title: Delta-9-tetrahydrocannabinol (THC) serum concentrations and pharmacological effects in males after smoking a combination of tobacco and cannabis containing up to 69 mg THC.
abstract: BACKGROUND
  Delta9-Tetrahydrocannabinol (THC) is the main active constituent of cannabis. In recent years, the average THC content of some cannabis cigarettes has increased up to approximately 60 mg per cigarette (20% THC cigarettes). The pharmacokinetics of THC after smoking cannabis cigarettes containing more than approximately 35 mg THC (3.55% THC cigarettes) is unknown. To be able to perform suitable exposure risk analysis, it is important to know if there is a linear relation at higher doses.
  
  
  OBJECTIVE
  The present study aimed to characterise the pharmacokinetics of THC, the active metabolite 11-OH-THC and the inactive metabolite THC-COOH after smoking a combination of tobacco and cannabis containing high THC doses.
  
  
  METHODS
  This double-blind, placebo-controlled, four-way, cross-over study included 24 male non-daily cannabis users (two to nine joints per month). Participants were randomly assigned to smoke cannabis cigarettes containing 29.3, 49.1 and 69.4 mg THC and a placebo. Serial serum samples collected over a period of 0-8 h were analysed by liquid chromatography electrospray tandem mass spectrometry. Effects on heart rate, blood pressure and 'high' feeling were also measured.
  
  
  RESULTS
  Mean maximal concentrations (Cmax) were 135.1, 202.9 and 231.0 microg/L for THC and 9.2, 16.4 and 15.8 microg/L for 11-OH-THC after smoking a 29.3-, 49.1- and 69.4-mg THC cigarette, respectively. A large inter-individual variability in Cmax was observed. Heart rate and 'high' feeling significantly increased with increasing THC dose.
  
  
  CONCLUSIONS
  This study demonstrates that the known linear association between THC dose and THC serum concentration also applies for high THC doses.
authors.affiliation: National Institute for Public Health and the Environment, P.O. Box 1, 3720 BA, Bilthoven, The Netherlands. claudine.hunault@rivm.nl
authors.forename: Claudine C
authors.initials: CC
authors.lastname: Hunault
authors.forename: Tjeert T
authors.initials: TT
authors.lastname: Mensinga
authors.forename: Irma
authors.initials: I
authors.lastname: de Vries
authors.forename: Hermien H
authors.initials: HH
authors.lastname: Kelholt-Dijkman
authors.forename: Jani
authors.initials: J
authors.lastname: Hoek
authors.forename: Maaike
authors.initials: M
authors.lastname: Kruidenier
authors.forename: Marianne E C
authors.initials: ME
authors.lastname: Leenders
authors.forename: Jan
authors.initials: J
authors.lastname: Meulenbelt
mesh_terms: D000293:Adolescent; D000328:Adult; D019540:Area Under Curve; D001794:Blood Pressure / Q000187:drug effects; D002188:Cannabis / Q000737:chemistry; D003071:Cognition / Q000187:drug effects; D018592:Cross-Over Studies; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D013759:Dronabinol / Q000031:analogs & derivatives / Q000097:blood / Q000737:chemistry / Q000378:metabolism* / Q000493:pharmacokinetics*; D004644:Emotions / Q000187:drug effects; D006207:Half-Life; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D008297:Male; D008385:Marijuana Smoking / Q000097:blood*; D011597:Psychomotor Performance / Q000187:drug effects; D012307:Risk Factors; D044967:Serum / Q000737:chemistry*; D012907:Smoking / Q000097:blood*; D013997:Time Factors; D055815:Young Adult
chemical_list: C001427:11-hydroxy-delta(9)-tetrahydrocannabinol; C016780:11-nor-delta(9)-tetrahydrocannabinol-9-carboxylic acid; D013759:Dronabinol