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

Psychopharmacology (Berl). 2008 Dec;201(2):171-81. doi: 10.1007/s00213-008-1260-2. Epub 2008 Aug 10.


Rationale: 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.

Objectives: 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.

Materials and 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.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Area Under Curve
  • Blood Pressure / drug effects
  • Cannabis / chemistry
  • Cognition / drug effects
  • Cross-Over Studies
  • Dose-Response Relationship, Drug
  • Double-Blind Method
  • Dronabinol / analogs & derivatives
  • Dronabinol / blood
  • Dronabinol / chemistry
  • Dronabinol / metabolism*
  • Dronabinol / pharmacokinetics*
  • Emotions / drug effects
  • Half-Life
  • Heart Rate / drug effects
  • Humans
  • Male
  • Marijuana Smoking / blood*
  • Psychomotor Performance / drug effects
  • Risk Factors
  • Serum / chemistry*
  • Smoking / blood*
  • Time Factors
  • Young Adult


  • 11-hydroxy-delta(9)-tetrahydrocannabinol
  • 11-nor-delta(9)-tetrahydrocannabinol-9-carboxylic acid
  • Dronabinol