Differentiating new cannabis use from residual urinary cannabinoid excretion in chronic, daily cannabis users.
OBJECTIVE
To develop and validate empirically a mathematical model for identifying new cannabis use in chronic, daily cannabis smokers.


METHODS
Models were based on urinary creatinine-normalized (CN) cannabinoid excretion in chronic cannabis smokers.


METHODS
For model development, participants resided on a secure research unit for 30 days. For model validation, participants were abstinent with daily observed urine specimens for 28 days.


METHODS
A total of 48 (model development) and 67 (model validation) daily cannabis smokers were recruited.


METHODS
All voided urine was collected and analyzed for 11-nor-9-carboxy-Δ9-tetrahydrocannabinol (THCCOOH) by gas chromatography-mass spectrometry (GCMS; limit of quantification 2.5 ng/ml) and creatinine (mg/ml). Urine THCCOOH was normalized to creatinine, yielding ng/mg CN-THCCOOH concentrations. Urine concentration ratios were determined from 123,513 specimen pairs collected 2-30 days apart.


RESULTS
A mono-exponential model (with two parameters, initial urine specimen CN-THCCOOH concentration and time between specimens), based on the Marquardt-Levenberg algorithm, provided a reasonable data fit. Prediction intervals with varying probability levels (80, 90, 95, 99%) provide upper ratio limits for each urine specimen pair. Ratios above these limits suggest cannabis re-use. Disproportionate numbers of ratios were higher than expected for some participants, prompting development of two additional rules that avoid misidentification of re-use in participants with unusual CN-THCCOOH excretion patterns.


CONCLUSIONS
For the first time, a validated model is available to aid in the differentiation of new cannabis use from residual creatinine-normalized 11-nor-9-carboxy-Δ9-tetrahydrocannabinol (CN-THCCOOH) excretion in chronic, daily cannabis users. These models are valuable for clinicians, toxicologists and drug treatment staff and work-place, military and criminal justice drug-testing programs.
Chemistry and Drug Metabolism, Intramural Research Program, National Institute on Drug Abuse, National Institutes of Health, Biomedical Research Center, Baltimore, MD 21146, USA.
Eugene W
EW
Schwilke
Rod G
RG
Gullberg
William D
WD
Darwin
C Nora
CN
Chiang
Jean Lud
JL
Cadet
David A
DA
Gorelick
Harrison G
HG
Pope
Marilyn A
MA
Huestis
D000328:Adult; D000465:Algorithms; D002908:Chronic Disease; D003404:Creatinine / Q000652:urine; D003937:Diagnosis, Differential; D013759:Dronabinol / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000652:urine; D004350:Drug Residues / Q000032:analysis; D005260:Female; D008401:Gas Chromatography-Mass Spectrometry; D006801:Humans; D008297:Male; D002189:Marijuana Abuse / Q000652:urine*; D008954:Models, Biological; D017711:Nonlinear Dynamics; D011237:Predictive Value of Tests; D011619:Psychotropic Drugs / Q000493:pharmacokinetics / Q000652:urine*; D012008:Recurrence; D015813:Substance Abuse Detection / Q000379:methods* / Q000706:statistics & numerical data; D013997:Time Factors; D055815:Young Adult
D011619:Psychotropic Drugs; C016780:11-nor-delta(9)-tetrahydrocannabinol-9-carboxylic acid; D013759:Dronabinol; D003404:Creatinine