dextromethorphan in wisconsin drivers* - journal of analytical

Journal of Analytical Toxicology, Vol. 31, May 2007

Dextromethorphan in Wisconsin Drivers*

Amy Cochems +, Patrick Harding, and Laura tiddicoat Wisconsin State Laboratory of Hygiene, Toxicology Section, 2601 Agriculture Drive, P.O. Box 7996, Madison, Wisconsin 53707-7996

Abstract I

Dextromethorphan is a synthetic analogue of codeine used in hundreds of over-the-counter medications for its antitussive effects. There have been numerous reports of dextromethorphan abuse by young adults. Dextromethorphan can produce psychoactive effects similar to that of marijuana, and higher doses will produce dissociative effects, including sensory enhancement and hallucinations. The Wisconsin State Laboratory of Hygiene examined data from blood samples submitted from January 1999 through December 2004 to determine the incidence of dextromethorphan in suspected impaired drivers. A total of 108 samples were found to be positive for dextromethorphan during this time. Dextromethorphan concentrations in these cases ranged from less than 5 to 1800 ng/mL (mean 207 ng/mL), compared to an expected therapeutic concentration range of 0.5-5.9 ng/ml.. Overall, the highest dextromethorphan concentrations observed were in males aged 16-20 years. Ninety-six percent of the specimens included in this study were also found to be positive for drugs other than dextromethorphan. A review of police and drug recognition expert reports from several of these cases showed that dextromethorphan-impaired drivers exhibited poor psychomotor performance on standardized field sobriety tests, horizontal gaze nystagmus, vertical gaze nystagmus, and overall signs of central nervous system depression.

Introduction

The Wisconsin State Laboratory of Hygiene (WSLH) Toxi- cology Section analyzes blood specimens from suspects in impaired driving cases. Over the last several years the WSLH has noted a marked increase in blood samples found to be positive for dextromethorphan. An examination of data from these samples was undertaken to characterize use and abuse of dextromethorphan in a driving population. Dextromethorphan (the d-isomer of 3-methoxy-N-methymorphinan) is a non- opioid synthetic analogue of codeine primarily used as an antitussive. It is available in liquid, tablet, capsule, and lozenge forms in hundreds of prescription and over-the-counter medications. When used as an antitussive, therapeutic doses of

* Presented at the Society of Forensic Toxicologists annual meeting in Nashville, TN, October 2005. Author to whom correspondence should be addressed. E-mail: [email protected],

dextromethorphan in adults (ages 12 and above) are 60-120 rag/day in divided doses. Peak plasma concentration after a single 20-rag dose was found to occur after 2.5 h (1). Thera- peutic doses for dextromethorphan yielded a plasma concentration range of 0.5-5.9 ng/mL (mean 2.4) for extensive metabolizers and 182-231 ng/mL (mean 207) for poor rnetabolizers (2). Approximately 7% of the Caucasian population and smaller proportions of the Chinese and African-American populations are poor rnetabolizers of dextromethorphan (3). Dextromethorphan is converted to its active metabolite dextrorphan via the cytochrome P450 2D6 isoenzyme (4) and has an elimination half-life of 3.2-3.6 h. Dextromethorphan is also prescribed in conjunction with opiate pain management therapy to mitigate tolerance (5).

There have been numerous reports of dextrornethorphan abuse, especially among teens and young adults. According to a popular drug users' Internet website, The Vaults of Erowid, Robitussin DM | and Coricidin HBP Cough and Cold | (CCC) tablets are frequently abused over-the-counter medications containing dextromethorphan (6). Each CCC tablet contains 30 mg of dextromethorphan and 4 mg of chlorpheniramine, and Robitussin DM contains 10 mg dextromethorphan per 5- mL dose and 100 mg of guaifenesin. Recreational doses are reported to begin at approximately 1.5 mg/kg (approximately 122 mg of dextromethorphan for a 180 Ib individual) and increase to more than 15 mg/kg. Low recreational doses are expected to result in effects such as general euphoria, balance disturbances, moderate stimulation, slight intoxication, inability to track time, and memory impairment similar to marijuana use. As the dextromethorphan dose increases, the resulting impairment can mimic that of a central nervous system (CNS) depressant and phencyclidine (PCP) such that the user experiences dysmetria and the inability to respond to pain and external stimuli. Minimal, if any, impairment is expected at therapeutic doses.

Since 1999, there have been several instances of dextrornethorphan impairment recorded by police Drug Recog- nition Experts (DRE) in Wisconsin. Using guidelines set forth by the Drug Evaluation and Classification (DEC) Training Pro- gram (7), DREs use clinical indicators such as pupil size and reaction to light, pulse, blood pressure, and body temperature, in addition to the battery of standardized field sobriety tests (SFST) (8), to identify impairment caused by one or more drug classes. The DEC program currently classifies dex-

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tromethorphan as a dissociative anesthetic, a group that also includes PCP and ketamine.

A retrospective evaluation of samples from Wisconsin drivers tested for drugs in addition to alcohol over a six-year period was undertaken to determine the incidence and characteristics of dextromethorphan use in this population.

Methods

Data from dextromethorphan-positive blood samples from impaired drivers submitted to the WSLH from 1999 to 2004 were compiled to examine age, gender, dextromethorphan concentration, alcohol concentration, and other drugs found in addition to dextromethorphan. Case histories are not rou- tinely provided when samples are submitted to the WSLH; however, histories from five DRE-evaluated cases involving four subjects were obtained and are presented to illustrate dextromethorphan impairment.

Whole blood specimens, treated with a combination of sodium fluoride and potassium oxalate, obtained from suspected impaired drivers were submitted to WSLH for testing. In the laboratory, specimens were initially tested for ethanol. Comprehensive drug testing for illicit, prescription, and other potentially impairing drugs was performed when requested, provided the blood ethanol concentration was less than 0.100 g/100 mL. Exceptions to this policy may be made on a case-by- case basis. Comprehensive drug analysis at the WSLH during the study period included two screening methods. Using an acetone precipitation extraction procedure, blood specimens were analyzed using the enzyme multiplied immunoassay technique (EMIT) on a Syva| | Plus analyzer for cannabinoids, cocaine, opiates, barbiturates, benzodiazepines, and PCP. The EMIT screen was followed by a separate liquid-liquid basic extraction and analysis by gas chromatography (GC) (Ag- ilent 5890 with a nitrogen-phosphorous detector or Shimadzu 2010 with a flame thermionic detector, both equipped with an HP-17, 15-m capillary column). Specimens with presumptive positive screening results were confirmed by GC with a mass selective detector (MSD) (Agilent 5890 GC with Agilent 5973 MSD, equipped with an HP-35, 15-m capillary column). Dex- tromethorphan is typically detected in the basic extraction. However, blood specimens with a dextromethorphan concentration of 1000 ng/mL and greater have been found to cross- react with the PCP EMIT assay in our laboratory. Confirmed positive dextromethorphan samples were quantitated using a separate modified alkaline liquid-liquid extraction analyzed by GC-MSD (Agilent 6890 GC with an HP-5 15-m capillary column and an Agilent 5973 MSD in selected ion monitoring mode) using ion 271 as the quantitation ion and 214, 171, and 150 as qualifiers. The standards in this method ranged from 10 to 250 ng/mL. The limit of quantitation for dextromethorphan using this method was 5 ng/mL. The highest standard concentration was 250 ng/mL, and specimens exceeding this concentration were diluted and re-extracted. The same screening, confirmation, and quantitative procedures were employed throughout the study period. Dextrorphan, the

major dextromethorphan metabolite, was not included in our testing protocol.

Results

From 1999 through 2004, the WSLH performed comprehensive drug testing on 13,439 blood samples from suspected impaired drivers. Of these submissions there were 108 specimens with a reported quantitative result for dextromethorphan. The incidence of positive dextromethorphan samples increased from 8 cases in 1999 to 34 in 2003, before declining to 21 in 2004 (Figure 1).

Of the 108 specimens studied, 58% were from male drivers (n = 63) and 42% were from female drivers (n = 45). The mean age for males was 29 years (median 23, range 16-68), and the mean age for females was 34 years (median 35, range 16-62). The mean dextromethorphan concentration for all specimens was 207 ng/mL (median 51, range < 5--1800). The mean dextromethorphan concentration for males was 249 ng/mL (median 59, range < 5-1800), and for females the mean concentration was 149 ng/mL (median 47, range < 5-1200). Mean dextromethorphan concentrations were also determined for each gender in selected age ranges (Figure 2).

Therapeutic dosing regimens generally produce dextromethorphan blood concentrations below 50 ng/mL. Fifty- one percent (n = 55) of the samples in this study had

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Figure 1. WSLH dextromethorphan cases 1999-2004.

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Figure 2. Age and mean dextromethorphan concentration, male versus female.

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Journal of Analytical Toxicology, Vol. 3 I, May 2007

dextromethorphan concentrations greater than 50 ng/mL (Figure 3). Within this group, the majority (65%) were males (n = 36) with a mean age of 25 years (median 20, range 17-68). Females (n = 19) had a mean age of 33 years (median 35, range 17-62). Dextromethorphan concentrations in six subjects were at or above 1000 ng/mL (range 1000-1800). Of these, four subjects were male, aged 17-24, and two were female, aged 18 and 19.

Of the 108 samples, 104 (96%) were found to be positive for other drugs in addition to dextromethorphan (Table I). Thirty- eight percent of these were positive for cannabinoids, 25% for chlorphenirarnine, 18% for ephedrine/pseudoephedrine, 18% for cocaine and/or cocaine metabolites, and 15% for one or more of the benzodiazepines. Ethanol was detected in 41% of the 108 cases with a mean blood ethanol concentration (BAC) of 0.030 g/100 mL (median 0.0, range 0.0-0.226).

Drug recognition expert cases Five of the cases in this study included complete DRE eval-

uation information. The dextromethorphan concentrations in this group ranged from 190 to 1000 ng/mL, with a mean concentration of 603 ng/mL (Table II). Two of these DRE evalua- tions were performed on the same subject during two separate traffic stops. All five DRE-evaluated cases were found to be positive for other drugs in addition to dextromethorphan. The DRE opinion in each case was that the subject was under the influence of a CNS depressant, with one subject additionally clas- sifted as being under the influence of a dissociative anesthetic.

SO-IN 101 - ~ 201 - 3eO 301-400 401-$00 ~ §

I X ~ r o m e t h o r l ~ m concemratlon (~VmL)

Figure 3. Dextromethorphan cases with concentrations > 50 ng/mL, male versus female.

Table I. Most Prevalent Drugs Found in Addition to Dextromethorphan

Drug n Percentage of Total

Ethanol 44 41 THC and metabolites 41 38 Chlorpheniramine 27 25 Ephedrine/pseudoephedrine 20 18 Cocaine and metabolites 19 18 Benzodiazepines 16 15 (diazepam most frequent)

All DRE-evaluated subjects demonstrated poor coordination, slurred speech, and ptosis. In all cases horizontal gaze nystagmus (HGN) and vertical gaze nystagmus (VGN) were present (Table III). Pupil dilation was noted in two cases, with rebound dilation observed in three cases. Reaction to light was slow in three cases and normal in the remaining two. The pulse was elevated in cases 3, 4, and 5, and in all but case 1, systolic blood pressure was either at the upper end or in excess of the normal range (Table IV). Body temperature was near normal for all but case 4. Results of the psychophysicai tests for the three subjects able to complete the walk-and-turn test showed at least six of eight total clues were present (Table V). For the four subjects that performed the one-leg-stand test a minimum three of four total clues were present. The four subjects completing the Romberg balance test exhibited at least a 2-in. sway.

DRE case histories Cases I and 2. A 20-year-old male was stopped for erratic

driving twice within three weeks by different police agencies. Officers recovered bottles of Robitussin Maximum Strength cough syrup and CCC pills in both cases. Arresting officers and DREs noted pronounced lethargy, slurred speech, and dilated pupils in both cases. During one evaluation, the subject con- tinually tipped over to the side and fell into a wall. The subject commented repeatedly that he abused cough syrup and cold pills to get high.

The subject's SFST performance during each arrest was poor. He was unable to maintain balance and demonstrated pronounced incoordination. HGN and VGN were both present, even at a resting state. The opinion of both DREs was that the subject was under the influence of a CNS depressant.

Toxicology findings for the first arrest were as follows: dextromethorphan, 340 ng/mL and sertraline, and norsertraline were reported as present. The second arrest revealed a dextromethorphan concentration of 190 ng/mL, chlorpheniramine at 130 ng/mL, and a BAC of 0.076 g/100 mL.

Table II. Toxicology Results for Dextromethorphan Cases Containing DRE Evaluation Information

Concentration BAC Case Drug Found (ng/mL) (g/100 mL)

I * Dextromethorphan 190 0.076 Chlorpheniramine 130

2* Dextromethorphan 340 ND Sertraline/norsertraline Present

3 Dextromethorphan 600 ND Atomoxetine 980 11 -nor-9-Carboxy-a% 11 tetrahydrocannabinol (THCCOOH) Sertraline/norsertraline Present

4 Dextromethorphan 970 ND Lorazepam 20

5 Dextromethorphan I000 0.033 Chlorpheniramine 380

* Same subject, two different arrests.

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Case 3. Sheriffs deputies responded to a report of a disabled vehicle parked approximately �90 on the roadway. The driver was an extremely incoherent 19-year-old male. He was unable to focus on the deputies' questions, was very confused, and seemed paranoid. The DRE noted that the subject's pupils did not constrict after exposure to a light stimulus. The subject was unable to form sentences and had great difficulty standing and walking. While trying to walk, the subject lifted each leg high into the air before placing it on the ground. His move- ments were very unsteady and showed a lack of coordination. Deputies recovered several cold medications and marijuana paraphernalia from the vehicle.

HGN and VGN were present, even at a resting state. The DRE noted the subject's difficulty focusing on a stimulus. The subject was so severely uncoordinated and unbalanced during the walk-and-turn test that the test was terminated for safety

Table III. DRE Eye Examination Observations

Eye Examination Case 1 Case 2 Case 3 Case 4 Case 5

Lack of smooth pursuit / / HGN at maximum deviation / / Onset prior to 45 ~ / / VGN ,/ / Pupil dilation Dilated Normal Rebound dilation / / Pupil reaction to light Normal Normal Lack of convergence ,/ None

,/ / / / / / / / / / / /

Dilated Normal Normal ,/ None None

Slow S low Slow ,/ ,/ None

Table IV. Observations of the Clinical Indicators by the DRE

Clinical Indicator* Case1 Case2 Case3 Case4 Case5

Pulse 86-88 74-80 124-132 98-147 90-106

Blood pressure 130/100 144/102 138/78 138/68 140/88

Body temperature 97.7 98.0 98.9 100.6 98.9

* Normal ranges: pulse, 60-90 bpm; blood pressure, 120-| 40/70-90; and body temperature, 98.6~

Table V. Clues and Observations Obtained by the DRE for the Psychophysical Tests

Field Test Case 1 Case 2 Case 3 Case 4 Case 5

Walk-and-turn (8 possible clues) 6 8 -* - 7

One-leg stand (4 possible clues) 4 4 4 - 3

Romberg 2 inch 2 inch 4-5 inch - 4 inch sway sway sway sway

* Unable to perform test.

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reasons. The one-leg-stand test was not attempted. After completing the evaluation, the DRE rendered an opinion that the subject was under the influence of a CNS depressant and cannabis.

Toxicology testing reported a dextromethorphan concentration of 600 ng/mL, 980 ng/mL of atomoxetine, 11 ng/mL of 11- nor-9-carboxy-A9-tetrahydrocannabinol, and both sertraline and norsertraline within therapeutic ranges. Ethanol was not detected.

Case 4. A 51-year-old male caused a multiple vehicle chain reaction accident. It was estimated that he was traveling be- tween 50 and 80 miles per hour in a 25 miles per hour zone. When officers arrived at the scene, the subject was wandering around the accident site limping. After much persuasion, the subject agreed to be transported to a hospital and receive med- ical treatment for injuries he had sustained in the crash. The subject stated that he enjoys using dextromethorphan and regularly consumes bottles of cough syrup.

A DRE was called in to perform an evaluation, but the subject was in a hospital bed and unable to perform SFSTs. The DRE obtained pulse and blood pressure information from the hospital monitors. Slurred speech, dysmetria, and lack of coordination were profound. HGN, VGN, and lack of convergence were present. The opinion of the DRE was that the subject was under the influence of a CNS depressant. The DRE also noted symptoms consistent with the use of a dissociative anesthetic. In response to a question regarding injuries sustained from the crash, the subject replied that he was not in- jured, but admitted experiencing some cramping in his left leg. He was later diagnosed with a fractured left hip socket.

Toxicology testing detected dextromethorphan at 970 ng/mL and lorazepam at 20 ng/mL. Ethanol was not detected.

Case 5. A witness reported an impaired driver to the police. When officers stopped the vehicle, they found a 19-year-old female driver who had 6 boxes of CCC with a total of 55 pills missing. Along with the cold medication, officers also found several empty 12-oz beer cans. The subject was noted to have poor balance and slurred speech.

The DRE observed that the subject's eyelids were droopy and her speech was slow. HGN and VGN were present. The subject was unable to maintain balance during both the walk- and-turn and one-leg-stand tests. The subject stated that she often takes 8 to 10 cold pills at a time because it feels "like a trip". When asked if she felt that the cold medication impaired her ability to operate a motor vehicle safely, she stated that she felt impaired. The DRE opined that the subject was under the influence of a CNS depressant.

Toxicology testing found a dextromethorphan concentration of 1000 ng/mL, chlorpheniramine at 380 ng/mL, and a blood ethanol concentration of 0.033 g/100mL.

Discussion

The incidence of subjects found to be driving after the in- gestion of dextromethorphan in Wisconsin increased during 1999 through 2004, as seen in Figure 1. Impaired driver blood specimens analyzed by the WSLH for drugs other than ethanol

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also increased during this period by 49% (from 1244 to 1859). This drug testing increase is due in large part to an overall increase in law enforcement awareness of drug-impaired drivers and an expanding DRE program in the state. The number of trained DREs in Wisconsin grew from 26 officers in 1999 to 100 in 2004.

Approximately half of the total sample population had dextromethorphan concentrations greater than 50 ng/mL, exceeding typical expected therapeutic concentrations. Although it is likely that the subjects in this group were abusing the drug, it is possible that some of these subjects were poor metabolizers and had used dextromethorphan appropriately. Males (58%) were found to drive after dextromethorphan use more frequently than females (42%), and they also abused the drug more frequently than females. Sixty-two percent of the subjects with dextromethorphan concentrations exceeding 50 ng/mL in this study were male.

Dextromethorphan abuse has been a concern since the 1960s (9). In 1990, responding to reports of dextromethorphan abuse from several sources, the Food and Drug Admin- istration (FDA) Drug Abuse Advisory Committee assessed dextromethorphan use by teenagers (10). The FDA concluded that the scope and significance of abuse, as well as the phar- macology of dextromethorphan, had not been fully character- ized and did not recommend placing the drug on the Federal Controlled Substance Schedule. According to the California Poison Control Systero (CPCS), from January I to October 1, 2000, there were 92 reported cases involving use of Coricidin HBP (11). Intentional abuse of the medication was reported in 71% of these cases. The vast majority (85%) of the patients in the CPCS report were in the age range of 13 to 17 years. The Wisconsin State Poison Center reported 392 dextromethorphan abuse cases from January 1, 2001 to October 31, 2006 (12). Seventy-eight percent (n = 306) of these cases involved users aged 13 to 19 years old. Within this age group, 173 of the cases were male and 133 were female. In the present study, 31% of the 108 subjects were under the age of 20 and had the highest dextroroethorphan concentrations, as illustrated in Figure 2. Within this age group, 79% of the subjects were male.

Even though the number of DREs increased during the study period, many areas of Wisconsin do not have DREs available. Only a few of the subjects in this study were evaluated by a DRE, and complete DRE evaluation information was available in only five cases. In all five of these cases, the DRE opinion was that the subjects were under the influence of a CNS depressant. According to the DEC program, an individual under the influence of a CNS depressant may exhibit HGN, VGN, and lack of convergence, with pulse and blood pressure below their normal ranges. In the DRE cases examined in this study, all subjects had HGN and VGN, with lack of convergence noted in three cases. Pulse and diastolic blood pressure were at the upper end or in excess of the normal range, consistent with a dissociative anesthetic rather than a CNS depressant. Like a CNS depressant, impairment exhibited by a dissociative anesthetic includes HGN, VGN, and lack of convergence, but pulse and blood pressure are elevated. In both the CNS depressant and dissociative anesthetic categories one would expect pupil sizes

to be normal. In the DRE cases reviewed here, pupil size was normal in three cases, but dilated in two. Rebound dilation, often associated with cannabis use, was present in three of the cases, only one of which actually had cannabinoids detected. Pupillary reaction to light was slow in three cases, consistent with CNS depressant use.

Elevated body temperature (> 99.6~ can be an indicator of dissociative anesthetic use. The subject in case 3 was the only DRE-evaluated subject with an elevated body temperature. Be- cause we did not test for the presence of fever reducers such as acetaminophen, which is commonly formulated with dextromethorphan, no conclusion can be inferred from the lack of body temperature elevation in the other four subjects.

The presence of drugs commonly associated with dextromethorphan use can make it difficult to categorize dextrornethorphan impairment. Ninety-six percent of the subjects in this study had additional drugs present. Chlorphenirarnine, ephedrine, and pseudoephedrine are commonly formulated with dextromethorphan in over-the-counter medications and are among the most prevalent drugs found in addition to dextromethorphan in this study. The commonly abused CCC tablets contain chlorphenirarnine in addition to dextromethorphan. Chlorphenirarnine, an antihistamine and CNS depressant that can cause HGN, decreased pulse and blood pressure, poor balance, and incoordination, was found in 25% of the subjects in this study. Eighteen percent of the subjects were found to be positive for ephedrine or pseudoephedrine, both of which are CNS stimulants that can cause symptoms such as increased pulse and blood pressure and dilated pupils. Over-the-counter products formulated with dextromethorphan and pseudoephedrine include Tylenol | Cold Plus Cough Con- centrated Drops, Sudafed | Severe Cold, and Thera-flu | Non- Drowsy Formula Maximum Strength.

Prior to 2006, dextromethorphan was classified by the DEC program as a CNS depressant. Currently, dextromethorphan is classified as a dissociative anesthetic. Much like PCP and ketamine, dextromethorphan is an n-MDA glutamate receptor an- tagonist. It is not surprising that individuals under the influence of dextromethorphan can exhibit impairment similar to that of PCP and other dissociative anesthetics, as described in case 4. ~pical PCP impairment includes blank stare, dis- orientation, hallucinations, dysmetria, and slow, slurred speech, many of the same behaviors observed in the five cases in this study. It is believed that the major metabolite dextrorphan is responsible for the PCP-like effects the dextromethorphan abuser experiences (13).

Conclusions

Dextromethorphan use in drivers shows no signs of abating. The number of positive dextromethorphan samples continues to increase in Wisconsin, with a 50% increase from 2004 to 2005. There is currently no specific EMIT assay for dextromethorphan; therefore, laboratories that rely strictly on enzyme immunoassay testing will not be able to detect this important drug. It is likely that persons abusing dextromethorphan will ex-

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hibit varying levels of impairment that may cross different drug categories, such as CNS depressant and dissociative anesthetic. Therefore, when evaluating cases in which dextromethorphan is involved, it is important to focus on observed impairment, not just DEC or pharmacological drug classifications.

References

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2. R.C. Baselt. Disposition of Toxic Drugs and Chemicals in Man, 5th ed. Chemical Toxicology Institute, Foster City, CA, 2000, pp 242-244.

3. UE. Pope, M.H. Khalil, J.E. Berg, M. Stiles, G.J. Yakatan, and E.M. Sellers. Pharmacokinetics of dextromethorphan after single or multiple dosing in combination with quinidine in extensive and poor metabolizers. J. Clin. Pharmaeol. 44:1132-1142 (2004).

4. L.A. Zawertailo, H.L. Kaplan, U.E. Busto, R.F. Tyndale, and E.M. Sellers. Psychotropic effects of dextromethorphan are altered by the CYP2D6 polymorphism: a pilot study. J. Olin. Psy- chopharmacol. 18:332-337 (1998).

5. T.H. Duedahl, J. Romsing, S. Moiniche, and J.B. Dahl. A qualita- tive systematic review of peri-operative dextromethorphan in post-operative pain. Acta Anaesthesiol. Scand. 50:1-13 (2006).

6. The Vaults of Erowid. DXM (dextromethorphan) vault, http://www.erowid.org/c hemicals/dxm/dxm.shtml, accessed March 2006.

7. Drug Evaluation and Classification Training Program, U.S. De- partment of Transportation, Transportation Safety Institute, Na- tional Highway Traffic Safety Administration, Washington, D.C., 2006.

8. M. Burns and H. Moskowitz, Psychophysical tests for DWl arrest, DOT-HS-5-01242. U.S. Department of Transportation, National Highway Traffic Safety Administration, Washington, D.C., 1977.

9. M.N. Darboe, G.R. Keenan, Jr., and T.K. Richards. The abuse of dextromethorphan-based cough syrup: a pilot study of the com- munity of Waynesboro, Pennsylvania. Adolescence 31: 633-644 (1996).

10. Food and Drug Administration. Drug Abuse Advisory Committee, Open Session, vol. 1. Public Health Service, Washington, D.C., 1990.

11. S. Banerji and I.B. Anderson. Abuse of Coricidin HBP cough and cold tablets: episodes recorded by a poison center. Am. J, Health Syst. Pharm. 58:1811-1814 (2001).

12. The Wisconsin Poison Control Center Annual Report. AAPCC Toxic Exposure Surveillance System, Milwaukee, WI, 2006.

13. J.l. Szekely, L.G. Sharpe, and J.H. Jaffe. Induction of phencyclidine-like behavior in rats by dextrorphan but not dextromethorphan. Pharm. Biochem. Behav. 40:381-386 (1991 ).

Manuscript received November 28, 2006; revision received February 2, 2007.

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dextromethorphan in wisconsin drivers* - journal of analytical

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