorder code (see the coding note for halluci-
nogen intoxication or specific hallucinogen-induced mental disorder). For example, if there is
comorbid hallucinogen-induced psychotic disorder and hallucinogen use disorder, only the
hallucinogen-induced psychotic disorder code is given, with the 4th character indicating wheth-
er the comorbid hallucinogen use disorder is mild, moderate, or severe: F16.159 for mild hal-


lucinogen use disorder with hallucinogen-induced  psychotic disorder or F16.259 for a
moderate or severe hallucinogen use disorder  with hallucinogen-induced psychotic disorder.
Specify current severity:
305.30 (F16.10) Mild:  Presence of 2–3 symptoms.
304.50 (F16.20) Moderate: Presence of 4–5 symptoms.
304.50 (F16.20) Severe:  Presence of 6 or more symptoms.
Specifiers
“In a controlled environment” app lies as a further specifier of remission if the individual is
both in remission and in a controlled environm ent (i.e., in early remission in a controlled
environment or in sustained remission in a controlled environmen t). Examples of these
environments are closely supe rvised and substanc e-free jails, therapeutic communities,
and locked hospital units.
Diagnostic Features
Hallucinogens comprise a diverse group of subs tances that, despite ha ving different chem-
ical structures and possibly involving diffe rent molecular mechan isms, produce similar
alterations of percepti on, mood, and cognition in users. Hallucinogens included are phenyl-
alkylamines (e.g., mescaline, DOM [2,5-d imethoxy-4-methylam phetamine], and MDMA
[3,4-methylenedioxymethamphetamine; also called “ecstasy ”]); the indoleamines, includ-
ing psilocybin (i.e., psilocin) and dimethyltryptamine (DMT); an d the ergolines, such as LSD
(lysergic acid diethylamide) and morning glory seeds. In addition, miscellaneous other


ethnobotanical compounds are classifi ed as “hallucinogens,” of which Salvia divinorum  and
jimsonweed are two examples. Excluded from the hallucinogen group are cannabis and its
active compound, delta-9-tetrahydrocannabino l (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, al though some forms are smoked (e.g., DMT,
salvia) or (rarely) taken intranasally or by in jection (e.g., ecstasy). Duration of effects varies


Other Hallucinogen Use Disorder 525
across types of hallucinogens. Some of th ese substances (i.e., LS D, MDMA) have a long
half-life and extended duration such that us ers may spend hours to days using and/or re-
covering from the effects of these drugs. Ho wever, 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 psyc hological effects. Cros s-tolerance exists be-
tween LSD and other hallucinogens (e.g., psil ocybin, mescaline) but does not extend to
other drug categories such as amphetamines and cannabis.
MDMA/ecstasy as a hallucinogen may have distin ctive effects attributable to both its hal-
lucinogenic and its stimulant properties. Amon g heavy ecstasy users, continued use despite
physical or psychological problems, tolerance,  hazardous use, and sp ending 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 persis-
tent desire/inability to quit are rarely reported. As found for other substances, diagnostic cri-
teria for other hallucinogen use disorder are arrayed along a single continuum of severity.
One of the generic criteria for substance us e disorders, a clinically significant with-
drawal syndrome, has not been consistently documented in humans, and therefore the di-
agnosis of hallucinogen withdrawal syndrome is not included in DSM-5. However, there
is evidence of withdrawal from MDMA, wi th endorsement of two or more withdrawal
symptoms observed in 59%–98% in selected samples of ecstasy users. Both psychological


symptoms observed in 59%–98% in selected samples of ecstasy users. Both psychological
and physical problems have been common ly reported as withdrawal problems.
Associated Features Supporting Diagnosis
The characteristic symptom feat ures of some of the hallucinogens can aid in diagnosis if
urine or blood toxicology result s are not available. For exam ple, 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 oppo site 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-mo nth prevalence of ot her hallucinogen use
disorder. Among youths ages 12–17 years, 12-month prevalence is higher among Native
Americans and Alaska Natives (1.2%) than am ong Hispanics (0.6%), whites (0.6%), Afri-
can 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


12-month prevalence of other hallucinogen use disorder is similar for Native Americans
and Alaska Natives, whites, and Hispanics (a ll 0.2%) but somewhat lower for Asian Amer-
icans and Pacific Islanders (0.07%) and Africa n Americans (0.03%). Past-year prevalence is
higher in clinical samples (e.g., 19% in ad olescents in treatment) . Among individuals cur-
rently using hallucinogens in the general popu lation, 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.
Development and Course


use), 73.5% of adults and 77% of adolescents have a problematic pattern of use that may
meet other hallucinogen use disorder criteria.
Development and Course
Unlike most substances where an early age at on set is associated with elevations in risk for
the corresponding use disorder, it is unclear wh ether there is an association of an early age


526 Substance-Related and Addictive Disorders
at onset with elevations in risk for other hallucinogen use disorder. However, patterns of
drug consumption have been found to differ by age at onset, with early-onset ecstasy users
more likely to be polydrug users than their later-onset counterpar ts. There may be a dis-
proportionate influence of use of specific hallu cinogens on risk of developing other hallu-
cinogen use disorder, with use of ecstasy/MDMA increasing the risk of the disorder
relative to use of other hallucinogens.
Little is known regarding the co urse of other hallucinogen use disorder, but it is generally
thought to have low incidence, low persistence, and high rates of recovery. Adolescents are es-
pecially at risk for using these drugs, and it is  estimated that 2.7% of youths ages 12–17 years
have used one or more of these drugs in the past 12 months, with 44 % having used ecstasy/
MDMA. Other hallucinogen use disorder is a disorder observed primarily in individuals
younger than 30 years, with rates vanishingly rare among older adults.
Risk and Prognostic Factors
Temperamental. In adolescents but not consistently in adults, MDMA use is associated with
an elevated rate of other hallucinogen use di sorder. Other substance use disorders, particu-
larly alcohol, tobacco, and cannabis, and major depressive disorder are associated with ele-
vated rates of other hallucino gen use disorder. Antisocial personality disorder may be
elevated among individuals who use more than two other drugs in addition to hallucinogens,
compared with their counterparts with less exte nsive use history. The influence of adult anti-
social behaviors—but not conduct disorder or antisocial personality disorder—on other hal-


social behaviors—but not conduct disorder or antisocial personality disorder—on other hal-
lucinogen use disorder may be stronger in female s than in males. Use of specific hallucinogens
(e.g., salvia) is prominent am ong individuals ages 18–25 years with other risk-taking behaviors
and illegal activities. Cannabis use has also been implicated as a precursor to initiation of use of
hallucinogens (e.g., ecstasy), along with early use of alcohol and tobacco. Higher drug use by
peers and high sensation seeking have also been associated with elevated rates of ecstasy use.
MDMA/ecstasy use appears to signify a more severe group of hallucinogen users.
Genetic and physiological. Among male twins, total varian ce due to additive genetics
has been estimated to range from 26% to 79%, with inconsistent evidence for shared envi-
ronmental influences.
Culture-Related Diagnostic Issues
Historically, hallucinogens have been used as part of established re ligious practices, such
as the use of peyote in the Native American Church and in Mexico. Ritual use by indige-
nous 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 União de Vegetal sects. Regular use of  peyote as part of religious rituals is not
linked to neuropsychological or psychological de ficits. For adults, no race or ethnicity dif-
ferences for the full criteria or for any indi vidual criterion are apparent at this time.
Gender-Related Diagnostic Issues
In adolescents, females may be less likely th an males to endorse “hazardous use,” and fe-
male gender may be associated with increase d odds of other hallucinogen use disorder.


male gender may be associated with increase d odds of other hallucinogen use disorder.
Diagnostic Markers
Laboratory testing can be useful in distin guishing among the different hallucinogens.
However, because some agents (e.g., LSD) are so potent that as little as 75 micrograms can
produce severe reactions, typical toxicologi cal examination will not always reveal which
substance has been used.


Phencyclidine Intoxication 527
Functional Consequences of
Other Hallucinogen Use Disorder
There is evidence for long-term neurotoxic effects of MDMA/ecstasy use, including im-
pairments in memory, psychological function , and neuroendocrine function; serotonin
system dysfunction; and sleep disturbance; as  well as adverse effects on brain microvas-
culature, white matter maturation, and damage to axons. Use of MDMA/ecstasy may di-
minish functional connectiv ity among brain regions.
Differential Diagnosis
Other substance use disorders. The effects of hallucinogens must be distinguished from
those of other substances (e.g., amphetamines ), especially because contamination of the
hallucinogens with other dr ugs is relatively common.
Schizophrenia. Schizophrenia also must be ruled out,  as some affected individuals (e.g.,
individuals with schizophrenia who exhibit paranoia) may falsely attribute their symp-
toms to use of hallucinogens.
Other mental disorders or medical conditions. Other potential disorders or conditions
to consider include panic disorder, depressive  and bipolar disorders, alcohol or sedative
withdrawal, hypoglycemia and other metabolic  conditions, seizure disorder, stroke, oph-
thalmological disorder, and central nervous sy stem tumors. Careful history of drug tak-
ing, collateral reports from family and friends (if possible), age, clin ical history, physical
examination, and toxicology reports should be useful in arriving at the final diagnostic de-
cision.
Comorbidity
Adolescents who use MDMA/ecstasy and other ha llucinogens, as well as adults who have
recently used ecstasy, have a higher preval ence of other substance use disorders compared
with nonhallucinogen substance users. Individuals who use halluc inogens exhibit eleva-


with nonhallucinogen substance users. Individuals who use halluc inogens exhibit eleva-
tions of nonsubstance mental disorders (espec ially anxiety, depressi ve, and bipolar disor-
ders), particularly with use of ecstasy and salvia. Rates of antisocial personality disorder (but
not conduct disorder) are significantly elevated among individuals with other hallucinogen
use disorder, as are rates of adult antisocial  behavior. However, it is unclear whether the
mental illnesses may be precursors to rather than consequences of other hallucinogen use
disorder (see the section “Risk and Prognostic Factors” for this disorder). Both adults and
adolescents who use ecstasy are mo re likely than other drug us ers to be polydrug users and
to have other drug use disorders.
Phencyclidine Intoxication
Diagnostic Criteria
A. Recent use of phencyclidine (or a pharmacologically similar substance).
B. Clinically significant problematic behavioral changes (e.g., belligerence, assaultive-
ness, impulsiveness, unpredictability, psychomotor agitation, impaired judgment) that
developed during, or shortly after, phencyclidine use.
C. Within 1 hour, two (or more) of the following signs or symptoms:
Note:  When the drug is smoked, “snorted,” or  used intravenously, the onset may be
particularly rapid.
1. Vertical or horizontal nystagmus.
2. Hypertension or tachycardia.


528 Substance-Related and Addictive Disorders
3. Numbness or diminished responsiveness to pain.
4. Ataxia.
5. Dysarthria.
6. Muscle rigidity.
7. Seizures or coma.
8. Hyperacusis.
D. The signs or symptoms are not attributable to another medical condition and are not better
explained by another mental disorder, including intoxication with another substance.
Coding note:  The ICD-9-CM code is 292.89.  The ICD-10-CM code depends on whether
there is a comorbid phencyclidine use disorder. If a mild phencyclidine use disorder is co-
morbid, the ICD-10-CM code is F16.129,  and if a moderate or severe phencyclidine use
disorder is comorbid, the ICD-10-CM code is F16.229.  If there is no comorbid phencycli-
dine use disorder, then the ICD-10-CM code is F16.929.
Note:  In addition to the section “Functional Co nsequences of Phencyclidine Intoxication,”
see the corresponding section in phencyclidine use disorder.
Diagnostic Features
Phencyclidine intoxication reflects the clinica lly 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, hallucination s or delusions, a catatonic-like syndrome,
and coma of varying severity. The intoxication typically last s for several hours but, de-
pending on the type of clinic al presentation and whether other drugs besides phencycli-
dine were consumed, may last for several days or longer.
Prevalence


dine were consumed, may last for several days or longer.
Prevalence
Use of phencyclidine or related substances ma y be taken as an estimate of the prevalence
of intoxication. Approximately 2.5% of the po pulation reports having ever used phency-
clidine. Among high school students, 2.3% of  12th graders report ever using phencycli-
dine, 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.
Diagnostic Markers
Laboratory testing may be useful, as phencycl idine is detectable in urine for up to 8 days
following use, although the levels are only weakly associated with an individual’s clinical
presentation and may therefore not be useful for case management. Creatine phosphoki-
nase and aspartate aminotransfe rase levels may be elevated.
Functional Consequences of  Phencyclidine Intoxication
Phencyclidine intoxication produces extensiv e cardiovascular and neurological (e.g., sei-
zures, dystonias, dyskinesias, catalepsy, hypothermia or hyperthermia) toxicity.
Differential Diagnosis
In particular, in the absence of intact realit y testing (i.e., without in sight into any percep-
tual abnormalities), an additional diagno sis of phencyclidine-induced psychotic disorder
should be considered.
Other substance intoxication. Phencyclidine intoxication should be differentiated from
intoxication due to other su bstances, including other hallucinogens; amphetamine, co-


Other Hallucinogen Intoxication 529
caine, or other stimulants; an d anticholinergics, as well as  withdrawal from benzodiaze-
pines. Nystagmus and bizarre and violent be havior may distinguish intoxication due to
phencyclidine from that due to other substances . Toxicological tests may be useful in mak-
ing this distinction, since phencyclidine is detectable in urine for up to 8 days after use.
However, there is a weak correlation between quantitative toxicology levels of phencycli-
dine and clinical presentation that diminishes the utility of the laboratory findings for pa-
tient management.
Other conditions. Other conditions to be considered  include schizophrenia, depression,
withdrawal from other drugs (e .g., sedatives, alcohol), cert ain metabolic disorders like hy-
poglycemia and hyponatremia, central nervous system tumors, seizur e disorders, sepsis,
neuroleptic malignant syndro me, and vascular insults.
Other Hallucinogen Intoxication
Diagnostic Criteria
A. Recent use of a hallucinogen (other than phencyclidine).
B. Clinically significant problematic behavioral or psychological changes (e.g., marked
anxiety or depression, ideas of reference, fear of “losing one’s mind,” paranoid ide-
ation, impaired judgment) that developed during, or shortly after, hallucinogen use.
C. Perceptual changes occurring in a state of full wakefulness and alertness (e.g., sub-
jective intensification of perceptions, depersonalization, derealization, illusions, hallu-
cinations, synesthesias) that developed during, or shortly after, hallucinogen use.


D. Two (or more) of the following signs developing during, or shortly after, hallucinogen
use:
1. Pupillary dilation.
2. Tachycardia.
3. Sweating.
4. Palpitations.
5. Blurring of vision.
6. Tremors.
7. Incoordination.
E. The signs or symptoms are not attributable to another medical condition and are not
better explained by another mental disorder, including intoxication with another sub-
stance.
Coding note:  The ICD-9-CM code is 292.89.  The ICD-10-CM code depends on whether
there is a comorbid hallucinogen use disorder. If a mild hallucinogen use disorder is co-
morbid, the ICD-10-CM code is F16.129,  and if a moderate or severe hallucinogen use
disorder is comorbid, the ICD-10-CM code is F16.229.  If there is no comorbid hallucinogen
use disorder, then the ICD-10-CM code is F16.929.
Note:  For information on Associated Features Supporting Diagnosis and Culture-Related
Diagnostic Issues, see the corresponding sections in other hallucinogen use disorder.
Diagnostic Features
Other hallucinogen intoxication reflects the c linically significant behavioral or psycholog-
ical changes that occur shortly after ingestio n 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 diethy lamide] or MDMA [3,4-methylenedioxymetham-
phetamine]).


530 Substance-Related and Addictive Disorders
Prevalence
The prevalence of other hallucinogen intoxica tion may be estimated by use of those sub-
stances. In the United States, 1.8% of individuals age 12 years or older report using hallu-
cinogens in the past year. Use is more preval ent 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 ag e 26 years or older. Twelve-month prevalence
for hallucinogen use is more common in ma les (2.4%) than in fe males (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 gen-
ders). These figures may be used as proxy es timates for gender-related differences in the
prevalence of other ha llucinogen intoxication.
Suicide Risk
Other hallucinogen intoxication may lead to in creased suicidality, al though suicide is rare
among users of hallucinogens.
Functional Consequences of
Other Hallucinogen  Intoxication
Other hallucinogen intoxication can have serious consequences. The perceptual distur-
bances and impaired judgment associated wi th other hallucinogen intoxication can result
in injuries or fatalities from  automobile crashes, physical fi ghts, or unintentional self-
injury (e.g., attempts to “fly” from high plac es). Environmental factors and the personality


and expectations of the individual using the hallucinogen may contribute to the nature of
and severity of halluc inogen intoxication. Continued use of hallucinogens, particularly
MDMA, has also been linked with neurotoxic effects.
Differential Diagnosis
Other substance intoxication. Other hallucinogen intoxication  should be differentiated
from intoxication with amphetamines, cocaine,  or other stimulants; anticholinergics; in-
halants; and phencyclidine. Toxicological tests are useful in making this distinction, and
determining the route of administration may also be useful.
Other conditions. Other disorders and conditions to be considered include schizophre-
nia, depression, withdrawal from other drugs (e.g., sedatives, alcohol), certain metabolic
disorders (e.g., hypoglycemia),  seizure disorders, tumors of  the central nervous system,
and vascular insults.
Hallucinogen persisting perception disorder. Other hallucinogen intoxication is dis-
tinguished from hallucinogen persisting percep tion disorder because the symptoms in the
latter continue episodically or continuously for weeks (or long er) after the most recent in-
toxication.
Other hallucinogen-induced disorders. Other hallucinogen intoxication is distinguished
from the other hallucinogen-induced disorder s (e.g., hallucinogen- induced anxiety disor-
der, with onset during intoxication) because the symptoms in these latter disorders pre-
dominate the clinical presentation and are severe enough to warrant independent clinical
attention.


Hallucinogen Persisting Perception Disorder 531
Hallucinogen Persisting Perception Disorder
Diagnostic Criteria 292.89 (F16.983)
A. Following cessation of use of a hallucinogen, the reexperiencing of one or more of the
perceptual symptoms that were experienced while intoxicated with the hallucinogen
(e.g., geometric hallucinations, false perceptions of movement in the peripheral visual
fields, flashes of color, intensified colors, trails of images of moving objects, positive
afterimages, halos around objects, macropsia and micropsia).
B. The symptoms in Criterion A cause clinically significant distress or impairment in so-
cial, occupational, or other important areas of functioning.
C. The symptoms are not attributable to another  medical condition (e.g., anatomical le-
sions and infections of the brain, visual epilepsies) and are not better explained by an-
other mental disorder (e.g., delirium, ma jor neurocognitive disorder, schizophrenia) or
hypnopompic hallucinations.
Diagnostic Features
The hallmark of hallucinogen persisting percep tion disorder is the reexperiencing, when the
individual is sober, of the pe rceptual disturbances that were  experienced while the individ-
ual was intoxicated with the hallucinogen (C riterion A). The symptoms may include any
perceptual perturbations, but visual disturbanc es tend to be predomin ant. Typical of the ab-
normal visual perceptions are geometric hallucinations, false percep tions of movement in
the peripheral visual fields, flashes of color, in tensified colors, trails of  images of moving ob-
jects (i.e., images left suspended in the path of  a moving object as seen in stroboscopic pho-


tography), perceptions of entire objects, po sitive 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 ep isodic 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 disor-
ders, 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 be-
tween hallucinogen persisting perception disord er and number of occasions of hallucino-
gen use, with some instances of hallucinogen  persisting perception disorder occurring in
individuals with minimal exposure to hallucinogens. Some instances of hallucinogen per-
sisting perception disorder may be triggered by use of other substa nces (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 dis-
order (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 approx-
imately 4.2%.


532 Substance-Related and Addictive Disorders
Development and Course
Little is known about the development of hallucinogen persisting perception disorder. Its
course, as suggested by its name, is persistent, lasting for weeks, months, or even years in
certain individuals.
Risk and Prognostic Factors
There is little evidence regarding risk factor s for hallucinogen persisting perception dis-
order, although genetic factors have been suggested as a possible explanation underlying
the susceptibility to LSD effects in this condition.
Functional Consequences of
Hallucinogen Persisting  Perception Disorder
Although hallucinogen persisting perception  disorder remains a chronic condition in
some cases, many individuals with the disord er are able to suppres s the disturbances and
continue to function normally.
Differential Diagnosis
Conditions to be ruled out include schizophrenia, other drug  effects, neurodegenerative
disorders, stroke, brain tumors, infections, an d head trauma. Neuroimaging results in hal-
lucinogen persisting perception disorder cases are typically negative. As noted earlier, re-
ality testing remains intact (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 (e.g., psychotic disorder, another
medical condition) might better ex plain the abnormal perceptions.
Comorbidity
Common comorbid mental disorders accomp anying hallucinogen persisting perception
disorder are panic disorder , alcohol use disorder, and major depressive disorder.
Other Phencyclidine-Induced Disorders
Other phencyclidine-induced diso rders are described in other chapters of the manual with
disorders with which they share phenomeno logy (see the substance/medication-induced
mental disorders in these chap ters): phencyclidine-induced psychotic disorder (“Schizo-


mental disorders in these chap ters): phencyclidine-induced psychotic disorder (“Schizo-
phrenia Spectrum and Other Psychotic Disord ers”); phencyclidine-induced bipolar dis-
order (“Bipolar and Related Disorders”); phencyclidine-induced depressive disorder
(“Depressive Disorders”); and phencyclidin e-induced anxiety disorder (“Anxiety Disor-
ders”). For phencyclidine-induced intoxication delirium, see the criteria and discussion of
delirium in the chapter “Neurocognitive Di sorders.” These phencyclidine-induced disor-
ders are diagnosed instead of phencyclidine in toxication only when the symptoms are suf-
ficiently severe to warrant in dependent clinical attention.
Other Hallucinogen-Induced Disorders
The following other hallucinogen- induced disorders are describe d in other chapters of the
manual with disorder s with which they share phenome nology (see the substance/medi-
cation-induced mental disorders in these chapters): other hallucinogen–induced psychotic
disorder (“Schizophrenia Spect rum and Other Psychotic Diso rders”); other hallucinogen–
induced bipolar disorder (“Bi polar and Related Disorders”); other hallucinogen–induced


Unspecified Phencyclidine-Related Disorder 533
depressive disorder (“Depressive Disorders” ); and other hallucinogen–induced anxiety
disorder (“Anxiety Disorders”). For other hallu cinogen intoxication delirium, see the cri-
teria and discussion of delirium in the chapter “Neurocognitive Di sorders.” These hallu-
cinogen-induced disorders are diagnosed inst ead of other hallucinogen intoxication only
when the symptoms are sufficiently severe to warrant independent clinical attention.
Unspecified Phencyclidine-Related Disorder
292.9 (F16.99)
This category applies to presentations in which symptoms characteristic of a phencycli-
dine-related disorder that cause clinically significant distress or impairment in social, oc-
cupational, or other important areas of functioning predominate but do not meet the full
criteria for any specific phencyclidine-related disorder or any of the disorders in the sub-
stance-related and addictive disorders diagnostic class.
Unspecified Hallucinogen-Related Disorder
292.9 (F16.99)
This category applies to presentations in which symptoms characteristic of a hallucinogen-
related disorder that cause clinically significant distress or impairment in social, occupa-
tional, or other important areas of functioning predominate but do not meet the full criteria
for any specific hallucinogen-related disorder or any of the disorders in the substance-
related and addictive disorders diagnostic class.
Inhalant-Related Disorders
Inhalant Use Disorder
Inhalant Intoxication
Other Inhalant-Induced Disorders
Unspecified Inhalant-Related Disorder
Inhalant Use Disorder
Diagnostic Criteria
A. A problematic pattern of use of a hydrocarbon-based inhalant substance leading to
clinically significant impairment or distress, as manifested by at least two of the follow-


clinically significant impairment or distress, as manifested by at least two of the follow-
ing, occurring within a 12-month period:
1. The inhalant substance is often taken in larger amounts or over a longer period than
was intended.
2. There is a persistent desire or unsuccessful efforts to cut down or control use of the
inhalant substance.


534 Substance-Related and Addictive Disorders
3. A great deal of time is spent in activities necessary to obtain the inhalant substance,
use it, or recover from its effects.
4. Craving, or a strong desire or urge to use the inhalant substance.
5. Recurrent use of the inhalant substance resulting in a failure to fulfill major role ob-
ligations at work, school, or home.
6. Continued use of the inhalant substance des pite having persistent or recurrent so-
cial or interpersonal problems caused or exacerbated by the effects of its use.
7. Important social, occupational, or recreat ional activities are given up or reduced be-
cause of use of the inhalant substance.
8. Recurrent use of the inhalant substance in situations in which it is physically haz-
ardous.
9. Use of the inhalant substance is continued despite knowledge of having a persis-
tent or recurrent physical or psychological problem that is likely to have been
caused or exacerbated by the substance.
10. Tolerance, as defined by either of the following:
a. A need for markedly increased amounts of the inhalant substance to achieve
intoxication or desired effect.
b. A markedly diminished effect with continued use of the same amount of the in-
halant substance.
Specify the particular inhalant: When possible, the particular substance involved should
be named (e.g., “solvent use disorder”).
Specify if:
In early remission:  After full criteria for inhalant use disorder were previously met,
none of the criteria for inhalant use disor der have been met for at least 3 months but
for less than 12 months (with the exception that Criterion A4, “Craving, or a strong de-
sire or urge to use the inhalant substance,” may be met).


sire or urge to use the inhalant substance,” may be met).
In sustained remission: After full criteria for inhalant use disorder were previously
met, none of the criteria for inhalant use disorder have been met at any time during a
period of 12 months or longer (with the exception that Criterion A4, “Craving, or a
strong desire or urge to use the inhalant substance,” may be met).
Specify if:
In a controlled environment:  This additional specifier is used if the individual is in an
environment where access to inhalant substances is restricted.
Coding based on current severity:  Note for ICD-10-CM codes: If an inhalant intoxication
or another inhalant-induced mental disorder is also present, do not use the codes below
for inhalant use disorder. Instead, the comorbid inhalant use disorder is indicated in the
4th character of the inhalant-induced disorder code (see the coding note for inhalant intox-
ication or a specific inhalant-induced mental di sorder). For example, if there is comorbid
inhalant-induced depressive disorder and i nhalant use disorder, only the inhalant-induced
depressive disorder code is given, with the 4th character indicating whether the comorbid
inhalant use disorder is mild, moderate, or severe: F18.14 for mild inhalant use disorder
with inhalant-induced depressive disorder or F 18.24 for a moderate or severe inhalant use
disorder with inhalant-induced depressive disorder.
Specify current severity:
305.90 (F18.10) Mild:  Presence of 2–3 symptoms.
304.60 (F18.20) Moderate: Presence of 4–5 symptoms.
304.60 (F18.20) Severe:  Presence of 6 or more symptoms.


Inhalant Use Disorder 535
Specifiers
This manual recognizes volatile hydrocarbon use meeting the above diagnostic criteria as
inhalant use disorder. Volatile hydrocarbons are toxic gases from glues, fuels, paints, and
other volatile compounds. When possible, th e particular substance involved should be
named (e.g., “toluene use disorder”). However, most compounds that are inhaled are a
mixture of several substances that can produce psychoactive effects, and it is often difficult
to ascertain the exact substance responsible fo r the disorder. Unless there is clear evidence
that a single, unmixed substance has been used , the general term inhalant should be used
in recording the diagnosis. Disorders arising from inhalation of nitrous oxide or of amyl-,
butyl-, or isobutylnitrite are considered as other (or unkn own) substance use disorder.
“In a controlled environment” applies as a fu rther specifier of remission if the individ-
ual is both in remission and in a controlled en vironment (i.e., in early remission in a con-
trolled environment or in su stained remission in a contro lled environment). Examples of
these environments are closely supervised and substance-free jails, therapeutic communi-
ties, and locked hospital units.
The severity of individuals’ inhalant use di sorder is assessed by the number of diag-
nostic criteria endorsed. Changing severity of individuals’ inhalant use disorder across
time is reflected by reductions in the frequency (e.g., days used per month) and/or dose
(e.g., tubes of glue per day) used, as assessed by the individual’s self-report, report of oth-
ers, clinician’s observations, and bi ological testing (when practical).
Diagnostic Features
Features of inhalant use disorder include repe ated use of an inhalant substance despite the


Features of inhalant use disorder include repe ated 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 re flected in the diagnostic criteria.
Missing work or school or inability to perform typical responsibilities at work or school
(Criterion A5), and continued us e of the inhalant substance even though it causes arguments
with family or friends, fights, and other social  or interpersonal proble ms (Criterion A6), may
be seen in inhalant use disorder. Limiting family contact, work or school obligations, or rec-
reational activities (e.g., sports , games, hobbies) may also occu r (Criterion A7). Use of inhal-
ants when driving or operating dangerous equipment (Criterion A8) is also seen.
Tolerance (Criterion A10) and mild withdraw al are each reported by about 10% of in-
dividuals who use inhalants, and a few individuals use inhalants to avoid withdrawal.
However, because the withdrawal symptoms ar e mild, this manual neither recognizes a
diagnosis of inhalant withdrawal nor counts withdrawal complaints as a diagnostic crite-
rion for inhalant use disorder.
Associated Features Supporting Diagnosis
A diagnosis of inhalant use disorder is suppo rted by recurring epis odes 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”; as-
sociation with other individuals known to use inhalants; membership in groups with prev-
alent inhalant use (e.g., some native or abor iginal communities, ho meless children in street
gangs); easy access to certain inhalant substances; paraphernalia possession; presence of


gangs); easy access to certain inhalant substances; paraphernalia possession; presence of
the disorder’s characteristic medical compli cations (e.g., brain white matter pathology,
rhabdomyolysis); and the presence of multiple  substance use disorders. Inhalant use and
inhalant use disorder are asso ciated with past suicide atte mpts, especially among adults
reporting previous episodes of low mood or anhedonia.
Prevalence
About 0.4% of Americans ages 12–17 years have a pattern of use that me ets criteria for in-
halant use disorder in the past 12 months. Among those youths, the prevalence is highest


536 Substance-Related and Addictive Disorders
in Native Americans and lowest in African Americans. Prevalence falls to about 0.1% among
Americans ages 18–29 years, and only 0.02% when all Americans 18 years or older are con-
sidered, with almost no females and a prepon derance of European Am ericans. Of course,
in isolated subgroups, prevalence may di ffer considerably from  these overall rates.
Development and Course
About 10% of 13-year-old American children re port having used inhalants at least once;
that percentage remains stable through age 17 years. Among those 12- to 17-year-olds who
use inhalants, the more-used substances includ e glue, shoe polish, or toluene; gasoline or
lighter fluid; or spray paints.
Only 0.4% of 12- to 17-year-olds progress to  inhalant use disorder; those youths tend to
exhibit multiple other problems. The declining prevalence of inhalant use disorder after
adolescence indicates that this disorder  usually remits in early adulthood.
Volatile hydrocarbon use disorder is rare in prepubertal children, most common in ad-
olescents and young adults, and uncommon in older persons. Calls to poison-control cen-
ters for “intentional abuse” of inhalants peak with calls involving individuals at age 14 years.
Of adolescents who use inhalants, perhaps on e-fifth develop inhalant use disorder; a few
die from inhalant-related accide nts, or “sudden sniffing death”. But the disorder apparently
remits in many individuals after adolescence.  Prevalence declines dramatically among in-
dividuals in their 20s. Those with inhalant use disorder extending into adulthood often


dividuals in their 20s. Those with inhalant use disorder extending into adulthood often
have severe problems: substance use disorder s, antisocial personality disorder, and sui-
cidal ideation with attempts.
Risk and Prognostic Factors
Temperamental. Predictors of progression from nonuse of inhalant s, to use, to inhalant
use disorder include comorbid non-inhalant substance use disorders and either conduct
disorder or antisocial personality disorder. Other predictors are ea rlier onset of inhalant
use and prior use of mental health services.
Environmental. Inhalant gases are widely and legally available, increasing the risk of mis-
use. Childhood maltreatment or  trauma also is associated with youthful progression from
inhalant non-use to inhalant use disorder.
Genetic and physiological. Behavioral disinhibition  is a highly heritable general propensity
to not constrain behavior in socially acceptable  ways, to break social norms and rules, and to
take dangerous risks, pursuing rewards excessi vely despite dangers of  adverse consequences.
Youths with strong behavioral disinhibition show  risk factors for inhala nt use disorder: early-
onset substance use disorder, multiple substa nce involvement, and ea rly conduct problems.
Because behavioral disinhibition is under stro ng genetic influence, youths in families with
substance and antisocial problems are at elevated risk for i nhalant use disorder.
Culture-Related Diagnostic Issues
Certain native or aboriginal communities have  experienced a high prevalence of inhalant
problems. Also, in some countr ies, groups of homeless children in street gangs have ex-
tensive inhalant use problems.
Gender-Related Diagnostic Issues
Although the prevalence of inhalant use disord er is almost identical in adolescent males
and females, the disorder is very rare among adult females.
Diagnostic Markers


and females, the disorder is very rare among adult females.
Diagnostic Markers
Urine, breath, or saliva tests may be valuable  for assessing concurrent use of non-inhalant
substances by individuals with inhalant us e disorder. However, technical problems and


Inhalant Use Disorder 537
the considerable expense of analyses make fr equent biological testing for inhalants them-
selves impractical.
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 produc e “sudden sniffing death” from cardiac ar-
rhythmia. 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, arrhythmia s, asphyxiation, aspiration of vomitus, or
accident and injury.
Differential Diagnosis
Inhalant exposure (unintentional) from industrial or other accidents. This designation
is used when findings suggest repeated or continuous inhalant exposure but the involved
individual and other informants deny an y history of purposeful inhalant use.
Inhalant use (intentional), without meeting criteria for inhalant use disorder. Inhalant use
is common among adolescents, but for most of th ose individuals, the inhalant use does not
meet the diagnostic standard of two or more Criterion A items for i nhalant use disorder in
the past year.
Inhalant intoxication, without meeting criteria for inhalant use disorder. Inhalant intox-
ication occurs frequently duri ng inhalant use disorder but also may occur among individ-
uals whose use does not meet criteria for inha lant use disorder, which requires at least two
of the 10 diagnostic criteria in the past year.


of the 10 diagnostic criteria in the past year.
Inhalant-induced disorders (i .e., inhalant-induced psychotic disorder, depressive dis-
order, anxiety disorder, neurocognitive disorder, other inhalant-induced disorders)
without meeting criteria for inhalant use disorder. Criteria are met for a psychotic, de-
pressive, anxiety, or major neurocognitive disorder, and there is evidence from history,
physical examination, or laboratory findings that the deficits are etiologically related to
the effects of inhalant substances. Yet, criter ia for inhalant use disorder may not be met
(i.e., fewer than 2 of the 10 criteria were present).
Other substance use disorders, especially those involving sedating substances (e.g.,
alcohol, benzodiazepines, barbiturates). Inhalant use disorder commonly co-occurs
with other substance use disorders, and the sy mptoms of the disorders may be similar and
overlapping. To disentangle symptom patterns, it is helpful to inquire about which symp-
toms persisted during periods when some of the substances were not being used.
Other toxic, metabolic, traumatic, neoplastic, or infectious disorders impairing central or
peripheral nervous system function. Individuals with inhalant use disorder may pre-
sent with symptoms of pernicious anemia, su bacute combined degeneration of the spinal
cord, psychosis, major or minor cognitive d isorder, brain atrophy, leukoencephalopathy,
and many other nervous system  disorders. Of co urse, these disorder s also may occur in
the absence of inhalant use disorder. A history of little or no inhalant use helps to exclude
inhalant use disorder as the source of these problems.
Disorders of other organ systems. Individuals with inhalant use disorder may present


Disorders of other organ systems. Individuals with inhalant use disorder may present
with symptoms of hepatic or renal damage, rhabdomyolysis, methemoglobinemia, or symp-
toms of other gastrointestinal, cardiovascular, or  pulmonary diseases. A history of little or no
inhalant use helps to exclude inhalant use diso rder as the source of such medical problems.


538 Substance-Related and Addictive Disorders
Comorbidity
Individuals with inhalant use disorder receiv ing clinical care often have numerous other
substance use disorders. Inhalant use disord er commonly co-occurs with adolescent con-
duct disorder and adult antisocial personality disorder. Adult inhalant use and inhalant
use disorder also are strongly associated wi th suicidal ideation and suicide attempts.
Inhalant Intoxication
Diagnostic Criteria
A. Recent intended or unintended short-term, high-dose exposure to inhalant sub-
stances, including volatile hydrocarbons such as toluene or gasoline.
B. Clinically significant problematic behavioral or psychological changes (e.g., belliger-
ence, assaultiveness, apathy, impaired judgment ) that developed during, or shortly af-
ter, exposure to inhalants.
C. Two (or more) of the following signs or symptoms developing during, or shortly after,
inhalant use or exposure:
1. Dizziness.
2. Nystagmus.
3. Incoordination.
4. Slurred speech.
5. Unsteady gait.
6. Lethargy.
7. Depressed reflexes.
8. Psychomotor retardation.
9. Tremor.
10. Generalized muscle weakness.
11. Blurred vision or diplopia.
12. Stupor or coma.
13. Euphoria.
D. The signs or symptoms are not attributable to another medical condition and are not bet-
ter explained by another mental disorder, including intoxication with another substance.
Coding note:  The ICD-9-CM code is 292.89.  The ICD-10-CM code depends on whether
there is a comorbid inhalant use disorder. If a mild inhalant use disorder is comorbid, the


ICD-10-CM code is F18.129,  and if a moderate or severe inhalant use disorder is comor-
bid, the ICD-10-CM code is F18.229.  If there is no comorbid inhalant use disorder, then
the ICD-10-CM code is F18.929.
Note:  For information on Developm ent and Course, Risk and Prognostic Factors, Culture-
Related Diagnostic Issues, and Diagnostic Markers, see the co rresponding sections in in-
halant use disorder.
Diagnostic Features
Inhalant intoxication is an inhalant-related, cl inically significant mental disorder that de-
velops during, or immediately after, intended or unintended inhalation of a volatile hy-
drocarbon substance. Volatile hydrocarbons are toxic gases fr om 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 th e exposure ends. Thus, inhalant intoxication
usually occurs in brief episodes that may recur.


Inhalant Intoxication 539
Associated Features Supporting Diagnosis
Inhalant intoxication may be indicated by eviden ce of possession, or lingering odors, of in-
halant substances (e.g., glue, paint thinner, gasoline, butane lighters); apparent intoxica-
tion 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 usu-
ally fail to identify inhalants.
Prevalence
The prevalence of actual episode s of inhalant intoxication in the general population is un-
known, 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 inhal-
ant use and the prevalence of inhalant intoxi cation 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 inhal-
ant intoxication, gender differences  in the prevalence of inhalant users  likely approximate
those in the proportions of males and females experiencing inhalant intoxication. Regard-
ing gender differences in the pr evalence 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 pre-


vious 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 occu r with various volatile inhalants. The en-
hanced toxicity of certain vola tile inhalants, such as butane or propane, also causes fatal-
ities. Although inhalant intoxication itself is of short duration, it may produce persisting
medical and neurological problems, especi ally if the intoxications are frequent.
Differential Diagnosis
Inhalant exposure, without meeting the criteria for inhalant intoxication disorder.
The individual intentionally or unintentionally inhaled substances, but the dose was in-
sufficient for the diagnostic criteria for inhalant use disorder to be met.
Intoxication and other substance/medica tion-induced disorders from other sub-
stances, especially from sedating substances (e.g., alcohol, benzodiazepines, barbi-
turates). These disorders may have similar signs and symptoms, but the intoxication is
attributable to other intoxicants that may be identified via a toxicology sc reen. Differenti-
ating the source of the intoxication may invo lve discerning evidence of inhalant exposure
as described for inhalant use disorder. A diag nosis of inhalant intoxication may be sug-
gested by possession, or linger ing odors, of inhalant substances (e.g., glue, paint thinner,


gasoline, butane lighters,); paraphernalia poss ession (e.g., rags or bags for concentrating
glue fumes); perioral or perinasal “glue-sniffe r’s rash”; reports from family or friends that
the intoxicated individual possesses or uses inhalants; apparent intoxication despite neg-
ative results on standard drug screens (which usually fail to identify inhalants); apparent
intoxication occurring in that age range with the highest prevalence of inhalant use (12–17


540 Substance-Related and Addictive Disorders
years); association with others known to use inhalants; membership in certain small com-
munities with prevalent inhalant use (e.g., so me native or aborigin al communities, home-
less street children and adoles cents); or unusual access to certain inhalant substances.
Other inhalant-related disorders. Episodes of inhalant intoxication do occur during,
but are not identical with, other inhalant-related  disorders. Those inha lant-related disorders
are recognized by their respective diagnostic  criteria: inhalant use disorder, inhalant-
induced neurocognitive disorder, inhalant-i nduced psychotic disorder, inhalant-induced
depressive disorder, inhalant-induced anxiet y disorder, and other inhalant-induced dis-
orders.
Other toxic, metabolic, traumatic, neoplastic, or infectious disorders that impair brain
function and cognition. Numerous neurological and other medical conditions may pro-
duce the clinically significant behavioral or  psychological changes (e.g., belligerence, as-
saultiveness, apathy, impaired judgment) that also characterize inhalant intoxication.
Other Inhalant-Induced Disorders
The following inhalant-induced  disorders are described in other chapters of the manual
with disorders with which they share ph enomenology (see the substance/medication-
induced mental disorders in these chapters): inhalant-induced psychotic disorder (“Schizo-
phrenia Spectrum and Other Psychotic Disord ers”); inhalant-induced depressive disorder
(“Depressive Disorders”); inhalant-induced an xiety disorder (“Anxiet y Disorders”); and in-
halant-induced major or mild neurocognitive disorder (“Neur ocognitive Disorders”). For
inhalant intoxication delirium, see the criteria and discussion of de lirium in the chapter


“Neurocognitive Disorders.” Thes e inhalant-induced disorders are diagnosed instead of in-
halant intoxication only when symptoms are sufficiently severe to  warrant independent
clinical attention.
Unspecified Inhalant-Related Disorder
292.9 (F18.99)
This category applies to presentations in which symptoms characteristic of an inhalant-
related disorder that cause clinically significant distress or impairment in social, occupa-
tional, or other important areas of functioning predominate but do not meet the full criteria
for any specific inhalant-related disorder or any  of the disorders in the substance-related
and addictive disorders diagnostic class.
Opioid-Related Disorders
Opioid Use Disorder
Opioid Intoxication
Opioid Withdrawal
Other Opioid-Induced Disorders
Unspecified Opioid -Related Disorder


Opioid Use Disorder 541
Opioid Use Disorder
Diagnostic Criteria
A. A problematic pattern of opioid use leading to clinically significant impairment or distress,
as manifested by at least two of the fo llowing, occurring within a 12-month period:
1. Opioids are often taken in larger amounts or over a longer period than was in-
tended.
2. There is a persistent desire or unsuccessful efforts to cut down or control opioid use.
3. A great deal of time is spent in activities necessary to obtain the opioid, use the opi-
oid, or recover from its effects.
4. Craving, or a strong desire or urge to use opioids.
5. Recurrent opioid use resulting in a failure to fulfill major role obligations at work,
school, or home.
6. Continued opioid use despite having persisten t or recurrent social or interpersonal
problems caused or exacerbated by the effects of opioids.
7. Important social, occupational, or recreat ional activities are given up or reduced be-
cause of opioid use.
8. Recurrent opioid use in situations in which it is physically hazardous.
9. Continued opioid use despite knowledge of having a persistent or recurrent physi-
cal or psychological problem that is likely to have been caused or exacerbated by
the substance.
10. Tolerance, as defined by either of the following:
a. A need for markedly increased amounts of opioids to achieve intoxication or de-
sired effect.
b. A markedly diminished effect with continued use of the same amount of an opioid.
Note:  This criterion is not considered to be met for those taking opioids solely under
appropriate medical supervision.
11. Withdrawal, as manifested by either of the following:
a. The characteristic opioid withdrawal syndr ome (refer to Criteria A and B of the


a. The characteristic opioid withdrawal syndr ome (refer to Criteria A and B of the
criteria set for opioid withdrawal, pp. 547–548).
b. Opioids (or a closely related substance) are taken to relieve or avoid withdrawal
symptoms.
Note:  This criterion is not considered to be met for those individuals taking opioids
solely under appropriate medical supervision.
Specify if:
In early remission: After full criteria for opioid use disorder were previously met, none
of the criteria for opioid use disorder have been met for at least 3 months but for less
than 12 months (with the exception that Criterion A4, “Craving, or a strong desire or
urge to use opioids,” may be met).
In sustained remission:  After full criteria for opioid us e disorder were previously met,
none of the criteria for opioid use disorder have been met at any time during a period
of 12 months or longer (with the exception that Criterion A4, “Craving, or a strong de-
sire or urge to use opioids,” may be met).
Specify if:
On maintenance therapy:  This additional specifier is used if the individual is taking a
prescribed agonist medication such as  methadone or buprenorphine and none of the
criteria for opioid use disorder have been met for that class of medication (except tol-
erance to, or withdrawal from, the agonist). This category also applies to those individ-


542 Substance-Related and Addictive Disorders
uals being maintained on a partial agonist, an agonist/antagonist, or a full antagonist
such as oral naltrexone or depot naltrexone.
In a controlled environment:  This additional specifier is used if the individual is in an
environment where access to opioids is restricted.
Coding based on current severity:  Note for ICD-10-CM codes: If an opioid intoxication,
opioid withdrawal, or another opioid-induced ment al disorder is also present, do not use
the codes below for opioid use disorder. Instead, the comorbid opioid use disorder is indi-
cated in the 4th character of the opioid-indu ced disorder code (see the coding note for opi-
oid intoxication, opioid withdrawal, or a spec ific opioid-induced mental disorder). For
example, if there is comorbid opioid-induc ed depressive disorder and opioid use disorder,
only the opioid-induced depressive disorder code is given, with the 4th character indicating
whether the comorbid opioid use disorder is mi ld, moderate, or severe: F11.14 for mild opi-
oid use disorder with opioid-induced depressive disorder or F11.24 for a moderate or se-
vere opioid use disorder with opi oid-induced depressive disorder.
Specify current severity:
305.50 (F11.10) Mild:  Presence of 2–3 symptoms.
304.00 (F11.20) Moderate: Presence of 4–5 symptoms.
304.00 (F11.20) Severe:  Presence of 6 or more symptoms.
Specifiers
The “on maintenance therapy” specifier applies as a further specifier of remission if the in-
dividual is both in remission and receiving maintenance therapy. “In a controlled environ-


dividual is both in remission and receiving maintenance therapy. “In a controlled environ-
ment” applies as a further specifier of remission if the individual is both in remission and in
a controlled environment (i.e., in  early remission in a controlled environment or in sustained
remission in a controlled envi ronment). Examples of these en vironments are closely super-
vised and substance-free jail s, therapeutic communities, an d locked hospital units.
Changing severity across time in an individual  is also reflected by reductions in the fre-
quency (e.g., days of use per month) and/or dose (e.g., injections or number of pills) of an
opioid, as assessed by the individual’s self-r eport, report of knowledgeable others, clini-
cian’s observations, and biological testing.
Diagnostic Features
Opioid use disorder includes signs and sympto ms that reflect compulsive, prolonged self-
administration of opioid substances that are used for no legitimate medical purpose or, if
another medical condition is pres ent that requires opioid treatment, that are used in doses
greatly in excess of the amount needed for th at medical condition. (F or example, an indi-
vidual prescribed analgesic opioids for pain re lief 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 administer ing opioids. Opioids are usually purchased
on the illegal market but may also be obtained  from physicians by falsifying or exagger-
ating general medical problems or by receiv ing simultaneous prescr iptions from several
physicians. Health care professionals with op ioid use disorder will often obtain opioids by
writing prescriptions for themselves or by dive rting opioids that have been prescribed for


writing prescriptions for themselves or by dive rting 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 opio id use disorder ofte n develop conditioned
responses to drug-related stimuli (e.g., cr aving on seeing any he roin powder–like sub-
stance)—a phenomenon that occu rs with most drugs that cause intense psychological
changes. These responses probably contribute to relapse, are difficult to extinguish, and typ-
ically persist long after detoxification is completed.


Opioid Use Disorder 543
Associated Features Supporting Diagnosis
Opioid use disorder can be asso ciated with a history of drug-r elated crimes (e.g., posses-
sion or distribution of drugs, forgery, burglary, robbery, larc eny, 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), un employment, and irregular employment are of-
ten associated with opioid use diso rder at all socioeconomic levels.
Prevalence
The 12-month prevalence of opioid use disord er 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 wi th 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 ad-
olescents may have a higher likelihood of developing opioid use disorders. The preva-
lence decreases with age, with the prevalence  highest (0.82%) among adults age 29 years or
younger, and decreasing to 0.09% among adul ts age 65 years and older. Among adults, the
prevalence of opioid use di sorder is lower among African Americans at 0.18% and over-
represented 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%).


Asian or Pacific Islanders (0.35%), and Hispanics (0.39%).
Among individuals in the United States ages 12–17 years, the overall 12-month prev-
alence 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 an-
algesics as a group of substances with significant health consequences.
The 12-month prevalence of problem opioid use in European countries in the commu-
nity population ages 15–64 years is betwee n 0.1% and 0.8%. The average prevalence of
problem opioid use in the European Unio n and Norway is between 0.36% and 0.44%.
Development and Course
Opioid use disorder can begin at any age, bu t problems associated with opioid use are
most commonly first observed in the late teens or early 20s. Once opioid use disorder
develops, it usually continues over a period of many years,  even though brief periods of
abstinence are frequent. In treated populati ons, relapse following abstinence is common.
Even though relapses do occur, and while so me long-term mortality rates may be as high
as 2% per year, about 20%–30% of individuals with opioid use disorder achieve long-term
abstinence. An exception concerns that of military service perso nnel who became depen-
dent on opioids in Vietnam; over 90% of this population who had been dependent on opi-
oids during deployment in Vietnam achieved  abstinence after they returned, but they
experienced increased rates of alcohol or amph etamine use disorder as  well as increased


experienced increased rates of alcohol or amph etamine use disorder as  well as increased
suicidality.
Increasing age is associated with a decrease in  prevalence as a result of early mortality
and the remission of sy mptoms after age 40 years (i.e., “maturing out”). However, many
individuals continue have presentations that m eet opioid use disorder  criteria for decades.
Risk and Prognostic Factors
Genetic and physiological. The risk for opiate use disorder can be related to individual,
family, peer, and social environmental factors,  but within these domains, genetic factors
play a particularly important role both dire ctly and indirectly. For instance, impulsivity
and novelty seeking are individu al temperaments that relate to the propensity to develop


544 Substance-Related and Addictive Disorders
a substance use disorder but may themselves be genetically determined. Peer factors may
relate to genetic predisposition in terms of how an individual selects his or her environ-
ment.
Culture-Related Diagnostic Issues
Despite small variations regarding individual criterion items, opioid use disorder diag-
nostic criteria perform equally well across most race/ethnicity groups. Individuals from
ethnic minority populations living in econom ically deprived area s have been overrep-
resented 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 so-
cial factors may impact prevalence. Medical personnel who have ready access to opioids
may be at increased risk for opioid use disorder.
Diagnostic Markers
Routine urine toxicology test re sults are often positive for opioid drugs in individuals with
opioid use disorder. Urine test results remain positive for most opioids (e.g., heroin, mor-
phine, codeine, oxycodone, propoxyphene) for 12–36 hours after administration. Fentanyl
is not detected by standard urine tests but can be identified by more specialized proce-
dures for several days. Methadone, buprenorphine (or buprenorphine/naloxone combi-
nation), and LAAM ( L-alpha-acetylmethadol) have to be specifically tested for and will not
cause a positive result on routine tests for opiates. They can be detected for several days up
to more than 1 week. Laboratory evidence of the presence of other substances (e.g., co-
caine, marijuana, alcohol, amphetamines, benzodiazepines) is common . Screening test re-


sults for hepatitis A, B, and C virus are positive in as many as 80%–90% of injection opioid
users, either for hepatitis antigen (signifying ac tive infection) or for hepatitis antibody (sig-
nifying past infection). HIV is prevalent in injection opioid users as well. Mildly elevated
liver function test results are common, either as a result of re solving hepatitis or from toxic
injury to the liver due to contaminants that have been mixed with the injected opioid. Sub-
tle changes in cortisol secretion patterns and body temperature regulation have been ob-
served for up to 6 months following opioid detoxification.
Suicide Risk
Similar to the risk generally observed for a ll substance use disorders, opioid use disorder
is associated with a heightened  risk for suicide attempts and completed suicides. Particu-
larly notable are both accidental  and deliberate opioid overdose s. Some suicide risk factors
overlap with risk factors for an opioid use di sorder. In addition, repeated opioid intoxica-
tion or withdrawal may be associated with severe depressions that, although temporary,
can be intense enough to lead to suicide attempts and completed su icides. Available data
suggest that nonfatal accidental opioid ov erdose (which is common) and attempted sui-
cide are distinct clinically significant proble ms that should not be mistaken for each other.
Functional Consequences of Opioid Use Disorder
Opioid use is associated with a lack of mu cous 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 im paired 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


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 su bcutaneous tissue (“sk in-popping”), resulting


Opioid Use Disorder 545
in cellulitis, abscesses, and circ ular-appearing scars from healed skin lesions. Tetanus and
Clostridium botulinum  infections are relatively rare bu t extremely serious consequences of
injecting opioids, especially with contaminated  needles. Infections may also occur in other
organs and include bacterial endocarditis, hepa titis, and HIV infection. Hepatitis C infec-
tions, for example, may occur in up to 90% of  persons who inject opioids. In addition, the
prevalence of HIV infection ca n be high among individuals who inject drugs, a large pro-
portion 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 Federati on. However, the incidence may also be 10% or
less in other areas, especially those where a ccess to clean injection material and parapher-
nalia is facilitated.
Tuberculosis is a particularly serious problem among individuals who use drugs in-
travenously, especially those who are dependen t on heroin; infection is usually asymptom-
atic and evident only by the presence of a posi tive tuberculin skin test. However, many cases
of active tuberculosis have been found, espe cially 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 be cause of impaired immune function.
Individuals who sniff heroin or other opioid s into the nose (“snorting”) often develop
irritation of the nasal mucosa, sometimes acco mpanied by perforation of the nasal septum.
Difficulties in sexual functioning are common. Males often experience erectile dysfunction


Difficulties in sexual functioning are common. Males often experience erectile dysfunction
during intoxication or chronic use. Female s commonly have disturbances of reproductive
function and irregular menses.
In relation to infections such as cellulitis, hepatitis, HIV infection, tuberculosis, and en-
docarditis, opioid use d isorder is associated with a mort ality 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 buy-
ing or selling drugs are common. In some areas,  violence accounts for more opioid-related
deaths than overdose or HIV infection. Phy siological dependence on opioids may occur in
about half of the infants born to females with opioid use disorder; this can produce a se-
vere 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.
Differential Diagnosis
Opioid-induced mental disorders. Opioid-induced disorders o ccur frequently in individ-
uals with opioid use disorder. Opioid-induced  disorders may be characterized by symptoms
(e.g., depressed mood) that rese mble primary mental disorders (e.g., persistent depressive dis-
order [dysthymia] vs. opioid-induced depressive disorder, with depressive features, with on-
set during intoxication). Opioids are less likel y to produce symptoms of mental disturbance
than are most other drug s of abuse. Opioid intoxication and opioid withdrawal are distin-
guished from the other opioid-induced disorder s (e.g., opioid-induced  depressive disorder,
with onset during intoxication ) because the symptoms in thes e latter disorders predominate


with onset during intoxication ) because the symptoms in thes e latter disorders predominate
the clinical presentation and are severe enou gh to warrant independent clinical attention.
Other substance intoxication. Alcohol intoxication and seda tive, hypnotic, or anxiolytic
intoxication can cause a clinical picture that resembles that for opioid intoxication. A diag-
nosis of alcohol or sedative, hypnotic, or anxiol ytic intoxication can usually be made based
on the absence of pupillary constriction or the lack of a response to naloxone challenge. In


nosis of alcohol or sedative, hypnotic, or anxiol ytic intoxication can usually be made based
on the absence of pupillary constriction or the lack of a response to naloxone challenge. In
some cases, intoxication may be  due both to opioids and to alcohol or other sedatives. In
these cases, the naloxone challenge will no t reverse all of the sedative effects.
Other withdrawal disorders. The anxiety and restlessness associated with opioid with-
drawal resemble symptoms seen in sedative-hypnotic withdrawal. However, opioid
withdrawal is also accompanied by rhinorrhea , lacrimation, and pupillary dilation, which


546 Substance-Related and Addictive Disorders
are not seen in sedative-type withdrawal. Dilated pupils ar e also seen in hallucinogen
intoxication and stimulant in toxication. However, other si gns or symptoms of opioid
withdrawal, such as nausea, vomiting, diarrhea, abdominal cramps, rhinorrhea, or lacri-
mation, are not present.
Comorbidity
The most common medical conditions associated with opioid use disorder are viral (e.g.,
HIV, hepatitis C virus) and bact erial infections, particularly among users of opioids by in-
jection. These infections are less common in opioid use disorder with prescription opioids.
Opioid use disorder is often associated with other substance use disord ers, especially those
involving tobacco, alcohol, cannabis, stimulants, and benzodiazepines, which are often
taken to reduce symptoms of op ioid withdrawal or craving for opioids, or to enhance the ef-
fects of administered opioids. Individuals with opioid use disorder are at risk for the devel-
opment of mild to moderate depression that  meets symptomatic and duration criteria for
persistent depressive disorder (dysthymia) or, in some cases, for major depressive disorder.
These symptoms may represent an opioid-induc ed depressive disorder  or an exacerbation
of a preexisting primary depres sive disorder. Periods of depression are especially common
during chronic intoxication or in association with physical or psychosocial stressors that are
related to the opioid use disorder. Insomnia is common, especially during withdrawal. An-
tisocial personality disorder is much more common in individuals with opioid use disorder
than in the general population. Posttraumatic stress disorder is also seen with increased fre-
quency. A history of conduct disorder in childh ood or adolescence has been identified as a


significant risk factor for substance-related disorders, especially opioid use disorder.
Opioid Intoxication
Diagnostic Criteria
A. Recent use of an opioid.
B. Clinically significant problematic behavioral or psychological changes (e.g., initial eu-
phoria followed by apathy, dysphoria, psychomotor agitation or retardation, impaired
judgment) that developed during, or shortly after, opioid use.
C. Pupillary constriction (or pupillary dilation due to anoxia from severe overdose) and
one (or more) of the following signs or symptoms developing during, or shortly after,
opioid use:
1. Drowsiness or coma.
2. Slurred speech.
3. Impairment in attention or memory.
D. The signs or symptoms are not attributable to another medical condition and are not
better explained by another mental disorder, including intoxication with another sub-
stance.
Specify if:
With perceptual disturbances: This specifier may be noted in the rare instance in
which hallucinations with intact reality testing or auditory, visual, or tactile illusions oc-
cur in the absence of a delirium.
Coding note:  The ICD-9-CM code is 292.89.  The ICD-10-CM code depends on whether
or not there is a comorbid opioid use disorder and whether or not there are perceptual dis-
turbances.
For opioid intoxication without  perceptual disturbances: If a mild opioid use dis-
order is comorbid, the ICD-10-CM code is F11.129,  and if a moderate or severe opioid


Opioid Withdrawal 547
use disorder is comorbid, the ICD-10-CM code is F11.229.  If there is no comorbid opi-
oid use disorder, then the ICD-10-CM code is F11.929.
For opioid intoxication wit h perceptual disturbances: If a mild opioid use disorder
is comorbid, the ICD-10-CM code is F11.122,  and if a moderate or severe opioid use
disorder is comorbid, the ICD-10-CM code is F11.222.  If there is no comorbid opioid
use disorder, then the ICD-10-CM code is F11.922.
Diagnostic Features
The essential feature of opioid intoxication is  the presence of clinically significant prob-
lematic behavioral or psychological changes (e .g., initial euphoria followed by apathy,
dysphoria, psychomotor agitation or retardat ion, impaired judgment) that develop dur-
ing, or shortly after, opioid use (Criteria A and B). Intoxication is accompanied by pupil-
lary constriction (unless ther e has been a severe overdose with consequent anoxia and
pupillary dilation) and one or more of the fo llowing signs: drowsiness (described as be-
ing “on the nod”), slurred speech, and impairme nt in attention or memory (Criterion C);
drowsiness may progress to co ma. 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 attributab le to another medical condition and are not
better explained by another me ntal disorder (Criterion D).
Differential Diagnosis
Other substance intoxication. Alcohol intoxication and se dative-hypnotic intoxication


Other substance intoxication. Alcohol intoxication and se dative-hypnotic intoxication
can cause a clinical picture that resembles op ioid intoxication. A diagnosis of alcohol or
sedative-hypnotic intoxication can usually be made based on the absence of pupillary con-
striction or the lack of a response to a naloxo ne challenge. In some cases, intoxication may
be due both to opioids and to alcohol or other sedatives. In these cases, the naloxone chal-
lenge will not reverse all of  the sedative effects.
Other opioid-related disorders. Opioid intoxication is distinguished from the other
opioid-induced disorders (e.g.,  opioid-induced depressive disorder, with onset during in-
toxication) because the symptoms  in the latter disorders predominate in the clinical pre-
sentation and meet full criteria  for the relevant disorder.
Opioid Withdrawal
Diagnostic Criteria 292.0 (F11.23)
A. Presence of either of the following:
1. Cessation of (or reduction in) opioid use that has been heavy and prolonged (i.e.,
several weeks or longer).
2. Administration of an opioid antagonist after a period of opioid use.
B. Three (or more) of the following developing within minutes to several days after Criterion A:
1. Dysphoric mood.
2. Nausea or vomiting.
3. Muscle aches.
4. Lacrimation or rhinorrhea.
5. Pupillary dilation, piloerection, or sweating.


548 Substance-Related and Addictive Disorders
6. Diarrhea.
7. Yawning.
8. Fever.
9. Insomnia.
C. The signs or symptoms in Criterion B cause clinically significant distress or impairment
in social, occupational, or other important areas of functioning.
D. The signs or symptoms are not attributable to another medical condition and are not
better explained by another mental disorder, including intoxication or withdrawal from
another substance.
Coding note: The ICD-9-CM code is 292.0. The IC D-10-CM code for opioid withdrawal is
F11.23. Note that the ICD-10-CM code indicates the comorbid presence of a moderate or
severe opioid use disorder, reflecting the fact that opioid withdrawal can only occur in the
presence of a moderate or severe opioid use disorder. It is not permissible to code a co-
morbid mild opioid use disorder with 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 (Cri terion A1). The withdrawal synd rome 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 ag-
onist such as buprenorphine to a person  currently using a full opioid agonist.
Opioid withdrawal is characte rized by a pattern of signs and symptoms that are oppo-
site 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 with drawal: dysphoric mood; nausea or vomiting;
muscle aches; lacrimation or rhinorrhea; pu pillary dilation, piloerection, or increased
sweating; diarrhea; yawning; fever; and insomn ia (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 with-
drawal becomes that far advanced. These sy mptoms of opioid withdrawal must cause
clinically significant distress or impairment in social, occupational, or other important ar-
eas of functioning (Criterion C). The symptoms  must not be attributable to another med-
ical condition and are not better explained by another mental diso rder (Criterion D).
Meeting diagnostic criteria for opioid withdr awal 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-10-CM codes only allow a diagnosis of
opioid withdrawal in the presence of comorb id moderate to severe opioid use disorder.
The speed and severity of withdrawal associat ed 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 th e case of longer-acting drugs such as metha-
done, LAAM ( L-alpha-acetylmethadol), or buprenorph ine. Acute withdrawal symptoms for


a short-acting opioid such as heroin usuall y 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.


Opioid Withdrawal 549
Associated Features Supporting Diagnosis
Males with opioid withdrawal may experien ce 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 o ccur in any individual after cessation of re-
peated use of an opioid, whether in the se tting of medical management of pain, during
opioid agonist therapy fo r opioid use disorder, in the contex t of private recreational use, or
following attempts to self-treat sympto ms of mental disorders with opioids.
Prevalence
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.
Development and Course
Opioid withdrawal is typical in the course of an opioid use disorder. It can be part of an es-
calating pattern in which an opioid is used to  reduce withdrawal symptoms, in turn lead-
ing to more withdrawal at a later time. Fo r persons with an established opioid use
disorder, withdrawal and attempts to  relieve withdrawal are typical.
Differential Diagnosis
Other withdrawal disorders. The anxiety and restlessness associated with opioid with-
drawal resemble symptoms seen  in sedative-hypnotic withdrawal. However, opioid with-
drawal is also accompanied by rhinorrhea, la crimation, and pupillary dilation, which are
not seen in sedative-type withdrawal.
Other substance intoxication. Dilated pupils are also seen in hallucinogen intoxication
and stimulant intoxication. However, other signs or symptoms of opioid withdrawal, such
as nausea, vomiting, diarrhea, abdominal cram ps, rhinorrhea, and lacrimation, are not


present.
Other opioid-ind uced disorders. Opioid withdrawal is distinguished from the other
opioid-induced disorders (e.g., opioid-induced depressive  disorder, with onset during
withdrawal) because the symptoms in these latt er disorders are in ex cess of those usually
associated with opioid withdrawal and meet  full criteria for th e relevant disorder.
Other Opioid-Induced Disorders
The following opioid-induced di sorders are described in other chapters of the manual with
disorders with which they share phenomenology (see the substance/medication-induced
mental disorders in these chapters): opioid-i nduced depressive diso rder (“Depressive Dis-
orders”); opioid-induced anxi ety disorder (“Anxiety Disord ers”); opioid-induced sleep
disorder (“Sleep-Wake Disord ers”); and opioid-induced sexual dysfunction (“Sexual Dys-
functions”). For opioid intoxica tion delirium and opioid with drawal delirium, see the crite-
ria and discussion of delirium in the chapter “Neurocognitive Disorders.” These opioid-
induced disorders are diagnosed instead of opio id intoxication or opioid withdrawal only
when the symptoms are suffici ently severe to warrant inde pendent clinical attention.


550 Substance-Related and Addictive Disorders
Unspecified Opioid-Related Disorder
292.9 (F11.99)
This category applies to presentations in which symptoms characteristic of an opioid-
related disorder that cause clinically significant distress or impairment in social, occupa-
tional, or other important areas of functioning predominate but do not meet the full criteria
for any specific opioid-related disorder or any  of the disorders in the substance-related and
addictive disorders diagnostic class.
Sedative-, Hypnotic-,
or Anxiolytic-Related Disorders
Sedative, Hypnotic, or Anxiolytic Use Disorder
Sedative, Hypnotic, or Anxiolytic Intoxication
Sedative, Hypnotic, or Anxiolytic Withdrawal
Other Sedative-, Hypnotic-, or Anxiolytic-Induced Disorders
Unspecified Sedative-, Hypnotic-, or Anxiolytic-R elated Disorder
Sedative, Hypnotic, or Anxiolytic Use Disorder
Diagnostic Criteria
A. A problematic pattern of sedative, hypnotic, or anxiolytic use leading to clinically signif-
icant impairment or distress, as manifested by at least two of the following, occurring
within a 12-month period:
1. Sedatives, hypnotics, or anxiolytics are often taken in larger amounts or over a lon-
ger period than was intended.
2. There is a persistent desire or unsuccessful efforts to cut down or control sedative,
hypnotic, or anxiolytic use.
3. A great deal of time is spent in activities necessary to obtain the sedative, hypnotic,
or anxiolytic; use the sedative, hypnotic, or anxiolytic; or recover from its effects.


4. Craving, or a strong desire or urge to use the sedative, hypnotic, or anxiolytic.
5. Recurrent sedative, hypnotic, or anxiolytic use resulting in a failure to fulfill major
role obligations at work, school, or home (e.g., repeated absences from work or
poor work performance related to sedative, hypnotic, or anxiolytic use; sedative-,
hypnotic-, or anxiolytic-related absences, suspensions, or expulsions from school;
neglect of children or household).
6. Continued sedative, hypnotic, or anxiolytic use despite having persistent or re-
current social or interpersonal problem s caused or exacerbated by the effects of
sedatives, hypnotics, or anxiolytics (e.g., arguments with a spouse about conse-
quences of intoxication; physical fights).
7. Important social, occupational, or recreat ional activities are given up or reduced be-
cause of sedative, hypnotic, or anxiolytic use.


Sedative, Hypnotic, or Anxiolytic Use Disorder 551
8. Recurrent sedative, hypnotic, or anxiolytic use in situations in which it is physically
hazardous (e.g., driving an automobile or  operating a machine when impaired by
sedative, hypnotic, or anxiolytic use).
9. Sedative, hypnotic, or anxiolytic use is continued despite knowledge of having a
persistent or recurrent physical or psychological problem that is likely to have been
caused or exacerbated by the sedative, hypnotic, or anxiolytic.
10. Tolerance, as defined by either of the following:
a. A need for markedly increased amounts of the sedative, hypnotic, or anxiolytic
to achieve intoxication or desired effect.
b. A markedly diminished effect with continued use of the same amount of the sed-
ative, hypnotic, or anxiolytic.
Note:  This criterion is not considered to be met for individuals taking sedatives,
hypnotics, or anxiolytics under medical supervision.
11. Withdrawal, as manifested by either of the following:
a. The characteristic withdrawal syndrome for sedatives, hypnotics, or anxiolytics
(refer to Criteria A and B of the criteria  set for sedative, hypnotic, or anxiolytic
withdrawal, pp. 557–558).
b. Sedatives, hypnotics, or anxiolytics (or a closely related substance, such as al-
cohol) are taken to relieve or  avoid withdrawal symptoms.
Note:  This criterion is not considered to be met for individuals taking sedatives,
hypnotics, or anxiolytics under medical supervision.
Specify if:


hypnotics, or anxiolytics under medical supervision.
Specify if:
In early remission:  After full criteria for sedative, hypnotic, or anxiolytic use disorder
were previously met, none of the criteria for sedative, hypnotic, or anxiolytic use disor-
der have been met for at least 3 months but for less than 12 months (with the exception
that Criterion A4, “Craving, or a strong desire or urge to use the sedative, hypnotic, or
anxiolytic,” may be met).
In sustained remission:  After full criteria for sedative, hypnotic, or anxiolytic use dis-
order were previously met, none of the criteria for sedative, hypnotic, or anxiolytic use
disorder have been met at any time during a period of 12 months or longer (with the
exception that Criterion A4, “Craving, or a strong desire or urge to use the sedative,
hypnotic, or anxiolytic,” may be met).
Specify if:
In a controlle d environment:  This additional specifier is used if the individual is in an
environment where access to sedatives, hypnotics, or anxiolytics is restricted.
Coding based on current severity:  Note for ICD-10-CM codes: If a sedative, hypnotic, or
anxiolytic intoxication; sedative, hypnotic, or anxiolytic withdrawal; or another sedative-,
hypnotic-, or anxiolytic-induced mental disor der is also present, do not use the codes be-
low for sedative, hypnotic, or anxiolytic use disorder. Instead the comorbid sedative, hyp-


notic, or anxiolytic use disorder is indicated in the 4th character of the sedative-, hypnotic-,
or anxiolytic-induced disorder (see the coding no te for sedative, hypnotic, or anxiolytic in-
toxication; sedative, hypnotic, or anxiolytic withdrawal; or specific sedative-, hypnotic-, or
anxiolytic-induced mental disorder). For example, if there is comorbid sedative-, hypnotic-,
or anxiolytic-induced depressive disorder and sedative, hypnotic, or anxiolytic use disor-
der, only the sedative-, hypnotic-, or anxiolyti c-induced depressive disorder code is given
with the 4th character indicating whether the comorbid sedative, hypnotic, or anxiolytic use
disorder is mild, moderate, or severe: F13.14 for mild sedative, hypnotic, or anxiolytic use
disorder with sedative-, hypnotic-, or anxiolytic-induced depressive disorder or F13.24 for
a moderate or severe sedative, hypnotic, or anxiolytic use disorder with sedative-, hypnotic-,
or anxiolytic-induced depressive disorder.


552 Substance-Related and Addictive Disorders
Specify current severity:
305.40 (F13.10) Mild:  Presence of 2–3 symptoms.
304.10 (F13.20) Moderate: Presence of 4–5 symptoms.
304.10 (F13.20) Severe:  Presence of 6 or more symptoms.
Specifiers
“In a controlled environment” app lies as a further specifier of remission if the individual is
both in remission and in a controlled environm ent (i.e., in early remission in a controlled
environment or in sustained remission in a controlled environmen t). Examples of these
environments are closely supe rvised and substanc e-free jails, therapeutic communities,
and locked hospital units.
Diagnostic Features
Sedative, hypnotic, or anxiolytic substances  include benzodiazepines, benzodiazepine-
like drugs (e.g., zolpidem, zaleplon), carb amates (e.g., glutethimide, meprobamate),
barbiturates (e.g., secobarbital), and barbitur ate-like hypnotics (e.g ., glutethimide, meth-
aqualone). This class of substances includes  all prescription slee ping medications and
almost all prescription antianxiety medica tions. Nonbenzodiazep ine 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 substa nce use disorders. Sedative, hypnotic, or anxiolytic sub-
stances are available both by prescription an d illegally. Some individuals who obtain these


stances are available both by prescription an d illegally. Some individuals who obtain these
substances by prescription will develop a seda tive, hypnotic, or anxi olytic use disorder,
while others who misuse these substances or use them for intoxicati on 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 intoxicati on purposes, although
longer acting substances in this clas s 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, in-
dividuals may use intoxicating doses of se datives or benzodiaze pines 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 expul-
sions, and neglect of children or household (Criterion A5) may be related to sedative, hyp-
notic, or anxiolytic use disorder, as may the continued use of the substances despite
arguments with a spouse abou t consequences of intoxication or despite physical fights
(Criterion A6). Limiting contact with family or  friends, avoiding work or school, or stop-
ping participation in hobbies, sports, or games (Criterion A7) and recurrent sedative,
hypnotic, or anxiolytic use when driving an automobile or operatin g a machine when im-