title: Controlled Cannabis Vaporizer Administration: Blood and Plasma Cannabinoids with and without Alcohol.
abstract: 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 Δ(9)-tetrahydrocannabinol (THC) and alcohol use is frequent, potential pharmacokinetic interactions are poorly understood. Here we studied blood and plasma vaporized cannabinoid disposition, 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 obtained 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) μg/L THC, respectively, and 2.8 (0-9.1) and 5.0 (0-14.2) μg/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) μg/L THC and 3.7 (1.4-6.0) and 6.0 (0-23.3) μg/L 11-OH-THC, significantly higher than without alcohol. With a THC detection cutoff of ≥1 μg/L, ≥16.7% of participants remained positive 8.3 h postdose, whereas ≤21.1% were positive by 2.3 h with a cutoff of ≥5 μg/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 performance impairment observed from cannabis-alcohol combinations. Chosen driving-related THC cutoffs should be considered carefully to best reflect performance impairment windows. Our results will help facilitate forensic interpretation and inform the debate on drugged driving legislation.
authors.affiliation: Chemistry and Drug Metabolism, Intramural Research Program, National Institute on Drug Abuse, NIH, Baltimore, MD; Program in Toxicology, University of Maryland, Baltimore, MD;
authors.forename: Rebecca L
authors.initials: RL
authors.lastname: Hartman
authors.affiliation: National Advanced Driving Simulator, University of Iowa, Iowa City, IA;
authors.forename: Timothy L
authors.initials: TL
authors.lastname: Brown
authors.affiliation: College of Pharmacy, University of Iowa, Iowa City, IA;
authors.forename: Gary
authors.initials: G
authors.lastname: Milavetz
authors.affiliation: College of Pharmacy, University of Iowa, Iowa City, IA;
authors.forename: Andrew
authors.initials: A
authors.lastname: Spurgin
authors.affiliation: Department of Psychiatry, University of Maryland School of Medicine, Baltimore, MD.
authors.forename: David A
authors.initials: DA
authors.lastname: Gorelick
authors.affiliation: Carver College of Medicine, University of Iowa, Iowa City, IA;
authors.forename: Gary
authors.initials: G
authors.lastname: Gaffney
authors.affiliation: Chemistry and Drug Metabolism, Intramural Research Program, National Institute on Drug Abuse, NIH, Baltimore, MD; mhuestis@intra.nida.nih.gov.
authors.forename: Marilyn A
authors.initials: MA
authors.lastname: Huestis
mesh_terms: D000284:Administration, Oral; D000328:Adult; D002186:Cannabinoids / Q000097:blood* / Q000493:pharmacokinetics; D013759:Dronabinol / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000097:blood; D000431:Ethanol / Q000008:administration & dosage*; D005260:Female; D006801:Humans; D008297:Male; D008385:Marijuana Smoking / Q000097:blood; D064086:Medical Marijuana / Q000008:administration & dosage* / Q000097:blood; D009330:Nebulizers and Vaporizers; D055815:Young Adult
chemical_list: D002186:Cannabinoids; D064086:Medical Marijuana; C001427:11-hydroxy-delta(9)-tetrahydrocannabinol; D000431:Ethanol; D013759:Dronabinol