Critical Reviews in Oral Biology and Medicine, 3(3):163-184 (1992)

Oral Effects of Drug Abuse

Terry D. Rees, D.D.S., M.S.D.
Chairman and Professor, Periodontics Department, Baylor College of Dentistry, 3302 Gaston
Avenue, Dallas, Texas 75246

ABSTRACT: Drug abuse is a major problem in the U.S. and most other countries of the world today. Many
studies, surveys, and case reports have described the adverse social and medical effects of drug abuse; yet
surprisingly little is known about the specific effects of many of these drugs in the oral cavity. This article
reviews the current state of knowledge concerning the systemic and oral effects of drugs of abuse and the dental
management of addicted patients.

KEY WORDS: opiates, hallucinogens, cannabis, cocaine, amphetamines, alcohol.

1. INTRODUCTION once, while 2 to 4 million Americans have used

Mood-altering drugs have been used by man
for many purposes throughout recorded history.
In some instances, such agents were used as com-
ponents of religious ceremonies, while in other
cultures substances such as coca leaves were
chewed by native populations to increase endur-
ance and to relieve hunger and fatigue (Gargiulo
et al., 1985, Hamner and Villegas, 1969). In
other circumstances, mood-altering agents were
and are used for medical purposes. Cocaine, for
example, was widely available in the U.S. during
the late 19th century for use as a stimulant, or a
local anesthetic in dentistry, opthalmology, and
otolaryngology (Friedlander and Gorelick, 1988).
Clearly, however, the most common use for
mood-altering drugs has essentially been for
"recreational" or social purposes. Although pos-
sessing some medicinal properties, alcohol has
been used recreationally for thousands of years
and alcoholism has been described since the 1st
century B.C. Cocaine and opium have been in
use at least since the 6th century (Council on
Dental Practice, 1987).
Today, the use and abuse of mood-altering
drugs in the U.S. creates staggering figures and
estimates. For example, it is reported that 22
million Americans have used cocaine at least
it regularly. At least one half million individuals
have significant problems with cocaine abuse
(Friedlander and Gorelick, 1988; Council on
Dental Practice, 1987). Despite these large num-
bers, cocaine ranks only third among drugs of
abuse, with ethyl alcohol representing the most
widely used substance, followed by cannabis
(such as marijuana and hashish).
The Federal Drug Enforcement Agency lists
at least 171 other drugs capable of being abused,
and new drugs with abuse potential are constantly
being developed. In addition to alcohol, the agents
of abuse fall into the general categories of nar-
cotics, depressants, stimulants, hallucinogens
(Council on Dental Practice, 1987), and solvents
and inhalants (Rosenbaum, 1981). A majority of
American teenagers and adults use ethyl alcohol
and an estimated 12 million suffer from some
aspect of alcohol abuse (Christen, 1983; Duggan
et al., 1991).
Despite these large estimates, relatively little
is known conclusively regarding the factors that
cause people to use such drugs and even less is
known regarding chemical dependency (Council
on Dental Practice, 1987; Jenike, 1991). In the
past, with the exception of alcohol, substance
dependency was a phenomenon that was pri-
marily limited to socially disadvantaged individ-

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© 1992 by CRC Press, Inc.

163
uals and to those of high socioeconomic status
who possess the financial means and access to
purchase drugs of abuse. Today, however, drug
users are distributed proportionately among the
general population in all social strata (Friedlander
and Mills, 1985). In general terms, initiation of
drug use begins between 15 and 35 years of age,
although wide age variations are often described
with the age of first-time users becoming pro-
gressively younger (Rosenbaum, 1981).
Polydrug use is extremely common. One sur-
vey indicated that 61% of U.S. high school sen-
iors had used a drug at least once and 40% had
used more than one type of drug. Marijuana and
alcohol are the two most commonly used "entry"
drugs, with others added subsequently. Polydrug
use compounds the difficulty of determining the
long-term effects of specific drugs. For example,
31% of all alcoholics and 51% of teenagers and
young adult alcoholics are addicted to other drugs
in addition to alcohol. Among individuals with
drug abuse problems causing hospitalization or
death, polydrug use ranges from 34 to 50%.
Among alcoholics, barbiturates, narcotic anal-
gesics, and stimulants are the most frequently
used additional drugs (Council on Dental Prac-
tice, 1987).
Drug abuse is commonly associated with sig-
nificant detrimental psychological, nutritional,
and social changes, any of which can markedly
affect the general and oral health of the individual
user. The stereotypical drug addict is pictured as
an undereducated individual living in a very low
socioeconomic environment. This individual is
unable to purchase adequate supplies of food,
general and oral hygiene are neglected, and there
is little interest in seeking medical or dental treat-
ment other than as a possible mechanism for ob-
taining prescription drugs of abuse (Rosenbaum,
1981; Mark, 1980; Scheutz, 1985; Scheutz,
1984a). Certainly, many users of drugs do fall
into this category, especially those addicted to
parenterally administered agents or to alcohol.
Conversely, however, drug abuse can and often
does occur in individuals who are financially sol-
vent and who lead reasonably normal lives.
The purpose of this article is to review the
current state of knowledge concerning the sys-
temic and oral effects of drugs of abuse and the
dental management of addicted patients. Many
164
studies, surveys, and case reports have been pre-
sented in the medical literature regarding sub-
stance abuse, but surprisingly little is conclu-
sively known today about the specific effects of
drugs of abuse in the oral cavity. Many studies
relative to dental effects were conducted in drug
treatment centers, meaning that oral health fea-
tures described are predominantly associated with
patients addicted to parenterally administered
agents. Case reports describe oral conditions
found in a particular individual or individuals,
but do not necessarily represent typical features
associated with a particular drug. In other in-
stances, animal experiments were described and
the results of such studies cannot necessarily be
applied to humans (Scheutz, 1985; Scheutz,
1984a; Scheutz, 1986b, Di Cungo et al., 1981;
Harbour and Smith, 1988; Davis and Baer, 1971;
Shapiro et al., 1970; Lowenthal, 1967; Colon,
1972; Silverstein, 1973; Scheutz, 1986a; Scheutz,
1984c; Scheutz et al., 1983; Williamson and
Davis, 1973; Kothur et al., 1991).
II. DEFINITIONS
The following definitions are important.
1. Addiction - physical and psychologic de-
pendency, associated with tolerance to a
drug and withdrawal symptoms with a per-
sistent disposition to relapse to drug use
after abstinence has been achieved and
physical dependency reversed (Newman,
1983).
2. Abuse - a pattern of pathologic behavior
associated with continued use of a drug or
drugs despite persistent social, psycho-
logic, or physical problems caused by drug
use (Friedlander and Mills, 1985).
3. Dependence - continued substance use
caused by a physical or psychological need
for a substance. Tolerance to the effects of
the drug and development of characteristic
withdrawal symptoms are required (Jenike,
1991).
4. Tolerance - a need for markedly increased
quantities of a drug in order to achieve the
desired results (Rosenbaum, 1981; Fried-
lander and Mills, 1985).
5. Withdrawal - psychological or physiolog-
ical symptoms developed following discon-
tinuance of drug use (Rosenbaum, 1981;
Friedlander and Mills, 1985).
III. THE PATIENT WHO ABUSES DRUGS
The psychologic makeup of substance abu-
sers was recently studied by Mirin et al. (1988)
and others (Jenike, 1991; Rounsaville et al., 1982;
De Leon and Jainchill, 1981). They found that
a substantial number of patients under treatment
for substance abuse disorders also manifested
nondrug-related psychiatric disorders. It should
be recognized, however, that findings in patient
populations within a substance abuse facility may
not be representative of all abusers. Institution-
alized addicts have either recognized that they
have a problem and have sought treatment for
that problem or they were forced by society to
seek assistance. Many of these patients are in-
stitutionalized repeatedly for their addiction
(Haddox and Jacobson, 1972). In contrast, a sig-
nificant number of individuals who are dependent
on alcohol or narcotics and who have developed
a high tolerance to such drugs are still able to
discontinue use of the drugs without relapse
(Newman, 1983; De Leon and Jainchill, 1981).
Psychiatric evaluation is difficult because the signs
and symptoms manifested may be the result of
an ongoing underlying psychiatric disorder or they
may reflect manifestations of drug intoxication
or of damage from chronic substance abuse. They
may also be features of drug withdrawal or any
combination of the above (Mirin et al., 1988).
It is certainly possible, however, that individuals
with affective disorders, such as depression or
excessive anxiety, may use drugs to alter their
psychologic states (Jenike, 1991). In any event,
patients withdrawing from drug abuse may ex-
perience affective disorders (De Leon et al., 1973;
Charlesworth and Dempsey, 1982). For exam-
ple, opiate withdrawal may be associated with
depression, while rapid methadone detoxification
may result in a severe psychosis such as schiz-
ophrenia (Mirin et al., 1988). Stimulant abusers
may use agents such as cocaine in a subconscious
attempt at self-treatment for depression and with-
drawal may result in a rebound depression (Jen-
ike, 1991; Mirin et al., 1988).
Patients who abuse depressive agents such
as benzodiazepines or sedatives may do so to
mask an anxiety disorder that will resurface upon
withdrawal. It is important for dentists to be aware
that patients under medical treatment for drug
detoxification may be taking prescribed drugs such
as tricyclic antidepressants, monoamine oxidase
inhibitors (MAOIs), or lithium to counteract the
psychiatric effects of their withdrawal (Mirin et
al., 1988). Drugs of this nature may have a pro-
found effect on the outcome of dental treatment
unless appropriate precautions are taken.
A familial component may be present in in-
dividuals who practice substance abuse. When
families of substance abuse patients were evalu-
ated, approximately 30% of relatives suffered
from at least one psychopathologic disorder.
Among male relatives, there was an increased
expectancy rate for alcoholism, while female rel-
atives had a higher expectancy rate for affective
disorders. As discussed later, propensity to al-
coholism appears to represent an inherited trait,
especially among men, but studies do not affim
a correlation between alcoholism in first-degree
relatives and abuse of other substances (Mirin et
al., 1988).
Drug addiction appears to be closely asso-
ciated with an increase in medical disorders, at
least as reflected by reports from drug addiction
treatment centers. In most instances, those re-
ports reflect data obtained from users of paren-
terally administered drugs, most commonly the
opiates and usually heroin. Commonly reported
disorders include AIDS (Barone et al., 1990;
Waterson, 1983) and hepatitis or other liver dis-
eases (Webster et al., 1977; White, 1973; Cher-
ubin et al., 1976). Other infections are common,
to include pulmonary disease, skin infections,
venereal diseases, and infective endocarditis
(Scheutz, 1986b; Webster et al., 1977; Davis et
al., 1983; Ayer and Cutright, 1974; Briggs et
al., 1967). The incidence of cardiovascular dis-
eases, diabetes mellitus, and gastrointestinal dis-
orders also increases (Webster et al., 1977; Briggs
et al., 1967). White (1973) reported that skin
infections were usually associated with subcu-
taneous injections of heroin ("skin popping"),
while uncontrolled diabetes mellitus was related
165
to the lifestyle of addiction that leads to incon-
sistent monitoring of blood glucose levels, spo-
radic administration of insulin, inadequate diet
control, and severe systemic illness. Most drug
addicts smoke tobacco and frequently overuse
analgesics, tranquilizers, sedatives, and laxatives
(Webster et al., 1977).
Parenteral drug users are especially suscep-
tible to human immunodeficiency virus (HIV)
infection and hepatitis A (HAV), hepatitis B
(HBV) (Scheutz et al., 1983; Cherubin, 1976;
Mangla et al., 1976; Centers for Disease Control,
1988; Mathiesen et al., 1979), and hepatitis C
(HCV) (Widell et al., 1982; Lenzi et al., 1990;
Bortolotti, 1982; Weiland, 1981). Hepatitis B or
C may be associated with chronic aggressive hep-
atitis in 15 to 25% of fonner addicts, as compared
to 5 to 10% of the general population who have
been infected with HBV or HCV (Scheutz, 1986b;
Lowenthal, 1967; Weiland et al., 1981). In a
related study, Schalm et al. (1983) found that
drug addicts were equally as capable as nonad-
dicted individuals in developing antibodies to
hepatitis B virus when vaccinated against the vi-
rus. Conversely, Rumi et al. (1991) reported that
a significant number of institutionalized drug users
failed to develop antibodies when vaccinated
against HBV, perhaps due to an altered immune
status in these individuals.
Liver function tests are often elevated in nar-
cotic addicts (Cherubin et al., 1976; Mangla et
al., 1976), suggesting the possibility of a direct
hepatotoxic effect of parenterally administered
opiates or their contaminants (Ireton et al., 1974).
Gorodetzky et al. (1968), however, conducted
an experiment on humans who were made de-
pendent on morphine administered subcutane-
ously and sustained in this state for 6 to 8 months.
They found no evidence of significant changes
in liver enzyme levels associated with long-term
moxphine administration. They concluded that the
high instance of abnormal liver enzymes found
in morphine and heroin addicts was not due to a
direct hepatotoxic effect of the drugs.
Viral hepatitis and HIV transmission among
drug addicts is almost certainly related to intra-
venous drug injection because of the use and
repeated reuse of unsterile needles and needle
sharing (Webster et al., 1977). It is probable,
however, that the lifestyle of chronic substance
166
abusers of low socioeconomic status may pre-
dispose abusers to transmission of HIV and viral
hepatitis. Sexual promiscuity is common, living
conditions may be unsanitary, and immune de-
ficiencies may result in association with malnu-
trition, multiple systemic diseases, and polydrug
use, especially with alcohol (Blanck et al., 1979).
Sexual transmission of HAV and HBV has been
demonstrated in humans and animals (Kani et al.,
1991; Perillo etal., 1979; Scott etal., 1980) and
suggested for hepatitis C (Tedder et al., 1991).
HBV has been isolated in human saliva and its
transmission demonstrated by subcutaneous in-
jections in monkeys, but oral and nasal exposure
to saliva did not result in transmission (Scott et
al., 1980; Bancroft et al., 1977).
Recent evidence has affirmed that hepatitis
C (formerly non-A, non-B hepatitis) is caused
by a specific virus transmitted in blood and blood
products (Velazquez et al., 1990; Zuckerman,
1990; Tremolada et al., 1991). Another form of
non-A, non-B hepatitis may be transmitted en-
demically in an unsanitary environment such as
that of drug abusers of low socioeconomic status
(Velazquez et al., 1990). Some 10 to 30% of
HCV-infected patients develop chronic liver dis-
ease and that number may be higher among in-
dividuals with depressed immune responses
(Moestrup et al., 1986).
The delta agent is a viral antigen often found
in liver cells of individuals suffering from acute
or chronic hepatitis. The virus is a defective RNA
agent capable of replicating within hepatocytes,
but it is not able to produce a protein coat (Scheutz,
1986b). The delta virus requires the presence of
HBV to be functional and its primary reservoir
appears to be parenteral drug users. It is believed
to be the major cause of the increased incidence
of severe liver disease and chronic hepatitis among
parenteral drug addicts (De Cock et al., 1986).
Experimentally, severe liver damage occurred
when HBV antigen and the delta antigen were
injected into chimpanzees susceptible to infection
with human hepatitis B virus (Rizzetto et al.,
1980).
Parenteral drug abusers are prone to multiple
infections related to the use of nonsterile equip-
ment. Additionally, however, it has been sug-
gested that materials used to dilute opiates (su-
crose, baking soda, starch, talc, quinine, and
powdered milk) (Rosenbaum, 1981; Ayer and
Cutright, 1974) may serve as a source of path-
ogenic microorganisms as well as foreign ma-
terial introduced into the bloodstream (The Med-
ical Letter, Inc., 1990). Endocarditis involving
the tricuspid valve on the right side of the heart
is often reported, but lesions are not limited to
that valve (Davis et al., 1983, Ayer and Cutright,
1974). Bacteremias caused by unusual organisms
may occur due to the abuser's compromised im-
mune status. Infective endocarditis has been de-
scribed from causative organisms such as neis-
seria mucosus (Davis et al., 1983), Escherichia
coli, Klebsiella-aerobacter, Pseudomonas aeru-
ginosa, and several species of candida (Louria et
al., 1967). In one incident of neisseria endocar-
ditis, the organism neisseria mucosus was cul-
tured from the sputum of a parenteral drug user
who habitually licked the injection needle (Davis
et al., 1983). In other instances, the infectious
agent may be obtained from the skin in the site
of injection (Rosenbaum et al., 1981).
Cocaine abuse has been associated with a
variety of cardiac disorders that include angina
pectoris and myocardial infarction (Cregler and
Mark, 1986; Pastemack et al., 1985; Isner et al.,
1986), and sudden cardiac death may occur due
to acute cocaine toxicity (Pallasch et al., 1989;
Cregler and Mark, 1985).
IV. EFFECTS ON THE IMMUNE SYSTEM
There is considerable evidence to suggest that
the immune system may be significantly altered
in patients practicing substance abuse (Donahoe,
1988). Additionally, there is increasing aware-
ness that the immune system engages in complex
regulatory interactions with the central nervous
system and the endocrine system (Harbour and
Smith, 1988; Donahoe, 1988; Weber, 1988).
Drugs of abuse may adversely affect various
components of this interactive system. Opiates,
for example, affect the central nervous system
and the immune system by competing with en-
dogenously manufactured opiates at various re-
ceptor sites in the brain and attaching to opiate
receptors on T lymphocytes and leukocytes (Har-
bour and Smith, 1988; Donahoe, 1988; Donahoe
and Falek, 1988). Cocaine, phencyclidine, mari-
juana, benzodiazepines, barbiturates, and alcohol
are all capable of suppressing or, in certain cir-
cumstances, enhancing immune function in vivo
and in vitro (Weber, 1988; MacGregor, 1987).
Cocaine and amphetamines are reported to de-
crease total lymphocyte counts in animals, but
no research data are available in man (Mac-
Gregor, 1987). Marijuana has been studied in
animals using doses and concentrations consid-
erably greater than those levels found in human
subjects. In animals, marijuana impairs cellular
and hormonal immune response, but, to date,
there is no conclusive evidence to associate mari-
juana abuse with an increased prevalence of op-
portunistic infections or malignancies (Hollister,
1988).
Amyl nitrite was reported to be associated
with altered lymphocyte counts and functions,
but this was not confirmed by experiments con-
ducted in mice (Waterson, 1983; MacGregor,
1987).
Alcohol abuse has been demonstrated to be
associated with immune suppression, but in many
instances, this may be the result of liver damage
or malnutrition (Jerrells et al., 1988; Dunne,
1989). Alcohol ingestion, however, may revers-
ibly alter the production and function of both T
and B lymphocytes, leading to reduced circulat-
ing lymphocyte counts. Macrophage activation
and phagocytic activity may be diminished, and
granulocyte chemotaxis and adherence to capil-
lary walls is adversely affected. Meanwhile, beta
endorphins in the brain are reduced, leading to
an altered activity of natural killer cells by the
immunoneuronal route (Donahoe, 1990; Jerrells
et al., 1988; Alcock, 1990).
Experimental and clinical findings as de-
scribed above suggest that abuse of opiates and
alcohol, and perhaps other drugs, may signifi-
cantly alter susceptibility to infection. At present,
there is no direct evidence to confirm a relation-
ship between alcohol abuse and development of
AIDS (MacGregor, 1987; Mohs and Watson,
1990). Some evidence, however, suggests that
HIV infection in parenteral drug addicts may lead
to exacerbation of complaints and, possibly, more
rapid progression to outright AIDS (MacGregor,
1987). Intravenous (i.v.) drug use has been clearly
associated with HIV transmission and i.v. drug
abusers constitute approximately 21 to 28% of
167
reported AIDS cases in the U.S. (U.S. Depart-
ment of Health and Human Services, 1990). This
relationship is undoubtedly attributable to needle
sharing in parenteral drug users (Friedlander and
Mills, 1985), but the immunosuppression clini-
cally demonstrated in opiate addicts who are not
HIV positive suggests that opiate-derived im-
munosuppression may enhance HIV infection and
the rate of progress to outright AIDS (Mac-
Gregor, 1987). The direct effect of opiate add-
iction on immune status is, however, still con-
jectural (Donahoe and Falek, 1988).
Mohs and Watson (1990) recently reviewed
the role of ethyl alcohol-induced malnutrition as
a potential cause of immunosuppression espe-
cially related to AIDS. Alcoholism is tradition-
ally associated with faulty dietary intake, leading
to protein and calorie deficiencies. Additionally,
alcohol abuse alters gastrointestinal absorption of
nutrients and their transformation to metaboli-
cally active forms. Simultaneously, alcohol in-
take increases the utilization requirements for a
variety of nutrients. Alcohol-associated liver
damage may have profound effects on metabo-
lism, activation, and storage of nutrients. Spe-
cific nutritional components such as vitamins A,
B,, B2, B6, B12, C, and D, folic acid, iron, and
zinc may also be adversely affected (Mohs and
Watson, 1990). The immunosuppressive effects
of these deficiencies may be generally reversible
with abstinence from alcohol unless liver damage
has occurred. Nonetheless, evidence such as this
suggests that excessive alcohol intake should be
avoided in HIV-positive individuals.
V. GENERAL ORAL FEATURES OF
CHEMICAL DEPENDENCY
The specific oral effects of various drugs of
abuse will be discussed later in this review. A
number of oral diseases and disorders have been
described, however, that may relate to most in-
dividuals who engage in substance abuse. For
example, chronic chemical abuse is generally as-
sociated with a markedly decreased self-image,
depression, and a lack of motivation, all of which
may impact oral health and adversely influence
compliance with oral hygiene procedures and
keeping dental appointments (Scheutz, 1985; U.S.
168
Department of Health and Human Services,
1990). Additionally, dental care assumes a low
priority in the life of an addict whose primary
preoccupation ultimately may become the need
to obtain drugs to support their habit. In many
instances, a distressed financial state discourages
addicts from seeking dental care, and, if treat-
ment is requested, the only financially acceptable
option may be extraction of involved teeth. Con-
versely, an addict may choose to retain an un-
treated carious tooth as a possible mechanism for
obtaining a prescription for a potent analgesic
agent. Finally, chronic use of some drugs may
mask the pain of untreated dental disease (Ro-
senbaum, 1981).
Several drugs of abuse such as opiates, am-
phetamines, barbiturates, miscellaneous hallu-
cinogens, marijuana, and alcohol have been re-
ported to produce xerostomia. This lowers salivary
pH and promotes plaque and calculus accumu-
lation, with resultant increases in incidence of
caries and periodontal disease (Scheutz, 1985;
Scheutz, 1984a; Scheutz, 1986b; Shapiro et al.,
1970; Colon, 1972; Westerhof et al., 1983; Drai-
zin et al., 1975). Not all studies confirm an as-
sociation, however, between drug abuse and xe-
rostomia (Di Cugno et al., 1981; Scheutz, 1984).
DiCugni et al. (1981) studied salivary secretion
in patients using amphetamines, marijuana, and
other drugs and were unable to detect reduced
parotid salivary flow in patients using marijuana
as their predominant drug. The authors did, how-
ever, identify alterations in salivary composition
in all groups, together with a higher caries index.
Many reports describe an increased caries
rate among drug addicts (Scheutz, 1984a; Scheutz,
1986b; Lowenthal, 1967; Scheutz, 1984b), and
cervical and smooth surface carious lesions have
been found much more frequently in drug addicts
than in the general population (Scheutz, 1984a;
Lowenthal, 1967; Hecht and Friedman, 1949).
Carious lesions may present with a smooth, darkly
stained, ebumated appearance in drug-using pa-
tients (Scheutz, 1984a).
The reported increase in the caries rate may
relate to the poor oral hygiene mentioned earlier.
Additionally, however, several authors have in-
dicated that addicts, particularly those using par-
enteral drugs, may crave refined carbohydrates
either in an effort to counteract xerostomia (Co-
Ion 1972, Colon 1974) - due to inherent nutri-
tional deficiencies or constipation associated with
drug use (Hecht and Friedman, 1949; Carter,
1978) - or for unexplained reasons (Lowenthal,
1967). Refined sugar is often used as a diluent
for injected drugs, and addicts are reported to
crave sweets and routinely ingest them at the time
of drug injection (Scheutz, 1986b).
Other general dental findings may include:
an increase in bruxism (Christen, 1983; Colon,
1972; Hecht and Friedman, 1949; Davis et al.,
1987; Friedlander et al., 1987), tooth hypersen-
sitivity (Scheutz, 1986a) and necrotizing ulcer-
ative gingivitis in patients undergoing drug with-
drawal (perhaps due to the psychological stress
of withdrawal) (Westerhof et al., 1983). An in-
crease in traumatic injuries to the face, jaws,- and
oral cavity may occur (Ayer and Cutright, 1974;
Scheutz, 1984b), possibly due to the technique
of slapping drug users in an effort to revive those
showing symptoms of overdose.
Drug-addicted dental patients may experi-
ence an inordinate degree of anxiety over dental
treatment, a fear of dental needles, and a low
pain tolerance (Scheutz, 1986a; Martin and In-
glis, 1965). The anxiety and low pain threshold
may relate to general personality traits of addicts,
who are often egocentric, immature, and insecure
(Scheutz, 1986a). Conversely, however, a tol-
erance to local anesthetics and conscious sedation
agents has been found in drug abusers, suggesting
that conventional quantities of local anesthetics
may be insufficient to allow the patient to undergo
a pain-free dental experience (Kimbrough, 1975).
Oral mucosal lesions may be more common
in drug-addicted individuals compared with the
nonaddicted (Scheutz, 1986b). Increased inci-
dence of leukoplakia and leukoedema of the pal-
ate have been described among institutionalized
addicts (Scheutz, 1984b). As previously noted,
however, the majority of drug abusers also use
tobacco regularly and perhaps excessively
(Scheutz, 1986b; Webster et al., 1977; Scheutz,
1984b). Salonen et al. (1990) examined 920
Swedish patients from the general population and
found a positive correlation between tobacco use
and leukoplakia, frictional white lesions, coated
tongue, hairy tongue, and excessive melanin pig-
mentation. Leukoplakia has been found to be
strongly associated with use of smokeless to-
bacco (Grady et at., 1990), and the relationship
of tobacco and alcohol as co-factors in oral, la-
ryngeal, and pharyngeal carcinoma is well es-
tablished (Craig and Friedman, 1986; McMichael
and Puzio, 1988; Barnes and Johnson, 1986;
Brugere et al., 1986; Macgregor, 1989). Smok-
ing has also been correlated with chronic oral
candidiasis and depressed polymorphonuclear
leukocyte chemotaxis and mobility (Macgregor,
1989). The net result is that heavy tobacco use
may contribute to the increase of oral mucosal
lesions reported in substance abusers, and to-
bacco consumption may enhance immune
depression in the drug-addicted population. Life-
style effects of substance abuse were recently
illustrated by a case report describing frostbite of
the oral cavity in an individual attempting to in-
hale an aerosolized propane propellant to achieve
euphoria (Elliott, 1991).
Increased hyperpigmentation of oral tissues
has been reported among parenteral drug abusers,
but a direct correlation has not been established
(Westerhof et al., 1983). There is, however,
presumptive evidence to suggest that lifestyle
factors within the drug community may be at least
partly responsible for such findings. Tobacco
smoking may result in increased gingival pig-
mentation (Amir et al., 1991). Polydrug use of
substances such as barbiturates or meprobamate
may result in fixed drug eruptions with associated
pigmentary incontinence. Use of agents such as
quinine to dilute or cut opiates may have a similar
effect. Oral contraceptives may be used com-
monly among sexually promiscuous female drug
abusers, leading to associated oral melasma
(Granstein and Sober, 1981). Oral melanotic ma-
cules have been described as a feature of HIV
infection, or of its treatment with zidovudine or
other therapeutic drugs (Ficarra et al., 1990; Furth
and Kazakis, 1987; Merenich et al., 1989). Re-
cently, Ficarro et al. (1990) compared HIV sero-
positive patients with a control group of health-
care workers at low risk for AIDS. They found
no significant difference in the incidence of oral
melanotic pigmentation between the two groups,
but progressive and recurrent pigmented lesions
were found exclusively in the HIV-positive
population.
169
VI. SPECIFIC DRUGS OF ABUSE
A. Opiates
Opiate drugs include morphine, heroin, me-
peridine (Demerol), hydromorphone (Dilaudid),
methadone, and codeine. Other nonopiate agents,
such as propoxyphene and pentazocine, may pro-
duce a similar addiction (Jenike, 1991). Opiates
primarily have sedative and analgesic effects on
the central nervous system. Euphoria and relief
from tension may often be the goal of those who
use these drugs excessively, although chronic op-
iate use can be accompanied by increasing
depression (Mirin et al., 1988).
Heroin is a semisynthetic opiate that contin-
ues to be heavily abused in the U.S. It is prepared
by extraction from the poppy (Papaver somni-
ferum) as morphine, then acetylated to diacetyl-
morphine (heroin). The drug is imported into the
U.S. in relatively pure form, then diluted with
various agents, including quinine, powdered milk,
lactose, mannitol, baking soda, or other materials
(The Medical Letter, Inc., 1990). The agent may
be injected intravenously or subcutaneously, and
it may be taken orally or nasally (Westerhof et
al., 1983). Complications include overdose, in-
fective endocarditis and other infections, pul-
monary emboli, fibrosis, and hepatitis or other
liver disorders (Briggs et al., 1967; Black et al.,
1979; Luria et al., 1967). Overdose leads to res-
piratory depression, coma, hypotension, and bra-
dycardia. The overdose can be reversed with nal-
oxone (Narcan) and withdrawal symptoms are
treated with methadone or clonidine (Catapres)
(The Medical Letter, Inc., 1990). Withdrawal
symptoms include severe agitation, but with-
drawal is not considered life threatening, al-
though recidivism is high (Rosenbaum, 1981).
Overdose with other opiates can also be reversed
with naloxone, but propoxyphene (Darvon) and
pentazocine (Talwin) may require considerably
larger dosages (The Medical Letter, Inc., 1990).
Habitual long-term use of heroin may occur
without addiction, but most reports suggest that
approximately 50% of users will become ad-
dicted. As mentioned earlier, the heroin addict
suffers from a marked increase in dental caries
and periodontal disease for a variety of reasons,
including neglect of oral health, failure to seek
170
dental care, malnutrition, intense craving for
sweets, and anxiety regarding dental treatment
(Colon, 1974; Rosenstein, 1975; Shapier et al.,
1970; Yahya and Watson, 1987; Picozzi et al.,
1972).
Shapiro (1971) compared oral health profiles
of active heroin addicts vs. former addicts and
found oral disease to be higher in active addicts,
but not significantly increased. No statistically
significant differences were found between for-
mer addicts and incarcerated nonaddicts, again
suggesting that the lifestyle of the socioecon-
omically disadvantaged leads to increased oral
disease in both addicted and nonaddicted
individuals.
Westerhoff et al. (1983) reported finding hy-
perpigmentation of the tongue with or without
ulceration in 9 of 47 individuals who smoked
heroin and methaqualone and inhaled the vapors.
Histologically, the tongue lesions were consistent
with a fixed drug eruption.
Morphine, a natural opiate, is believed to
depress the body's immune system, which could
at least contribute to the propensity for perio-
dontal disease described in opiate addicts. Mor-
phine primarily affects the cellular immune sys-
tem, and T-cell defects have been associated with
increases in oral fungal and viral infections and
has also been associated with advancing perio-
dontal disease (Kinane et al., 1989).
Opiate withdrawal is usually not life-threat-
ening, unlike withdrawal from substances such
as barbiturates or other sedative hypnotics. With-
drawal signs, however, may provide clues of add-
iction. Early features of heroin or morphine with-
drawal usually begin 8 to 12 h after the last
injection and include sweating, a slightly ele-
vated body temperature, rhinorrhea, lacrimation,
and dilated pupils. Later signs include agitation
with muscular twitching and joint pain, nausea,
vomiting, diarrhea, and tachycardia (Jenike,
1991).
Methadone is often used to detoxify patients
addicted to other opiates. The detoxification pro-
cess in the U.S. must be completed within 21 d,
but methadone maintenance may be continued
following detoxification under special circum-
stances. The drug is taken orally and does not
induce tolerance or known long-term adverse ef-
fects (Jenike, 1991). Some methadone mixtures,
however, contain large quantities of sugar that
may predispose the individual to dental caries
(Scheutz, 1986a; Lewis, 1990; Bigwood and
Coelho, 1990; Hutchinson, 1990).
B. Hallucinogens
Hallucinogens have the capability of distort-
ing perception, leading to difficulty in differen-
tiating reality from the imagined. Tolerance is a
feature of excessive use, but withdrawal symp-
toms do not occur and hallucinogens do not pro-
duce physical dependence. The most commonly
used hallucinogens include lysergic acid diethy-
lamide (LSD), mescaline (peyote), phencyclidine
(PCP), and psilocybin. Dose effect of these drugs
usually lasts from 8 to 12 h. Patients may ex-
perience strong feelings of introspection or de-
personalization, but a toxic psychosis may also
be associated with bizarre behavior, extreme ex-
citement, or panic reaction. On occasion, patients
may require hospitalization for weeks because of
prolonged post-agent psychoses (Jenike, 1991).
C. Cannabis
Cannabis is sometimes classified as a hal-
lucinogenic agent (Rosenbaum, 1981; Nahas,
1986), but a high dosage of the drug is required
to produce that effect. Cannabis (marijuana and
hashish) may be the most frequently used illegal
drug in the U.S. (Nahas, 1986). It is reported
that approximately 60% of Americans have ex-
perimented with the drug and an estimated 20
million use marijuana regularly (Jenike, 1991).
Hashish is prepared by obtaining resin from the
tops of the hemp plant (cannabis sativa), while
marijuana is prepared from the entire plant. Hash-
ish may be from five to ten times more potent as
a euphoric than marijuana (Tennant et al., 1971),
and hashish oil is even more potent (Nahas, 1986).
Cannabis may be smoked as a cigarette or in
a pipe. As many as 2000 metabolites are pro-
duced in the body when cannabis is smoked.
These accumulate in fat, liver, lung, and spleen
and may remain in fat stores for weeks after
ingestion. The primary euphoric found in can-
nabis is A-9-tetrahydrocannabinol (THC), al-
though many other cannabinoids have been iden-
tified, as well as a multitude of other chemical
compounds. The smoke of cannabis may contain
numerous potential carcinogens such as carbon
monoxide, acetaldehyde, toluene, nitrosamine,
naphthalene, benzanthracene, and benzopyrene.
In fact, marijuana may contain twice as many
carcinogens as an equivalent weight of tobacco
(Nahas, 1986).
The effect sought by users of cannabis is
euphoria, producing a state of contentment, loss
of inhibitions, and heightened self-awareness
(Jenike, 1991). Tolerance does not occur in man
with small infrequent doses, but it has been dem-
onstrated with heavy prolonged use of the drug
(Nahas, 1986; Hollister, 1986). Physical depen-
dence may occur with heavy use, although with-
drawal reactions are relatively mild. Neither tol-
erance nor withdrawal are commonly reported
with social use of the drug (Hollister, 1986).
Hollister (1986) has stated that the adverse
effects of cannabis are difficult to determine con-
clusively for several reasons. Animal studies usu-
ally involve the administration of very large
quantities of the drug over short periods of time,
while in humans the use patterns are generally
intermittent and the agent is consumed in rela-
tively low dosages. Additionally, the use of can-
nabis is often combined with tobacco, alcohol,
and a variety of other illegal drugs. Finally, can-
nabis is frequently used by young individuals
who are in relatively good health.
Tennant et al. (1971) studied the effect of
heavy chronic hashish use in a group of 31 sol-
diers. They reported an increased incidence of
bronchial complaints very similar to those found
in tobacco smokers. Rhinopharyngitis was rela-
tively prevalent and, in some incidences, appar-
ently related to a hypersensitivity response to the
drug. Diarrhea and abdominal cramps occurred
in some of the patients. Later reports have con-
firmed respiratory impairment with heavy mari-
juana use. Tachycardia has been described during
intoxication, but to date there is little evidence
to suggest that the cardiovascular system is per-
manently affected (Nahas, 1986). There is, how-
ever, increasing evidence that precancerous
changes may occur within the respiratory tract
and the oral cavity as a result of heavy cannabis
use, especially if the material is used in con-
171
junction with other carcinogenic substances such
as tobacco and alcohol (Nahas, 1986; Donald,
1986).
Cannabis smoking may produce adverse ef-
fects on the brain, resulting in an acute panic
reaction or a toxic psychosis, such as acute par-
anoia, or mania with associated delusions and
hallucinations. A specific cannabis psychosis such
as the amotivational syndrome has not been con-
firmed (Hollister, 1986). Behavioral dysfunction
and psychiatric illnesses are associated with heavy
cannabis use, but it is likely that the mental dis-
turbance precedes the heavy cannabis consump-
tion rather than vice versa (Jenike, 1991; Hollis-
ter, 1986). On occasion, severe dysphoric
reactions to marijuana may be treated with ben-
zodiazepines, but a specific treatment is usually
not required (The Medical Letter, Inc., 1990).
Flashback memories of events associated with
drug use have been described during the non-
drugged state in some cannabis users, although
this phenomenon is more commonly associated
with LSD and related hallucinogens (Hollister,
1986).
Recently, marijuana has been found to be
capable of retarding maturation of monocytes,
perhaps partially explaining its reported ability
to impair immune system functions (Tennant et
al., 1971; Stockwell, 1988). Decreased numbers
of T and B lymphocytes have also been reported,
although these effects appear to be temporary and
reversible after cessation of use of the drug (Ya-
hya and Watson, 1987; Nahas, 1986). The im-
munosuppressive effect of the drug is much more
profound in experimental animals than in man,
and its importance in humans has not been clearly
established (Hollister, 1988).
Cannabis has been used for many centuries
as a therapeutic agent in a variety of disorders
that include neuralgia, postpartum psychosis, and
insomnia. More recently, it has been advocated
as an antiemetic for patients receiving cancer che-
motherapy and to alleviate pain and anxiety in
terminally ill cancer patients. It has also been
demonstrated to reduce intraocular pressure when
topically applied to the eye in treatment of glau-
coma. It is also reported to be of some value in
relief of involuntary muscle spasms and as an
anticonvulsant (Hollister, 1986). A recent case
report offered evidence suggesting that marijuana
172
use may ameliorate ulcerative colitis, although
the mechanism of action is not clear (Baron et
al., 1990).
Adverse effects of cannabis on the oral cavity
have been reported, but not studied extensively
under experimental conditions. Several reports
have identified xerostomia as a possible physi-
ologic effect of heavy use (Di Cugno et al., 1981;
Valentine et al., 1985). Warnock and Shalla
(1975) described a shift toward an immature ep-
ithelial cell type on the tongue and palate of heavy
marijuana smokers. Edema and erythema of the
uvula have been reported with heavy use of hash-
ish (Schwartz, 1984). All of these changes may
relate to the fact that cannabis burns at a higher
temperature than tobacco and is, therefore, po-
tentially even more irritating to oral mucosa.
Gingival enlargement resembling phenytoin-
induced gingival hyperplasia has been reported
in conjunction with heavy cannabis use (Baddour
et al., 1984; Layman, 1978). This may be ac-
companied by gingivitis and alveolar bone loss.
Leukoplakia also was reported as a common fea-
ture of heavy marijuana use by the same authors.
Colon (1980) described frequent occurrence of
oral papillomas in three groups of incarcerated
patients who were heavy marijuana users and
who displayed poor oral hygiene. Lesions were
located in unusual oral sites, such as lingual gin-
giva, which are not normally exposed to exten-
sive trauma or chronic irritation. Oral leuko-
edema and occasional hyperkeratosis has also been
described in conjunction with marijuana smoking
(Baddour et al., 1984).
Donald (1986) recently offered clinical evi-
dence associating heavy marijuana use with an
increased incidence of squamous cell carcinoma.
He attributed this to the epithelial changes as-
sociated with the drug (Warnock and Shalla, 1975)
and the potential carcinogens found in marijuana
smoke.
Silverstein et al. (1978) detected a higher
incidence of caries and periodontal disease in
individuals who were heavy users of marijuana,
assumably as a result of the lifestyle effects of
habitual drug abuse (Silverstein et al., 1978; Pal-
lasch and Joseph, 1987).
Horowitz and Nersasian (1978) reviewed the
pharmacological action of marijuana in relation
to therapeutic drugs used in dentistry. They con-
cluded that the sympathomimetic effects of mari-
juana might be synergistically enhanced by
administration of local anesthetics containing
epinephrine or by the use of gingival retraction
cord containing epinephrine. The tachycardia and
peripheral vasodilation associated with acute
marijuana toxicity could be enhanced and even
reach life-threatening levels if epinephrine is used
and anxiety could be significantly elevated. The
authors concluded that dental patients who use
marijuana heavily should be advised to discon-
tinue use for at least 1 week before dental
treatment.
D. Cocaine
Cocaine is an ancient drug, and evidence has
been found of its use before the beginning of
recorded history. The coca leaf was apparently
chewed for its euphoric effect, but the drug also
played a role in religious ceremonies among In-
dian cultures in Peru and other countries and it
may have served as a general anesthetic for early
surgical procedures. Through the centuries, its
use increased and today millions of people are
addicted to chewing the coca leaf (Hamner and
Villegas, 1969; Cregler and Mark, 1986).
Cocaine is a hydrochloride salt extract of the
coca leaf. Sigmund Freud, among others, pop-
ularized its medical use in the treatment of a
variety of illnesses and as a local anesthetic (Gar-
giulo et al., 1985; Lee et al., 1991). It was also
used to treat alcoholism and opiate addiction
(Gargiulo et al., 1985; Friedlander and Gorelick,
1988; Lee et al., 1991). Ultimately, the highly
addictive properties of the drug were recognized
and it became illegal in the U.S. in 1914 (Lee et
al., 1991).
Since the 1950s, cocaine has been primarily
abused by individuals of middle to upper soci-
oeconomic class who could afford the high cost
of the agent (Washton et al., 1983). It is available
as a white crystalline powder, which can be taken
orally, intranasally, vaginally, rectally, or in-
jected subcutaneously or intravenously (Cregler
and Mark, 1986). Beginning in 1986, however,
a technique was developed allowing the material
to be prepared in solid form (crack) and smoked.
Subsequently, the substance became available to
drug users of all socioeconomic levels. It is es-
timated that as many as 30 million Americans
have used cocaine since 1986 (Lee et al., 1991).
Cocaine is a euphoric, capable of producing
hallucinations and enhanced feelings of mental
and physical prowess. The drug is rapidly ab-
sorbed when smoked or injected intravenously,
creating an intense euphoria and the potential for
rapid tolerance. There is an increased risk for
toxicity and a powerful addiction to crack (Jen-
ike, 1991; Lee et al., 1991).
Cocaine abuse may result in severe psycho-
pathologic effects such as delirium, paranoia,
anxiety or depression, schizophrenia, or mania
(cocaine psychosis) (Friedlander and Gorelick,
1988). Toxicity may produce anxiety, convul-
sions, hypertension, cardiac erythema, and ele-
vated body temperature (Friedlander and Gore-
lick, 1988; Jenike, 1991; Cregler and Mark, 1986;
Pastemack et al., 1985; Pallasch et al., 1989;
Lee et al., 1991; Leary and Johnson, 1987).
Atypical angina, myocardial ischemia, infarc-
tion, and death may occur (Cregler and Mark,
1986; Cregler and Mark, 1985; Mathias, 1986).
Withdrawal may feature severe depression mixed
with irritability and anxiety (Jenike, 1991).
Snorting of cocaine powder intranasally often
results in irritation of the nasal mucosa, causing
sneezing, sniffing, rhinitis, and ulceration or per-
foration of the nasal septum following heavy long-
term use (Lee et al., 1991).
Cocaine has been demonstrated in vitro to
depress the immune response with very high con-
centrations of drug, but in vivo studies are con-
flicting, some indicating immune suppression
while others show stimulation of the immune sys-
tem or no effect under various experimental cir-
cumstances. Neurohumoral alterations of im-
munity, however, have been confirmed (Watzl
and Watson, 1990). The greatest risk of infection
appears to be the potential for transmission of
HIV and other agents through i.v. administration.
Chronic long-term cocaine abuse is associ-
ated with the lifestyle-related oral conditions de-
scribed previously. Friedlander and Gorelick
(1988) indicated that cocaine intoxication may be
associated with cervical abrasion of teeth and
gingival laceration due to overly vigorous tooth
brushing and flossing while "high". Severe
bruxism and flattened cuspal inclines may also
be more common among cocaine addicts, accom-
173
panied by increased frequency of temporoman-
dibular joint disorders. The authors, however,
offered no experimental evidence to support these
impressions.
In a recent case report, Leary and Johnson
(1987) described severe dental erosion of occlu-
sal and cervical surfaces of posterior teeth ac-
companied by masticatory muscular tenderness,
temporomandibular joint clicking, and hypersen-
sitivity of the involved dentition. The patient was
ultimately diagnosed as an abuser of cocaine and
other drugs, having applied nitric acid to his teeth
during the manic phase of a psychopathologic
disorder in an effort to stop "voices" emitting
from his teeth.
Occasionally, cocaine users rub the drug on
the gingiva or oral mucosa either to obtain relief
from oral discomfort by taking advantage of co-
caine's local anesthetic effects or to test the drug's
purity by its ability to produce gingival numbness
(Waterson, 1983). This method is also used to
absorb the drug without adverse intranasal ef-
fects. It has been reported to occasionally result
in the development of grossly inflamed, pro-
fusely bleeding gingiva associated with epithelial
desquamation (Gargiulo et al., 1985; Dello Russo
and Temple, 1982). Yukna (1991) presented a
series of case reports describing gingival and al-
veolar bone damage due to chronic gingival ap-
plication of cocaine. Gargiulo et al. (1985) stud-
ied histologic specimens of such a lesion and
noted superficial vasculitis and necrosis in in-
volved areas, suggesting an ischemic effect from
the vasoconstricting action of the cocaine.
Addicts who chew coca leaves often mix the
leaf with slaked lime (calcium hydroxide) prior
to use. The leaf wad is then chewed for 2 to 3
h. This technique is reported to be frequently
associated with glossitis and leukoedema of the
buccal mucosal on the side where the wad is held
while being chewed. No evidence of epithelial
dysplasia or malignancy was found, however, in
a review of 46 buccal biopsies obtained from coca
leaf chewers unless the individual was also using
alcohol and tobacco (Hamner and Villegas, 1969).
E. Amphetamines and Related
Compounds
Stimulants such as amphetamines are sym-
pathomimetic agents that induce tachycardia, va-
174
soconstriction, and elevated blood pressure. Lo-
cal or systemic vasculitis and renal failure have
been reported (Jenike, 1991). Most stimulants in
this class are prescription drugs, yet they are fre-
quently abused because they cause a sense of
well-being, combat sleepiness, suppress appetite,
and are relatively easy to obtain. Tolerance de-
velops with reasonable rapidity. Drugs in this
category include dextroamphetamine (dexed-
rine), methamphetamine, phentermine, phen-
metrazine, phenylpropanolamine, methylpheni-
date, prophylhexedrine, and ephedrine (Jenike,
1991; The Medical Letter, Inc., 1990). The drugs
are usually swallowed or injected intravenously,
but one solid form, d-methamphetamine (ice,
crystal), can be smoked. Phenylpropanolamine
is often found in over-the-counter medications
(The Medical Letter, Inc., 1990). 3,4-Methyle-
nedioxymethamphetamine (MDMA, ecstasy,
XTC, Adam) is an underground amphetamine
derivative that is highly toxic (Davis et al., 1987).
Acute overdose of stimulants may feature severe
hyperthermia, hypertension, tachycardia, and oc-
casionally refractory shock and death. Bruxism
and increased muscle tension are noted frequently
(Davis et al., 1987).
Symptoms of intoxication may include head-
ache, nausea, tremor of extremities, anorexia,
and dilated pupils. Physical withdrawal is not
difficult, but profound psychologic dependence
may develop. Patients may become anxious, ex-
tremely labile, and paranoid during withdrawal.
Benzodiazepines, haloperidol, or propranolol may
be used during withdrawal. A long-lasting post-
withdrawal depression may occur that requires
treatment with antidepressants (Jenike, 1991).
Any of the above-mentioned therapeutic agents
may be associated with severe oral xerostomia.
F. Alcohol
Alcoholism is chronic, progressive, and po-
tentially fatal. Tolerance and physical depend-
ency develop and pathologic organ changes may
occur as a direct or indirect consequence of al-
cohol ingestion (Christen, 1983; Friedlander et
al., 1987).
Although ethyl alcohol is not an illicit drug,
it is the most widely used mood-altering sub-
stance in the U.S., Europe, and much of the
world (Christen, 1983). Additionally, it is fre-
quently used by those who abuse illicit drugs;
alcohol, along with tobacco, may often play a
significant role in the development of adverse
medical and dental effects among drug abusers
(Council on Dental Practice, 1987).
As many as 100 million Americans over the
age of 15 regularly use alcohol, and an estimated
12 million are alcohol abusers (Council on Dental
Practice, 1987; Christen, 1983). Alcohol is being
consumed with increasing frequency by children
and young teenagers (Christen, 1983).
Unlike users of many of the illicit drugs of
abuse, alcoholics are found in all socioeconomic
and educational strata. For example, alcohol abuse
is reported to be very common among the Ab-
origines of Australia, a group of low socioeco-
nomic status, yet the condition is only somewhat
less frequent in the general population of Aus-
trialia (Thomson, 1984).
As a socially accepted mood-altering sub-
stance, ethyl alcohol has been used throughout
history for a variety of religious, societal, and
medicinal purposes. Alcohol is classified as a
central nervous system depressant, although in-
itially, and in smaller quantities, it has a transient
stimulatory effect (Christen, 1983).
Considerable controversy exists regarding
factors that lead to alcoholism. At present, it
appears that a complicated combination of phys-
iological and psychological factors interact to
produce a compulsion to ingest excessive amounts
of the substance. There is strong evidence that
genetic factors have a role in alcoholism. Alco-
holism tends to run in families, while other types
of mental illnesses are no more common in fam-
ilies of alcoholics than in the general population
(Tabakoff and Hoffman, 1988). A family tend-
ency to alcoholism could reflect environmental
influences conducive to alcohol ingestion, but
studies on adopted siblings and twins confirm that
identical twins demonstrate a higher concordance
rate for alcoholism than fraternal twins. Genetic
factors seem to play a role in individual responses
to alcohol, alcohol metabolism, and drinking pat-
terns (Tabakoff and Hoffman, 1988).
As mentioned earlier, drug abusers also tend
to come from families with a high rate of alco-
holism (Mirin et al., 1988), while in many in-
stances alcoholics with or without a family his-
tory of the disease may manifest a primary
psychiatric disorder. This suggests a synergism
between the genetic trait and psychiatric factors.
In a recent review, West et al. (1986) noted that
at least four studies strongly support a relation-
ship between loneliness and depression and al-
coholism. Evidence of a genetically derived tend-
ency to alcoholism has led to a search for
physiological and biochemical markers that will
be predictive of the tendency. Some evidence
links low levels of monoamine oxidase (MAO)
and high blood levels of alanine transferase with
alcoholic vulnerability. Liver enzymes such as
alkaline phosphatase, aspartate aminotransferase
(AST), alanine aminotransferase (ALT), and
gamma glutamyl transferase (GGT) may be el-
evated in habitual problem drinkers with liver
disease (Watson et al., 1986). Although such
results are promising, to date no clearly distinc-
tive biological markers have been identified (Ta-
bakoff and Hoffman, 1988).
Other biologic factors tend to correlate with
the genetic risk of alcoholism. High genetic risk
individuals, for example, appear to have an in-
nate tolerance to the substance and demonstrate
less effect at ingestion levels that may be intox-
icating for those who are not genetically at risk.
Encephalographic changes are sometimes noted
in alcoholics, suggesting altered neurotransmitter
responses in the brain (Tabakoff and Hoffman,
1988).
Duggan et al. (1991) recently reported suc-
cessful identification of alcoholism in families of
hospitalized children by using a questionnaire re-
garding family demographics and questions con-
cerning alcohol use. They found evidence of al-
coholism in 15% of the 147 families studied and
the families were distributed among all socio-
economic and demographic strata. Pediatricians
had failed to recognize any but one of the alcohol-
dependent families, suggesting that all families
must be screened if those with problems with
alcohol are to be identified. This information of-
fers the hope that an effective screening mech-
anism for detection of alcoholics can be devel-
oped for clinical use in medicine and dentistry
(Duggan et al., 1991; Graham, 1991; Mac-
Donald, 1991).
Many studies affirm a relationship between
excessive alcohol consumption and medical dis-
orders. The fetal alcohol syndrome is found in
175
the offspring of mothers who consume relatively
large quantities of alcohol during pregnancy. This
condition features fetal changes that include
growth retardation, facial abnormalities, and
mental retardation, but even moderate alcohol
consumption during pregnancy is associated with
fetal effects such as low birth weight, especially
if the mother also smoked cigarettes (Wright et
al., 1983).
Chronic alcohol abuse has many metabolic
effects. Ethyl alcohol is principally metabolized
in the liver by means of a variety of pathways,
including (1) ethanol dehydrogenase that con-
verts ethanol to acetaldehyde, (2) the microsomal
ethanol oxidating system that affects lipid me-
tabolism, and (3) the catalase system that oxy-
genizes ethanol in the presence of hydrogen per-
oxide (Girard et al., 1987). The microsomal
alterations in the microsomal ethanol-oxygenat-
ing system associated with chronic use leads to
enhanced metabolism of other drugs. This may
explain the increased tolerance noted in alcohol-
ics for local anesthetics and other drugs (Lieber,
1987). There is also an increased conversion of
prescription drugs into potential hepatotoxins or
carcinogenic agents. Meanwhile, acute ethanol
ingestion may be associated with metabolic in-
hibition of some drugs, increasing blood levels
of drugs and the risk of toxic effects (Lieber,
1987; Kumar and Rex, 1991).
The sinusoidal cells that filter blood in the
liver are adversely affected by alcohol ingestion,
perhaps contributing to the accumulation of fat
in the liver (Fraser et al., 1986). Phagocytosis is
decreased in the liver, altering the host resistance
to viral infection and perhaps predisposing the
alcoholic to viral hepatitis.
Liver dysfunction may affect clearance of
very low-density serum lipoproteins, putting the
patient at an increased risk for cardiovascular
disease (Girard et al., 1987). Folate deficiency
and other nutritional disorders may occur, such
as defects in storage of vitamin B12 and mega-
loblastic or hemolytic anemia (Girard et al., 1987;
Lindenbaum, 1987). Iron deficiency anemia may
occur due to gastrointestinal bleeding, but serum
iron levels are more often elevated (Lindenbaum,
1987). Meanwhile, toxic effects of alcoholism
result in damage to bone marrow hematopoietic
precursor cells. Platelet function and numbers are
176
diminished (Lindenbaum, 1987, Javors and
Bowden, 1987, Mikhailidis et al., 1990, Ballard,
1989) and white blood cell abnormalities result,
including leukopenia and altered polymorphonu-
clear neutrophilic migration. Circulatory lym-
phocytes are diminished in number and macro-
phage killing may be diminished (Girard et al.,
1987; Lindenbaum, 1987; Ballard, 1989; Mufti
et al., 1989). The cumulative results of these
hematologic disruptions include hemorrhagic
complications associated with delayed coagula-
tion, an increased tendency to cardiovascular
thrombosis and altered response to infection (Gir-
ard et al., 1987; Ballard, 1989).
Diseases of the skin have been associated
with alcoholism by case reports, but there is little
evidence of specific cutaneous signs associated
with alcohol ingestion. The cutaneous effects of
alcohol-related liver disease, alcohol-induced nu-
tritional deficiency, and alcohol-related meta-
bolic disturbances are, however, fairly well es-
tablished (Shellow, 1983). Spider angiomata are
prominently dilated subcutaneous arterioles that
may appear on the face of individuals with al-
coholic liver dysfunction. Small pinpoint to pea-
sized white spots may also occur, reflecting a
neurovascular dysfunction related to spider
angiomata.
Acnea rosacea does not occur exclusively in
patients with alcoholic liver disease, but it is
commonly associated with that disorder. The
condition manifests as a flushing or rubefacience
of the skin, usually in the center of the face and
often affecting the nose, creating a bulbous,
flushed condition known as rhinophyma (Rees,
1980). Hepatic disease may be associated with
jaundice or a dirty, gray pigmentation of skin
known as biliary melanoderma that is associated
with liver cirrhosis (Shellow, 1983).
Nutritional deficiencies occur in alcoholic
patients for a variety of reasons. Metabolic de-
mands are increased with alcohol consumption,
but anorexia may be a feature of the disease.
Gastrointestinal inflammation caused by alcohol
may lead to iron loss from internal bleeding. Con-
versely, iron levels sometimes increase in alco-
holics due to ingestion of beer and wine or the
exaggerated absorption of ferric iron caused by
the action of alcohol on gastric mucosa. Absorp-
tion of nutrients is often impaired, however, and
as mentioned earlier, metabolism in the liver may
be disrupted. Chronic pancreatitis occasionally
occurs in association with low intake of protein,
fat, and carbohydrate. Trace metals may be de-
ficient, including zinc, selenium, and magne-
sium. These deficiencies may adversely affect
immune function (Dunne, 1989; Alcock, 1990;
Davis, 1986; Christen, 1983).
The milieu of disorders associated with al-
coholism results in significantly altered host re-
sistance and predisposes patients to general and
oral infections. It is also possible that alcohol-
induced immune suppression may accelerate the
progress of disorders such as AIDS, diabetes mel-
litus, malignancy, and many others (Dunne,
1989).
Alcohol consumption may affect most cells
of the body, making tissues more sensitive to
carcinogens by increasing the permeability of cell
membranes (Mufti et al., 1989). Oral epithelial
cells have been demonstrated to atrophy in ani-
mals subjected to large quantities of ethanol. Basal
cell pleomorphism occurs and there is a tendency
toward epithelial dysplasia. Valentine et al. (1985)
studied tongue biopsies in humans who ingested
known levels of alcohol and tobacco. In high
alcohol and tobacco users, the lingual epithelium
was thinner and the basal cell layer was hyper-
trophied. These changes occurred in the absence
of clinically visible tissue damage. Information
such as this, coupled with the nutritional defi-
ciencies and liver diseases commonly found in
alcoholics, may signify that the host immune de-
fenses are suppressed, while simultaneously oral
epithelium is structurally altered. This may ren-
der the individual or animal far more susceptible
to malignancy.
A direct relationship has been demonstrated
between oropharyngeal cancer and alcohol con-
sumption coupled with tobacco smoking (Chris-
ten, 1983; Craig and Triedman, 1986; Mc-
Michael and Puzio, 1988; Brugere et al., 1986).
Ethyl alcohol may be a cancer promoter capable
of causing chemical irritation and increased ab-
sorption of carcinogens dissolved in the alcohol.
For example, beer and wine may contain a larger
quantity of carcinogenic contaminants and they
are more closely associated with oral malignancy
than whiskey, although some brands of Scotch
whiskey have been found to contain trace amounts
of the carcinogen N-nitrosodimethylamine
(Baden, 1987).
Recently, Bergler et al. (1989) examined oral
mucosal tissue samples for expression of epithe-
lial growth factors. They compared tissue from
patients with oral squamous cell carcinoma against
samples of tissue from patients who heavily used
alcohol and tobacco, but who had no tumors.
Tumor-free nonsmokers and nondrinkers acted
as controls. The authors found significantly in-
creased levels of epidermal growth factor expres-
sion in both experimental groups vs. controls.
This suggests that chronic irritation with agents
such as tobacco and alcohol may stimulate cel-
lular proliferation and that such proliferation may
be associated with oral malignant transformation.
Oral changes include desiccation and inflam-
mation of the mucosa, producing a magenta dis-
coloration. This may be associated with the drying
effect of alcohol with concomitant nutritional de-
ficiencies or with candidiasis (Shellow, 1983;
Rees, 1980). Salivary gland function may be im-
paired in alcoholics and asymptomatic enlarge-
ment of the parotid glands and, occasionally, the
submandibular gland occur (Christen, 1983). In-
itially, high concentrations of alcohol are asso-
ciated with increased salivary flow, but, ulti-
mately, fatty degeneration of the salivary glands
may take place for unexplained reasons, leading
to xerostomia.
It is highly likely that the cellular changes
associated with the nutritional and metabolic ef-
fects of alcoholism may predispose alcoholics to
more rapidly destructive periodontal disease, but
this has not been proven or adequately studied.
Increased incidence of dental caries, periodontal
disease, and tooth loss has been described (Chris-
ten, 1983; Friedlander et al., 1987; Kranzler et
al., 1990), however, especially in males, al-
though Kranzler et al. (1990) found no associ-
ation between alcohol consumption and oral hy-
giene effectiveness.
The incidence of dental attrition is increased
secondary to an increased tendency to bruxism,
especially during sleep (Christen, 1983; Fried-
lander et al., 1987).
Increased incidence of craniofacial trauma
and reduced responsiveness to local anesthetics
occur as described previously for other drug abu-
sers, and alcoholic patients may require larger
17-7
quantities of general anesthesia to induce sleep.
Ultimately, however, the central nervous system
depressant effects of general anesthesia may be
more profound in the alcoholic patient (Grady et
al., 1990). Increased tolerance to other drugs
such as the diazepines may occur, while drug
metabolism may be increased in alcoholic pa-
tients free of liver disease and decreased in those
with liver disorders. Alcoholic patients may be
particularly prone to postoperative bleeding
diatheses, delayed wound healing, and postop-
erative infections (Friedlander et al., 1987).
G. Nicotine
Recent evidence has confmned that tobacco
(nicotine) should be classified as a drug of abuse.
Nicotine stimulates the release of dopamine in
the brain and may affect the neuroendocrine sys-
tem in a manner similar to cocaine, heroin, or
other addictive drugs. Nicotine generates toler-
ance and withdrawal symptoms, and it may serve
as the initial drug of abuse in addicted individ-
uals. The adverse effects of tobacco on the oral
cavity have been reviewed recently (Christen et
al., 1991) and, therefore, will not be included in
this review.
VIl. DENTAL MANAGEMENT
Dental management of the addicted patient
is predicated on the clinician being aware of the
possibility of substance abuse in the American
population. In many instances, the patient may
be able to mask the addiction (Council on Dental
Practice, 1987), but the alert practitioner may
sometimes detect the previously described signs
and symptoms. Williamson and Davis (1973)
identified general symptoms of abuse as marked
anxiety, multiple physical complaints, depres-
sion, obsessive thoughts, belligerent behavior,
paranoia, obesity, suicidal thoughts, and bizarre
appearance or dress. These symptoms, of course,
may also be reflective of a nondrug-related psy-
chosis, but they are indications that medical con-
sultation may be necessary.
The health questionnaire and follow-up ver-
bal questioning should provide the patient with
178
the opportunity to indicate an existing drug prob-
lem. It is certainly proper to question the patient
about past and current use of drugs. If drug use
is acknowledged, what is the substance being
used? What is the quantity and is it being used
currently? Close medical/dental coordination is
imperative in the known or suspected drug abuser
(Friedlander and Mills, 1985).
Scheutz (1986a) has demonstrated that par-
enteral drug abusers are more anxious than the
general population and more fearful of dental
treatment. On occasion, addictive patients may
use their drug of preference prior to a dental
appointment to alleviate their anxiety. If this
should occur, the dental treatment should be post-
poned. If patients are receiving methadone main-
tenance, it is probably best to continue regular
administration of the methadone throughout den-
tal treatment to avoid development of withdrawal
symptoms (Jenike, 1991).
Parenteral drug abusers may experience a re-
duced response to local anesthetics (Friedlander
and Mills, 1985; Bigwood and Coelho, 1990) and
significantly larger amounts of anesthetics may
be required to provide pain-free dental therapy
(Council on Dental Practice, 1987; Kimbrough,
1975; Splaver and Williams, 1970). Parenteral
abusers are also more prone to oral infections
(Lewis, 1990).
Dental management of the cocaine-addicted
patient may prove frustrating because of the tend-
ency to recurrent caries and periodontal disease
associated with any drug abuse. Management
should be directed toward avoidance of a medical
emergency in the dental office. Addicts may have
a tendency to premedicate themselves with co-
caine prior to dental appointments to reduce their
anxiety. Therefore, careful observation of the pa-
tient is necessary to detect symptoms of intoxi-
cation. General anesthesia should be avoided and
local anesthetics containing epinephrine should
be used with caution to prevent enhancement of
sympathomimetic effects of the drug. A special
concern, of course, is the avoidance of a cardi-
ovascular crisis featuring tachycardia and myo-
cardial ischemia (Friedlander and Gorelick, 1988;
Lee et al., 1991; Chiodo and Rosenstein, 1986;
Isaacs et al., 1987). Pallasch et al. (1989) sug-
gested medical consultations be considered for
cocaine-addicted patients. They advocated con-
scious sedation plus local anesthesia for dental
procedures. Benzodiazepines would be the ther-
apeutic choice for sedation since these agents are
used in treatment of cocaine toxicity. Patients
under treatment should be carefully monitored
for changes in vital signs.
In most instances, elective surgical proce-
dures should be avoided in the alcoholic patient.
If surgery is necessary, however, or if the patient
is only suspected of alcohol abuse, the dentist
should consider the use of screening blood tests
prior to the procedure. The following tests have
been recommended: complete blood count with
differential and platelet count, prothrombin time
(PI), partial thromboplastin time (PTT), and se-
quential multiple analysis (SMA) to include total
protein, albumin, and liver transaminases such
as AST, ALT, and GGT. Of the transaminases,
GTT may be the most sensitive indicator of liver
dysfunction associated with alcohol abuse (Fried-
lander et al., 1987). Patients with blood test ab-
normalities should be referred to their physician
for appropriate evaluation and treatment prior to
performing extensive dental procedures (Rees,
1980).
Dental treatment is no different in the ad-
dicted patient than in the nonaddicted (William-
son and Davis, 1973). Postoperative pain med-
ication should be avoided, however, when
possible. If pain medication is necessary, aspirin,
acetaminophen, or a nonsteroidal antiinflamma-
tory agent such as ibuprofen is preferred (Council
on Dental Practice, 1987). These drugs may be
contraindicated, however, if the patient is ex-
periencing complications such as gastrointestinal
disorders, liver dysfunction, or a blood dyscrasia.
If pain medication is required, only the minimal
amount necessary should be prescribed and the
patient monitored carefully during use. If pain is
relatively severe, a mild narcotic such as codeine
may be necessary (Splaver and Williams, 1970).
If so, medication should be controlled, if pos-
sible, by a reliable family member or friend to
minimize the chance of abuse (Council on Dental
Practice, 1987).
Intravenous sedation and nitrous oxide oxy-
gen sedation should probably be avoided due to
the potential for cardiovascular or respiratory de-
pression in drug or alcohol abusers (Friedlander
and Mills, 1985; Kimbrough, 1975; Splaver and
Williams, 1970; Henry et al., 1990; Miers and
Smith, 1989). Nitrous oxide oxygen itself is a
mood-altering inhalant capable of being abused,
especially by dentists and others with access to
the necessary equipment (Sterman and Coyle,
1983).
Addicted patients may experience xerosto-
mia as a feature of their drug abuse. Conse-
quently, mouth rinses containing alcohol should
be avoided or only minimally prescribed. Use of
a mouth rinse with high alcohol content might
even precipitate relapse into alcohol abuse in the
abstaining polydrug abuser. It should also be noted
that some evidence exists to suggest an increased
risk of oral malignancy in association with long-
term use of mouth rinses with high alcohol con-
tent (Winn et al., 1991).
The parenteral drug abuser may be suffering
from undiagnosed HBV or HIV infection or be
potentially susceptible to development of infec-
tive endocarditis in the event dental treatment
induces a bacteremia. Wound healing may be
markedly retarded and patients may be especially
prone to infection. All of these factors must be
taken under consideration, but it is incorrect to
assume that drug-dependent patients are unman-
ageable. A basic knowledge of symptomatology
coupled with close medical/dental cooperation and
consideration of the patient's health status can
result in successful dental therapy without undue
stress or risk to the addicted or abstaining drug
abuser (Williamson and Davis, 1973).
REFERENCES
Alcock, N. W.: Vitamin and trace metal disturbances in
alcoholism: potential effects of the immune system. Prog.
Clin. Biol. Res. 325:419-432 (1990).
Amir, E., M. Gorsky, A. Buchner, H. Samat, and H. Gat:
Physiologic pigmentation of the oral mucosa in Israeli
children. Oral Surg. Oral Med. Oral Pathol. 71:396-
398 (1991).
Ayer, W. A. and D. E. Cutright: Dental treatment and heart
valve complications in narcotic addicts. Oral Surg. Oral
Med. Oral Pathol. 37(3):359-363 (1974).
Baddour, H. M., T. B. Audemorte, and F. D. Layman:
The occurrence of diffuse gingival hyperplasia in a patient
using marijuana. J. Tenn. Dent. Assoc. :39-43 (1984).
Baden, E.: Prevention of cancer of the oral cavity and phar-
ynx, CA: Cancer J. Clin. 37(1):49-47 (1987).
179
Ballard, H. S.: Hematological complications of alcoholism.
Alcoholism: Clin. Exp. Res. 13(5):706-720 (1989).
Bancroft, W. H., R. Snitbhan, R. M. Scott, M.
Tingpalapong, W. T. Watson, P. Tanticharoenyos, J. J.
Karwacki and S. Srimarut: Transmission of hepatitis B
virus to Gibbons by exposure to human saliva containing
hepatitis B surface antigen. J. Infect. Dis. 135(1):79-
85 (1977).
Barnes, L. and J. T. Johnson: Pathologic and clinical
considerations in the evaluation of major head and neck
specimens resected for cancer, Part 1. Pathol. Annu.
21:173-250 (1986).
Baron, J. A., R. D. Folan, and M. L. Kelley, Jr.: Ulcerative
colitis and marijuana. Ann. Intern. Med. 112(6):471
(1990).
Barone, R., G. Ficarra, D. Gaglioti, A. Orsi, and F.
Mazzotta: Prevalence of oral lesions among HIV-infected
intravenous drug abusers and other risk groups. Oral
Surg. Oral Med. Oral Pathol. 69:169-173 (1990).
Bergler, W., H. Bier, and U. Ganzer: The expression of
epidermal growth factor receptors in the oral mucosa of
patients with oral cancer. Arch. Otorhinolaryngol.
246:121-125 (1989).
Bigwood, C. S. and A. J. Coelho: Methadone and caries.
Br. Dent. J. 168:231 (1990).
Blanck, R. R., N. Ream, and M. Conrad: Hepatitis B antigen
and antibody in heroin users. Am. J. Gastroenterol.
71(2):164-167 (1979).
Bortolotti, F., A. Bertaggia, P. Cadrobbi, C. Crivellaro, E.
Pomaro, and G. Realdi: Epidemiological aspects of acute
viral hepatitis in drug abusers. Infection. 10(5):277-279
(1982).
Briggs, J. H., C. G. McKerron, R. L. Souhamai, D. J. E.
Taylor, and H. Andrews: Severe systemic infections
complicating "mainline" heroin addiction. Lancet.
1I:1227-1231 (1967).
Brugere, J., P. Guenel, A. Leclerc, and J. Rodriguez:
Differential effects of tobacco and alcohol in cancer of
the larynx, pharynx, and mouth. Cancer. 57:391-395
(1986).
Carter, E. F.: Dental implications of narcotic addiction.
Aust. Dent. J. 23(4):308-310 (1978).
Centers for Disease Control: Changing patterns of groups
at high risk for hepatitis B in the United States. MMWR.
37(28):429-437 (1988).
Charlesworth, E. A. and G. Dempsey: Trait anxiety
reductions in a substance abuse population trained in
stress management. J. Clin. Psychol. 38(4):764-768
(1982).
Cherubin, C. E., R. A. Schaefer, W. S. Rosenthal, T.
McGinn, F. Forte, R. Purcell, and P. Walmsley: The
natural history of liver disease in former drug users. Am.
J. Med. Sci. 272(3):244-253 (1976).
Chiodo, G. T. and D. I. Rosenstein: Cocaine use and dental
treatment. Gen. Dent. 34:218-219 (1986).
Christen, A. G.: Dentistry and the alcoholic patient. Dent.
Clin. North Am. 27(2):341-361 (1983).
Christen, A. G., J. L. McDonald, Jr. and J. A. Christen:
The impact of tobacco use and cessation of nonmalignant
180
and precancerous oral and dental diseases and condi-
tions, Monograph, Indiana University School of Den-
tistry, 1-73 (1991).
Colon, P. G.: Oral papilloma in marijuana users. Quin-
tessence Int. 11(1):75-80 (1980).
Colon, P. G., Jr.: The effects of heroin addiction on teeth.
J. Psychedelic Drugs. 6(1):57-60 (1974).
Colon, P. G., Jr.: Dental disease in the narcotic addict. Oral
Surg. 33(6):905-910 (1972).
Council on Dental Practice: Chemical dependency and dental
practice. J. Am. Dent. Assoc. 114:509-515 (1987).
Craig, D. M. and L. J. Triedman: Four primary malignant
neoplasms in a single patient. J. Surg. Oncol. 32:8-10
(1986).
Cregler, L. L. and H. Mark: Relation to acute myocardial
infarction to cocaine abuse. Am. J. Cardiol. 56(12):794-
795 (1985).
Cregler, L. L. and H. Mark: Special report, medical
complications of cocaine abuse. N. Engl. J. Med.
315(23):1495-1500 (1986).
Davis, C. L., M. Towns, W. L. Henrich, and K. Melby:
Neisseria mucosus endocarditis following drug abuse.
Arch. Intern. Med. 143:583-585 (1983).
Davis, R. E.: Clinical chemistry of folic acid, Adv. Clin.
Chem. 25:233-294 (1986).
Davis, R. K. and P. N. Baer: Necrotizing ulcerative gingivitis
in drug addict patients being withdrawn from drugs. Oral
Surg. Oral Med. Oral Pathol. 31(2):200-204 (1971).
Davis, W. M., H. T. Hatoum, and I. W. Waters: Minireview,
toxicity of MDA (3,4-methylenedioxyamphetamine)
considered for relevance to hazards of MDMA (ecstasy)
abuse. Alcohol Drug Res. 7:123-134 (1987).
De Cock, K. M., S. Govindarajan, K. P. Chin, and A. G.
Redeker: Delta hepatitis in the Los Angeles area: a report
of 126 cases. Ann. Intern. Med. 105(1):108-114 (1986).
De Leon, G. and N. Jainchill: Male and female drug abusers:
social and psychological status 2 years after treatment
in a therapeutic community. Am. J. Drug Alcohol Abuse.
8(4):465-497 (1981).
De Leon, G., A. Skodol, and M. S. Rosenthal: Pheonix
House, changes in psychopathological signs of resident
drug addicts. Arch. Gen. Psychiatry. 28:131-135 (1973).
Dello Russo, N. M. and H. V. Temple: Cocaine effects on
gingiva. J. Am. Dent. Assoc. Letters to the Editor, 104:13
(1982).
Di Cugno, F., C. J. Perec, and A. A. Tocci: Salivary secretion
and dental caries experience in drug addicts. Arch. Oral
Biol. 26:363-367 (1981).
Donahoe, R.: Opiates as immunocompromising drugs: the
evidence and possible mechanisms. NIDA Res. Monogr.
90:105-114 (1988).
Donahoe, R. M.: Receptor modulation as a primary target
of the immunological effects of alcohol and other drugs
of abuse. Alcohol, Immunomodulation, AIDS. 305-312
(1990).
Donahoe, R. M. and A. Falek: Neuroimmunomodulation
by opiates and other drugs of abuse: relationship to HIV
infection and AIDS. Adv. Biochem. Psychopharmacol.
44:145-148 (1988).
Donald, P. J.: Marijuana smoking - possible cause of head
and neck carcinoma in young patients. Otolaryngol. Head
Neck Surg. 94:517-521 (1986).
Draizin, C., J. Gillespie, L. Eisenbud, M. Shakin, and T.
Klopman: Dental Needs of a Methadone Maintenace
Population. N.Y. State Dent. J. 41(6):351-354 (1975).
Duggan, A. K., H. Adger, Jr., E. M. McDonald, E. J.
Stokes, and R. Moore: Detection of alcoholism in
hospitalized children and their families. AJDC. 145:613-
617 (1991).
Dunne, F. J.: Alcohol and the immune system. Br. Med.
J. 298:543-544 (1989).
Elliott, D. C.: Frostbite of the mouth: a case report. Milit.
Med. 156(1):18-19 (1989).
Ficarra, G., E. J. Shillitoe, K. Adler-Storthz, D. Gaglioti,
M. Di Pietro, R. Riccardi, and G. Forti: Oral melanotic
macules in patients infected with human
immunodeficiency virus. Oral Surg. Oral Med. Oral
Pathol. 70(6):748-755 (1990).
Fraser, R., W. A. Day, and N. S. Femando: Review: the
liver sinusoidal cells. Their role in disorders of the liver,
lipoprotein metabolism and atherogenesis. Pathology.
18:5-11 (1986).
Friedlander, A. H. and D. A. Gorelick: Dental management
of the cocaine addict. Oral Surg. Oral Med. Oral Pathol.
65:45-48 (1988).
Friedlander, A. H. and M. J. Mills: The dental management
of the drug-dependent patient. Oral Surg. Oral Med.
Oral Pathol. 60:489-492 (1985).
Friedlander, A. H., M. J. Mills, and D. A. Gorelick:
Alcoholism and dental management. Oral Surg. Oral
Med. Oral Pathol. 63(1):42-46 (1987).
Furth, P. A. and A. M. Kazakis: Nail pigmentation changes
associated with azidothymidine (zidovudine). Ann. In-
tern. Med. 107(3):350 (1987).
Gargiulo, A. V., Jr., P. D. Toto, and A. W. Gargiulo:
Cocaine-induced gingival necrosis. Periodontal Case Rep.
7:44-45 (1985).
Girard, D. E., K. L. Kumar, and J. H. McAfee: Hematologic
effects of acute and chronic alcohol abuse. Hematol.
Oncol. Clin. North Am. 1(2):321-334 (1987).
Gorodetzky, C. W., J. D. Sapira, D. R. Jasinski, and W. R.
Martin: Liver disease in narcotic addicts. Clin. Phar-
macol. Ther. 9(6):720-724 (1968).
Grady, D., T. E. Daniels, P. B. Robertson, D. Greenspan,
and S. Silverman, Jr.: Oral mucosal lesions found in
smokeless tobacco users. J. Am. Dent. Assoc. 121:117-
123 (1990).
Graham, A. W.: Screening for alcoholism by life-style risk
assessment in a community hospital. Arch. Intern. Med.
151:958-964 (1991).
Granstein, R. D. and A. J. Sober: Continuing medical
education, drug- and heavy metal-induced hyperpig-
mentation. Am. Acad. Dermatol. 5(1):1-18 (1981).
Haddox, V. G. and M. D. Jacobson: Psychological
adjustment- mood and personality fluctuations of long-
term methadone maintenance patients. Int. J. Addict.
7(4):619-627 (1972).
Hamner, J. E., Ill, and 0. L. Villegas: The effect of coca
leaf chewing on the buccal mucosa of Aymara and
Quechua indians in Bolivia. Oral Surg. Oral Med. Oral
Pathol. 28:287-295 (1969).
Harbour, D. and E. Smith: Drug abuse and immune-
neuroendocrine connections. NIDA Res. Monogr. 90:87-
98 (1988).
Hecht, S. S. and J. Friedman: The high incidence of cervical
dental caries among drug addicts. Oral Surg. Oral Med.
Oral Pathol. 2:1428-1442 (1949).
Henry, R. J., M. M. Ishii, and R. M. Quock: Influence of
chronic ethanol exposure on nitrous oxide analgesia in
mice. J. Dent. Res. 69(10):1674-1677 (1990).
Hollister, L. E.: Health aspects of cannabis. J. Pharmacol.
Rev. 38:1-20 (1986).
Hollister, L. E.: Marijuana and immunity. J. Psychoactive
Drugs. 20(1):3-8 (1988).
Horowitz, L. G. and R. R. Nersasian: A review of marijuana
in relation to stress-response mechanisms in the dental
patient. J. Am. Dent. Assoc. 96:983-986 (1978).
Hutchinson, S.: Methadone and caries. Br. Dent. J. 168:430
(1990).
Ireton, H. J. C., I. D. Gust, W. J. Moon, N. Lehmann,
G. F. Stening, and R. A. Smallwood: The covert liver
disease of drug addicts. Aust. N.Z. J. Med. 4(5):444-
449 (1974).
Isaacs, S. O., P. Martin, and J. H. Willoughby: "Crack"
(an extra potent form of cocaine) abuse: a problem of
the eighties. Oral Surg. Oral Med. Oral Pathol. 63(1):12-
16 (1987).
Isner, J. M., M. Estes, IH, P. D. Thompson, M. R. Costanzo-
Nordin, R. Subramanian, G. Miller, G. Katsas, K.
Sweeney, and W. Q. Stumer: Acute cardiac events
temporally related to cocaine abuse. N. Engl. J. Med.
315:1438-1443 (1986).
Javors, M. A. and C. L. Bowden: The human platelet as a
model for calcium metabolism in central nerve endings
in the study of alcoholism. Alcohol Drug Res. 7:311-
319 (1987).
Jenike, M. A.: Drug abuse. In: Scientific American, Chap.
13 (VI), E. Rubenstein and D. F. Federman, Eds. Sci-
entific American, New York. (1991) 1-8.
Jerrells, T. R., C. A. Marietta, G. Bone, F. F. Weight,
and M. J. Eckardt: Ethanol-associated immunosuppres-
sion. Adv. Biochem. Psychopharmacol. 44:173-185
(1988).
Kani, J., R. J. C. Gilson, R. Nandwani, and A. M. Johnson:
Hepatitis A virus infection among homosexual men. Br.
Med. J. 302:1399 (1991).
Kimbrough, H. M. Jr.: Local anesthetic and the addictive
patient. Tex. Dent. J. 93(5):7-9 (1975).
Kinane, D. F., F. A. Johnston, and C. W. Evans: Depressed
helper-to-suppressor T-cell ratios in early-onset forms of
periodontal disease. J. Periodont. Res. 24:161-164
(1989).
Kothur, R., F. Marsh, Jr., and G. Posner: Liver function
tests in nonparenteral cocaine users. Arch. Intern. Med.
151:1126-1128 (1991).
Kranzler, H. R., T. F. Babor, L. Goldstein, and J. Gold:
Dental pathology and alcohol-related indicators in an
181
 outpatient clinic sample. Community Dent. Oral Epi-
demiol. 18:204-207 (1990).
Kumar, S. and D. K. Rex: Failure of physicians to recognize
acetaminophen hepatotoxicity in chronic alcoholics. Arch.
Intern. Med. 151:1189-1191 (1991).
Layman, F. D.: Marijuana - harmful or not? Tex. Dent.
J. 9:6-8 (1978).
Leary, J. M. and G. K. Johnson: An unusual case of dental
erosion caused by nitric acid. Gen. Dent. 35(3):210-
211 (1987).
Lee, C. Y. S., H. Mohammadi, and R. A. Dixon: Medical
and dental implications of cocaine abuse. J. Oral Max-
illofac. Surg. 49:290-293 (1991).
Lenzi, M., G. Ballardini, M. Fusconi, F. Cassani, L. Selleri,
U. Volta, D. Zauli, and F. B. Bianchi: Type 2
autoimmune hepatitis and hepatitis C virus infection.
Lancet. 335:258-259 (1990).
Lewis, D. A.: Methadone and caries. Br. Dent. J. 168:349
(1990).
Lieber, C. S.: Microsomal ethanol-oxidizing system. En-
zyme. 37:45-56 (1987).
Lindenbaum, J.: Hematologic complications of alcohol
abuse. Semin. Liver Dis. 7(3):169-181 (1987).
Louria, D. B., T. Hensle, and J. Rose: The major medical
complications of heroin addiction. Ann. Intern. Med.
67(1):1-21 (1967).
Lowenthal, A. H.: Atypical caries of the narcotics addict.
Dent. Surv. 43(12):44-47 (1967).
MacDonald, D. I.: Parental alcoholism, a neglected pediatric
responsibility. AJDC Editorial 145:609-610 (1991).
MacGregor, I. D. M.: Effects of smoking on oral ecology,
a review of the literature. Clin. Prevent Dent. 11(1):3-
6 (1989).
MacGregor, R. R.: Alcohol and drugs as co-factors for
AIDS. Adv. Alcohol Subst. Abuse. 7:47-71 (1987).
Mangla, J. C., Y. M. Kim, M. R. Brown, D. Schwob, and
S. E. Hanson: Liver tests, HB-Ag and HB-Ab in
asymptomatic drug addicts. Am. J. Gastroenterol.
165:121-126 (1976).
Mark, I.: Addicted mothers, Acta Psychiatrica Scand.
62(S.285):353-364 (1980).
Martin, J. E. and J. Inglis: Pain tolerance and narcotic
addiction. Br. J. Soc. Clin. Psychol. 4:224-229 (1965).
Mathiesen, L. R. P. Skinhoj, F. Hardt, J. 0. Nielsen, K.
Sloth, H. Zoffmann, A. M. Moller, D. Wong, R. H.
Purcell, and the Copenhagen Hepatitis Acuta Programme:
Epidemiology and clinical characteristics of acute hepatitis
types A, B, and non-A non-B. Scand. J. Gastroenterol.
14:849-856 (1979).
Mathis, D. W.: Cocaine-associated myocardia ischemia,
review of clinical and angiographic findings. Am.J. Med.
81:675-678 (1986).
McMichael, A. J. and A. Puzio: Time trends in upper
alimentary tract cancer rates and alcohol and tobacco
consumption in Australia. Community Health Stud.
XXI(3):289-295 (1988).
Merenich, J. A., R. N. Hannon, R. H. Gentry, and S. M.
Harrison: Azidothymidine-induced hyperpigmentation
mimicking primary adrenal insufficieny. Am. J. Med.
86:469-470 (1989).
182
Miers, D. and D. P. Smith: Guidelines for the treatment of
recovering chemically dependent dental patients. J. Am.
Coll. Dent. 56(4):6-8 (1989).
Mikhailidis, D. P., M. A. Barradas, and J. Y. Jeremy: The
effect of ethanol on platelet function and vascular pros-
tanoids. Alcohol. 7:171-180 (1990).
Mirin, S. M., R. D. Weiss, J. Michael, and M. L. Griffin:
Psychopathology in substance abusers: diagnosis and
treatment, Am. J. Drug Alcohol Abuse. 14(2): 139-157
(1988).
Moestrup, T., B. G. Hansson, A. Widell, E. Nordenfelt,
and I. Hagerstrand: Long-term follow-up of chronic
hepatitis B virus infection in intravenous drug abusers
and homosexual men. Br. Med. J. 292:854-857 (1986).
Mohs, M. E. and R. R. Watson: Ethanol induced
malnutrition, a potential cause of immunosuppression
during AIDS. Prog. Clin. Biol. Res. 325:433 444 (1990).
Mufti, S. I., H. R. Darban, and R. R. Watson: Alcohol,
cancer, and immunomodulation. Crit. Rev. Oncol. Hem-
atol. 9(3):243-261 (1989).
Nahas, G. G.: Therapeutics - cannabis: toxicological
properties and epidemiological aspects. Med. J. Aust.
145:82-87 (1986).
Newman, R. G.: The need to redefine "addiction". N.
Engl. J. Med. 308:1096-1098 (1983).
Pallasch, T. J. and C. E. Joseph: Oral manifestations of
drug abuse. J. Psychoactive Drugs. 19(4):375-377
(1987).
Pallasch, T. J., F. M. McCarthy, and J. T. Jastak: Cocaine
and sudden cardiac death. J. Oral Maxillofac. Surg.
47:1188-1191 (1989).
Pasternack, P. F., S. B. Colvin, and F. G. Baumann:
Cocaine-induced angina pectoris and acute myocardial
infarction in patients younger than 40 years. Am. J.
Cardiol. 55:847 (1985).
Perrillo, R. P., L. Gelb, C. Campbell, W. Wellinghoff,
F. R. Ellis, L. Overby, and R. D. Aach: Hepatitis B E
antigen, DNA polymerase activity, and infection of
household contacts with hepatitis B virus. Gastroenter-
ology. 76(6):1319-1325 (1979).
Picozzi, A., S. F. Dworkin, J. G. Leeds, and J. Nash:
Dental and associated attitudinal aspects of heroin
addiction: a pilot study. J. Dent. Res. 51(3):869 (1972).
Rees, T. D.: Dental management of the medically
compromised patient. In Current Therapy in Dentistry,
1. R. E. McDonald, W. C. Hurt, H. W. Gilmore, and
R. A. Middleton, Eds., C. V. Mosby, St. Louis. (1980)
3-30.
Rizzetto, M., M. G. Canese, J. L. Gerin, W. T. London,
D. L. Sly, and R. H. Purcell: Transmission of the hepatitis
B virus-associated delta antigen to chimpanzees. J. In-
fect. Dis. 141(5):590-602 (1980).
Rosenbaum, C. H.: Did you treat a drug addict today? Int.
Dent. J. 31:307-312 (1981).
Rosenstein, D. I.: Effect of long-term addiction to heroin
on oral tissues. J. Public Health Dent. 35(2):118-122
(1975).
Rounsaville, B. J., M. M. Weissman, H. Kleber, and C.
Wilber: Heterogeneity of psychiatric diagnosis in treated
opiate addicts. Arch. Gen. Psychiatry. 39:161-166
(1982).
Rumi, M., M. Colombo, R. Romeo, A. Boschini, A. Zanetti,
A. Gringeri, and P. M. Mannucci: Suboptimal response
to hepatitis B vaccine in drug users. Arch. Intern. Med.
151:574-578 (1991).
Salonen, L., T. Axell, and L. Hellden: Occurrence of oral
mucosal lesions, the influence of tobacco habits and an
estimate of treatment time in an adult Swedish popula-
tion. J. Oral Pathol. Med. 19:170-176 (1990).
Schalm, S. W., R. A. Heytink, H. Mannaerts, and A.
Vreugdenhil: Immune response to hepatitis B vaccine in
drug addicts. J. Infect. 7(I):41-45 (1983).
Scheutz, F., P. Skinhoj, and I. Mark: Viral hepatitis among
parenteral drug addicts attending a Danish addiction clinic.
Scand. J. Infect. Dis. 15:139-143 (1983).
Scheutz, F.: Dental health in a group of drug addicts attending
an addiction-clinic. Community Dent. Oral Epidemiol.
12:23-28 (1984a).
Scheutz, F.: Five-year evaluation of a dental care delivery
system for drug addicts in Denmark. Community Dent.
Oral Epidemiol. 12:29-34 (198b).
Scheutz, F.: Saliva secretion rate in a group of drug addicts
(short communication). Scand. J. Dent. Res. 92:496-
498 (1984c).
Scheutz, F.: Dental habits, knowledge, and attitudes of young
drug addicts. Scand. J. Soc. Med. 13:35-40 (1985).
Scheutz, F.: Anxiety and dental fear in a group of parenteral
drug addicts. Scand. J. Dent. Res. 94:241-247 (1986a).
Scheutz, F.: Drug addiction and viral hepatitis in the dental
patient. Dan. Med. Bull. 33(5):228-249 (1986b).
Schwartz, R.: Uvular edema and erythema. Pediatr. Infect.
Dis. J. 3:187 (1984).
Scott, R. M., R. Snitbhan, W. H. Bancroft, H. J. Alter,
and M. Tingpalapong: Experimental transmission of
hepatitis B virus by semen and saliva. J. Infect. Dis.
142:67-71 (1980).
Shapiro, S.: Effects of heroin deprivation on oral health.
Oral Surg. Oral Med. Oral Pathol. 32(5):731-738
(1971).
Shapiro, S., B. R. Pollack, and D. Gallant: Periodontal
disease in narcotic addicts. J. Dent. Res. 49(6):1556
(1970).
Shapiro, S., B. R. Pollack, and D. Gallant: The oral health
of narcotic addicts. J. Pub. Health Dent. 30(4):244-249
(1970).
Shellow, W. V. R.: The skin in alcoholism. Int. J. Der-
matol. 22(9):506-510 (1983).
Silverstein, S. J.: Relation between social drug use/abuse
and dental disease in California, U.S.A. Community Dent.
Oral Epidemiol. 1:89-93 (1973).
Silverstein, S. J., D. Noel, and D. Heilbron: Social drug
use/abuse and dental disease. Can. Dent. Assoc. J. 6:32-
39 (1978).
Splaver, T. E. and A. C. Williams: Management of the
narcotic-addicted surgical patient: concepts of medical
and surgical care. J. Oral Surg. 28:346-352 (1970).
Sterman, A. B. and P. K. Coyle: Subacute toxic delirium
following nitrous oxide abuse. Arch. Neurol. 40:466-
447 (1983).
Stockwell, S.: Marijuana's ability to impair immune system
is clarified. Oncol. Times. Jan. 1 (1988).
Tabakoff, B. and P. L. Hoffman: Genetics and biological
markers of risk for alcholism. Pub. Health Rep. 103:690-
698 (1988).
Tedder, R. S., R. J. C. Gilson, M. Briggs, C. Loveday,
C. H. Cameron, J. A. Garson, G. E. Kelly, and I. V. D.
Weller: Hepatitis C virus: evidence for sexual transmis-
sion. Br. Med. J. 302:1299-1302 (1991).
Tennant, F. S., M. Preble, T. J. Prendergast, and P. Ventry:
Medical manifestation associated with hashish, JAMA.
216(12):1965-1969 (1971).
Tremolada, F., C. Casarin, A. Tagger, M. L. Ribero, G.
Realdi, A. Alberti, and A. Ruol: Antibody to hepatitis
C virus in post-transfusion hepatitis. Ann. Intern. Med.
114:277-281 (1991).
The Medical Letter, Inc.: Acute reactions to drugs of abuse,
Med. Leu. Drugs Therapeut. 32(828):91-94 (1990).
Thomson, N.: Aboriginal health - current status. Aust.
N.Z. J. Med. 14:705-718 (1984).
U.S. Department of Health and Human Services: HIV/AIDS
Surveillance Rep. 1-22 (1990).
Valazquez, O., H. C. Stetler, C. Avila, G. Omelas, C.
Alvarez, S. C. Hadler, D. W. Bradley, and J. Sepulveda:
Epidemic transmission of enterically transmitted non-A,
non-B hepatitis in Mexico, 1986-1987. JAMA.
263(24):3281-3285 (1990).
Valentine, J. A., J. Scott, C. R. West, and C. A. St. Hill:
A histological analysis of the early effects of alcohol and
tobacco usage on human lingual epithelium. J. Oral
Pathol. 14:654-665 (1985).
Warnock, G. R. and C. L. Shalla: Effects of marijuana
smoking on maturation of oral epithelium. AADS Abstr.
173: No. 512 (1975).
Washton, A. M., M. S. Gold, and A. C. Pottash: Intranasal
cocaine addiction. Lancet. 2:1374 (1983).
Waterson, A. P.: Acquired immune deficiency syndrome.
Br. Med. J. 286:743-746 (1983).
Watson, R. R., M. E. Mohs, C. Eskelson, R. E. Sampliner
and B. Hartmann: Identification of alcohol abuse and
alcoholism with biological parameters. Alcoholism: Clin.
Exp. Res. 10(4):364-385 (1986).
Watzl, B. and R. R. Watson: Minireview,
immunomodulation by cocaine - a neuroendocrine
mediated response. Life Sci. 46(19):1319-1329 (1990).
Weber, R.: Immunologic effects of drugs of abuse (1988).
NIDA Res. Monogr. 90:99-104 (1988).
Webster, I. W., N. Waddy, L. V. Jenkins, and L. Y. C.
Lai: Health status of a group of narcotic addicts in a
methadone treatment programme. Med. J. Aust. 2:485-
491 (1977).
Weiland, O., R. J. V. Berg, B. Flehmig, G. Lindh, and P.
Lundbergh: Acute viral hepatitis, types A, B and non-
A, non-B: a prospective study of the epidemiological,
laboratory and prognostic aspects in 280 consecutive
cases. Scand. J. Infect. Dis. 13:247-255 (1981).
West, D. A., R. Kellner, and M. Moore-West: The effects
of loneliness: a review of the literature. Compr. Psy-
chiatry. 27(4):351-363 (1986).
Westerhof, W., E. Ch. Wolters, J. T. W. Brookbakker,
R. E. Boelen, and M. E. I. Schipper: Pigmented lesions
183
 of the tongue in heroin addicts - fixed drug eruption.
Br. J. Dermatol. 109:605-610 (1983).
White, A. G.: Medical disorders in drug addicts, 20
consecutive admissions. JAMA. 223(13):1469-1471
(1973).
Widell, A., B. G. Hansson, T. Moestrup, Z. Serleus, L. R.
Mathiesen, and T. Johnsson: Acute hepatitis A, B and
non-A, non-B in a Swedish community studies over a
ten-year period. Scand. J. Infect. Dis. 14:253-259 (1982).
Williamson, R. and C. L. Davis: Drug-dependent, alcohol-
dependent, and mental patients: clinical study of oral
surgery procedures. J. Am. Dent. Assoc. 36:416-419
(1973).
Winn, D. M., W. J. Blot, J. K. McLaughlin, D. F. Austin,
R. S. Greenberg, S. Preston-Martin, J. B. Schoenberg,
and J. F. Fraumeni, Jr.: Mouthwash use and oral
conditions in the risk of oral and pharyngeal cancer.
Cancer Res. 15:3044-3047 (1991).
Wright, J. T., I. G. Barrison, I. G. Lewis, K. D. Macrae,
E. J. Waterson, P. J. Toplis, M. G. Gordon, N. F.
Morris, and I. M. Murray-Lyon: Alcohol consumption,
pregnancy, and low birthweight. Lancet. I:663-665
(1983).
Yahya, M. D. and R. R. Watson: Minireview,
immunomodulation by morphine and marijuana. Life Sci.
41:2503-2510 (1987).
Yukna, R. A.: Cocaine periodontitis. Int. J. Periodontics
Restorative Dent. 11(1):73-79 (1991).
Zuckennan, A. J.: Hepatitis E virus. Br. Med. J. 300:1475-
1476 (1990).

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