Pharmacokinetic and pharmacodynamic profile of supratherapeutic oral doses of D9-THC in cannabis users

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28 Scopus citations


Oral D9-tetrahydrocannabinol (D9-THC) has been evaluated as a medication for cannabis dependence, but repeated administration of acute oral doses up to 40 mg has not been effective at reducing drug-taking behavior. Larger doses might be necessary to affect cannabis use. The purpose of the present study was therefore to determine the physiological and behavioral effects of oral D9-THC at acute doses higher than those tested previously. The pharmacokinetic and pharmacodynamic profile of oral D9-THC, administered in ascending order in 15 mg increments across separate sessions, up to a maximum of 90 mg, was determined in seven cannabis users. Five subjects received all doses and two experienced untoward side effects at lower doses. D9-THC produced a constellation of effects consistent with previous clinical studies. Low cannabinoid concentrations were associated with significant effects on drug-sensitive measures, although progressively greater levels did not lead to proportionately larger drug effects. Considerable variability in Cmax and tmax was observed. Doses of oral D9-THC larger than those tested previously can be administered to individuals with a history of cannabis use, although given the pharmacokinetic variability of oral D9-THC and individual differences in sensitivity, individualized dose adjustment is needed to avoid side effects and maximize therapeutic response.

Original languageEnglish
Pages (from-to)680-690
Number of pages11
JournalJournal of Clinical Pharmacology
Issue number7
StatePublished - Jul 2013


  • Cannabis
  • Digit-symbol-substitution task
  • Marijuana
  • Repeated acquisition task
  • Subjective effects

ASJC Scopus subject areas

  • Pharmacology
  • Pharmacology (medical)


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