Evidence that cannabidiol does not significantly alter the pharmacokinetics of tetrahydrocannabinol in man


The pharmacokinetics of Δ 9 -tetrahydrocannabinol (THC) administered intravenously was evaluated in four subjects after oral administration of placebo and 1500 mg of cannabidiol (CBD) according to a crossover design. The cannabidiol pretreatment had no apparent effect on THC pharmacokinetics, yet there may have been minimal effect on the formation and excretion of metabolites. The total (metabolic) blood clearance of THC averaged 17.4 ml/min/kg without CBD and 20.9 ml/min/kg with CBD, and was probably hepatic blood flow limited. The apparent steady-state volume of distribution averaged 9.86 (with CBD, 10.54) liters/kg. Irrespective of CBD pretreatment, the renal clearance of THC metabolites ranged from 17 ml/min after approximately 1 hr to 1.13 ml/min 3.5days after dosing with THC. The apparent terminal half life for metabolites averaged 8.2 days.

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Correspondence to C. Anthony Hunt.

Additional information

This work was supported by National Institute on Drug Abuse Grant DA-01773, Program Project Grant DA-01696 and Contract No. HSM-42-73-181.

Recipient of National Institute on Drug Abuse Research Scientist Award DA-00053.

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Hunt, C.A., Jones, R.T., Herning, R.I. et al. Evidence that cannabidiol does not significantly alter the pharmacokinetics of tetrahydrocannabinol in man. Journal of Pharmacokinetics and Biopharmaceutics 9, 245–260 (1981). https://doi.org/10.1007/BF01059266

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Key words

  • cannabidiol
  • tetrahydrocannabinol
  • pharmacokinetics
  • cannabinoids
  • pharmacodynamics
  • metabolism
  • renal clearance
  • protein binding