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 GastonAvenue, Dallas, Texas 75246

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

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

1. INTRODUCTION

Mood-altering drugs have been used by manfor many purposes throughout recorded history.In some instances, such agents were used as com-ponents of religious ceremonies, while in othercultures substances such as coca leaves werechewed by native populations to increase endur-ance and to relieve hunger and fatigue (Gargiuloet al., 1985, Hamner and Villegas, 1969). Inother circumstances, mood-altering agents wereand are used for medical purposes. Cocaine, forexample, was widely available in the U.S. duringthe late 19th century for use as a stimulant, or alocal anesthetic in dentistry, opthalmology, andotolaryngology (Friedlander and Gorelick, 1988).Clearly, however, the most common use formood-altering drugs has essentially been for"recreational" or social purposes. Although pos-sessing some medicinal properties, alcohol hasbeen used recreationally for thousands of yearsand alcoholism has been described since the 1stcentury B.C. Cocaine and opium have been inuse at least since the 6th century (Council onDental Practice, 1987).

Today, the use and abuse of mood-alteringdrugs in the U.S. creates staggering figures andestimates. For example, it is reported that 22million Americans have used cocaine at least

once, while 2 to 4 million Americans have usedit regularly. At least one half million individualshave significant problems with cocaine abuse(Friedlander and Gorelick, 1988; Council onDental Practice, 1987). Despite these large num-bers, cocaine ranks only third among drugs ofabuse, with ethyl alcohol representing the mostwidely used substance, followed by cannabis(such as marijuana and hashish).

The Federal Drug Enforcement Agency listsat least 171 other drugs capable of being abused,and new drugs with abuse potential are constantlybeing developed. In addition to alcohol, the agentsof abuse fall into the general categories of nar-cotics, depressants, stimulants, hallucinogens(Council on Dental Practice, 1987), and solventsand inhalants (Rosenbaum, 1981). A majority ofAmerican teenagers and adults use ethyl alcoholand an estimated 12 million suffer from someaspect of alcohol abuse (Christen, 1983; Dugganet al., 1991).

Despite these large estimates, relatively littleis known conclusively regarding the factors thatcause people to use such drugs and even less isknown regarding chemical dependency (Councilon Dental Practice, 1987; Jenike, 1991). In thepast, with the exception of alcohol, substancedependency was a phenomenon that was pri-marily limited to socially disadvantaged individ-

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uals and to those of high socioeconomic statuswho possess the financial means and access topurchase drugs of abuse. Today, however, drugusers are distributed proportionately among thegeneral population in all social strata (Friedlanderand Mills, 1985). In general terms, initiation ofdrug use begins between 15 and 35 years of age,although wide age variations are often describedwith 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% hadused more than one type of drug. Marijuana andalcohol are the two most commonly used "entry"drugs, with others added subsequently. Polydruguse compounds the difficulty of determining thelong-term effects of specific drugs. For example,31% of all alcoholics and 51% of teenagers andyoung adult alcoholics are addicted to other drugsin addition to alcohol. Among individuals withdrug abuse problems causing hospitalization ordeath, polydrug use ranges from 34 to 50%.Among alcoholics, barbiturates, narcotic anal-gesics, and stimulants are the most frequentlyused 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 markedlyaffect the general and oral health of the individualuser. The stereotypical drug addict is pictured asan undereducated individual living in a very lowsocioeconomic environment. This individual isunable to purchase adequate supplies of food,general and oral hygiene are neglected, and thereis 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 fallinto this category, especially those addicted toparenterally administered agents or to alcohol.Conversely, however, drug abuse can and oftendoes occur in individuals who are financially sol-vent and who lead reasonably normal lives.

The purpose of this article is to review thecurrent state of knowledge concerning the sys-temic and oral effects of drugs of abuse and thedental management of addicted patients. Many

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 ofdrugs of abuse in the oral cavity. Many studiesrelative to dental effects were conducted in drugtreatment centers, meaning that oral health fea-tures described are predominantly associated withpatients addicted to parenterally administeredagents. Case reports describe oral conditionsfound in a particular individual or individuals,but do not necessarily represent typical featuresassociated with a particular drug. In other in-stances, animal experiments were described andthe results of such studies cannot necessarily beapplied 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 andDavis, 1973; Kothur et al., 1991).

II. DEFINITIONS

The following definitions are important.

1. Addiction - physical and psychologic de-pendency, associated with tolerance to adrug and withdrawal symptoms with a per-sistent disposition to relapse to drug useafter abstinence has been achieved andphysical dependency reversed (Newman,1983).

2. Abuse - a pattern of pathologic behaviorassociated with continued use of a drug ordrugs despite persistent social, psycho-logic, or physical problems caused by druguse (Friedlander and Mills, 1985).

3. Dependence - continued substance usecaused by a physical or psychological needfor a substance. Tolerance to the effects ofthe drug and development of characteristicwithdrawal symptoms are required (Jenike,1991).

4. Tolerance- a need for markedly increasedquantities of a drug in order to achieve thedesired results (Rosenbaum, 1981; Fried-lander and Mills, 1985).

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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 thata substantial number of patients under treatmentfor substance abuse disorders also manifestednondrug-related psychiatric disorders. It shouldbe recognized, however, that findings in patientpopulations within a substance abuse facility maynot be representative of all abusers. Institution-alized addicts have either recognized that theyhave a problem and have sought treatment forthat problem or they were forced by society toseek 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 dependenton alcohol or narcotics and who have developeda high tolerance to such drugs are still able todiscontinue use of the drugs without relapse(Newman, 1983; De Leon and Jainchill, 1981).Psychiatric evaluation is difficult because the signsand symptoms manifested may be the result ofan ongoing underlying psychiatric disorder or theymay reflect manifestations of drug intoxicationor ofdamage from chronic substance abuse. Theymay also be features of drug withdrawal or anycombination of the above (Mirin et al., 1988).It is certainly possible, however, that individualswith affective disorders, such as depression orexcessive anxiety, may use drugs to alter theirpsychologic 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 withdepression, while rapid methadone detoxificationmay result in a severe psychosis such as schiz-ophrenia (Mirin et al., 1988). Stimulant abusersmay use agents such as cocaine in a subconsciousattempt 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 suchas benzodiazepines or sedatives may do so tomask an anxiety disorder that will resurface uponwithdrawal. It is important for dentists to be awarethat patients under medical treatment for drugdetoxification may be taking prescribed drugs suchas tricyclic antidepressants, monoamine oxidaseinhibitors (MAOIs), or lithium to counteract thepsychiatric effects of their withdrawal (Mirin etal., 1988). Drugs of this nature may have a pro-found effect on the outcome of dental treatmentunless appropriate precautions are taken.

A familial component may be present in in-dividuals who practice substance abuse. Whenfamilies of substance abuse patients were evalu-ated, approximately 30% of relatives sufferedfrom at least one psychopathologic disorder.Among male relatives, there was an increasedexpectancy rate for alcoholism, while female rel-atives had a higher expectancy rate for affectivedisorders. As discussed later, propensity to al-coholism appears to represent an inherited trait,especially among men, but studies do not affima correlation between alcoholism in first-degreerelatives and abuse of other substances (Mirin etal., 1988).

Drug addiction appears to be closely asso-ciated with an increase in medical disorders, atleast as reflected by reports from drug addictiontreatment centers. In most instances, those re-ports reflect data obtained from users of paren-terally administered drugs, most commonly theopiates and usually heroin. Commonly reporteddisorders 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 etal., 1983; Ayer and Cutright, 1974; Briggs etal., 1967). The incidence of cardiovascular dis-eases, diabetes mellitus, and gastrointestinal dis-orders also increases (Webster et al., 1977; Briggset al., 1967). White (1973) reported that skininfections were usually associated with subcu-taneous injections of heroin ("skin popping"),while uncontrolled diabetes mellitus was related

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to the lifestyle of addiction that leads to incon-sistent monitoring of blood glucose levels, spo-radic administration of insulin, inadequate dietcontrol, and severe systemic illness. Most drugaddicts smoke tobacco and frequently overuseanalgesics, 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 orC may be associated with chronic aggressive hep-atitis in 15 to 25% of fonner addicts, as comparedto 5 to 10% of the general population who havebeen infected with HBV or HCV (Scheutz, 1986b;Lowenthal, 1967; Weiland et al., 1981). In arelated study, Schalm et al. (1983) found thatdrug addicts were equally as capable as nonad-dicted individuals in developing antibodies tohepatitis B virus when vaccinated against the vi-rus. Conversely, Rumi et al. (1991) reported thata significant number of institutionalized drug usersfailed to develop antibodies when vaccinatedagainst HBV, perhaps due to an altered immunestatus in these individuals.

Liver function tests are often elevated in nar-cotic addicts (Cherubin et al., 1976; Mangla etal., 1976), suggesting the possibility of a directhepatotoxic effect of parenterally administeredopiates or their contaminants (Ireton et al., 1974).Gorodetzky et al. (1968), however, conductedan 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 changesin liver enzyme levels associated with long-termmoxphine administration. They concluded that thehigh instance of abnormal liver enzymes foundin morphine and heroin addicts was not due to adirect hepatotoxic effect of the drugs.

Viral hepatitis and HIV transmission amongdrug addicts is almost certainly related to intra-venous drug injection because of the use andrepeated reuse of unsterile needles and needlesharing (Webster et al., 1977). It is probable,however, that the lifestyle of chronic substance

abusers of low socioeconomic status may pre-dispose abusers to transmission of HIV and viralhepatitis. Sexual promiscuity is common, livingconditions may be unsanitary, and immune de-ficiencies may result in association with malnu-trition, multiple systemic diseases, and polydruguse, especially with alcohol (Blanck et al., 1979).Sexual transmission of HAV and HBV has beendemonstrated in humans and animals (Kani et al.,1991; Perillo etal., 1979; Scott etal., 1980) andsuggested for hepatitis C (Tedder et al., 1991).HBV has been isolated in human saliva and itstransmission demonstrated by subcutaneous in-jections in monkeys, but oral and nasal exposureto saliva did not result in transmission (Scott etal., 1980; Bancroft et al., 1977).

Recent evidence has affirmed that hepatitisC (formerly non-A, non-B hepatitis) is causedby a specific virus transmitted in blood and bloodproducts (Velazquez et al., 1990; Zuckerman,1990; Tremolada et al., 1991). Another form ofnon-A, non-B hepatitis may be transmitted en-demically in an unsanitary environment such asthat of drug abusers of low socioeconomic status(Velazquez et al., 1990). Some 10 to 30% ofHCV-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 foundin liver cells of individuals suffering from acuteor chronic hepatitis. The virus is a defective RNAagent capable of replicating within hepatocytes,but it is not able to produce a protein coat (Scheutz,1986b). The delta virus requires the presence ofHBV to be functional and its primary reservoirappears to be parenteral drug users. It is believedto be the major cause of the increased incidenceof severe liver disease and chronic hepatitis amongparenteral drug addicts (De Cock et al., 1986).Experimentally, severe liver damage occurredwhen HBV antigen and the delta antigen wereinjected into chimpanzees susceptible to infectionwith human hepatitis B virus (Rizzetto et al.,1980).

Parenteral drug abusers are prone to multipleinfections 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

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powdered milk) (Rosenbaum, 1981; Ayer andCutright, 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 involvingthe tricuspid valve on the right side of the heartis often reported, but lesions are not limited tothat valve (Davis et al., 1983, Ayer and Cutright,1974). Bacteremias caused by unusual organismsmay 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), Escherichiacoli, Klebsiella-aerobacter, Pseudomonas aeru-ginosa, and several species of candida (Louria etal., 1967). In one incident of neisseria endocar-ditis, the organism neisseria mucosus was cul-tured from the sputum of a parenteral drug userwho habitually licked the injection needle (Daviset al., 1983). In other instances, the infectiousagent may be obtained from the skin in the siteof injection (Rosenbaum et al., 1981).

Cocaine abuse has been associated with avariety of cardiac disorders that include anginapectoris and myocardial infarction (Cregler andMark, 1986; Pastemack et al., 1985; Isner et al.,1986), and sudden cardiac death may occur dueto acute cocaine toxicity (Pallasch et al., 1989;Cregler and Mark, 1985).

IV. EFFECTS ON THE IMMUNE SYSTEM

There is considerable evidence to suggest thatthe immune system may be significantly alteredin patients practicing substance abuse (Donahoe,1988). Additionally, there is increasing aware-ness that the immune system engages in complexregulatory interactions with the central nervoussystem and the endocrine system (Harbour andSmith, 1988; Donahoe, 1988; Weber, 1988).Drugs of abuse may adversely affect variouscomponents of this interactive system. Opiates,for example, affect the central nervous systemand the immune system by competing with en-dogenously manufactured opiates at various re-ceptor sites in the brain and attaching to opiatereceptors on T lymphocytes and leukocytes (Har-bour and Smith, 1988; Donahoe, 1988; Donahoeand Falek, 1988). Cocaine, phencyclidine, mari-

juana, benzodiazepines, barbiturates, and alcoholare all capable of suppressing or, in certain cir-cumstances, enhancing immune function in vivoand in vitro (Weber, 1988; MacGregor, 1987).Cocaine and amphetamines are reported to de-crease total lymphocyte counts in animals, butno research data are available in man (Mac-Gregor, 1987). Marijuana has been studied inanimals using doses and concentrations consid-erably greater than those levels found in humansubjects. In animals, marijuana impairs cellularand 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 associatedwith 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 beassociated with immune suppression, but in manyinstances, this may be the result of liver damageor malnutrition (Jerrells et al., 1988; Dunne,1989). Alcohol ingestion, however, may revers-ibly alter the production and function of both Tand B lymphocytes, leading to reduced circulat-ing lymphocyte counts. Macrophage activationand phagocytic activity may be diminished, andgranulocyte chemotaxis and adherence to capil-lary walls is adversely affected. Meanwhile, betaendorphins in the brain are reduced, leading toan altered activity of natural killer cells by theimmunoneuronal route (Donahoe, 1990; Jerrellset al., 1988; Alcock, 1990).

Experimental and clinical findings as de-scribed above suggest that abuse of opiates andalcohol, 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 ofAIDS (MacGregor, 1987; Mohs and Watson,1990). Some evidence, however, suggests thatHIV infection in parenteral drug addicts may leadto exacerbation of complaints and, possibly, morerapid progression to outright AIDS (MacGregor,1987). Intravenous (i.v.) drug use has been clearlyassociated with HIV transmission and i.v. drugabusers constitute approximately 21 to 28% of

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reported AIDS cases in the U.S. (U.S. Depart-ment of Health and Human Services, 1990). Thisrelationship is undoubtedly attributable to needlesharing in parenteral drug users (Friedlander andMills, 1985), but the immunosuppression clini-cally demonstrated in opiate addicts who are notHIV positive suggests that opiate-derived im-munosuppression may enhance HIV infection andthe 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 reviewedthe role of ethyl alcohol-induced malnutrition asa potential cause of immunosuppression espe-cially related to AIDS. Alcoholism is tradition-ally associated with faulty dietary intake, leadingto protein and calorie deficiencies. Additionally,alcohol abuse alters gastrointestinal absorption ofnutrients and their transformation to metaboli-cally active forms. Simultaneously, alcohol in-take increases the utilization requirements for avariety of nutrients. Alcohol-associated liverdamage 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, andzinc may also be adversely affected (Mohs andWatson, 1990). The immunosuppressive effectsof these deficiencies may be generally reversiblewith abstinence from alcohol unless liver damagehas occurred. Nonetheless, evidence such as thissuggests that excessive alcohol intake should beavoided in HIV-positive individuals.

V. GENERAL ORAL FEATURES OFCHEMICAL DEPENDENCY

The specific oral effects of various drugs ofabuse will be discussed later in this review. Anumber of oral diseases and disorders have beendescribed, however, that may relate to most in-dividuals who engage in substance abuse. Forexample, chronic chemical abuse is generally as-sociated with a markedly decreased self-image,depression, and a lack of motivation, all of whichmay impact oral health and adversely influencecompliance with oral hygiene procedures andkeeping dental appointments (Scheutz, 1985; U.S.

Department of Health and Human Services,1990). Additionally, dental care assumes a lowpriority in the life of an addict whose primarypreoccupation ultimately may become the needto obtain drugs to support their habit. In manyinstances, a distressed financial state discouragesaddicts from seeking dental care, and, if treat-ment is requested, the only financially acceptableoption may be extraction of involved teeth. Con-versely, an addict may choose to retain an un-treated carious tooth as a possible mechanism forobtaining a prescription for a potent analgesicagent. Finally, chronic use of some drugs maymask 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 salivarypH and promotes plaque and calculus accumu-lation, with resultant increases in incidence ofcaries 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 secretionin patients using amphetamines, marijuana, andother drugs and were unable to detect reducedparotid salivary flow in patients using marijuanaas their predominant drug. The authors did, how-ever, identify alterations in salivary compositionin all groups, together with a higher caries index.

Many reports describe an increased cariesrate among drug addicts (Scheutz, 1984a; Scheutz,1986b; Lowenthal, 1967; Scheutz, 1984b), andcervical and smooth surface carious lesions havebeen found much more frequently in drug addictsthan in the general population (Scheutz, 1984a;Lowenthal, 1967; Hecht and Friedman, 1949).Carious lesions may present with a smooth, darklystained, ebumated appearance in drug-using pa-tients (Scheutz, 1984a).

The reported increase in the caries rate mayrelate 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 carbohydrateseither in an effort to counteract xerostomia (Co-

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Ion 1972, Colon 1974) - due to inherent nutri-tional deficiencies or constipation associated withdrug use (Hecht and Friedman, 1949; Carter,1978)- or for unexplained reasons (Lowenthal,1967). Refined sugar is often used as a diluentfor injected drugs, and addicts are reported tocrave sweets and routinely ingest them at the timeof 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 stressof withdrawal) (Westerhof et al., 1983). An in-crease in traumatic injuries to the face, jaws,- andoral cavity may occur (Ayer and Cutright, 1974;Scheutz, 1984b), possibly due to the techniqueof slapping drug users in an effort to revive thoseshowing symptoms of overdose.

Drug-addicted dental patients may experi-ence an inordinate degree of anxiety over dentaltreatment, a fear of dental needles, and a lowpain tolerance (Scheutz, 1986a; Martin and In-glis, 1965). The anxiety and low pain thresholdmay 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 sedationagents has been found in drug abusers, suggestingthat conventional quantities of local anestheticsmay be insufficient to allow the patient to undergoa pain-free dental experience (Kimbrough, 1975).

Oral mucosal lesions may be more commonin drug-addicted individuals compared with thenonaddicted (Scheutz, 1986b). Increased inci-dence of leukoplakia and leukoedema of the pal-ate have been described among institutionalizedaddicts (Scheutz, 1984b). As previously noted,however, the majority of drug abusers also usetobacco regularly and perhaps excessively(Scheutz, 1986b; Webster et al., 1977; Scheutz,1984b). Salonen et al. (1990) examined 920Swedish patients from the general population andfound a positive correlation between tobacco useand leukoplakia, frictional white lesions, coatedtongue, 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 relationshipof tobacco and alcohol as co-factors in oral, la-ryngeal, and pharyngeal carcinoma is well es-tablished (Craig and Friedman, 1986; McMichaeland Puzio, 1988; Barnes and Johnson, 1986;Brugere et al., 1986; Macgregor, 1989). Smok-ing has also been correlated with chronic oralcandidiasis and depressed polymorphonuclearleukocyte chemotaxis and mobility (Macgregor,1989). The net result is that heavy tobacco usemay contribute to the increase of oral mucosallesions reported in substance abusers, and to-bacco consumption may enhance immunedepression in the drug-addicted population. Life-style effects of substance abuse were recentlyillustrated by a case report describing frostbite ofthe oral cavity in an individual attempting to in-hale an aerosolized propane propellant to achieveeuphoria (Elliott, 1991).

Increased hyperpigmentation of oral tissueshas 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 lifestylefactors within the drug community may be at leastpartly responsible for such findings. Tobaccosmoking may result in increased gingival pig-mentation (Amir et al., 1991). Polydrug use ofsubstances such as barbiturates or meprobamatemay result in fixed drug eruptions with associatedpigmentary incontinence. Use of agents such asquinine to dilute or cut opiates may have a similareffect. Oral contraceptives may be used com-monly among sexually promiscuous female drugabusers, leading to associated oral melasma(Granstein and Sober, 1981). Oral melanotic ma-cules have been described as a feature of HIVinfection, or of its treatment with zidovudine orother therapeutic drugs (Ficarra et al., 1990; Furthand 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 foundno significant difference in the incidence of oralmelanotic pigmentation between the two groups,but progressive and recurrent pigmented lesionswere found exclusively in the HIV-positivepopulation.

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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). Opiatesprimarily have sedative and analgesic effects onthe central nervous system. Euphoria and relieffrom tension may often be the goal of those whouse these drugs excessively, although chronic op-iate use can be accompanied by increasingdepression (Mirin et al., 1988).

Heroin is a semisynthetic opiate that contin-ues to be heavily abused in the U.S. It is preparedby extraction from the poppy (Papaver somni-ferum) as morphine, then acetylated to diacetyl-morphine (heroin). The drug is imported into theU.S. in relatively pure form, then diluted withvarious agents, including quinine, powdered milk,lactose, mannitol, baking soda, or other materials(The Medical Letter, Inc., 1990). The agent maybe injected intravenously or subcutaneously, andit may be taken orally or nasally (Westerhof etal., 1983). Complications include overdose, in-fective endocarditis and other infections, pul-monary emboli, fibrosis, and hepatitis or otherliver 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 aretreated with methadone or clonidine (Catapres)(The Medical Letter, Inc., 1990). Withdrawalsymptoms 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 reversedwith naloxone, but propoxyphene (Darvon) andpentazocine (Talwin) may require considerablylarger dosages (The Medical Letter, Inc., 1990).

Habitual long-term use of heroin may occurwithout addiction, but most reports suggest thatapproximately 50% of users will become ad-dicted. As mentioned earlier, the heroin addictsuffers from a marked increase in dental cariesand periodontal disease for a variety of reasons,including neglect of oral health, failure to seek

dental care, malnutrition, intense craving forsweets, 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 profilesof active heroin addicts vs. former addicts andfound oral disease to be higher in active addicts,but not significantly increased. No statisticallysignificant differences were found between for-mer addicts and incarcerated nonaddicts, againsuggesting that the lifestyle of the socioecon-omically disadvantaged leads to increased oraldisease in both addicted and nonaddictedindividuals.

Westerhoff et al. (1983) reported finding hy-perpigmentation of the tongue with or withoutulceration in 9 of 47 individuals who smokedheroin and methaqualone and inhaled the vapors.Histologically, the tongue lesions were consistentwith a fixed drug eruption.

Morphine, a natural opiate, is believed todepress the body's immune system, which couldat 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 withincreases in oral fungal and viral infections andhas also been associated with advancing perio-dontal disease (Kinane et al., 1989).

Opiate withdrawal is usually not life-threat-ening, unlike withdrawal from substances suchas 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 lastinjection and include sweating, a slightly ele-vated body temperature, rhinorrhea, lacrimation,and dilated pupils. Later signs include agitationwith muscular twitching and joint pain, nausea,vomiting, diarrhea, and tachycardia (Jenike,1991).

Methadone is often used to detoxify patientsaddicted to other opiates. The detoxification pro-cess in the U.S. must be completed within 21 d,but methadone maintenance may be continuedfollowing detoxification under special circum-stances. The drug is taken orally and does notinduce tolerance or known long-term adverse ef-fects (Jenike, 1991). Some methadone mixtures,

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however, contain large quantities of sugar thatmay predispose the individual to dental caries(Scheutz, 1986a; Lewis, 1990; Bigwood andCoelho, 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 afeature of excessive use, but withdrawal symp-toms do not occur and hallucinogens do not pro-duce physical dependence. The most commonlyused hallucinogens include lysergic acid diethy-lamide (LSD), mescaline (peyote), phencyclidine(PCP), and psilocybin. Dose effect of these drugsusually lasts from 8 to 12 h. Patients may ex-perience strong feelings of introspection or de-personalization, but a toxic psychosis may alsobe associated with bizarre behavior, extreme ex-citement, or panic reaction. On occasion, patientsmay require hospitalization for weeks because ofprolonged 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 requiredto produce that effect. Cannabis (marijuana andhashish) may be the most frequently used illegaldrug in the U.S. (Nahas, 1986). It is reportedthat approximately 60% of Americans have ex-perimented with the drug and an estimated 20million use marijuana regularly (Jenike, 1991).Hashish is prepared by obtaining resin from thetops of the hemp plant (cannabis sativa), whilemarijuana is prepared from the entire plant. Hash-ish may be from five to ten times more potent asa euphoric than marijuana (Tennant et al., 1971),and hashish oil is even more potent (Nahas, 1986).

Cannabis may be smoked as a cigarette or ina pipe. As many as 2000 metabolites are pro-duced in the body when cannabis is smoked.These accumulate in fat, liver, lung, and spleenand may remain in fat stores for weeks afteringestion. 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 chemicalcompounds. The smoke of cannabis may containnumerous potential carcinogens such as carbonmonoxide, acetaldehyde, toluene, nitrosamine,naphthalene, benzanthracene, and benzopyrene.In fact, marijuana may contain twice as manycarcinogens as an equivalent weight of tobacco(Nahas, 1986).

The effect sought by users of cannabis iseuphoria, producing a state of contentment, lossof inhibitions, and heightened self-awareness(Jenike, 1991). Tolerance does not occur in manwith 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 reportedwith social use of the drug (Hollister, 1986).

Hollister (1986) has stated that the adverseeffects of cannabis are difficult to determine con-clusively for several reasons. Animal studies usu-ally involve the administration of very largequantities of the drug over short periods of time,while in humans the use patterns are generallyintermittent 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 individualswho are in relatively good health.

Tennant et al. (1971) studied the effect ofheavy chronic hashish use in a group of 31 sol-diers. They reported an increased incidence ofbronchial complaints very similar to those foundin tobacco smokers. Rhinopharyngitis was rela-tively prevalent and, in some incidences, appar-ently related to a hypersensitivity response to thedrug. Diarrhea and abdominal cramps occurredin some of the patients. Later reports have con-firmed respiratory impairment with heavy mari-juana use. Tachycardia has been described duringintoxication, but to date there is little evidenceto suggest that the cardiovascular system is per-manently affected (Nahas, 1986). There is, how-ever, increasing evidence that precancerouschanges may occur within the respiratory tractand the oral cavity as a result of heavy cannabisuse, especially if the material is used in con-

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junction with other carcinogenic substances suchas tobacco and alcohol (Nahas, 1986; Donald,1986).

Cannabis smoking may produce adverse ef-fects on the brain, resulting in an acute panicreaction or a toxic psychosis, such as acute par-anoia, or mania with associated delusions andhallucinations. A specific cannabis psychosis suchas the amotivational syndrome has not been con-firmed (Hollister, 1986). Behavioral dysfunctionand psychiatric illnesses are associated with heavycannabis 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 dysphoricreactions to marijuana may be treated with ben-zodiazepines, but a specific treatment is usuallynot required (The Medical Letter, Inc., 1990).

Flashback memories of events associated withdrug use have been described during the non-drugged state in some cannabis users, althoughthis phenomenon is more commonly associatedwith LSD and related hallucinogens (Hollister,1986).

Recently, marijuana has been found to becapable of retarding maturation of monocytes,perhaps partially explaining its reported abilityto impair immune system functions (Tennant etal., 1971; Stockwell, 1988). Decreased numbersofT and B lymphocytes have also been reported,although these effects appear to be temporary andreversible after cessation of use of the drug (Ya-hya and Watson, 1987; Nahas, 1986). The im-munosuppressive effect of the drug is much moreprofound in experimental animals than in man,and its importance in humans has not been clearlyestablished (Hollister, 1988).

Cannabis has been used for many centuriesas a therapeutic agent in a variety of disordersthat include neuralgia, postpartum psychosis, andinsomnia. More recently, it has been advocatedas an antiemetic for patients receiving cancer che-motherapy and to alleviate pain and anxiety interminally ill cancer patients. It has also beendemonstrated to reduce intraocular pressure whentopically applied to the eye in treatment of glau-coma. It is also reported to be of some value inrelief of involuntary muscle spasms and as ananticonvulsant (Hollister, 1986). A recent casereport offered evidence suggesting that marijuana

use may ameliorate ulcerative colitis, althoughthe mechanism of action is not clear (Baron etal., 1990).

Adverse effects of cannabis on the oral cavityhave been reported, but not studied extensivelyunder experimental conditions. Several reportshave 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 ofheavymarijuana smokers. Edema and erythema of theuvula have been reported with heavy use of hash-ish (Schwartz, 1984). All of these changes mayrelate to the fact that cannabis burns at a highertemperature than tobacco and is, therefore, po-tentially even more irritating to oral mucosa.

Gingival enlargement resembling phenytoin-induced gingival hyperplasia has been reportedin conjunction with heavy cannabis use (Baddouret 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 oforal papillomas in three groups of incarceratedpatients who were heavy marijuana users andwho displayed poor oral hygiene. Lesions werelocated 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 beendescribed in conjunction with marijuana smoking(Baddour et al., 1984).

Donald (1986) recently offered clinical evi-dence associating heavy marijuana use with anincreased 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 marijuanasmoke.

Silverstein et al. (1978) detected a higherincidence of caries and periodontal disease inindividuals who were heavy users of marijuana,assumably as a result of the lifestyle effects ofhabitual drug abuse (Silverstein et al., 1978; Pal-lasch and Joseph, 1987).

Horowitz and Nersasian (1978) reviewed thepharmacological action of marijuana in relationto therapeutic drugs used in dentistry. They con-

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cluded that the sympathomimetic effects of mari-juana might be synergistically enhanced byadministration of local anesthetics containingepinephrine or by the use of gingival retractioncord containing epinephrine. The tachycardia andperipheral vasodilation associated with acutemarijuana toxicity could be enhanced and evenreach life-threatening levels if epinephrine is usedand anxiety could be significantly elevated. Theauthors concluded that dental patients who usemarijuana heavily should be advised to discon-tinue use for at least 1 week before dentaltreatment.

D. Cocaine

Cocaine is an ancient drug, and evidence hasbeen found of its use before the beginning ofrecorded history. The coca leaf was apparentlychewed for its euphoric effect, but the drug alsoplayed a role in religious ceremonies among In-dian cultures in Peru and other countries and itmay have served as a general anesthetic for earlysurgical procedures. Through the centuries, itsuse increased and today millions of people areaddicted to chewing the coca leaf (Hamner andVillegas, 1969; Cregler and Mark, 1986).

Cocaine is a hydrochloride salt extract of thecoca leaf. Sigmund Freud, among others, pop-ularized its medical use in the treatment of avariety of illnesses and as a local anesthetic (Gar-giulo et al., 1985; Lee et al., 1991). It was alsoused to treat alcoholism and opiate addiction(Gargiulo et al., 1985; Friedlander and Gorelick,1988; Lee et al., 1991). Ultimately, the highlyaddictive properties of the drug were recognizedand it became illegal in the U.S. in 1914 (Lee etal., 1991).

Since the 1950s, cocaine has been primarilyabused by individuals of middle to upper soci-oeconomic class who could afford the high costof the agent (Washton et al., 1983). It is availableas a white crystalline powder, which can be takenorally, intranasally, vaginally, rectally, or in-jected subcutaneously or intravenously (Creglerand Mark, 1986). Beginning in 1986, however,a technique was developed allowing the materialto 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 Americanshave used cocaine since 1986 (Lee et al., 1991).

Cocaine is a euphoric, capable of producinghallucinations and enhanced feelings of mentaland physical prowess. The drug is rapidly ab-sorbed when smoked or injected intravenously,creating an intense euphoria and the potential forrapid tolerance. There is an increased risk fortoxicity 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 mixedwith irritability and anxiety (Jenike, 1991).

Snorting of cocaine powder intranasally oftenresults in irritation of the nasal mucosa, causingsneezing, 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 todepress the immune response with very high con-centrations of drug, but in vivo studies are con-flicting, some indicating immune suppressionwhile 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 (Watzland Watson, 1990). The greatest risk of infectionappears to be the potential for transmission ofHIV 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 beassociated with cervical abrasion of teeth andgingival laceration due to overly vigorous toothbrushing and flossing while "high". Severebruxism and flattened cuspal inclines may alsobe more common among cocaine addicts, accom-

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panied by increased frequency of temporoman-dibular joint disorders. The authors, however,offered no experimental evidence to support theseimpressions.

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 wasultimately diagnosed as an abuser of cocaine andother drugs, having applied nitric acid to his teethduring the manic phase of a psychopathologicdisorder in an effort to stop "voices" emittingfrom his teeth.

Occasionally, cocaine users rub the drug onthe gingiva or oral mucosa either to obtain relieffrom oral discomfort by taking advantage of co-caine's local anesthetic effects or to test the drug'spurity by its ability to produce gingival numbness(Waterson, 1983). This method is also used toabsorb the drug without adverse intranasal ef-fects. It has been reported to occasionally resultin the development of grossly inflamed, pro-fusely bleeding gingiva associated with epithelialdesquamation (Gargiulo et al., 1985; Dello Russoand Temple, 1982). Yukna (1991) presented aseries 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 andnoted superficial vasculitis and necrosis in in-volved areas, suggesting an ischemic effect fromthe vasoconstricting action of the cocaine.

Addicts who chew coca leaves often mix theleaf with slaked lime (calcium hydroxide) priorto use. The leaf wad is then chewed for 2 to 3h. This technique is reported to be frequentlyassociated with glossitis and leukoedema of thebuccal mucosal on the side where the wad is heldwhile being chewed. No evidence of epithelialdysplasia or malignancy was found, however, ina review of46 buccal biopsies obtained from cocaleaf chewers unless the individual was also usingalcohol and tobacco (Hamner and Villegas, 1969).

E. Amphetamines and RelatedCompounds

Stimulants such as amphetamines are sym-pathomimetic agents that induce tachycardia, va-

soconstriction, and elevated blood pressure. Lo-cal or systemic vasculitis and renal failure havebeen reported (Jenike, 1991). Most stimulants inthis class are prescription drugs, yet they are fre-quently abused because they cause a sense ofwell-being, combat sleepiness, suppress appetite,and are relatively easy to obtain. Tolerance de-velops with reasonable rapidity. Drugs in thiscategory include dextroamphetamine (dexed-rine), methamphetamine, phentermine, phen-metrazine, phenylpropanolamine, methylpheni-date, prophylhexedrine, and ephedrine (Jenike,1991; The Medical Letter, Inc., 1990). The drugsare usually swallowed or injected intravenously,but one solid form, d-methamphetamine (ice,crystal), can be smoked. Phenylpropanolamineis often found in over-the-counter medications(The Medical Letter, Inc., 1990). 3,4-Methyle-nedioxymethamphetamine (MDMA, ecstasy,XTC, Adam) is an underground amphetaminederivative that is highly toxic (Davis et al., 1987).Acute overdose of stimulants may feature severehyperthermia, hypertension, tachycardia, and oc-casionally refractory shock and death. Bruxismand 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 notdifficult, but profound psychologic dependencemay develop. Patients may become anxious, ex-tremely labile, and paranoid during withdrawal.Benzodiazepines, haloperidol, or propranolol maybe used during withdrawal. A long-lasting post-withdrawal depression may occur that requirestreatment with antidepressants (Jenike, 1991).Any of the above-mentioned therapeutic agentsmay 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 mayoccur as a direct or indirect consequence of al-cohol ingestion (Christen, 1983; Friedlander etal., 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 theworld (Christen, 1983). Additionally, it is fre-

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quently used by those who abuse illicit drugs;alcohol, along with tobacco, may often play asignificant role in the development of adversemedical and dental effects among drug abusers(Council on Dental Practice, 1987).

As many as 100 million Americans over theage of 15 regularly use alcohol, and an estimated12 million are alcohol abusers (Council on DentalPractice, 1987; Christen, 1983). Alcohol is beingconsumed with increasing frequency by childrenand young teenagers (Christen, 1983).

Unlike users of many of the illicit drugs ofabuse, alcoholics are found in all socioeconomicand educational strata. For example, alcohol abuseis reported to be very common among the Ab-origines of Australia, a group of low socioeco-nomic status, yet the condition is only somewhatless frequent in the general population of Aus-trialia (Thomson, 1984).

As a socially accepted mood-altering sub-stance, ethyl alcohol has been used throughouthistory for a variety of religious, societal, andmedicinal purposes. Alcohol is classified as acentral nervous system depressant, although in-itially, and in smaller quantities, it has a transientstimulatory effect (Christen, 1983).

Considerable controversy exists regardingfactors that lead to alcoholism. At present, itappears that a complicated combination of phys-iological and psychological factors interact toproduce a compulsion to ingest excessive amountsof the substance. There is strong evidence thatgenetic factors have a role in alcoholism. Alco-holism tends to run in families, while other typesof 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 environmentalinfluences conducive to alcohol ingestion, butstudies on adopted siblings and twins confirm thatidentical twins demonstrate a higher concordancerate for alcoholism than fraternal twins. Geneticfactors seem to play a role in individual responsesto alcohol, alcohol metabolism, and drinking pat-terns (Tabakoff and Hoffman, 1988).

As mentioned earlier, drug abusers also tendto 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 synergismbetween the genetic trait and psychiatric factors.In a recent review, West et al. (1986) noted thatat 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 forphysiological and biochemical markers that willbe predictive of the tendency. Some evidencelinks low levels of monoamine oxidase (MAO)and high blood levels of alanine transferase withalcoholic vulnerability. Liver enzymes such asalkaline phosphatase, aspartate aminotransferase(AST), alanine aminotransferase (ALT), andgamma glutamyl transferase (GGT) may be el-evated in habitual problem drinkers with liverdisease (Watson et al., 1986). Although suchresults are promising, to date no clearly distinc-tive biological markers have been identified (Ta-bakoff and Hoffman, 1988).

Other biologic factors tend to correlate withthe genetic risk of alcoholism. High genetic riskindividuals, for example, appear to have an in-nate tolerance to the substance and demonstrateless effect at ingestion levels that may be intox-icating for those who are not genetically at risk.Encephalographic changes are sometimes notedin alcoholics, suggesting altered neurotransmitterresponses in the brain (Tabakoff and Hoffman,1988).

Duggan et al. (1991) recently reported suc-cessful identification of alcoholism in families ofhospitalized 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 andthe families were distributed among all socio-economic and demographic strata. Pediatricianshad failed to recognize any but one of the alcohol-dependent families, suggesting that all familiesmust be screened if those with problems withalcohol 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 betweenexcessive alcohol consumption and medical dis-orders. The fetal alcohol syndrome is found in

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the offspring of mothers who consume relativelylarge quantities of alcohol during pregnancy. Thiscondition features fetal changes that includegrowth retardation, facial abnormalities, andmental retardation, but even moderate alcoholconsumption during pregnancy is associated withfetal effects such as low birth weight, especiallyif the mother also smoked cigarettes (Wright etal., 1983).

Chronic alcohol abuse has many metaboliceffects. Ethyl alcohol is principally metabolizedin the liver by means of a variety of pathways,including (1) ethanol dehydrogenase that con-verts ethanol to acetaldehyde, (2) the microsomalethanol 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 microsomalalterations in the microsomal ethanol-oxygenat-ing system associated with chronic use leads toenhanced metabolism of other drugs. This mayexplain the increased tolerance noted in alcohol-ics for local anesthetics and other drugs (Lieber,1987). There is also an increased conversion ofprescription drugs into potential hepatotoxins orcarcinogenic agents. Meanwhile, acute ethanolingestion may be associated with metabolic in-hibition of some drugs, increasing blood levelsof drugs and the risk of toxic effects (Lieber,1987; Kumar and Rex, 1991).

The sinusoidal cells that filter blood in theliver are adversely affected by alcohol ingestion,perhaps contributing to the accumulation of fatin the liver (Fraser et al., 1986). Phagocytosis isdecreased in the liver, altering the host resistanceto viral infection and perhaps predisposing thealcoholic to viral hepatitis.

Liver dysfunction may affect clearance ofvery low-density serum lipoproteins, putting thepatient at an increased risk for cardiovasculardisease (Girard et al., 1987). Folate deficiencyand other nutritional disorders may occur, suchas defects in storage of vitamin B12 and mega-loblastic or hemolytic anemia (Girard et al., 1987;Lindenbaum, 1987). Iron deficiency anemia mayoccur due to gastrointestinal bleeding, but serumiron levels are more often elevated (Lindenbaum,1987). Meanwhile, toxic effects of alcoholismresult in damage to bone marrow hematopoieticprecursor cells. Platelet function and numbers are

diminished (Lindenbaum, 1987, Javors andBowden, 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; Muftiet al., 1989). The cumulative results of thesehematologic disruptions include hemorrhagiccomplications associated with delayed coagula-tion, an increased tendency to cardiovascularthrombosis and altered response to infection (Gir-ard et al., 1987; Ballard, 1989).

Diseases of the skin have been associatedwith alcoholism by case reports, but there is littleevidence of specific cutaneous signs associatedwith alcohol ingestion. The cutaneous effects ofalcohol-related liver disease, alcohol-induced nu-tritional deficiency, and alcohol-related meta-bolic disturbances are, however, fairly well es-tablished (Shellow, 1983). Spider angiomata areprominently dilated subcutaneous arterioles thatmay appear on the face of individuals with al-coholic liver dysfunction. Small pinpoint to pea-sized white spots may also occur, reflecting aneurovascular dysfunction related to spiderangiomata.

Acnea rosacea does not occur exclusively inpatients with alcoholic liver disease, but it iscommonly associated with that disorder. Thecondition manifests as a flushing or rubefacienceof the skin, usually in the center of the face andoften affecting the nose, creating a bulbous,flushed condition known as rhinophyma (Rees,1980). Hepatic disease may be associated withjaundice or a dirty, gray pigmentation of skinknown as biliary melanoderma that is associatedwith liver cirrhosis (Shellow, 1983).

Nutritional deficiencies occur in alcoholicpatients 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 alcoholmay lead to iron loss from internal bleeding. Con-versely, iron levels sometimes increase in alco-holics due to ingestion of beer and wine or theexaggerated absorption of ferric iron caused bythe action of alcohol on gastric mucosa. Absorp-tion of nutrients is often impaired, however, and

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as mentioned earlier, metabolism in the liver maybe disrupted. Chronic pancreatitis occasionallyoccurs 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 affectimmune 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 andoral infections. It is also possible that alcohol-induced immune suppression may accelerate theprogress of disorders such as AIDS, diabetes mel-litus, malignancy, and many others (Dunne,1989).

Alcohol consumption may affect most cellsof the body, making tissues more sensitive tocarcinogens by increasing the permeability of cellmembranes (Mufti et al., 1989). Oral epithelialcells have been demonstrated to atrophy in ani-mals subjected to large quantities of ethanol. Basalcell pleomorphism occurs and there is a tendencytoward epithelial dysplasia. Valentine et al. (1985)studied tongue biopsies in humans who ingestedknown levels of alcohol and tobacco. In highalcohol and tobacco users, the lingual epitheliumwas thinner and the basal cell layer was hyper-trophied. These changes occurred in the absenceof clinically visible tissue damage. Informationsuch as this, coupled with the nutritional defi-ciencies and liver diseases commonly found inalcoholics, may signify that the host immune de-fenses are suppressed, while simultaneously oralepithelium is structurally altered. This may ren-der the individual or animal far more susceptibleto malignancy.

A direct relationship has been demonstratedbetween 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 capableof causing chemical irritation and increased ab-sorption of carcinogens dissolved in the alcohol.For example, beer and wine may contain a largerquantity of carcinogenic contaminants and theyare more closely associated with oral malignancythan whiskey, although some brands of Scotchwhiskey have been found to contain trace amounts

of the carcinogen N-nitrosodimethylamine(Baden, 1987).

Recently, Bergler et al. (1989) examined oralmucosal tissue samples for expression of epithe-lial growth factors. They compared tissue frompatients with oral squamous cell carcinoma againstsamples of tissue from patients who heavily usedalcohol and tobacco, but who had no tumors.Tumor-free nonsmokers and nondrinkers actedas 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 agentssuch as tobacco and alcohol may stimulate cel-lular proliferation and that such proliferation maybe 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 dryingeffect 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, thesubmandibular 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 glandsmay take place for unexplained reasons, leadingto xerostomia.

It is highly likely that the cellular changesassociated with the nutritional and metabolic ef-fects of alcoholism may predispose alcoholics tomore rapidly destructive periodontal disease, butthis has not been proven or adequately studied.Increased incidence of dental caries, periodontaldisease, and tooth loss has been described (Chris-ten, 1983; Friedlander et al., 1987; Kranzler etal., 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 increasedsecondary to an increased tendency to bruxism,especially during sleep (Christen, 1983; Fried-lander et al., 1987).

Increased incidence of craniofacial traumaand reduced responsiveness to local anestheticsoccur 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 systemdepressant effects of general anesthesia may bemore profound in the alcoholic patient (Grady etal., 1990). Increased tolerance to other drugssuch as the diazepines may occur, while drugmetabolism may be increased in alcoholic pa-tients free of liver disease and decreased in thosewith liver disorders. Alcoholic patients may beparticularly prone to postoperative bleedingdiatheses, 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 inthe brain and may affect the neuroendocrine sys-tem in a manner similar to cocaine, heroin, orother addictive drugs. Nicotine generates toler-ance and withdrawal symptoms, and it may serveas the initial drug of abuse in addicted individ-uals. The adverse effects of tobacco on the oralcavity have been reviewed recently (Christen etal., 1991) and, therefore, will not be included inthis review.

VIl. DENTAL MANAGEMENT

Dental management of the addicted patientis predicated on the clinician being aware of thepossibility of substance abuse in the Americanpopulation. In many instances, the patient maybe able to mask the addiction (Council on DentalPractice, 1987), but the alert practitioner maysometimes detect the previously described signsand symptoms. Williamson and Davis (1973)identified general symptoms of abuse as markedanxiety, multiple physical complaints, depres-sion, obsessive thoughts, belligerent behavior,paranoia, obesity, suicidal thoughts, and bizarreappearance 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

the opportunity to indicate an existing drug prob-lem. It is certainly proper to question the patientabout past and current use of drugs. If drug useis acknowledged, what is the substance beingused? What is the quantity and is it being usedcurrently? Close medical/dental coordination isimperative in the known or suspected drug abuser(Friedlander and Mills, 1985).

Scheutz (1986a) has demonstrated that par-enteral drug abusers are more anxious than thegeneral population and more fearful of dentaltreatment. On occasion, addictive patients mayuse their drug of preference prior to a dentalappointment to alleviate their anxiety. If thisshould occur, the dental treatment should be post-poned. If patients are receiving methadone main-tenance, it is probably best to continue regularadministration of the methadone throughout den-tal treatment to avoid development of withdrawalsymptoms (Jenike, 1991).

Parenteral drug abusers may experience a re-duced response to local anesthetics (Friedlanderand Mills, 1985; Bigwood and Coelho, 1990) andsignificantly larger amounts of anesthetics maybe required to provide pain-free dental therapy(Council on Dental Practice, 1987; Kimbrough,1975; Splaver and Williams, 1970). Parenteralabusers are also more prone to oral infections(Lewis, 1990).

Dental management of the cocaine-addictedpatient may prove frustrating because of the tend-ency to recurrent caries and periodontal diseaseassociated with any drug abuse. Managementshould be directed toward avoidance of a medicalemergency in the dental office. Addicts may havea tendency to premedicate themselves with co-caine prior to dental appointments to reduce theiranxiety. Therefore, careful observation of the pa-tient is necessary to detect symptoms of intoxi-cation. General anesthesia should be avoided andlocal anesthetics containing epinephrine shouldbe used with caution to prevent enhancement ofsympathomimetic effects of the drug. A specialconcern, 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 forcocaine-addicted patients. They advocated con-

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scious sedation plus local anesthesia for dentalprocedures. Benzodiazepines would be the ther-apeutic choice for sedation since these agents areused in treatment of cocaine toxicity. Patientsunder treatment should be carefully monitoredfor 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 patientis only suspected of alcohol abuse, the dentistshould consider the use of screening blood testsprior to the procedure. The following tests havebeen recommended: complete blood count withdifferential and platelet count, prothrombin time(PI), partial thromboplastin time (PTT), and se-quential multiple analysis (SMA) to include totalprotein, albumin, and liver transaminases suchas AST, ALT, and GGT. Of the transaminases,GTT may be the most sensitive indicator of liverdysfunction associated with alcohol abuse (Fried-lander et al., 1987). Patients with blood test ab-normalities should be referred to their physicianfor appropriate evaluation and treatment prior toperforming 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, whenpossible. If pain medication is necessary, aspirin,acetaminophen, or a nonsteroidal antiinflamma-tory agent such as ibuprofen is preferred (Councilon Dental Practice, 1987). These drugs may becontraindicated, however, if the patient is ex-periencing complications such as gastrointestinaldisorders, liver dysfunction, or a blood dyscrasia.If pain medication is required, only the minimalamount necessary should be prescribed and thepatient monitored carefully during use. If pain isrelatively severe, a mild narcotic such as codeinemay be necessary (Splaver and Williams, 1970).If so, medication should be controlled, if pos-sible, by a reliable family member or friend tominimize the chance of abuse (Council on DentalPractice, 1987).

Intravenous sedation and nitrous oxide oxy-gen sedation should probably be avoided due tothe potential for cardiovascular or respiratory de-pression in drug or alcohol abusers (Friedlanderand Mills, 1985; Kimbrough, 1975; Splaver and

Williams, 1970; Henry et al., 1990; Miers andSmith, 1989). Nitrous oxide oxygen itself is amood-altering inhalant capable of being abused,especially by dentists and others with access tothe 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 shouldbe avoided or only minimally prescribed. Use ofa mouth rinse with high alcohol content mighteven precipitate relapse into alcohol abuse in theabstaining polydrug abuser. It should also be notedthat some evidence exists to suggest an increasedrisk 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 sufferingfrom undiagnosed HBV or HIV infection or bepotentially susceptible to development of infec-tive endocarditis in the event dental treatmentinduces a bacteremia. Wound healing may bemarkedly retarded and patients may be especiallyprone to infection. All of these factors must betaken under consideration, but it is incorrect toassume that drug-dependent patients are unman-ageable. A basic knowledge of symptomatologycoupled with close medical/dental cooperation andconsideration of the patient's health status canresult in successful dental therapy without unduestress or risk to the addicted or abstaining drugabuser (Williamson and Davis, 1973).

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