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Pharmacokinetic Characterization of 11-nor-9-carboxy-Δ9-tetrahydrocannabinol in Urine Following Acute Oral Cannabis Ingestion in Healthy Adults.
J Anal Toxicol. 2018 May 01; 42(4):232-247.JA

Abstract

Understanding the urine excretion profile for Δ9-tetrahydrocannabinol (THC) metabolites is important for accurate detection and interpretation of toxicological testing for cannabis use. Prior literature has primarily evaluated the urinary pharmacokinetics of the non-psychoactive THC metabolite 11-nor-9-carboxy-Δ9-tetrahydrocannabinol (THCCOOH) following smoked cannabis administration. The present study examined the urine THCCOOH excretion profile following oral cannabis administration in 18 healthy adults. Following ingestion of a cannabis-containing brownie with 10, 25 or 50 mg of THC (N = 6 per dose), urine specimens were collected on a closed residential research unit for 6 days, followed by three outpatient visits on Days 7-9. Average maximum concentrations (Cmax) of THCCOOH were 107, 335 and 713 ng/mL, and average times to maximum concentration (Tmax) were 8, 6 and 9 h for the 10, 25 and 50 mg THC doses, respectively. Detection windows to first positive and last positive varied as a function of dose; higher doses had shorter time to first positive and longer time to last positive. Considerable inter-subject variability was observed on study outcomes. Gas chromatography/mass spectrometry (GC/MS; 15 ng/mL cutoff) was used as the criterion to assess sensitivity, specificity and agreement for THCCOOH qualitative immunoassay tests using 20, 50 and 100 ng/mL cutoffs. The 50 ng/mL cutoff displayed good sensitivity (92.5%), specificity (92.4%) and overall agreement (92.4%), whereas the 20 ng/mL cutoff demonstrated poor specificity (58.4%), and the 100 ng/mL cutoff exhibited reduced sensitivity (70.9%). Ingestion of cannabis brownies containing the 10 and 25 mg THC doses yielded THCCOOH concentrations that differed in magnitude and time course from those previously reported for the smoked route of administration of comparable doses.

Authors+Show Affiliations

Behavioral Pharmacology Research Unit, Johns Hopkins University School of Medicine, 5510 Nathan Shock Drive, Baltimore, MD 21224, USA.Behavioral Pharmacology Research Unit, Johns Hopkins University School of Medicine, 5510 Nathan Shock Drive, Baltimore, MD 21224, USA.Battelle Memorial Institute, 6115 Falls Road, Suite 200, Baltimore, MD 21209, USA.Behavioral Pharmacology Research Unit, Johns Hopkins University School of Medicine, 5510 Nathan Shock Drive, Baltimore, MD 21224, USA.RTI International, 3040 East Cornwallis Road, Research Triangle Park, NC 27709, USA.Behavioral Pharmacology Research Unit, Johns Hopkins University School of Medicine, 5510 Nathan Shock Drive, Baltimore, MD 21224, USA.Substance Abuse and Mental Health Services Administration (SAMHSA), Division of Workplace Programs (DWP), 5600 Fishers Lane, Rockville, MD 20857, USA.Substance Abuse and Mental Health Services Administration (SAMHSA), Division of Workplace Programs (DWP), 5600 Fishers Lane, Rockville, MD 20857, USA.Substance Abuse and Mental Health Services Administration (SAMHSA), Division of Workplace Programs (DWP), 5600 Fishers Lane, Rockville, MD 20857, USA.Behavioral Pharmacology Research Unit, Johns Hopkins University School of Medicine, 5510 Nathan Shock Drive, Baltimore, MD 21224, USA.

Pub Type(s)

Journal Article
Randomized Controlled Trial

Language

eng

PubMed ID

29300962

Citation

Schlienz, Nicolas J., et al. "Pharmacokinetic Characterization of 11-nor-9-carboxy-Δ9-tetrahydrocannabinol in Urine Following Acute Oral Cannabis Ingestion in Healthy Adults." Journal of Analytical Toxicology, vol. 42, no. 4, 2018, pp. 232-247.
Schlienz NJ, Cone EJ, Herrmann ES, et al. Pharmacokinetic Characterization of 11-nor-9-carboxy-Δ9-tetrahydrocannabinol in Urine Following Acute Oral Cannabis Ingestion in Healthy Adults. J Anal Toxicol. 2018;42(4):232-247.
Schlienz, N. J., Cone, E. J., Herrmann, E. S., Lembeck, N. A., Mitchell, J. M., Bigelow, G. E., Flegel, R., LoDico, C. P., Hayes, E. D., & Vandrey, R. (2018). Pharmacokinetic Characterization of 11-nor-9-carboxy-Δ9-tetrahydrocannabinol in Urine Following Acute Oral Cannabis Ingestion in Healthy Adults. Journal of Analytical Toxicology, 42(4), 232-247. https://doi.org/10.1093/jat/bkx102
Schlienz NJ, et al. Pharmacokinetic Characterization of 11-nor-9-carboxy-Δ9-tetrahydrocannabinol in Urine Following Acute Oral Cannabis Ingestion in Healthy Adults. J Anal Toxicol. 2018 May 1;42(4):232-247. PubMed PMID: 29300962.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Pharmacokinetic Characterization of 11-nor-9-carboxy-Δ9-tetrahydrocannabinol in Urine Following Acute Oral Cannabis Ingestion in Healthy Adults. AU - Schlienz,Nicolas J, AU - Cone,Edward J, AU - Herrmann,Evan S, AU - Lembeck,Natalie A, AU - Mitchell,John M, AU - Bigelow,George E, AU - Flegel,Ronald, AU - LoDico,Charles P, AU - Hayes,Eugene D, AU - Vandrey,Ryan, PY - 2017/08/16/received PY - 2017/11/29/accepted PY - 2018/1/5/pubmed PY - 2018/10/23/medline PY - 2018/1/5/entrez SP - 232 EP - 247 JF - Journal of analytical toxicology JO - J Anal Toxicol VL - 42 IS - 4 N2 - Understanding the urine excretion profile for Δ9-tetrahydrocannabinol (THC) metabolites is important for accurate detection and interpretation of toxicological testing for cannabis use. Prior literature has primarily evaluated the urinary pharmacokinetics of the non-psychoactive THC metabolite 11-nor-9-carboxy-Δ9-tetrahydrocannabinol (THCCOOH) following smoked cannabis administration. The present study examined the urine THCCOOH excretion profile following oral cannabis administration in 18 healthy adults. Following ingestion of a cannabis-containing brownie with 10, 25 or 50 mg of THC (N = 6 per dose), urine specimens were collected on a closed residential research unit for 6 days, followed by three outpatient visits on Days 7-9. Average maximum concentrations (Cmax) of THCCOOH were 107, 335 and 713 ng/mL, and average times to maximum concentration (Tmax) were 8, 6 and 9 h for the 10, 25 and 50 mg THC doses, respectively. Detection windows to first positive and last positive varied as a function of dose; higher doses had shorter time to first positive and longer time to last positive. Considerable inter-subject variability was observed on study outcomes. Gas chromatography/mass spectrometry (GC/MS; 15 ng/mL cutoff) was used as the criterion to assess sensitivity, specificity and agreement for THCCOOH qualitative immunoassay tests using 20, 50 and 100 ng/mL cutoffs. The 50 ng/mL cutoff displayed good sensitivity (92.5%), specificity (92.4%) and overall agreement (92.4%), whereas the 20 ng/mL cutoff demonstrated poor specificity (58.4%), and the 100 ng/mL cutoff exhibited reduced sensitivity (70.9%). Ingestion of cannabis brownies containing the 10 and 25 mg THC doses yielded THCCOOH concentrations that differed in magnitude and time course from those previously reported for the smoked route of administration of comparable doses. SN - 1945-2403 UR - https://www.unboundmedicine.com/medline/citation/29300962/Pharmacokinetic_Characterization_of_11_nor_9_carboxy_Δ9_tetrahydrocannabinol_in_Urine_Following_Acute_Oral_Cannabis_Ingestion_in_Healthy_Adults_ L2 - https://academic.oup.com/jat/article-lookup/doi/10.1093/jat/bkx102 DB - PRIME DP - Unbound Medicine ER -