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Publication Title | Controlled Cannabis Vaporizer Administration: Blood and Plasma Cannabinoids with and without Alcohol

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Clinical Chemistry 61:6 Drug Monitoring and Toxicology 850–869 (2015)

Controlled Cannabis Vaporizer Administration: Blood and Plasma Cannabinoids with and without Alcohol

Rebecca L. Hartman,1,2 Timothy L. Brown,3 Gary Milavetz,4 Andrew Spurgin,4 David A. Gorelick,5 Gary Gaffney,6 and Marilyn A. Huestis1*

BACKGROUND: Increased medical and legal cannabis intake is accompanied by greater use of cannabis vaporization and more cases of driving under the influence of cannabis. Although simultaneous 9-tetrahydrocannabinol (THC) and alcohol use is frequent, potential pharma- cokinetic interactions are poorly understood. Here we studied blood and plasma vaporized cannabinoid dis- position, with and without simultaneous oral low-dose alcohol.

METHODS: Thirty-two adult cannabis smokers ( 1 time/3 months, 3 days/week) drank placebo or low- dose alcohol (target approximately 0.065% peak breath- alcohol concentration) 10 min before inhaling 500 mg placebo, low-dose (2.9%) THC, or high-dose (6.7%) THC vaporized cannabis (6 within-individual alcohol- cannabis combinations). Blood and plasma were ob- tained before and up to 8.3 h after ingestion.

RESULTS: Nineteen participants completed all sessions. Median (range) maximum blood concentrations (Cmax) for low and high THC doses (no alcohol) were 32.7 (11.4–66.2) and 42.2 (15.2–137) g/L THC, respec- tively, and 2.8 (0 –9.1) and 5.0 (0 –14.2) g/L 11-OH- THC. With alcohol, low and high dose Cmax values were 35.3 (13.0 –71.4) and 67.5 (18.1–210) g/L THC and 3.7 (1.4 – 6.0) and 6.0 (0 –23.3) g/L 11-OH-THC, sig- nificantly higher than without alcohol. With a THC de- tection cutoff of 1 g/L, 16.7% of participants re- mained positive 8.3 h postdose, whereas 21.1% were positive by 2.3 h with a cutoff of 5 g/L.

CONCLUSIONS: Vaporization is an effective THC delivery route. The significantly higher blood THC and 11-OH- THC Cmax values with alcohol possibly explain increased

1 Chemistry and Drug Metabolism, Intramural Research Program, National Institute on Drug Abuse, NIH, Baltimore, MD; 2 Program in Toxicology, University of Maryland, Bal- timore, MD; 3 National Advanced Driving Simulator, University of Iowa, Iowa City, IA; 4 College of Pharmacy, University of Iowa, Iowa City, IA; 6 Carver College of Medicine, University of Iowa, Iowa City, IA; 5 Department of Psychiatry, University of Maryland School of Medicine, Baltimore, MD.

* Address correspondence to this author at: Biomedical Research Center, Suite 200, Rm 05A-721, 251 Bayview Blvd, Baltimore, MD 21224. Fax 443-740-2823; e-mail mhuestis@intra.nida.nih.gov.

performance impairment observed from cannabis- alcohol combinations. Chosen driving-related THC cut- offs should be considered carefully to best reflect perfor- mance impairment windows. Our results will help facilitate forensic interpretation and inform the debate on drugged driving legislation.

© 2015 American Association for Clinical Chemistry

Currently, 23 states and the District of Columbia have legalized medical cannabis, and Colorado, Washington, Oregon, and Alaska have decriminalized recreational cannabis intake (1 ). Per se cannabinoid blood cutoffs for driving under the influence (DUI)7 include zero toler- ance or 1, 2, or 5 g/L 9-tetrahydrocannabinol (THC) (2 ); the District of Columbia enacted a 5 g/L per se law, and Colorado, a 5 g/L “permissible inference” law. These legal changes have resulted in increased DUI can- nabis cases (3– 4 ) and more complicated enforcement of cannabinoid drugged driving laws (5–7). A major con- founding factor is extended cannabinoid excretion with chronic frequent intake (6). Cannabis plus alcohol, among the most frequent drug combinations identified in driving cases worldwide, shows evidence of increased performance impairment (5 ). Despite frequent concom- itant THC and alcohol intake, little is known about a potential pharmacokinetic interaction. Thus, under- standing cannabinoid blood disposition, with and with- out simultaneous alcohol, is critical for proper test inter- pretation (8 ).

Although smoking is the most common cannabis administration route (9), the use of vaporization is in- creasing rapidly; it provides similar effects (10 –11 ) while reducing exposure to harmful pyrolytic byproducts (12 )

Received January 10, 2015; accepted March 19, 2015.

Previously published online at DOI: 10.1373/clinchem.2015.238287

© 2015 American Association for Clinical Chemistry

7 Nonstandard abbreviations: DUI, driving under the influence; THC, Δ9-tetrahydro-

cannabinol; CBD, cannabidiol; CBN, cannabinol; NIDA, National Institute on Drug Abuse; 11-OH-THC, 11-hydroxy-THC; THCCOOH, 11-nor-9-carboxy-THC; Cmax, max- imum concentration; tmax, time to maximum concentration; AUC, area under the curve; tlast, time of last observed concentration; Clast, last observed concentration; LOQ, limit of quantification.

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