Concentration Distribution of the Marijuana Metabolite Ag ...

Journalof Analytical Toxicology,Vol. 32, July/August2008

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Concentration Distributionof the Marijuana Metabolite Ag-Tetrahydrocannabinol-9-CarboxylicAcid and the Cocaine Metabolite Benzoylecgoninein the Department of DefenseUrine Drug-TestingProgram'

John F. Jemionek1,t, Curtis t. Copley 2, Michael L. Smith 1, and Marilyn R. Past1

1Division of Forensic Toxicology, TheArmed ForcesMedical ExaminerSystem,Armed Forces Instituteof Pathology,

Rockville, Maryland 20850 and 2dNovus RDI, U.S.Army Medical Information TechnologyCenter,FortSam Houston,

SanAntonio Texas78234

[Abstract

Urine drug testing has been employed for punitive purposes by the Department of Defense since December 1981 (Memorandum 62884, Deputy Secretary of Defense Frank C. Carlucci). Federal Workplace Drug Testing Programs were initiated in response to Executive Order 12564 issued on September 15, 1986, that required Drug-Free Federal Workplaces be established. In their respective programs, a positive urine drug test may be referred to a military court martial or to an administrative board. To address safety and insurance requirements, the testing of civilians has expanded beyond Federal Programs to include pre-employment and post-accident urine drug testing. During adjudication, an Expert Toxicologist may be asked to opine what can be discerned from the concentration of drug or drug metabolite found in the urine. Little can be opined with certainty from a positive urine drug test as to the amount of drug ingested, when the drug was ingested, and in most instances, whether the individual felt the effects of the drug, or was under the influence of the drug found in the urine. What may be useful to both the Expert and to the Trierof-Facts is the frequency that a particular urine drug concentration is encountered in positive drug tests. The finding that 50% of all positive marijuana and cocaine urine metabolite concentrations in the military testing program over the three-year period of October 1, 2004 through September 30, 2007, are below a median value of 65 and 968 ng/mL, respectively, provide reference points. A median drug concentration combined with the percentile or frequency that a particular urine drug concentration occurs may provide evaluative information for a determination of the facts and the outcome of judicial or administrative proceedings. This may be especially useful to jurors when the concentration of marijuana or cocaine metabolite is perceptibly low. The information would also be applicable to medical review officers, medical examiners, drug treatment professionals, probation officers, and program analysts coordinating drug policy decisions.

" Disclaimer: The opinion nr assertions herein are those of the authors and do not ne(essarily reflect the view ~Jfthe Departments of the Army, Navy, or the Department of Defense. Author to whom correspondence ~hould be addre,.sed. [ mail: jemionek@afip.osd.rnil.

Introduction

There are a number of publications regarding the pharmacokinetics and urinary excretion profiles for marijuana and cocaine in controlled single and multiple dose studies (1-9). The cocaine excretion studies generally employed pure formulations of cocaine hydrochloride, while the marijuana excretory studies employed smoked marijuana, containing concentrations of 1.7% or 3.6% A~-tetrahydryocannabino[(THC) (1-4). The wide variability in excretory profiles between subjects is evident from the range of urine A~-tetrahydrocannabinol-9-carboxylic acid (THC-COOH) metabolite concentrations as a function of time. In testimony,an Expert may cite excretoryprofilestudies to opine that the concentration of drug identified in the urine may be consistent with an individual using a corresponding amount of drug within the cited time period of the study.

However, the purity of street cocaine and the increased potencyofmarijuana cultivars may differdramaticallyfromthe concentrations and purity of drugs(s) used in controlled laboratory studies.The purity of street cocainereported in 2005was predominantly 70-85% with a range of 5% to 95% (10). Likewise, the average THC content of marijuana has increased from 3.5% in 1985 to approximately 8.5% in 2007, with THC content as high as 27% in marijuana seized in the Northwest area of the U.S. (]1,12). A coca tea study demonstrated that urine collectedafter the oral ingestion of cocaine could screen positive for benzoylecgonine (BZE)using the Department of Defense (DoD) and the Federal Workplace Drug Testing Program immunoassay cutoff concentrations of 150 and 300 ng/mL, respectively (9). In light of these variables, interpretation of a urine drug test concentration may be facilitated by the knowledgeof the frequencythat a givendrug concentration is encountered and what percentage ofpositivedrug test specimens occur in a given range of drug concentrations.

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Journal of Analytical Toxicology, Vol. 32, July/August 2008

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The DoD urine drug-testing program database provided information on testing conducted within the uniformed military population overthe course ofthree years.The federalfiscalyear (FY) begins on October 1, ends on September 30, and is designated numericallyas the year in which it ends;for example,FY 2005 begins on October 1, 2004, and ends on September 30, 2005. During FY 2005 through 2007, a total of 11.28 million drug test results from ActiveDutyand Reservepersonnel were reported. By individual FY, 3.743 million, 3.784 million, and 3.754 million urine drug test results were reported in FY2005, FY2006, and FY2007, respectively.The databasewas reviewed for THC-COOHand BZE concentrations at or above the DoD gas chromatography-mass spectrometry (GC-MS) confirmatory test cutoff concentrations of 15 and 100 ng/mL, respectively, for FY2005 through 2007. Specimens collected for the reason "probable cause" made up no more than 6% of the THC-COOH-positivetest results and no more than 7% of the BZE-positivetest results reported in the data sets.

Data Collection and Analysis

A summary of individual drug-positive results by drug and drug concentration was obtained through the DoD Military Drug TestingProgram Office.The database captured the drug test results of urine specimens collected from Active Duty and Reservist personnel. No personal identifiers were provided and the data listed only the Service affiliation of the military member providing the specimen. The data were assembled and compiled as a function of the number of specimens encountered at various drug concentrations by fiscal year. A median drug concentration was used in the data analysis to minimize the influence of a small number of specimens, abovethe 95th percentile, so that a few specimens with extremely high drug concentrationwould not distort the statistical evaluation.

Results

Table I displaysthe distribution frequencyof THC-COOHat various concentration ranges for specimenstested in FY05-07. In specimens tested in FY05,a total of 13,804 specimens from Active Dutyand Reservemilitary personnel were identified as containing THC-COOHin urine equal to or above 15 ng/mL. The THC-COOHGC-MSconcentration in positive specimens ranged from 15 to 6129 ng/mL. The median THC-COOHconcentration in those specimens tested in FY05was 68 ng/mL. Based upon the number of positive samples observed, a 5 ng/mL interval was utilized in the percentile distribution for concentrations lessthan 130 ng/mLof BZE,and a 10 ng/mL interval was selected for concentrations between 130 and 199 ng/mL. Because of the lower frequency of specimens in the upper concentration ranges, 25, 100, and 1000 ng/mL intervals were subsequently utilized.

In specimens tested in FY06, there was an 8.5% decline in

the number ofTHC-COOHpositive specimens as compared to those tested in FY05, and a 6 ng/mL decrease in the median THC-COOH urine concentration for the specimens tested in those two years.For specimens tested in FY06,a total of 12,631 specimens from Active Duty and Reserve military personnel were identifiedas containing THC-COOHequal to or above 15 ng/mL. The THC-COOH positive specimen concentrations ranged from 15 to 4414 ng/mL. The median THC-COOHconcentration in those specimens tested in FY06was 62 ng/mL. For FY07,a total of 13,097 urine specimens from ActiveDuty and Reserve military personnel were identified as containing THC-COOH above 15 ng/mL. The THC-COOHpositive specimen concentration ranged from 15 to 4213 ng/mL. In those specimens tested in FY07,the median THC-COOHconcentration was 66 ng/mL.

Table II displaysthe distribution frequency for the cocaine metabolite, BZE, at various concentration ranges for specimens tested in FY05-07. In specimens tested in FY05,a total of 6647 specimens from Active Duty and Reserve military personnel were identified as containing BZE in urine equal to or greater than 100 ng/mL. The BZE GC-MSconcentration in positive specimens ranged from 100 to 1,387,585 ng/mL. The median BZE concentration in specimens tested in FY05was 892 ng/mL. Because of the declining frequency of positive specimens in the higher drug concentrations, various concentration intervals of 50, 250, 500, 1000, 5000, 10,000, and 100,000 ng/mL were selected in presentation of the data.

An 18.6% increase in the number of BZE-positive specimens was observed between FY05 and FY06. In specimens tested in FY06,a total of 7883 specimens from ActiveDutyand Reserve military personnel contained BZE equal to greater than 100 ng/mL.The BZEconcentration in positivespecimens ranged from 100 to 2,102,485 ng/mL. The median BZE concentration in specimenstested in FY06was 1016ng/mL,which is 13.9% higher than specimens tested in FY05.The doubling ofthe highest BZE concentration noted in specimens tested in FY06 as compared to specimens tested in FY05 did not affect the overall specimen concentration frequency distribution.

In FY07, a total of 7336 BZE positive specimens were identified. The concentration range was 100 ng/mL to 2,454,962 ng/mL. The median BZE concentration in specimens tested in FY07was 978 ng/mL

Table III summarizes the THC-COOHand BZE concentration data across all three fiscal years. A total of 39,532 THCCOOH-positive specimens were recorded with a median concentration of65 ng/mL.The THC-COOHconcentration ranged from 15 ng/mL to a high of 6129 ng/mL.

Atotal of21,866 BZEpositivespecimenswere recordedwith a median BZE concentration of 968 ng/mL. The BZE concentration ranged from a low of 100 ng/mL to a high of 2,454,962 ng/mL.

Discussion

The military population as a whole tends to be younger and more male-dominated than the general U.S.population. How-

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Journalof Analytical Toxicology,Vol. 32, July/August2008

Table I. Marijuana Metabolite THC-COOH Urine Drug Concentration and Positive Specimen Percentile Distribution for Fiscal Years 2005-2007

FY 2005 Marijuana Metabolite THC* Acid Positive Specimens*

FY 2006 Marijuana Metabolite THC Acid PositiveSpecimenst

FY 2007 Marijuana Metabolite THC Acid Positive Specimens*

Concentration Range (ng/mL)

Number of specimens

within range

Cumulative percentageof specimenswithin Percentof cutoffand total concentration specimens range

Number of specimens

within range

Cumulative percentageof specimenswithin Percenot f cutoffand total concentration specimens range

Number of specimens

within range

Cumulative percentageof specimenswithin Percentof cutoffand total concentration specimens range

15-19

494

3.6

3.6

20-24

734

5.3

8.9

25-29

891

6.5

15.4

30-34

944

6.8

22.2

35-39

841

6.1

28.3

40-44

724

5.2

33,5

45-49

609

4.4

37.9

50-54

526

3.8

41.7

55-59

485

3.5

45.3

60-64

386

2.8

48.1

65-69

380

2.8

50.8

70-74

324

2.3

53.2

75-79

277

2.0

55.2

80-84

293

2.1

57.3

85-89

281

2.0

59.3

90-94

230

1.7

61.0

95-99

233

1.7

62.7

100-104

176

1.3

64.0

105-109

194

1.4

65.4

110-114

172

1.2

66.6

115-119

165

1.2

67.8

120-124

154

1.1

68.9

125-129

148

1.1

70.0

130-139

266

1.9

71.9

140-149

227

1.6

73.6

150-159

222

1.6

75.2

160-169

178

1.3

76.5

170-179

162

1.2

77.6

180-189

161

1.2

78.8

190-199

159

1.2

79.9

200-224

299

2.2

82.1

225-249

247

1.8

83.9

250-274

212

1.5

85.4

478

3.8

3.8

788

6.2

10.0

942

7,5

17.5

923

7.3

24.8

830

6.6

31.4

693

5.5

36.8

567

4.5

41.3

464

3.7

45.0

4O9

3.2

48.2

370

2.9

51.2

322

2.5

53.7

290

2.3

56.0

256

2.0

58.0

260

2.1

60.1

193

1.5

61.6

195

1.5

63.2

192

1.5

64.7

180

1.4

66.1

165

1.3

67.4

139

1.1

68.5

145

1.1

69.7

148

1.2

7O.8

143

1.1

72.0

220

1.7

73.7

210

1.7

75.4

181

1.4

76.8

169

1.3

78.2

142

1.1

79.3

151

1.2

80.5

130

1.0

81.5

287

2.3

83.8

242

1.9

85.7

186

1.5

87.2

491

3.7

3.7

773

5.9

9.7

94O

7.2

16.8

985

7.5

24.3

795

6.1

30.4

676

5.2

35.6

538

4.1

39.7

465

3.6

43.2

421

3.2

46.5

384

2.9

49.4

340

2.6

52.0

305

2.3

54.3

263

2.0

56.3

227

1.7

58.1

227

1.7

59.8

215

1.6

61.4

197

1.5

62.9

178

1.4

64.3

161

1.2

65.5

164

1.3

66.8

144

1.1

67.9

154

1.2

69.0

134

1.0

70.1

247

1.9

72.0

209

1.6

73.6

213

1.6

75.2

192

1.5

76.6

175

1.3

78.0

150

1.1

79.1

136

1.0

80.2

281

2.1

82.3

250

1.9

84.2

235

1.8

86.0

Tablecontinues on next page

* Numberof specimenspositive13,804;medianconcentration68 nglmL. * Numberof specimenspositive12,631;medianconcentration62 nglmL. * Numberof specimenspositive13,097;medianconcentration66 nglmL.

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Journal of Analytical Toxicology, Vol. 32, July/August 2008

ever, drug use in the military is significantly lower in terms of age and gender demographic factors as compared to the civilian counterparts because of a rigorous drug education and testing program. The comparison of data between military and civilian urine drug test results may differ only in the number of drug positive specimens encountered rather than the distribution and percentile of drug concentrations observed. In the 2005 DoD Survey of drug use among military personnel (13), 6.8% of military personnel in the 18-25 age group in an anonymous survey instrument admitted to any drug use within the past 30 days.The percentages were 2.9% for the 26-55 military age group and 4.6% for all military in the 18 and older age group. In comparison, the 2006 Department of Health and Human Services (DHHS) National Survey on Drug Use and Health (14)found that 18.8% ofthe 18-25 age group admitted to any drug use within the past 30 days.The percentages in the 2006 DHHS National Survey were 8.3% for the 26-55 age group and 12.8% for those 18 years and older.

In the 2005 DoD Survey (13, 1.3% of all military personnel

admitted to marijuana use within the past 30 days. In comparison, the 2005 data reported in Monitoring the Future-National Results on Adolescent Drug Use (15) showed that 19.8% of 12th grade students admitted to marijuana use within the past 30 days. The 2006 DHHS National Survey on Drug Use and Health Report (14) cited a 6.8% and 16.6% past 30-day marijuana use among youths aged 12-17 and 18-25, respectively, for 2005.

In the 2005 DoD Survey (13), 0.6% of all military personnel admitted to cocaine use within the past 30 days as compared to 2.5% of 12th grade students (15). Past 30-day cocaine use for 2005 reported in the 2006 National Survey of Drug Use and Health cited a cocaine prevalence rate of 2.6% in the 18-25 age group and 1.0% for ages 12 and older.

In a news release dated June 2006 (16), Quest Diagnostics reported that in calendar year 2005, 4.5% of the general U.S. workforce samples tested by Quest Diagnostics were positive for drug(s). The Quest Diagnostics reported drug-positive rates for marijuana and cocaine of 2.54% and 0.7%, respectively.

Table I. Marijuana Metabolite THC-COOH Urine Drug Concentration and Positive Specimen Percentile Distribution for Fiscal Years 2005-2007 (Continued)

FY2005 MarijuanaMetaboliteTHC* Acid PositiveSpecimens*

FY2006 MarijuanaMetaboliteTHC AcidPositiveSpecimenst

FY2007 MarijuanaMetaboliteTHC Acid PositiveSpecimens*

Concentration Range (ng/mL)

Number of specimens

within range

Cumulative percentageof specimenswithin Percenot f cutoff and total concentration specimens range

Number of specimens

within range

Cumulative percentageof specimenswithin Percenot f cutoff and total concentration specimens range

Number of specimens

within range

Cumulative

percentageof

specimenswithin

Percenot f

cutoff and

total concentration

specimens

range

275-299

204

300-324

180

325-349

157

350-374

146

375-399

123

400-499

331

500-599

232

600-699

154

700-799

112

800-899

81

900-999

46

1000-1999

197

2000-2999

31

3000-3999

13

4000-4999

1

5000-5999

0

6000-6999

2

1.5

86.9

1.3

88.2

1.1

89.4

1.1

90.4

0.9

91.3

2.4

93.7

1.7

95.4

1.1

96.5

0.8

97.3

0.6

97.9

0.3

98.2

1.4

99.7

0.2

99.9

0.09

99.98

0.01

99.99

0.00

99.99

0.01

100.00

169

1.3

88.5

171

1.4

89.9

126

1.0

90.9

101

0.8

91.7

100

0.8

92.4

290

2.3

94.7

168

1.3

96.1

106

0.8

96.9

89

0.7

97.6

57

0.5

98.1

42

0.3

98.4

174

1.4

99.8

20

0.2

99.9

4

O.O3

99.97

4

0.03

100.00

0

0.00

100.00

0

0.00

100.00

181

1.4

169

1.3

155

1.2

120

0.9

110

0.8

320

2.4

215

1.6

155

1.2

95

0.7

59

0.5

53

0.4

171

1.3

22

0.2

6

0.05

1

0.01

0

0.00

0

0.00

87.4 88.7 89.9 90.8 91.6 94.1 95.7 96.9 97.6 98.1 98.5 99.8 99.9 99.99 100.00 100.00

100.00

* Number of specimens positive 13,804; median concentration 68 ng/mL. t Number of specimens positive 12,631; median concentration 62 ng/mL. * Number of specimens positive 13,097; median concentration 66 ng/mL.

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Journalof Analytical Toxicology,Vol. 32, July/August2008

Table II. Cocaine Metabolite BZE Urine Drug Concentration and Positive Specimen Percentile Distribution for Fiscal Years 2005-2007

FY 2005 Cocaine Melabolite BZE-Positive Specimens*

FY 2006 Cocaine Metabolite BZE-PositiveSpecimens*

FY 2007 Cocaine Metabolite BZE-Positive Specimens*

Concentration Range (ng/mL)

Cumulative

percentageof

Numberof

specimenswithin

specimens Percenot f cutoffand

within

total concentration

range specimens range

Number of specimens

within range

Cumulative percentageof specimenswithin Percenot f cutoffand total concentration specimens range

Numberof specimens

within range

Cumulative

percentageof

specimenswithin

Percenot f cutoffand

total

concentration

specimens range

100-149

688

10.4

10.4

150-199

524

7.9

18.2

200-249

355

5.3

23.6

250-299

313

4.7

28.3

300-349

216

3.2

31.5

350-399

200

3.0

34.5

400-449

172

2.6

37.1

450-499

132

2.0

39.1

500-549

121

1.8

40.9

550-599

109

1.6

42.6

600-649

109

1.6

44.2

650-699

103

1.5

45.8

700-749

89

1.3

47.1

750-799

76

1.1

48.2

800-849

68

1.0

49.3

850-899

59

0.9

50.2

900-949

56

0.8

51.0

950-999

55

0.8

51.8

1000-1249

227

3.4

55.2

1250-1499

173

2.6

57.8

1500-1749

140

2.1

60.0

1750-1999

114

1.7

61.7

2000-2249

116

1.7

63.4

2250-2499

97

1.5

64.9

2500-2749

68

1.0

65.9

2750-2999

63

0.9

66.8

3000-3499

113

1.7

68.5

3500-3999

114

1.7

70.3

4000--4499

94

1.4

71.7

4500-4999

81

1.2

72.9

5000-5999

127

1.9

74.8

6000-6999

92

1.4

76.2

7000-7999

84

1.3

77.4

695

8.8

8.8

596

7.6

16.4

445

5.6

22.0

357

4.5

26.6

259

3.3

29.8

218

2.8

32.6

199

2.5

35.1

154

2.0

37.1

151

1.9

39.0

130

1.6

40.6

109

1.4

42.0

111

1.4

43.4

113

1.4

44.9

83

1.1

45.9

66

0.8

46.8

90

1.1

47.9

59

0.7

48.6

82

1.0

49.7

273

3.5

53.2

224

2.8

56.0

168

2.1

58.1

132

1.7

59.8

119

1.5

61.3

95

1.2

62.5

81

1.0

63.5

91

1.2

64.7

134

1.7

66.4

126

1.6

68.0

89

1.1

69.1

87

1.1

70.2

149

1.9

72.1

128

1.6

73.7

105

1.3

75.1

679

9.3

9.3

579

7.9

17.1

423

5.8

22.9

30O

4.1

27.0

271

3.7

30.7

212

2.9

33.6

181

2.5

36.1

143

1.9

38.0

148

2.O

40.0

123

1.7

41.7

76

1.0

42.7

108

1.5

44.2

98

1.3

45.5

71

1.0

46.5

68

0.9

47.4

79

1.1

48.5

70

1.0

49.5

64

0.9

50.3

271

3.7

54.0

186

2.5

56.6

149

2.0

58.6

127

1.7

60.3

105

1.4

61.8

89

1.2

63.0

88

1.2

64.2

70

1.0

65.1

150

2.0

67.2

97

1.3

68.5

102

1.4

69.9

76

1.0

70.9

134

1.8

72.8

115

1.6

74.3

99

1.3

75.7

Tablecontinues on next page

* Numberof specimenspositive13,804;medianconcentration68 nglmL. t Numberof specimenspositive12,631;medianconcentration62 nglmL. * Numberof specimenspositive13,097;medianconcentration66 nglmL.

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