- Email: [email protected]
Drug testing: Medical, legal, and ethical issues
Journal
of Substance Abuse Treatment, Vol. 7, pp.239-244, 1990
0740-5472/w
Printed in the USA. All rights reserved.
ORIGINAL
Copyright
0
$3.00 + .oo
1990Pergamon Press plc
CONTRIBUTION
Drug Testing: Medical, Legal, and Ethical Issues NORMANS. MILLER, MD,* A. J-s
GIANNINI, MD,+ MARK S. GOLD, MD,~ AND JAMES A. PHILOMENA, TD$
*Cornell University Medical College, New York Hospital-Cornell Medical Center, White Plains, New York; +Ohio State University, Northeast Ohio Universities College of Medicine, and Chemical Abuse Centers, Inc., Austintown, Ohio; $Fair Oaks Hospital, Summit, New Jersey; and *County Prosecutor, Mahoning County, Youngstown, Ohio
Abstract-Laboratory testing for drugs is a controversial ksue in America. The authors present arguments for mandatory use under specific circumstances. Physical limitations of each test are discussed in terms of applicability as well as protection of the person being tested. Keywords- Drug testing, privacy, legal issues, civil rights, drug abuse.
development of drug testing. Well-documented epidemics of drug use in American and world populations are currently demanding attention. The Occupational Safety and Health Act of 1970, known as OSHA, and the development of forensic techniques used in morgues and emergency rooms have stressed the importance of preventive drug testing. Furthermore, increased competition in the world marketplace has forced an attack on drug use to improve the safety of the worker as well as the productivity of the workplace (Paige, 1990). Today, governmental agencies, private corporations, amateur and professional bodies, and other organizations responsible for safety and performance are utilizing drug testing. Opponents to drug testing stress the rights of the individual to privacy. Ongoing debates and controversy will likely continue until a balance between the safety and health needs of the individual and of those with whom he or she interacts is finally developed. As practiced, drug testing can be performed anytime in the United States whenever there is an agreement between whoever is doing the testing and whomever is being tested. Legal contention may result when such an agreement does not exist and drug testing is imposed (National Treasury Employees Union v. von Raab, 1989). Nevertheless, with its social risks, drug testing can provide an effective tool and adjunct to industry and the courts. Medicine as a profession has been slow to adopt drug testing. This is curious, as medicine tends readily
MANDATORY LABORATORYTESTING for
drugs has arisen from a perceived need to reduce the prevalence of drug use. Movement in this direction accelerated when the United States Navy instituted routine laboratory testing for drugs after a Navy jet crashed on the aircraft carrier, USS Nimitz, in 1981. The crash left 14 sailors dead and 42 injured. The finding that changed the Navy’s operating procedure was that drug use was determined to be directly responsible for the crash. A prior survey in 1980 revealed that one-third to onehalf of the Navy’s junior enlisted officers smoked marijuana regularly. The Navy reduced the size of this problem by instituting drug testing for all military personnel. By August 1986, the number of sailors testing positive for drugs was less than 10%. Occupational drug testing originated in the American occupational medicine movement. In 1916, the American Association of Industrial Physicians and Surgeons (now known as AOMA - American Occupational Medicine Association) was formed. AOMA has now established medical departments throughout American industry. From this grew the EAP (Employee Assistance Programs) movement. This workplace-based movement has developed programs to assist the American employee with a drug problem towards a solution rather than job termination. Other major motivating factors have paralleled the
Request for reprints should be sent to A. James Giannini, MD, P.O. Box 2169, 3040 Belmont Avenue, Youngstown, OH 44504. 239
N.S. Miller
240
to favor and adopt testing procedures which improve diagnosis and treatment for a variety of conditions. A possible reason why drug testing has not been accepted in medicine is the intrinsic nature of chemical abuse and addiction. Physicians rely on patient cooperation and compliance for diagnostic tests they order. Drug abuse and addiction are conditions in which denial and resistance to both their detection and therapeutic modification are inherent. The denial and resistance reside in all those concerned, including the physician and the patient. Chemical abuse is often viewed as a personal preference under the control of the individual and not as an illness to be treated by medical practice. What is needed is a medical approach that includes an orientation towards intervention and treatment for substance abuse and addiction (Giannini, Gold, and Sternberg, in press). Physicians are powerful forces in the lives of those who are afflicted with drug and alcohol problems. Most abusers and addicts are seen by a physician at some point in their drug use for drug-related or coincidental health problems. A thorough history and examination for drug and alcohol use would yield enormous benefits for the patients. Drug testing from this perspective may be viewed as an integral part of the evaluation, just as a chest x-ray or EKG is for other conditions (Miller & Gold, 1987; Miller & Giannini, in press). Demography
The need for drug testing is illustrated by some statistical review. Random sampling has shown that one in six members of the United States federal work force uses illicit drugs regularly and 44% of all new employees had used drugs such as marijuana or cocaine within the prior year. One-third of applicants to the New York City Transit Authority had positive tests for drugs in their urine on preemployment screening. A spot check of U.S. Navy personnel in San Diego and Portsmouth in 1983 revealed 48% were smoking marijuana, but that this number was dramatically decreased to 2% after widespread adoption of screening program (Pottash, Gold, & Extein, 1982; Gold, Pottash, & Extein, 1984; White House, 1989). Of American alcoholics under the age of 30, 80% use another drug in addition to alcohol, most commonly marijuana, followed by cocaine and phencyclidine (PCP). Of all cocaine abusers, 98% have abused marijuana. Of opiate users, 50% to 75% have abused or are abusing marijuana, benzodiazepines, or cocaine. Ninety percent of Americans have at least tried alcohol, and 10% to 20% have difficulty controlling alcohol consumption. Twenty-five million Americans have at least tried cocaine: 5 to 6 million use it regularly.
et al.
Every year 12 to 13 million Americans abuse cocaine (Miller & Gold, in press; Miller, Millman, & Keskinen, 1989). Eighty-one million prescriptions were filled for Americans in 1985 for benzodiazepines. In 1985, 3.7 billion “benzodiazepines pills” were prescribed. This translates to 15 pills per each American child and adult or 148 pills prescribed per patient. The lifetime prevalence of abuse by those in the age range of 18 to 25 years old is 60.5% for marijuana, 11.5% for hallucinogens, 17.3% for stimulants, 11.0% for sedatives, 12.2% for tranquilizers, 11.4% for analgesics, and 1.2% for heroin. According to a U.S. Governmentsponsored survey, over half the American population has used marijuana, and substantial numbers have abused other drugs. Drug use is no longer the province of the less fortunate. Convenient cliches and stereotypes can no longer be used to explain drug abuse since drugs are abused by many, everywhere (National Institute on Drug Abuse, 1988). Diagnosis
Virtually any medical or psychiatric symptom or syndrome can be caused by drugs and alcohol. The symptoms and syndromes caused by drugs and alcohol are indistinguishable from other causes, including those of idiopathic origins. The only accurate and efficient way to differentiate among the various etiologies is to test for drugs, just as other disease pathologies would be tested for, that is, infectious processes are frequently confirmed by laboratory tests. The psychiatric syndromes produced by drugs and alcohol include mania, depression, anxiety disorders, personality disorders, schizophrenia, eating disorders, and delirium and dementia (organic mental disorders). The more common medical syndromes include gastrointestinal, cardiovascular, endocrinological, traumatic, rheumatological, and dermatological diseases. These conditions are produced either during the period of drug intoxication or withdrawal or both (Giannini & Miller, 1989). Cocaine, for instance, causes mania, personality disturbances, hypertension, cardiac arrhythmias, anorexia, and self-inflicted excoriating lesions of the skin during intoxication. During withdrawal, it produces depression with suicidal thinking, hyperphagia, and hypersomnia (Vereby, Gold, & Mule, 1986). PCP intoxication produces mania, personality disturbances with violent outbursts, hypertension, cardiac arrhythmias, and vivid visual and auditory hallucinations; PCP withdrawal is characterized by depression with suicidal thoughts (Giannini, Giannini, & Price, 1984). Heroin is associated with depression as well as endocarditis, arthritis, and other consequences of intravenous drug use (Weissman, Pottenger, & Kleber, 1977).
241
Drug Testing Issues
Inhalation of organic solvents produces organic brain syndromes such as delirium and dementia, cardiac arrhythmias, and hepatocellular damage (Miller & Giannini, in press; Giannini et al., in press). The diagnosis of a drug or alcohol problem is enhanced by having a suspicion of drug use under clinical conditions that suggest symptoms and signs of an abuse, addiction, tolerance, or dependence. Knowing the definitions of terms that are used to diagnose and describe drug problems is strongly suggested in order to utilize drug testing effectively and efficiently (Miller & Gold, 1987). Drug or alcohol “abuse” refers to the use of a psychoactive substance outside of an accepted norm or standard for a particular society. For instance, recreational use of certain drugs is generally accepted for relaxation or to complement a social or recreational event. Thus, alcohol, caffeine, khat, and even coca leaf are accepted in certain societies under certain conditions (Giannini, Price, Burge, & Shaheen, 1986). However, when the drug becomes the center or priority for the user, “abuse” is the term that applies. “Addiction” refers to a preoccupation with the acquisition of drugs, compulsive use in spite of adverse consequences, a pattern of recurrent use, relapse after abstinence, or an inability to control or reduce the use effectively. The manifestations of addiction are universal and transcend societal norms or standards of use (Jaffe, 1985). “Tolerance” is the need to increase a dose of a drug to maintain the same effect or, conversely, the loss of an effect at the same dose of a drug. “Dependence” is the appearance of signs and symptoms of distress upon the cessation of the drug. These “withdrawal” symptoms are stereotypic and predictable for a given drug. Furthermore, the signs and symptoms of withdrawal are suppressed by the drug. Tolerance and dependence are not specific for addiction. Addiction can occur with tolerance and/or dependence and conversely tolerance and dependence can occur without an addiction. Opiate analgesics can be used in the treatment of acute pain with the development of tolerance and a withdrawal syndrome but without a preoccupation, compulsive use, or relapse. Tolerance and dependence are usual adaptations of the brain and body to regular use. However, because addictive use is frequently regular, tolerance and dependence readily occur in addiction, that is, cocaine addiction (Miller, Dackis, & Gold, 1987). Also, the detection of tolerance may be limited by denial of use, low margin of tolerance, (e.g., alcohol) and a subtle, insidious onset of the tolerance. It is important to recognize obstacles to the clinical diagnosis in order to treat substance abuse successfully. These include denial, rationalization, and minimization. They are employed by the abusers as well
as their friends and family. Lack of skill and knowledge in the diagnosis of elements of abuse/addiction/tolerance/dependence, lack of awareness that effective treatments for drug and alcohol addiction are available, and restricted reimbursement for drug and alcohol problems complicate this. Drug testing aids in circumventing these obstacles by providing documentation and confirmation of drug use and addiction (Gold, Pottash, & Estroff, 1984; National Institute on Drug Abuse, 1988). Methodologies The analytical tests available for drug testing are of two basic types, chromatographic and competitive-binding/ immunoreactive. The available types of chromatographic techniques include thin layer chromatography (TLC), gas liquid chromatography (GLC), high-pressure liquid chromatography (HPLC), and combined gas chromatography-mass spectrometry (GWMS). The competitive-binding/ immunoreactive techniques are radioimmunoassay (RIA) and enzyme immunoassay (EIA) (Gold & Estroff, 1985; Vereby et al., 1986). The sensitivity and specificity of the drug test determines the utility of the test. “Sensitivity” is the ability to detect the presence of the drug at low levels. “Specificity” is the degree of accuracy of detecting only the drug desired. The tests used for the drug testing vary greatly in their sensitivity and specificity. Unfortunately, some of the laboratory tests most frequently used tend to be low in both sensitivity and specificity. Moreover, some tests are only qualitative and detect the presence of the drug without reliable information on the quantity of the drug. Only quantitative tests can give information on the amount of drug that is present (Gunn & Frank, 1975). The target of drug testing is either the parent drug or its metabolite. The urine and blood are both assayed, but the urine commonly contains 1000 times more drug than the blood. Blood, however, useful to identify recent use since detection indicates that the drug has not been present long enough to be biotransformed and eliminated (e.g., positive cocaine blood tests indicate abuse within 3-4 hours). Unfortunately, most drug screens are not standardized for either the number or types of drugs assayed. Also, the type of test performed for each drug varies from laboratory to laboratory. A clinician, therefore, must specify both the drugs of interest and the type of tests, otherwise only those drugs deemed routine by a particular laboratory will be done (Hansen, Caudill, & Boone, 1985; Stewart, 1989). The elimination time of a particular drug is important in legal situations. Some drugs have a relatively long elimination time (e.g., PCP) while others have a long-lived metabolite (e.g., marijuana). Even short-
242
acting drugs like cocaine are identified by the presence of their metabolites (e.g., cocaine is 98% eliminated from the blood in 5 hours, whereas the metabolite, benzoylecgonine is detectable for 2-4 days). Alcohol is metabolized quickly so that blood and urine are positive for only hours after last use. Its metabolites such as acetic acid are too common to the body to be reliably measured. The cutoff value is also critical in determining if a drug test is to be reported as positive or negative. The cutoff value is ordinarily selected by the laboratory, but can be specified by the physician. Frequently the level is set high to avoid false positives and litigation. A physician, however, can order whatever cutoff value is needed or desired. This, however, should be ordered according to strict diagnostic needs in medical cases and according to strict community standards in legal cases. In no case should arbitrary or “floating” cutoff levels be tolerated (Skinner v. Railway Labor Executives Association, 1989). The meaning of a positive or negative result should be carefully interpreted. A “false negative” result is a negative result from the test when the drug is actually present. A “false positive” result is the positive result from a test when the drug is not actually present. False negative results are far more common than false positive results. A study done by the CDC (Centers for Disease Control) found that 75% of the participating laboratories reported false negatives on a urine specimen containing 4000 ng/mL of the cocaine metabolite, far above concentrations that produce clinically evident symptoms. Another survey by the CDC confirmed the high rate of false negative results by finding 91% of the laboratories had unacceptably high false negative rates for cocaine and benzoylecgonine. Marijuana, PCP, LSD, and other commonly used/ abused illicit drugs are not identified at all in most TLC systems. False positive results are quite unusual but can be reduced with a more specific test such as GC-MS (Kogan, Verebey, & DePace, 1977). Unfortunately, other more specific tests are not always used as backups in the workplace or the courts. Another problem arising from the use of drug testing is due to ordering and interpreting of a myriad of clinical variables. Detectability of the drug depends on the type of drug, size of the dose, frequency of use, route of administration, and individual variation of drug metabolism. These variables are dependent on the size of the last dose, the sample collection time, and the sensitivity of the analytical method used for drug testing. These variables are infrequently explored in evidentiary proceeding in the American courts and rarely in job settings (Turner, El-Sohly, & Martin, 1989; Stewart, 1989). TLC is often used to screen for drugs. It is relatively fast and inexpensive but requires an experienced technician to read the TLC plates. TLC, furthermore,
N.S. Miller
et al.
is a qualitative test and cannot be quantified; it yields only a “positive” or “negative” result. Another major drawback is its low sensitivity and low specificity. The minimum amount of drug or metabolite necessary to yield a positive result is 1000-2000 n/mL. Also, because of subjectivity in the interpretations of results, admissibility in hearings and trials is questionable. TLC relies on a reproducible migration pattern by the drug on a thin layer (e.g., a silica-coated glass plate). Characterization of a particular drug is achieved by color reactions produced by spraying the plate with color-complexing reagents. This method was designed to detect very high-dose recent drug use or toxic blood levels of a large variety of drugs. It is often used in the emergency room, where the drugs taken are unknown and quick determination of toxic levels is necessary (Turner et al., 1989; Vereby, Gold, 8~ Mule, 1986). Lower levels of drugs relevant to producing behavioral changes are not detected with TLC, nor are TLC screens generally admissible as forensic evidence. TLC should be ordered with extreme caution and interpreted with suspicion. Negative results for cocaine and other drugs are meaningless by TLC method, and positive results should be confirmed by a second, more specific method because of TLC’s low specificity and sensitivity (Gold & Dackis, 1986). GLC is an analytical method that separates molecules by use of a glass or metal tube that is packed with material of a particular polarity. A sample of drug is vaporized at the injection site and carried through the column by a steady flow of gas. The column terminates at a detector that permits recording and quantification. The time required to pass through the column is the “retention time.” Each drug has a unique retention time in a given column. HPLC is similar to GLC. The major difference is the use of liquid rather than a gas to propel the sample through the column in HPLC. Some drug classes are better chromatographed on HPLC (i.e., tricyclic antidepressants and benzodiazepines), while other drugs are better detected with GLC, (e.g., marijuana) so that they are complementary in a given laboratory. GLC and HPLC are significantly more specific and sensitive than TLC (Kogan et al., 1977). The ultimate laboratory method of detection is by gas chromatography-mass spectrometry (GC-MS). GC-MS analyzes a drug according to its fragmentation pattern. Weaker bonds of the molecules are broken under stress to produce a fragmentation pattern. A perfect match with a fragmentation pattern in a computer library is considered an absolute confirmation of the drug and is referred to as “fingerprinting” of the molecules. The range of sensitivity for the drugs is below 50 ng/mL. This is 100 to 1000 times more sensitive and far more specific than the TLC system. Common drugs of abuse and addiction are readily identified in low amounts (i.e., marijuana, cocaine,
Drug Testing Issues heroin). The expense of the technique make GC-MS impractical for routine screening but vital for confirmation of drug presence and identity. Because of the low amount of false positives, it is more commonly accepted in criminal court than any other test (Joseph, 1968). The RIA and EIA are immunologic methods that employ antibodies or enzymes against the specific drug. For ease of detection, these are labelled with a radioactive tracer. The antibody binding sites are limited in number. The number of radioactively tagged molecules displaced is used to calculate the amount of unlabeled drug in the mixture. Because the sensitivity and specificity are reasonably high, the EIA and RIA are commonly employed screening techniques. The major drawback is the cross-reactivity of drugs and metabolites with the antibodies. Cross-reactivity can produce a false positive result. In no case should RIA and EIA be used as anything more than a screen. Job security as well as legal prosecution should not depend on these tests. Drug Testing in Treatment It is essential to have tight supervision over all aspects of specimen collection. Urine samples can be easily substituted, contaminated, or adulterated. Sealing the specimens ensures both the integrity of the specimen and protection of the subject. A first-void urine (the first urination in the a.m. has the highest concentration of drug) that is also tested for specific gravity (to detect dilution of urine) will be most likely to result in detection of a specific drug. The drugs of interest and the type of test to be employed need to be specified by the physician. The cutoff value for the sensitivity selected should be consistent with past tests. Drug testing during treatment acts to deter drug use as well as to identify abusers who relapse (NIDA, 1988; Turner et al., 1989). Drug testing can be a useful tool in treatment. It can also protect the abusing individual as well as the public in those special situations in which the effects of drug abuse present a clear danger. These include all aspects of the transportation industry, including private cars, trucks, trains, planes, and commercial shipping. Recent U.S. Supreme Court decisions support the constitutionality of mandated drug tests in these areas (Skinner v. Railway Labor Executive Association, 1989). Laboratory testing has likewise been ordered in those court cases where inadvertent drug ingestion may mitigate charges associated with the commission of the crime (Ohio v. Burke, 1982). Also, drug testing may be ordered if “reasonable” indirect concerns for public safety or welfare exist (National Treasury Employees Union v. von Raab, 1989). Conversely, courts have ruled that drug testing may not always be used as a screen where drug-related perfor-
243 mance danger has not been clearly demonstrated (National Treasury Employees Union v. von Raab, 1989). American society’s tolerance for drug abuse is decreasing (Paige, 1990). Abuse of illicit drugs has dropped 37%. Drug-related health risks and drug-related crime, however, are increasing (Presidential Documents, 1986; Russia’s antidrink campaign, 1989). As a result, the U.S. government as well as governments of most other nations have targeted the reduction of abuse as a major policy goal (Presidential Documents, 1986). In promoting the concept of a “drug-free workplace,” the White House has endorsed, through Executive Order 12584, mandatory laboratory testing for all employees in “safety-sensitive” positions (Presidential Documents, 1986). With the Executive Branch mandating drug testing for governmental employees and the Judicial Branch supporting the constitutionality of this testing, laboratory drug tests are part of the job landscape (White House National Drug Control Strategy, 1989). It is, therefore, not surprising that this mind-set has spread to the private sector. IBM, General Motors, and numerous other Fortune 500 companies require drug tests for all job applicants, regardless of whether these employees are in safety-sensitive positions. Laboratory drug tests are currently viewed by an increasing number of criminal courts as a nonextraordinary test, regardless of protests by defense attorneys (Stewart, 1989). While drug testing is still viewed as controversial, it enjoys broad public support (Hansen et al., 1985; Paige, 1990; White House National Drug Control Strategy, 1989). Since it appears that mandatory drug-testing will continue to be an expanding part of the American experience, it is important that these tests be intelligently applied. Familiarity with the capabilities and limitations of each test will do much to protect the individual even as the public’s interests are satisfied. REFERENCES Giannini, A.J. (in press). Tossicodipendenza e’ la psichiatrica moderna. Ricerce P Salute. Giannini, A.J., Giannini, M.C., & Price, W.A. (1984). Antidotal strategies in phencyclidine intoxication. International Journal of Psychiatry in Medicine, 4, 513-519. Giannini, A.J., Gold, M.D., & Sternberg, D.E. (Eds.). (in press). Treating drug abuse. New York: Marcel Dekker. Giannini, A.J., & Miller, N.S. (1989). Drug abuse: A biopsychiatric model. American Family Physician, 40(S), 173-182. Giannini, A.J., Price, W.A., Burge, H.M., & Shaheen, J. (1986). Khat: Another drug of abuse? Journal of Psychoactive Drugs, 18, 155-159. Gold, MS., & Dackis, C.A. (1986). Role of the laboratory in the evaluation of suspected drug abuse. Journal of Clinical Psychiatry, 47(Suppl), 17-23. Gold, M.S., & Estroff, T.W. 1985. The comprehensive evaluation of cocaine and opiate abusers. In R.C.W. Hall & T.P. Beresford (Eds.), Handbook of psychiatric diagnostic procedures. New York: Spectrum Publications.
244 Gold, MS., Pottash, A.L.C., & Estroff, T.W. (1984). Laboratory evaluation in treatment planning. In T.B. Karasu (Ed.), Thepsychiatric therapies: Part I. The somatic therapies. Washington, DC: American Psychiatric Association Commission of Psychiatry Therapies. Gold, M.S., Pottash, A.C., & Extein, I. (1984). The psychiatric laboratory. In J.G. Bernstein (Ed.), Clinicalpsychopharmacology (pp. 29-58). New York: John Wright PSG. Gunn, J.W., & Frank, R.S. 1975. Planning a forensic science lab. In J.L. Peterson (Ed.), Forensic science: Scientific investigation in criminal justice (pp. 289-300). New York: AMS Press. Hansen, H. J., Caudill, S.P., & Boone, D. J. (1985). Crisis in drug testing- Results of CDC blind study. Journal of the American Medical Association, 25, 2382-2387. Jaffe, J.H. (1985). Drug addiction and drug abuse. In A.G. Gillman, L.S. Goodman, T.W. Roll, & F. Murad (Eds.), The pharmacological basis of therapeutics (7th ed., Chapter 23, pp. 532-581). New York: Macmillan. Joseph, A. (1968). Study of needs and development of curricula in the field of forensic science. Crime laboratories: Three study reports. Laboratory Evaluation and Analysis (LEAA) Project Report, Washington, DC. Kogan, M.J., Verebey, K.G., & DePace, A.C. (1977). Quantitative determination of cocaine in human biofluids. Analytical Chemistry, 49, 1965-1969. Miller, N.S., Dackis, C.A., & Gold, M.S. (1987). The relationship of addiction, tolerance, and dependence: A neurochemical approach. Journal of Substance Abuse Treatment, 4, 197-207. Miller, N.S., & Giannini, A.J. (in press). Implication of concurrent drug abuse in alcoholics. Addictive Behaviors. Miller, N.S., & Gold, M.S. (1987). The medical diagnosis and treatment of alcohol dependence. Medical Times, 115(9), 109-126. Miller, N.S., & Gold, M.S. (in press). The diagnosis of alcohol dependence and cannabis dependence among cocaine addicts. Advances in Alcohol and Substance Abuse. Miller, N.S., Millman, R.B., Keskinen, S. (1989). The diagnosis of alcohol, cocaine, and other drug dependence in an inpatient
N.S. Miller et al. treatment population. Journal of Substance Abuse Treatment. 6, 37-40. National Institute on Drug Abuse. (1988). Medical review office manual: A guide to evaluation of urine drug analysis. Washington, DC: U.S. Government Printing Office. National Institute on Drug Abuse. (1985). National Household Survey on Drug Abuse. Washington, DC: U.S. Government Printing Office. National Treasury Employee’s Union v. von Raab, 86-1879 (U.S. Supreme Court 1989). Ohio v. Burke, C-193 (1982). Paige, C. (1990, January 1). Real enemy is nations drug habit: War on illegal drugs should be brought home. Chicago Tribune, section B, p. 15. Pottash, A.L.C., Gold, M.S., & Extein, I. (1982). The use of the clinical laboratory. In L.I. Sedered (Ed.), Inpatient psychiatry: Diagnosis and treatment. Baltimore: Williams & Wilkins. Presidential Documents. (1986). Executive Order 12584. Federal Register, 51, 180, September 17. Russia’s antidrink campaign. (1989). The Economist, 313(7634), 50-54. Skinner v. Railway Labor Executives Association, 1989, 87-1555 (U.S. Supreme Court 1989). Stewart, D.O. (1989). Slouching towards Orwell. Journal of American Bar Association. 100(6), 44-50. Turner, C.E., El-Sohly, M.A., & Martin, D.M. (1989). Laboratory and psychiatric aspects of drug testing. In A.J. Giannini & A.E. Slaby (Eds.), Drugs of abuse. Oradell, NJ: Medical Economics. Vereby K., Gold, M.S., &Mule, S.J. (1986). Laboratory testing in the diagnosis of marijuana intoxication and withdrawal. Psychiatric Annals, 16, 235-241. Weissman, N.M., Pottenger, M., & Kleber, H. (1977). Symptom pattern in primary depression: A comparison of primary depressives with depressed opiate addicts, alcoholics and schizophrenics. Archives of General Psychiatry, 34, 854-862. White House National Drug Control Strategy. (1989). Washington, DC: U.S. Government Printing Office.
of Substance Abuse Treatment, Vol. 7, pp.239-244, 1990
0740-5472/w
Printed in the USA. All rights reserved.
ORIGINAL
Copyright
0
$3.00 + .oo
1990Pergamon Press plc
CONTRIBUTION
Drug Testing: Medical, Legal, and Ethical Issues NORMANS. MILLER, MD,* A. J-s
GIANNINI, MD,+ MARK S. GOLD, MD,~ AND JAMES A. PHILOMENA, TD$
*Cornell University Medical College, New York Hospital-Cornell Medical Center, White Plains, New York; +Ohio State University, Northeast Ohio Universities College of Medicine, and Chemical Abuse Centers, Inc., Austintown, Ohio; $Fair Oaks Hospital, Summit, New Jersey; and *County Prosecutor, Mahoning County, Youngstown, Ohio
Abstract-Laboratory testing for drugs is a controversial ksue in America. The authors present arguments for mandatory use under specific circumstances. Physical limitations of each test are discussed in terms of applicability as well as protection of the person being tested. Keywords- Drug testing, privacy, legal issues, civil rights, drug abuse.
development of drug testing. Well-documented epidemics of drug use in American and world populations are currently demanding attention. The Occupational Safety and Health Act of 1970, known as OSHA, and the development of forensic techniques used in morgues and emergency rooms have stressed the importance of preventive drug testing. Furthermore, increased competition in the world marketplace has forced an attack on drug use to improve the safety of the worker as well as the productivity of the workplace (Paige, 1990). Today, governmental agencies, private corporations, amateur and professional bodies, and other organizations responsible for safety and performance are utilizing drug testing. Opponents to drug testing stress the rights of the individual to privacy. Ongoing debates and controversy will likely continue until a balance between the safety and health needs of the individual and of those with whom he or she interacts is finally developed. As practiced, drug testing can be performed anytime in the United States whenever there is an agreement between whoever is doing the testing and whomever is being tested. Legal contention may result when such an agreement does not exist and drug testing is imposed (National Treasury Employees Union v. von Raab, 1989). Nevertheless, with its social risks, drug testing can provide an effective tool and adjunct to industry and the courts. Medicine as a profession has been slow to adopt drug testing. This is curious, as medicine tends readily
MANDATORY LABORATORYTESTING for
drugs has arisen from a perceived need to reduce the prevalence of drug use. Movement in this direction accelerated when the United States Navy instituted routine laboratory testing for drugs after a Navy jet crashed on the aircraft carrier, USS Nimitz, in 1981. The crash left 14 sailors dead and 42 injured. The finding that changed the Navy’s operating procedure was that drug use was determined to be directly responsible for the crash. A prior survey in 1980 revealed that one-third to onehalf of the Navy’s junior enlisted officers smoked marijuana regularly. The Navy reduced the size of this problem by instituting drug testing for all military personnel. By August 1986, the number of sailors testing positive for drugs was less than 10%. Occupational drug testing originated in the American occupational medicine movement. In 1916, the American Association of Industrial Physicians and Surgeons (now known as AOMA - American Occupational Medicine Association) was formed. AOMA has now established medical departments throughout American industry. From this grew the EAP (Employee Assistance Programs) movement. This workplace-based movement has developed programs to assist the American employee with a drug problem towards a solution rather than job termination. Other major motivating factors have paralleled the
Request for reprints should be sent to A. James Giannini, MD, P.O. Box 2169, 3040 Belmont Avenue, Youngstown, OH 44504. 239
N.S. Miller
240
to favor and adopt testing procedures which improve diagnosis and treatment for a variety of conditions. A possible reason why drug testing has not been accepted in medicine is the intrinsic nature of chemical abuse and addiction. Physicians rely on patient cooperation and compliance for diagnostic tests they order. Drug abuse and addiction are conditions in which denial and resistance to both their detection and therapeutic modification are inherent. The denial and resistance reside in all those concerned, including the physician and the patient. Chemical abuse is often viewed as a personal preference under the control of the individual and not as an illness to be treated by medical practice. What is needed is a medical approach that includes an orientation towards intervention and treatment for substance abuse and addiction (Giannini, Gold, and Sternberg, in press). Physicians are powerful forces in the lives of those who are afflicted with drug and alcohol problems. Most abusers and addicts are seen by a physician at some point in their drug use for drug-related or coincidental health problems. A thorough history and examination for drug and alcohol use would yield enormous benefits for the patients. Drug testing from this perspective may be viewed as an integral part of the evaluation, just as a chest x-ray or EKG is for other conditions (Miller & Gold, 1987; Miller & Giannini, in press). Demography
The need for drug testing is illustrated by some statistical review. Random sampling has shown that one in six members of the United States federal work force uses illicit drugs regularly and 44% of all new employees had used drugs such as marijuana or cocaine within the prior year. One-third of applicants to the New York City Transit Authority had positive tests for drugs in their urine on preemployment screening. A spot check of U.S. Navy personnel in San Diego and Portsmouth in 1983 revealed 48% were smoking marijuana, but that this number was dramatically decreased to 2% after widespread adoption of screening program (Pottash, Gold, & Extein, 1982; Gold, Pottash, & Extein, 1984; White House, 1989). Of American alcoholics under the age of 30, 80% use another drug in addition to alcohol, most commonly marijuana, followed by cocaine and phencyclidine (PCP). Of all cocaine abusers, 98% have abused marijuana. Of opiate users, 50% to 75% have abused or are abusing marijuana, benzodiazepines, or cocaine. Ninety percent of Americans have at least tried alcohol, and 10% to 20% have difficulty controlling alcohol consumption. Twenty-five million Americans have at least tried cocaine: 5 to 6 million use it regularly.
et al.
Every year 12 to 13 million Americans abuse cocaine (Miller & Gold, in press; Miller, Millman, & Keskinen, 1989). Eighty-one million prescriptions were filled for Americans in 1985 for benzodiazepines. In 1985, 3.7 billion “benzodiazepines pills” were prescribed. This translates to 15 pills per each American child and adult or 148 pills prescribed per patient. The lifetime prevalence of abuse by those in the age range of 18 to 25 years old is 60.5% for marijuana, 11.5% for hallucinogens, 17.3% for stimulants, 11.0% for sedatives, 12.2% for tranquilizers, 11.4% for analgesics, and 1.2% for heroin. According to a U.S. Governmentsponsored survey, over half the American population has used marijuana, and substantial numbers have abused other drugs. Drug use is no longer the province of the less fortunate. Convenient cliches and stereotypes can no longer be used to explain drug abuse since drugs are abused by many, everywhere (National Institute on Drug Abuse, 1988). Diagnosis
Virtually any medical or psychiatric symptom or syndrome can be caused by drugs and alcohol. The symptoms and syndromes caused by drugs and alcohol are indistinguishable from other causes, including those of idiopathic origins. The only accurate and efficient way to differentiate among the various etiologies is to test for drugs, just as other disease pathologies would be tested for, that is, infectious processes are frequently confirmed by laboratory tests. The psychiatric syndromes produced by drugs and alcohol include mania, depression, anxiety disorders, personality disorders, schizophrenia, eating disorders, and delirium and dementia (organic mental disorders). The more common medical syndromes include gastrointestinal, cardiovascular, endocrinological, traumatic, rheumatological, and dermatological diseases. These conditions are produced either during the period of drug intoxication or withdrawal or both (Giannini & Miller, 1989). Cocaine, for instance, causes mania, personality disturbances, hypertension, cardiac arrhythmias, anorexia, and self-inflicted excoriating lesions of the skin during intoxication. During withdrawal, it produces depression with suicidal thinking, hyperphagia, and hypersomnia (Vereby, Gold, & Mule, 1986). PCP intoxication produces mania, personality disturbances with violent outbursts, hypertension, cardiac arrhythmias, and vivid visual and auditory hallucinations; PCP withdrawal is characterized by depression with suicidal thoughts (Giannini, Giannini, & Price, 1984). Heroin is associated with depression as well as endocarditis, arthritis, and other consequences of intravenous drug use (Weissman, Pottenger, & Kleber, 1977).
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Inhalation of organic solvents produces organic brain syndromes such as delirium and dementia, cardiac arrhythmias, and hepatocellular damage (Miller & Giannini, in press; Giannini et al., in press). The diagnosis of a drug or alcohol problem is enhanced by having a suspicion of drug use under clinical conditions that suggest symptoms and signs of an abuse, addiction, tolerance, or dependence. Knowing the definitions of terms that are used to diagnose and describe drug problems is strongly suggested in order to utilize drug testing effectively and efficiently (Miller & Gold, 1987). Drug or alcohol “abuse” refers to the use of a psychoactive substance outside of an accepted norm or standard for a particular society. For instance, recreational use of certain drugs is generally accepted for relaxation or to complement a social or recreational event. Thus, alcohol, caffeine, khat, and even coca leaf are accepted in certain societies under certain conditions (Giannini, Price, Burge, & Shaheen, 1986). However, when the drug becomes the center or priority for the user, “abuse” is the term that applies. “Addiction” refers to a preoccupation with the acquisition of drugs, compulsive use in spite of adverse consequences, a pattern of recurrent use, relapse after abstinence, or an inability to control or reduce the use effectively. The manifestations of addiction are universal and transcend societal norms or standards of use (Jaffe, 1985). “Tolerance” is the need to increase a dose of a drug to maintain the same effect or, conversely, the loss of an effect at the same dose of a drug. “Dependence” is the appearance of signs and symptoms of distress upon the cessation of the drug. These “withdrawal” symptoms are stereotypic and predictable for a given drug. Furthermore, the signs and symptoms of withdrawal are suppressed by the drug. Tolerance and dependence are not specific for addiction. Addiction can occur with tolerance and/or dependence and conversely tolerance and dependence can occur without an addiction. Opiate analgesics can be used in the treatment of acute pain with the development of tolerance and a withdrawal syndrome but without a preoccupation, compulsive use, or relapse. Tolerance and dependence are usual adaptations of the brain and body to regular use. However, because addictive use is frequently regular, tolerance and dependence readily occur in addiction, that is, cocaine addiction (Miller, Dackis, & Gold, 1987). Also, the detection of tolerance may be limited by denial of use, low margin of tolerance, (e.g., alcohol) and a subtle, insidious onset of the tolerance. It is important to recognize obstacles to the clinical diagnosis in order to treat substance abuse successfully. These include denial, rationalization, and minimization. They are employed by the abusers as well
as their friends and family. Lack of skill and knowledge in the diagnosis of elements of abuse/addiction/tolerance/dependence, lack of awareness that effective treatments for drug and alcohol addiction are available, and restricted reimbursement for drug and alcohol problems complicate this. Drug testing aids in circumventing these obstacles by providing documentation and confirmation of drug use and addiction (Gold, Pottash, & Estroff, 1984; National Institute on Drug Abuse, 1988). Methodologies The analytical tests available for drug testing are of two basic types, chromatographic and competitive-binding/ immunoreactive. The available types of chromatographic techniques include thin layer chromatography (TLC), gas liquid chromatography (GLC), high-pressure liquid chromatography (HPLC), and combined gas chromatography-mass spectrometry (GWMS). The competitive-binding/ immunoreactive techniques are radioimmunoassay (RIA) and enzyme immunoassay (EIA) (Gold & Estroff, 1985; Vereby et al., 1986). The sensitivity and specificity of the drug test determines the utility of the test. “Sensitivity” is the ability to detect the presence of the drug at low levels. “Specificity” is the degree of accuracy of detecting only the drug desired. The tests used for the drug testing vary greatly in their sensitivity and specificity. Unfortunately, some of the laboratory tests most frequently used tend to be low in both sensitivity and specificity. Moreover, some tests are only qualitative and detect the presence of the drug without reliable information on the quantity of the drug. Only quantitative tests can give information on the amount of drug that is present (Gunn & Frank, 1975). The target of drug testing is either the parent drug or its metabolite. The urine and blood are both assayed, but the urine commonly contains 1000 times more drug than the blood. Blood, however, useful to identify recent use since detection indicates that the drug has not been present long enough to be biotransformed and eliminated (e.g., positive cocaine blood tests indicate abuse within 3-4 hours). Unfortunately, most drug screens are not standardized for either the number or types of drugs assayed. Also, the type of test performed for each drug varies from laboratory to laboratory. A clinician, therefore, must specify both the drugs of interest and the type of tests, otherwise only those drugs deemed routine by a particular laboratory will be done (Hansen, Caudill, & Boone, 1985; Stewart, 1989). The elimination time of a particular drug is important in legal situations. Some drugs have a relatively long elimination time (e.g., PCP) while others have a long-lived metabolite (e.g., marijuana). Even short-
242
acting drugs like cocaine are identified by the presence of their metabolites (e.g., cocaine is 98% eliminated from the blood in 5 hours, whereas the metabolite, benzoylecgonine is detectable for 2-4 days). Alcohol is metabolized quickly so that blood and urine are positive for only hours after last use. Its metabolites such as acetic acid are too common to the body to be reliably measured. The cutoff value is also critical in determining if a drug test is to be reported as positive or negative. The cutoff value is ordinarily selected by the laboratory, but can be specified by the physician. Frequently the level is set high to avoid false positives and litigation. A physician, however, can order whatever cutoff value is needed or desired. This, however, should be ordered according to strict diagnostic needs in medical cases and according to strict community standards in legal cases. In no case should arbitrary or “floating” cutoff levels be tolerated (Skinner v. Railway Labor Executives Association, 1989). The meaning of a positive or negative result should be carefully interpreted. A “false negative” result is a negative result from the test when the drug is actually present. A “false positive” result is the positive result from a test when the drug is not actually present. False negative results are far more common than false positive results. A study done by the CDC (Centers for Disease Control) found that 75% of the participating laboratories reported false negatives on a urine specimen containing 4000 ng/mL of the cocaine metabolite, far above concentrations that produce clinically evident symptoms. Another survey by the CDC confirmed the high rate of false negative results by finding 91% of the laboratories had unacceptably high false negative rates for cocaine and benzoylecgonine. Marijuana, PCP, LSD, and other commonly used/ abused illicit drugs are not identified at all in most TLC systems. False positive results are quite unusual but can be reduced with a more specific test such as GC-MS (Kogan, Verebey, & DePace, 1977). Unfortunately, other more specific tests are not always used as backups in the workplace or the courts. Another problem arising from the use of drug testing is due to ordering and interpreting of a myriad of clinical variables. Detectability of the drug depends on the type of drug, size of the dose, frequency of use, route of administration, and individual variation of drug metabolism. These variables are dependent on the size of the last dose, the sample collection time, and the sensitivity of the analytical method used for drug testing. These variables are infrequently explored in evidentiary proceeding in the American courts and rarely in job settings (Turner, El-Sohly, & Martin, 1989; Stewart, 1989). TLC is often used to screen for drugs. It is relatively fast and inexpensive but requires an experienced technician to read the TLC plates. TLC, furthermore,
N.S. Miller
et al.
is a qualitative test and cannot be quantified; it yields only a “positive” or “negative” result. Another major drawback is its low sensitivity and low specificity. The minimum amount of drug or metabolite necessary to yield a positive result is 1000-2000 n/mL. Also, because of subjectivity in the interpretations of results, admissibility in hearings and trials is questionable. TLC relies on a reproducible migration pattern by the drug on a thin layer (e.g., a silica-coated glass plate). Characterization of a particular drug is achieved by color reactions produced by spraying the plate with color-complexing reagents. This method was designed to detect very high-dose recent drug use or toxic blood levels of a large variety of drugs. It is often used in the emergency room, where the drugs taken are unknown and quick determination of toxic levels is necessary (Turner et al., 1989; Vereby, Gold, 8~ Mule, 1986). Lower levels of drugs relevant to producing behavioral changes are not detected with TLC, nor are TLC screens generally admissible as forensic evidence. TLC should be ordered with extreme caution and interpreted with suspicion. Negative results for cocaine and other drugs are meaningless by TLC method, and positive results should be confirmed by a second, more specific method because of TLC’s low specificity and sensitivity (Gold & Dackis, 1986). GLC is an analytical method that separates molecules by use of a glass or metal tube that is packed with material of a particular polarity. A sample of drug is vaporized at the injection site and carried through the column by a steady flow of gas. The column terminates at a detector that permits recording and quantification. The time required to pass through the column is the “retention time.” Each drug has a unique retention time in a given column. HPLC is similar to GLC. The major difference is the use of liquid rather than a gas to propel the sample through the column in HPLC. Some drug classes are better chromatographed on HPLC (i.e., tricyclic antidepressants and benzodiazepines), while other drugs are better detected with GLC, (e.g., marijuana) so that they are complementary in a given laboratory. GLC and HPLC are significantly more specific and sensitive than TLC (Kogan et al., 1977). The ultimate laboratory method of detection is by gas chromatography-mass spectrometry (GC-MS). GC-MS analyzes a drug according to its fragmentation pattern. Weaker bonds of the molecules are broken under stress to produce a fragmentation pattern. A perfect match with a fragmentation pattern in a computer library is considered an absolute confirmation of the drug and is referred to as “fingerprinting” of the molecules. The range of sensitivity for the drugs is below 50 ng/mL. This is 100 to 1000 times more sensitive and far more specific than the TLC system. Common drugs of abuse and addiction are readily identified in low amounts (i.e., marijuana, cocaine,
Drug Testing Issues heroin). The expense of the technique make GC-MS impractical for routine screening but vital for confirmation of drug presence and identity. Because of the low amount of false positives, it is more commonly accepted in criminal court than any other test (Joseph, 1968). The RIA and EIA are immunologic methods that employ antibodies or enzymes against the specific drug. For ease of detection, these are labelled with a radioactive tracer. The antibody binding sites are limited in number. The number of radioactively tagged molecules displaced is used to calculate the amount of unlabeled drug in the mixture. Because the sensitivity and specificity are reasonably high, the EIA and RIA are commonly employed screening techniques. The major drawback is the cross-reactivity of drugs and metabolites with the antibodies. Cross-reactivity can produce a false positive result. In no case should RIA and EIA be used as anything more than a screen. Job security as well as legal prosecution should not depend on these tests. Drug Testing in Treatment It is essential to have tight supervision over all aspects of specimen collection. Urine samples can be easily substituted, contaminated, or adulterated. Sealing the specimens ensures both the integrity of the specimen and protection of the subject. A first-void urine (the first urination in the a.m. has the highest concentration of drug) that is also tested for specific gravity (to detect dilution of urine) will be most likely to result in detection of a specific drug. The drugs of interest and the type of test to be employed need to be specified by the physician. The cutoff value for the sensitivity selected should be consistent with past tests. Drug testing during treatment acts to deter drug use as well as to identify abusers who relapse (NIDA, 1988; Turner et al., 1989). Drug testing can be a useful tool in treatment. It can also protect the abusing individual as well as the public in those special situations in which the effects of drug abuse present a clear danger. These include all aspects of the transportation industry, including private cars, trucks, trains, planes, and commercial shipping. Recent U.S. Supreme Court decisions support the constitutionality of mandated drug tests in these areas (Skinner v. Railway Labor Executive Association, 1989). Laboratory testing has likewise been ordered in those court cases where inadvertent drug ingestion may mitigate charges associated with the commission of the crime (Ohio v. Burke, 1982). Also, drug testing may be ordered if “reasonable” indirect concerns for public safety or welfare exist (National Treasury Employees Union v. von Raab, 1989). Conversely, courts have ruled that drug testing may not always be used as a screen where drug-related perfor-
243 mance danger has not been clearly demonstrated (National Treasury Employees Union v. von Raab, 1989). American society’s tolerance for drug abuse is decreasing (Paige, 1990). Abuse of illicit drugs has dropped 37%. Drug-related health risks and drug-related crime, however, are increasing (Presidential Documents, 1986; Russia’s antidrink campaign, 1989). As a result, the U.S. government as well as governments of most other nations have targeted the reduction of abuse as a major policy goal (Presidential Documents, 1986). In promoting the concept of a “drug-free workplace,” the White House has endorsed, through Executive Order 12584, mandatory laboratory testing for all employees in “safety-sensitive” positions (Presidential Documents, 1986). With the Executive Branch mandating drug testing for governmental employees and the Judicial Branch supporting the constitutionality of this testing, laboratory drug tests are part of the job landscape (White House National Drug Control Strategy, 1989). It is, therefore, not surprising that this mind-set has spread to the private sector. IBM, General Motors, and numerous other Fortune 500 companies require drug tests for all job applicants, regardless of whether these employees are in safety-sensitive positions. Laboratory drug tests are currently viewed by an increasing number of criminal courts as a nonextraordinary test, regardless of protests by defense attorneys (Stewart, 1989). While drug testing is still viewed as controversial, it enjoys broad public support (Hansen et al., 1985; Paige, 1990; White House National Drug Control Strategy, 1989). Since it appears that mandatory drug-testing will continue to be an expanding part of the American experience, it is important that these tests be intelligently applied. Familiarity with the capabilities and limitations of each test will do much to protect the individual even as the public’s interests are satisfied. REFERENCES Giannini, A.J. (in press). Tossicodipendenza e’ la psichiatrica moderna. Ricerce P Salute. Giannini, A.J., Giannini, M.C., & Price, W.A. (1984). Antidotal strategies in phencyclidine intoxication. International Journal of Psychiatry in Medicine, 4, 513-519. Giannini, A.J., Gold, M.D., & Sternberg, D.E. (Eds.). (in press). Treating drug abuse. New York: Marcel Dekker. Giannini, A.J., & Miller, N.S. (1989). Drug abuse: A biopsychiatric model. American Family Physician, 40(S), 173-182. Giannini, A.J., Price, W.A., Burge, H.M., & Shaheen, J. (1986). Khat: Another drug of abuse? Journal of Psychoactive Drugs, 18, 155-159. Gold, MS., & Dackis, C.A. (1986). Role of the laboratory in the evaluation of suspected drug abuse. Journal of Clinical Psychiatry, 47(Suppl), 17-23. Gold, M.S., & Estroff, T.W. 1985. The comprehensive evaluation of cocaine and opiate abusers. In R.C.W. Hall & T.P. Beresford (Eds.), Handbook of psychiatric diagnostic procedures. New York: Spectrum Publications.
244 Gold, MS., Pottash, A.L.C., & Estroff, T.W. (1984). Laboratory evaluation in treatment planning. In T.B. Karasu (Ed.), Thepsychiatric therapies: Part I. The somatic therapies. Washington, DC: American Psychiatric Association Commission of Psychiatry Therapies. Gold, M.S., Pottash, A.C., & Extein, I. (1984). The psychiatric laboratory. In J.G. Bernstein (Ed.), Clinicalpsychopharmacology (pp. 29-58). New York: John Wright PSG. Gunn, J.W., & Frank, R.S. 1975. Planning a forensic science lab. In J.L. Peterson (Ed.), Forensic science: Scientific investigation in criminal justice (pp. 289-300). New York: AMS Press. Hansen, H. J., Caudill, S.P., & Boone, D. J. (1985). Crisis in drug testing- Results of CDC blind study. Journal of the American Medical Association, 25, 2382-2387. Jaffe, J.H. (1985). Drug addiction and drug abuse. In A.G. Gillman, L.S. Goodman, T.W. Roll, & F. Murad (Eds.), The pharmacological basis of therapeutics (7th ed., Chapter 23, pp. 532-581). New York: Macmillan. Joseph, A. (1968). Study of needs and development of curricula in the field of forensic science. Crime laboratories: Three study reports. Laboratory Evaluation and Analysis (LEAA) Project Report, Washington, DC. Kogan, M.J., Verebey, K.G., & DePace, A.C. (1977). Quantitative determination of cocaine in human biofluids. Analytical Chemistry, 49, 1965-1969. Miller, N.S., Dackis, C.A., & Gold, M.S. (1987). The relationship of addiction, tolerance, and dependence: A neurochemical approach. Journal of Substance Abuse Treatment, 4, 197-207. Miller, N.S., & Giannini, A.J. (in press). Implication of concurrent drug abuse in alcoholics. Addictive Behaviors. Miller, N.S., & Gold, M.S. (1987). The medical diagnosis and treatment of alcohol dependence. Medical Times, 115(9), 109-126. Miller, N.S., & Gold, M.S. (in press). The diagnosis of alcohol dependence and cannabis dependence among cocaine addicts. Advances in Alcohol and Substance Abuse. Miller, N.S., Millman, R.B., Keskinen, S. (1989). The diagnosis of alcohol, cocaine, and other drug dependence in an inpatient
N.S. Miller et al. treatment population. Journal of Substance Abuse Treatment. 6, 37-40. National Institute on Drug Abuse. (1988). Medical review office manual: A guide to evaluation of urine drug analysis. Washington, DC: U.S. Government Printing Office. National Institute on Drug Abuse. (1985). National Household Survey on Drug Abuse. Washington, DC: U.S. Government Printing Office. National Treasury Employee’s Union v. von Raab, 86-1879 (U.S. Supreme Court 1989). Ohio v. Burke, C-193 (1982). Paige, C. (1990, January 1). Real enemy is nations drug habit: War on illegal drugs should be brought home. Chicago Tribune, section B, p. 15. Pottash, A.L.C., Gold, M.S., & Extein, I. (1982). The use of the clinical laboratory. In L.I. Sedered (Ed.), Inpatient psychiatry: Diagnosis and treatment. Baltimore: Williams & Wilkins. Presidential Documents. (1986). Executive Order 12584. Federal Register, 51, 180, September 17. Russia’s antidrink campaign. (1989). The Economist, 313(7634), 50-54. Skinner v. Railway Labor Executives Association, 1989, 87-1555 (U.S. Supreme Court 1989). Stewart, D.O. (1989). Slouching towards Orwell. Journal of American Bar Association. 100(6), 44-50. Turner, C.E., El-Sohly, M.A., & Martin, D.M. (1989). Laboratory and psychiatric aspects of drug testing. In A.J. Giannini & A.E. Slaby (Eds.), Drugs of abuse. Oradell, NJ: Medical Economics. Vereby K., Gold, M.S., &Mule, S.J. (1986). Laboratory testing in the diagnosis of marijuana intoxication and withdrawal. Psychiatric Annals, 16, 235-241. Weissman, N.M., Pottenger, M., & Kleber, H. (1977). Symptom pattern in primary depression: A comparison of primary depressives with depressed opiate addicts, alcoholics and schizophrenics. Archives of General Psychiatry, 34, 854-862. White House National Drug Control Strategy. (1989). Washington, DC: U.S. Government Printing Office.