Testing for the presence of tobacco, alcohol, other drugs, or all three is routine during insurance examinations, in the workplace, at roadside checks, in the military, and in the criminal justice system. The testing of athletes has become mainstream as team owners attempt to protect their multi-million dollar investments from drug-related loss of athletic skills. Testing has even led to controversy over whether marijuana should be on the list of banned substances, as it is performance detracting. Breath testing for alcohol has become a standard part of the roadside assessment for driving impairment. Successful drug-free outcomes for addiction treatment are defined by negative results on urine testing rather than by asking patients whether they have stopped using drugs. The definition of a drug-free employee is a negative result on preemployment and random drug tests.
Intoxication or overdoses are the common medical indications to test for drugs. However, testing should not be neglected when evaluating an individual with altered mood or behavior. Drug testing is an underused, but essential, part of the prevention, diagnosis, assessment, and treatment of substance abuse disorders.
HISTORY OF DRUG TESTING
Forensic drug testing has evolved from postmortem tests to identify drug overdoses to tests used to facilitate decisions in the legal and treatment systems. Drug screens have long been part of the routine work-up in the emergency department for patients who are unresponsive or confused on admission. However, drug tests alone cannot identify addiction or impairment. A blood test determines the concentration of a specific drug in the blood. This concentration is closely related to the amount of drug in the brain at the time the sample is taken. The amount of drug in other parts of the body can be correlated with blood and brain concentrations. Advances in the reliability and the repeatability of drug tests have resulted from increased quality control and documented control testing. Laboratories are now certified under the U.S. Department of Health and Human Services.1 Chain-of-custody handling now follows a sample from the time it is obtained, through its transport to the laboratory, and for as long as it is preserved.
Forensic standards for alcohol testing using breath and blood have evolved primarily for use in driving under the influence cases and federal regulations resulting from public transit accidents. Alcohol is the only drug of abuse tested by breath analysis. A number of instruments are available that can provide forensic quality even on the roadside when properly used and maintained. Direct measurement of alcohol concentration in a blood sample remains an option, but is not necessary for most forensic purposes.
Clinical correlations between concentrations in the body and effects on behavior are not well accepted for drugs of abuse other than tobacco and alcohol. Therapeutic and toxic levels have been established through clinical trials for prescription drugs.2,3 Knowledge of the behavioral effects of specific drugs and the likelihood that they are responsible for observed actions is still markedly enhanced by the documentation of specific drugs in a specific individual.
CHOICE OF SAMPLE FOR DRUG TESTING
Drugs and their metabolites can be isolated and identified in nearly all body fluids and tissues, even cerebrospinal fluid and vitreous humor.4 The fluids and tissues most commonly sampled in living humans include urine, blood, hair, sweat, saliva, and nails. Exhaled breath can also be easily sampled and tested for volatilized alcohol.
Urine testing for drugs and their metabolites has become more easily accessible. Mass produced urine test kits are currently available and can provide highly reliable, but not yet forensically acceptable, on-site results within minutes of sample collection.5"7 Standards related to workplace drug testing have been based on federal regulations8 and have been revised several times. Other than alcohol, which may be tested for by breath sampling, workplace drug testing is limited by federal guidelines to five drugs (ie, codeme-morphine, amphetamine-methamphetamine, phencyclidine [PCP], marijuana, and cocaine) and is performed only on urine. Heroin (diacetylmorphine) use is detected by testing mo^hine-positive specimens for 6-monoacetylmorphine, heroin's unique metabolite.9 Other drugs of abuse are not tested for and therefore are not detected, including lysergic acid diethylamide (LSD),10 methylenedioxymethamphetamine (MDMA), synthetic opiates (eg, hydromorphone hydrochloride, oxycodone hydrochloride, and fentanyl citrate and its analogues), and stimulants (eg, methylphenidate hydrochloride).
Advantages of urine testing include relative ease in obtaining a sample; well-accepted testing standards, including quantitative results11; ability to retain and retest samples, including chain-ofcustody option; approximate testing windows for commonly abused drugs; and relatively low cost. Disadvantages include privacy issues and sample dilution, substitution, and adulteration.12"14 Falsepositive results for opiates have received a great deal of attention. Poppy seeds contain some morphine and codeine; therefore, if a urine test has a positive result for mo^hine, this is accurate but may be wrong. Most experts consider opiate tests to have negative results without other clinical evidence of heroin use. The finding of 6monoacetylmorphine in the urine confirms heroin use, as poppy seeds do not contain this metabolite. Changing the cutoff value to 2,000 ng/mL for opiates also makes poppy seeds a nonissue, as they produce low levels of opiates in the urine.
Testing laboratories are continuously improving methods in an attempt to limit these problems by estabUshing personal urine profile characteristics,15 DNA testing for donor confirmation (D. I. MacDonald, MD, personal communication, 1999), and adjustment for differences in urine creatinine and pH in consecutive samples from the same donor.16 Testing has improved during the past decade, with the number of drugs that can be tested increasing and détection limits decreasing. Smaller concentrations of drugs of abuse are now detectable.
Blood sampling and testing can be performed for almost any drug or drug metabolite and is well standardized.17'18 This method of testing is highly quantitative, allowing distinction among light, moderate, and heavy use.19 Other advantages of blood testing include the ability to retain and retest the same sample, relatively few problems with sample tampering, and the availability of the chain-of-custody option. Drugs are generally rapidly cleared from the blood, resulting in a small window of detection. The presence of a drug in the blood is often the definition of intoxication. Blood testing is relatively expensive and invasive.
Hair is laid down in a matrix, growing outward from the follicle at a rate of approximately \i in per month. Ingested drugs are incorporated into the matrix, resulting in a chronological intake history. Approximately 1 week is required for hair to grow long enough for a sample to be clipped. Consequently, hair testing does not provide information about the prior week of drug use. A lx/4-in sample of hair can be used to identify drug use in the previous 90 days.
Some consider hair testing to be superior to urine, breath, or blood testing because it affords a wider window of detection.20 Hair testing presents fewer problems with dilution, substitution, and adulteration than does urine testing, allows for the chain-of-custody option, and minimizes privacy issues.
Analysis along the length of the hair sample allows for approximate time of use correlation.21 Incorporation rates, defined as the ratio of drug concentration in the hair to the area under the concentration versus time curve in plasma, are affected by the degree of basicity and lipophilicity of the particular drug.22,23 Interpretations about the intensity of drug use must be made with caution because of incorporation of drug from sweat (false higher results) and slow removal by washing false lower results).24 More significant drug use is required to create positive test results (a higher threshold), eliminating the positive results for opiate after poppy seed ingestion frequently seen with urine testing.25 Controversy exists regarding the possibility of differential incorporation of drug into hair of different melanin content.26,27 Some hair treatments, such as coloring, bleaching, perming, or straightening, may reduce drug levels, resulting in negative test results.28
Sweat patch testing uses tamper-resistant devices applied to the skin for several hours to 2 to 4 weeks that continuously absorb perspiration. Ingested drug is trapped in the absorbent interior of the patch and water escapes through the outer layer. After being removed, the patch is sent for laboratory testing. Sweat patch testing is currently available for codeine-morphine, amphetamme-memamphetamine, PCP, marijuana, and cocaine.29 Sweat patches for alcohol detection have already been tested, and patches for the detection of other drugs should be available in the near future.
Advantages of sweat patch testing include resistance to dilution, substitution, and adulteration; availability of the chain-of-custody option; approximate quantitation of the extent of drug use; and failure to produce positive results for opiate after poppy seed ingestion.
Saliva testing has been frequently used to detect the nicotine metabolite cotinine. More recently, saliva tests for cocaine, marijuana, opiates, amphetamines, benzodiazepines, barbiturates, PCP, and alcohol have been produced.30
Saliva testing is ininimally invasive compared with blood, urine, and hair testing and can easily be performed on-site. However, saliva testing can detect only recent drug use (past 6 to 12 hours) because saliva is continuously produced in equilibrium with blood.31 Also, there is currently no chain-of-custody option and it can be difficult to retain and retest samples.
Nail clippings from the fingers and the toes can also be used for testing. Ingested drugs are laid down in the nail matrix similarly to in the hair matrix. Rates of nail growth vary between fingernails and toenails and the windows of detection for these sources have yet to be determined, but do provide indications of chronic versus acute use.32'33
Multiple Substrate Testing
Combinations of the available test modalities improve the yield over one test modality. Use of the characteristics of the various tests allows the disadvantages of individual tests to be minimized. For example, in cases of narcotic overdose, the combination of urine, blood, and hair testing allows differentiation of acute versus chronic abuse34 and single versus multiple uses on the day of overdose.35 Testing different biological substrates is also usually essential for diagnosis. The finding of a single drug and its metabolites in high concentrations in multiple samples is strong evidence that the drug is responsible for an aberrant behavior or outcome.36
DIAGNOSIS OF ALCOHOL INTOXICATION AND THE DSM-IV
The diagnosis of alcohol intoxication, abuse, or dependence is a good case study of the role of testing in the DSM-IV37 or in psychiatry. Although the DSM-IV does not include alcohol testing in the diagnosis of alcohol intoxication, alcohol is the only drug for which intoxication has been legally defined solely on the result of a drug test. This has occurred despite the fact that the actual blood alcohol concentration (BAC) and the resulting behavioral effects of alcohol are influenced by many factors, including absorption, distribution, elimination, body weight, gender, rate of consumption, alcohol consumed, food, medication, fatigue, and tolerance. Although alcohol testing is a logical addition to the psychiatric diagnosis, what it means for a particular patient requires a full understanding of and the ability to interpret the test.
Blood Alcohol Concentration (BAC) and Its Effects
Blood Alcohol Concentration
Regardless of all the factors mentioned in the previous paragraph, BAC is used by federal and state law to prove impairment. As BAC increases, an individual's response to stimuli decreases markedly, speech becomes slurred, and he or she becomes unsteady and has difficulty walking (Table 1). At 25 to 50 mg/dL, changes in behavior are extremely variable and complex. The American Medical Association considers a BAC of 0.04 g/100 mL of blood (equivalent to 0.04 g /210 L of breath) to be impairment for all individuals. The state of Florida considers a motor vehicle operator to be legally under the influence at a BAC of 0.08 or greater. With high concentrations - greater than 0.35 g/ dL - an individual can become comatose and die.
DSMkV Criteria for the Diagnosis of Alcohol Intoxication
Although law enforcement and forensic criteria for alcohol intoxication are based entirely on BAC, a psychiatric diagnosis is entirely behavioral. The DSM-IV criteria for the diagnosis of alcohol intoxication are listed in Table 2.37Of note is the absence of any mention of measuring alcohol levels in the breath, blood, or urine. The DSM-IV relies on signs and behaviors, which are easily hidden or denied. Furthermore, the signs and behaviors are nonspecific and have questionable relevance to the core features of alcohol intoxication. The DSM-IV takes the addict or abuser at his or her word, something few addiction specialists would ever do. Denial of alcohol ingestion excludes criteria A, B, and C. In addition, the DSM-IV defines the diagnosis of alcohol intoxication on the basis of end stage, infrequently observed behaviors. Slurred speech is the first sign listed in criterion C. Actors instructed to sound drunk and intoxicated actors who attempted to sound sober have been shown to fool listeners more than half of the time.38 Drug testing can confirm the clinical suspicion of alcohol intoxication. It makes the diagnosis of alcohol intoxication more scientific, relevant, and accurate.
THE USE OF TESTING IN DRUG TREATMENT
Once the diagnosis of a substance use disorder has been made using the DSM-TV, drug testing continues to be an essential tool for the psychiatrist. The outcome or goal of most addiction treatment programs is drug-free status. Although selfreport is important, the psychiatrist cannot rely solely on the patient to report relapse because the disease of addiction is characterized by denial. When self-report is verified by random drug testing, the patient who has relapsed and is in denial will be identified. Additionally, a patient who has relapsed may realize that the result of the test could be positive and will be encouraged to admit the relapse and more toward a more solid recovery.
Drug testing has become standard procedure in new treatment development protocols so that investigators and the Food and Drug Adrninistration can detennine which patients given which treatment are drug-free for what length of time. Use of the DSM-ÎV or asking a patient has not survived as a reliable measure in treatment outcomes research. Such research requires objective measures of success or failure.
Maintenance drug treatment programs for recovering heroin addicts use drug testing. Continuation of methadone maintenance is often contingent on negative results of urine drug screening for other drugs.
The DSM-IV criteria fail to take advantage of the years of experience that addiction professionals have had using drug testing to confirm a diagnosis of dependence or abuse and to identify patients who are intoxicated. Laboratory tests for drugs of abuse, especially alcohol and tobacco, have become so common that it seems peculiar to us that psychiatrists have failed to incorporate them into practice.
However, laboratory tests alone cannot make a diagnosis of intoxication, dependence, or addiction. A positive result on testing for alcohol or other drugs does not prove anything other than the existence of that particular substance or its unique metabolite in the body. A measured level of illicit drug in a sample does not make a diagnosis. But, the result of a drug test does offer evidence that, when combined with appropriate history, physical examination, and collateral information, may enable the psychiatrist to more appropriately evaluate and care for a patient. We propose that the following criterion be added to the DSM-IV criteria for substance abuse: Presence of the drug of abuse or its metabolite in the patient's hair or body fluids.
1. Shults TF, St Clair S. The Medical Review Officer Handbook, 6th ed. Research Triangle Park, NC: Quadrangle Research; 1995:14.
2. Medical Economics Company. Physicians' Desk Reference, 53rd ed. Montvale, NJ: Medical Economics Company; 1999.
3. Repetto MR, Repetto M. Therapeutic, toxic, and lethal concentrations of 73 drugs affecting respiratory system in human fluids. J Toxical Clin Toxicol. 1998;36:287-293.
4. Prägst F, Spiegel K, Leuschner U, Hager A. Detection of 6acetylmorphine in vitreous humor and cerebrospinal fluid: comparison with urinary analysis for proving heroin administration in opiate fatalities. J Anal Toxicol. 1999; 23:168-172.
5. Crouch DJ, Frank JF, Farrell LJ, Karsch HM, Klaunig JE. A multiple-site laboratory evaluation of three on-site urinalysis drug-testing devices. J Anal Toxicol. 1998;22:493-502.
6. Wennig R, Moeller MR, Haguenoer JM, et al. Development and evaluation of immunochromatographic rapid tests for screening of cannabinoids, cocaine, and opiates Ln urine. J Anal Toxicol. 1998;22:148-155.
7. Crouch DJ, Cheever ML, Andrenyak DM, Kuntz DJ, LoughmiUer DL. A comparison of ONTRAK TESTCUP, abusereen ONTRAK, abuscreen ONLINE, and GC /MS urinalysis test results. J Forensic Sd. 1998;43:35-40.
8. U.S. Department of Health and Human Services. Mandatory Guidelines for Federal Workplace Drug Testing Programs. Federal Register. 1988;11979-11989.
9. Fuller DC. A statistical approach to the prediction of verifiable heroin use from total codeine and total morphine concentrations in urine. J Forensic Sci. 1997;42:685-689.
10. de Kanel J, Vickery WE, Waldner B, Monahan RM, Diamond FX. Automated extraction of lysergic acid diethylamide (LSD) and N-demethyl-LSD from blood, serum, plasma, and urine samples using the Zymark RapidTrace with LC /MS /MS confirmation, J Forensic Sci. 1998;43:622-625.
11. Poortman-van der Meer AJ, Huizer H. A contribution to the improvement of accuracy in the quantitation of THC. Forensic Sd Int. 1999;101:1-8.
12. Tsai SC, ElSohly MA, Dubrovsky T, Twarowska B, Towt J, Salamone SJ. Determination of five abused drugs in nitriteadulterated urine by immunoassays and gas chromatography-mass spectrometry. J Anal Toxicol. 1998;22:474-480.
13. Cone EJ, Lange R, Darwin WD. In vivo adulteration: excess fluid ingestion causes false-negative marijuana and cocaine urine test results. J Anal Toxicol. 1998;22:460-473.
14. Lewis SASr, Lewis LA, Tuinman A. Potassium nitrite reaction with 11-nor-delta 9-tetrahydrocannabinol-9-carboxylic acid in urine in relation to the drug screening analysis. J Forensic Sci. 1999;44:951-955.
15. Kapur B, Hershkop S, Koren G, Gaughan V. Urine fingerprinting: detection of sample tampering in an opiate dependency program. Ther Drug Monit. 1999;21:243-250.
16. Smith-Kielland A, Skuterud B, Morland J. Urinary excretion of amphetamine after termination of drug abuse. J Anal Toxicol. 1997;21:325-329.
17. Moeller MR, Steiruneyer S, Kraemer T. Determination of drugs of abuse in blood. J Chromatogr B Biomed Sd Appi 1998;713:91-109.
18. Collison IB, Spiehler VR, Guluzian S, Sedgwick PR. Setting cutoff concentrations for immunoassay screening of postmortem blood. J Forensic Sd. 1998;43:390-394.
19. Allen DL, Scott KS, Oliver JS. Comparison of solid-phase extraction and supercritical fluid extraction for the analysis of morphine in whole blood. J Anal Toxicol. 1999;23:216-218.
20. DuPont RL, Baumgartner WA. Drug testing by urine and hair analysis: complementary features and scientific issues. Forensic Sci Int. 1995;70:63-76.
21. Wainhaus SB, Tzanani N, Dagan S, Milier ML, Amirav A. Fast analysis of drugs in a single hair. J Am Soc Mass Spectrom. 1998;9:1311-1120.
22. Kikura R, Nakahaxa Y. Studies on mechanism of drug incorporation into hair. Kokuritsu lyakuhin Shokuhin Eisei Kenkyusho Hofaku. 1998;116:30-45.
23. Kalasinsky KS. Drug distribution in human hair by infrared microscopy. Cell MoI Biol. 1998;44:81-87.
24. Rothe M, Prägst F, Spiegel K, Harrach T, Fischer K, Kunkel J. Hair concentrations and self-reported abuse history of 20 amphetamine and ecstasy users. J Forensic Sci Int. 1997;89:111-128.
25. ElSohly MA, Jones AB. Source differentiation for morphine and codeine in urine: general guidelines. Forensic Sdence Review. 1989;1:14-22.
26. Kronstrand R, Forstberg-Peterson S, Kagedal B, Ahlner J, Larson G. Codeine concentration in hair after oral administration is dependent on melanin content. Clin Chem. 1999;45:1485-1494.
27. Hold KM, Hubbard DL, Wilkins DG, Rollins DE. Quantitation of cocaine in human hair: the effect of centrifugation of hair digests. J Anal Toxicol. 1998;22:414-417.
28. Takayama N, Tanaka S, Kizu R, Hayakawa K. High-performance liquid chromatography study on effects of permanent wave, dye and decolorant treatments on methamphetarnine and amphetamine in hair. Biomed Chromatogr. 1999;13:257-261.
29. Preston KL, Huestis MA, Wong CJ, Umbricht A, Goldberger BA, Cone EJ. Monitoring cocaine use in substance-abuse-treatment patients by sweat and urine testing. J Anal Toxicol. 1999;23:313-322.
30. Kidwell DA, Holland JC, Athanaselis S. Testing for drugs of abuse in saliva and sweat. J Chromatogr B Biomed Sci Appi. 1998;713:111-135.
31. Skopp G, Potsch L. Perspiration versus saliva: basic aspects concerning their use in roadside drug testing, lnt J Legal Med. 1999;112:213-221.
32. Garside D, Ropero-Miller JD, Goldberger BA, Hamilton WF, Maples WR. Identification of cocaine analytes in fingernail and toenail specimens. J Forensic Sci. 1998;43:974979.
33. Lemos NP, Anderson RA, Robertson JR. Nail analysis for drugs of abuse: extraction and determination of cannabis in fingernails by RIA and GC-MS. J Anal Toxicol. 1999; 23:147-152.
34. Kronstrand R, Grundin R, Jonsson J. Fatal cases of heroin overdose. Forensic Sci Int. 1998;92:29-38.
35. Levine B, Smialek JE. Considerations in the interpretation of urine analyses in suspected opiate intoxications. J Forensic Sd. 1998;43:388-390.
36. Weinmann W, Bohnert M. Lethal monointoxication by overdosage of MDEA. Forensic Sci Int. 1998;91:91-101.
37. American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders, 4th ed. Washington, DC: American Psychiatrie Association; 1994:194-204.\
38. Hollien H, DeJong G, Martin CA. Production of intoxication states by actors: perception by lay listeners. J Forensic Sd. 1998;43:1153-1162.
Blood Alcohol Concentration (BAC) and Its Effects
DSMkV Criteria for the Diagnosis of Alcohol Intoxication