Impact of Prolonged Cannabinoid Excretion in Chronic Daily Cannabis Smokers' Blood on Per Se Drugged Driving Laws

M.M. Bergamaschi, E.L. Karschner, R.S. Goodwin, K.B. Scheidweiler, J. Hirvonen, R.H.C. Queiroz, and M.A. Huestis

March 2013

www.clinchem.org/content/59/3/519.full

© Copyright 2013 by the American Association for Clinical Chemistry

© Copyright 2009 by the American Association for Clinical Chemistry

IntroductionIntroduction Cannabis (marijuana)

Most commonly used illicit drug worldwide Estimated 17.4 million Americans age 12 years or older

smoked cannabis in 2010, with 6600 new initiates daily Primary psychoactive component, ∆9-tetrahydrocannabinol

(THC) metabolized 11-hydroxy-THC (11-OH-THC) and 11-nor-9-carboxy-THC (THCCOOH)

Cannabis & driving Cannabis 2nd only to alcohol for causing impaired driving

and motor vehicle accidents In 2007 National Roadside Survey, more drivers tested

positive for drugs (16.6%) than for alcohol (12.4%)

© Copyright 2009 by the American Association for Clinical Chemistry

IntroductionIntroduction

Cannabis & driving Cannabis smokers had 10-fold increase in car crash injury

compared with infrequent or nonusers THC blood concentrations ≥5 μg/L associated with 6.6-fold

increase in driver responsibility for driving fatalities

Legal blood THC concentration limits 15 US states and 12 European countries have established

THC concentration limits in blood 4 European countries established limits in plasma or serum

© Copyright 2009 by the American Association for Clinical Chemistry

IntroductionIntroduction

THC blood concentrations may be low or not detected while brain concentrations might be sufficient to cause impairment

Difficult to identify minimum blood THC concentration consistently associated with impairment

No study has characterized cannabinoid elimination in blood from daily cannabis smokers during monitored sustained abstinence for up to 33 days

© Copyright 2009 by the American Association for Clinical Chemistry

QuestionsQuestions

How does prolonged cannabinoid excretion complicate interpretation of cannabinoid blood concentrations in clinical and forensic cases?

Are there other cannabinoids in blood and/or other cutoffs to indicate recent cannabis smoking?

© Copyright 2009 by the American Association for Clinical Chemistry

Materials & MethodsMaterials & Methods Participants

30 male chronic daily cannabis smokers resided on a secure research unit for up to 33 days under 24-hour surveillance

Sample collection Blood collected once daily and stored at -20˚C

Blood cannabinoid analysis THC,11-OH-THC and THCCOOH simultaneously

quantified by 2-dimensional gas chromatography-mass spectrometry

© Copyright 2009 by the American Association for Clinical Chemistry

Materials & MethodsMaterials & Methods

Limits of quantification (LOQ) THC and THCCOOH: 0.25 µg/L 11-OH-THC: 0.5 µg/L

Data analysis Correlation: Spearman rank correlation Comparative analysis: Wilcoxon rank test Survival analysis: Kaplan-Meier analysis

© Copyright 2009 by the American Association for Clinical Chemistry

QuestionQuestion

Why were cannabinoid blood detection rates calculated at different cutoffs?

© Copyright 2009 by the American Association for Clinical Chemistry

ResultsResults 30 male chronic daily cannabis smokers provided

a total of 570 blood samples over 1 – 4 weeks Mean (SD) age 28.3 (7.9) years Mean (SD) 10.2 (6.3) joints/day for 11.7 (7.5) years

326 THC positive (57.2%) 0.25 – 6.3 μg/L

33 11-OH-THC positive (5.8%) ≤4.1 μg/L

531 THCCOOH (93.2%) 0.25 – 93.4 μg/L

© Copyright 2009 by the American Association for Clinical Chemistry

ResultsResults Cannabinoid excretion during sustained

abstinence in 30 chronic cannabis smokers Admission: 27 of 30 participants THC positive, 77.8% ≥

1.0 μg/L and 11.1% ≥ 5.0 μg/L Only 1 of 11 was negative at 26 days, 2 of 5 remained

THC-positive (0.3 μg/L) for 30 days Median 11-OH-THC 1.1 µg/L on admission, all ≤1.0 by

24 hours THCCOOH detection rates 96.7% on admission, 95.7%

day 8, 85.7% day 22 4 of 5 THCCOOH positive for 30 days (0.6 – 2.7 μg/L).

All subjects’ blood THC ≤ 1 μg/L within 7 days

© Copyright 2009 by the American Association for Clinical Chemistry

ResultsResults

Cannabinoid excretion during sustained abstinence in 30 chronic cannabis smokers

2 participants were THC-positive on day 30 (0.3 μg/L) 1 participant had THCCOOH of 0.7 μg/L on day 33 of

abstinence

© Copyright 2009 by the American Association for Clinical Chemistry

ResultsResults

© Copyright 2009 by the American Association for Clinical Chemistry

ResultsResults

Median THC & 11-OH-THC last detection times were 22 days (95% CI 17.8 – 26.2 days) and 1 day (95% CI 0 days)

THC last detection times were significantly correlated with number of cannabis joints smoked per day (r = 0.372; P = 0.047)

© Copyright 2009 by the American Association for Clinical Chemistry

QuestionQuestion

What are the possible advantages of using different cannabinoids for interpretation of cannabinoid test results?

© Copyright 2009 by the American Association for Clinical Chemistry

ConclusionsConclusions

Cannabinoids detected in blood of chronic daily cannabis smokers during 1 month sustained abstinence

Consistent with time course of persisting neurocognitive and psychomotor impairment reported in recent studies

Extended residual THC excretion in chronic daily cannabis smokers complicates interpretation of cannabinoid tests

Strong public safety need to reduce morbidity and mortality from cannabis-impaired driving

© Copyright 2009 by the American Association for Clinical Chemistry

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