Matthew N Newmeyer1,2, Madeleine J Swortwood1, Allan J Barnes1, Osama A Abulseoud1, Karl B Scheidweiler3, Marilyn A Huestis1,4. 1. Chemistry and Drug Metabolism Section, IRP, National Institute on Drug Abuse, National Institutes of Health, Baltimore, MD. 2. Program in Toxicology, University of Maryland, Baltimore, Baltimore, MD. 3. Chemistry and Drug Metabolism Section, IRP, National Institute on Drug Abuse, National Institutes of Health, Baltimore, MD; kscheidweiler@intra.nida.nih.gov. 4. University of Maryland School of Medicine, Baltimore, MD.
Abstract
BACKGROUND: There is increasing interest in markers of recent cannabis use because following frequent cannabis intake, Δ9-tetrahydrocannabinol (THC) may be detected in blood for up to 30 days. The minor cannabinoids cannabidiol, cannabinol (CBN), and THC-glucuronide were previously detected for ≤2.1 h in frequent and occasional smokers' blood after cannabis smoking. Cannabigerol (CBG), Δ9-tetrahydrocannabivarin (THCV), and 11-nor-9-carboxy-THCV might also be recent use markers, but their blood pharmacokinetics have not been investigated. Additionally, while smoking is the most common administration route, vaporization and edibles are frequently used. METHODS: We characterized blood pharmacokinetics of THC, its phase I and phase II glucuronide metabolites, and minor cannabinoidsin occasional and frequent cannabis smokers for 54 (occasional) and 72 (frequent) hours after controlled smoked, vaporized, and oral cannabis administration. RESULTS: Few differences were observed between smoked and vaporized blood cannabinoid pharmacokinetics, while significantly greater 11-nor-9-carboxy-THC (THCCOOH) and THCCOOH-glucuronide concentrations occurred following oral cannabis. CBG and CBN were frequently identified after inhalation routes with short detection windows, but not detected following oral dosing. Implementation of a combined THC ≥5 μg/L plus THCCOOH/11-hydroxy-THC ratio <20 cutoff produced detection windows <8 h after all routes for frequent smokers; no occasional smoker was positive 1.5 h or 12 h following inhaled or oral cannabis, respectively. CONCLUSIONS: Vaporization and smoking provide comparable cannabinoid delivery. CBG and CBN are recent-use cannabis markers after cannabis inhalation, but their absence does not exclude recent use. Multiple, complimentary criteria should be implemented in conjunction with impairment observations to improve interpretation of cannabinoid tests. Clinicaltrials.gov Identifier: NCT02177513.
RCT Entities:
BACKGROUND: There is increasing interest in markers of recent cannabis use because following frequent cannabis intake, Δ9-tetrahydrocannabinol (THC) may be detected in blood for up to 30 days. The minor cannabinoidscannabidiol, cannabinol (CBN), and THC-glucuronide were previously detected for ≤2.1 h in frequent and occasional smokers' blood after cannabis smoking. Cannabigerol (CBG), Δ9-tetrahydrocannabivarin (THCV), and 11-nor-9-carboxy-THCV might also be recent use markers, but their blood pharmacokinetics have not been investigated. Additionally, while smoking is the most common administration route, vaporization and edibles are frequently used. METHODS: We characterized blood pharmacokinetics of THC, its phase I and phase II glucuronide metabolites, and minor cannabinoids in occasional and frequent cannabis smokers for 54 (occasional) and 72 (frequent) hours after controlled smoked, vaporized, and oral cannabis administration. RESULTS: Few differences were observed between smoked and vaporized blood cannabinoid pharmacokinetics, while significantly greater 11-nor-9-carboxy-THC (THCCOOH) and THCCOOH-glucuronide concentrations occurred following oral cannabis. CBG and CBN were frequently identified after inhalation routes with short detection windows, but not detected following oral dosing. Implementation of a combined THC ≥5 μg/L plus THCCOOH/11-hydroxy-THC ratio <20 cutoff produced detection windows <8 h after all routes for frequent smokers; no occasional smoker was positive 1.5 h or 12 h following inhaled or oral cannabis, respectively. CONCLUSIONS: Vaporization and smoking provide comparable cannabinoid delivery. CBG and CBN are recent-use cannabis markers after cannabis inhalation, but their absence does not exclude recent use. Multiple, complimentary criteria should be implemented in conjunction with impairment observations to improve interpretation of cannabinoid tests. Clinicaltrials.gov Identifier: NCT02177513.
Authors: Tory R Spindle; Edward J Cone; Evan S Herrmann; John M Mitchell; Ronald Flegel; Charles LoDico; George E Bigelow; Ryan Vandrey Journal: J Anal Toxicol Date: 2020-10-12 Impact factor: 3.367
Authors: Marilyn A Huestis; Cristina Sempio; Matthew N Newmeyer; Maria Andersson; Allan J Barnes; Osama A Abulseoud; Benjamin C Blount; Jennifer Schroeder; Michael L Smith Journal: J Anal Toxicol Date: 2020-10-12 Impact factor: 3.367
Authors: Mallory J E Loflin; Brian D Kiluk; Marilyn A Huestis; Will M Aklin; Alan J Budney; Kathleen M Carroll; Deepak Cyril D'Souza; Robert H Dworkin; Kevin M Gray; Deborah S Hasin; Dustin C Lee; Bernard Le Foll; Frances R Levin; Joshua A Lile; Barbara J Mason; Aimee L McRae-Clark; Ivan Montoya; Erica N Peters; Tatiana Ramey; Dennis C Turk; Ryan Vandrey; Roger D Weiss; Eric C Strain Journal: Drug Alcohol Depend Date: 2020-04-26 Impact factor: 4.492
Authors: Cristina Sempio; Marilyn A Huestis; Susan K Mikulich-Gilbertson; Jost Klawitter; Uwe Christians; Thomas K Henthorn Journal: Br J Clin Pharmacol Date: 2020-01-20 Impact factor: 4.335
Authors: Tory R Spindle; Edward J Cone; Nicolas J Schlienz; John M Mitchell; George E Bigelow; Ronald Flegel; Eugene Hayes; Ryan Vandrey Journal: J Anal Toxicol Date: 2019-05-01 Impact factor: 3.367
Authors: Tory R Spindle; Edward J Cone; Nicolas J Schlienz; John M Mitchell; George E Bigelow; Ronald Flegel; Eugene Hayes; Ryan Vandrey Journal: J Anal Toxicol Date: 2020-01-07 Impact factor: 3.367
Authors: Nina Pocuca; T Jordan Walter; Arpi Minassian; Jared W Young; Mark A Geyer; William Perry Journal: Arch Clin Neuropsychol Date: 2021-07-19 Impact factor: 2.813