title: Plasma Cannabinoid Pharmacokinetics After Controlled Smoking and Ad libitum Cannabis Smoking in Chronic Frequent Users.
abstract: More Americans are dependent on cannabis than any other illicit drug. The main analytes for cannabis testing include the primary psychoactive constituent, Δ(9)-tetrahydrocannabinol (THC), equipotent 11-hydroxy-THC (11-OH-THC) and inactive 11-nor-9-carboxy-THC (THCCOOH). Eleven adult chronic frequent cannabis smokers resided on a closed research unit with unlimited access to 5.9% THC cannabis cigarettes from 12:00 to 23:00 during two ad libitum smoking phases, followed by a 5-day abstinence period in seven participants. A single cigarette was smoked under controlled topography on the last day of the smoking and abstinence phases. Plasma cannabinoids were quantified by two-dimensional gas chromatography-mass spectrometry. Median plasma maximum concentrations (Cmax) were 28.3 (THC), 3.9 (11-OH-THC) and 47.0 μg/L (THCCOOH) 0.5 h after controlled single cannabis smoking. Median Cmax 0.2-0.5 h after ad libitum smoking was higher for all analytes: 83.5 (THC), 14.2 (11-OH-THC) and 155 μg/L (THCCOOH). All 11 participants' plasma samples were THC and THCCOOH-positive, 58.3% had THC ≥5 μg/L and 79.2% were 11-OH-THC-positive 8.1-14 h after last cannabis smoking. Cannabinoid detection rates in seven participants 106-112 h (4-5 days) after last smoking were 92.9 (THC), 35.7 (11-OH-THC) and 100% (THCCOOH), with limits of quantification of 0.5 μg/L for THC and THCCOOH, and 1.0 μg/L for 11-OH-THC. These data greatly expand prior research findings on cannabinoid excretion profiles in chronic frequent cannabis smokers during ad libitum smoking. Smoking multiple cannabis cigarettes led to higher Cmax and AUC compared with smoking a single cigarette. The chronic frequent cannabis smokers exhibited extended detection windows for plasma cannabinoids, reflecting a large cannabinoid body burden.
authors.affiliation: Chemistry and Drug Metabolism, IRP, National Institute on Drug Abuse, NIH, Biomedical Research Center, 251 Bayview Blvd. Room 05A721, Baltimore, MD 21224, USA.
authors.forename: Dayong
authors.initials: D
authors.lastname: Lee
authors.affiliation: Chemistry and Drug Metabolism, IRP, National Institute on Drug Abuse, NIH, Biomedical Research Center, 251 Bayview Blvd. Room 05A721, Baltimore, MD 21224, USA School of Pharmaceutical Sciences, University of São Paulo, Ribeirão Preto, SP 14040-903, Brazil.
authors.forename: Mateus M
authors.initials: MM
authors.lastname: Bergamaschi
authors.affiliation: Chemistry and Drug Metabolism, IRP, National Institute on Drug Abuse, NIH, Biomedical Research Center, 251 Bayview Blvd. Room 05A721, Baltimore, MD 21224, USA.
authors.forename: Garry
authors.initials: G
authors.lastname: Milman
authors.affiliation: Chemistry and Drug Metabolism, IRP, National Institute on Drug Abuse, NIH, Biomedical Research Center, 251 Bayview Blvd. Room 05A721, Baltimore, MD 21224, USA.
authors.forename: Allan J
authors.initials: AJ
authors.lastname: Barnes
authors.affiliation: School of Pharmaceutical Sciences, University of São Paulo, Ribeirão Preto, SP 14040-903, Brazil.
authors.forename: Regina H C
authors.initials: RH
authors.lastname: Queiroz
authors.affiliation: Johns Hopkins University School of Medicine, Baltimore, MD 21224, USA.
authors.forename: Ryan
authors.initials: R
authors.lastname: Vandrey
authors.affiliation: Chemistry and Drug Metabolism, IRP, National Institute on Drug Abuse, NIH, Biomedical Research Center, 251 Bayview Blvd. Room 05A721, Baltimore, MD 21224, USA mhuestis@intra.nida.nih.gov.
authors.forename: Marilyn A
authors.initials: MA
authors.lastname: Huestis
mesh_terms: D000328:Adult; D001822:Body Burden; D002186:Cannabinoids / Q000493:pharmacokinetics*; D005260:Female; D006801:Humans; D008297:Male; D008385:Marijuana Smoking; D008875:Middle Aged
chemical_list: D002186:Cannabinoids