Mixed-effect meta-analysis of published NCA data for Cannabidiol

Introduction: Cannabidiol (CBD) is non-psychotomimetic phytocannabinoid obtained from Cannabis Sativa (marijuana). It has received significant interest in the medical field due to its anti-inflammatory, anti-oxidative and anti-necrotic effects. Moreover, CBD has promising safety and tolerability profile making it a potential treatment for several diseases including Parkinson’s disease, Alzheimer’s disease, and Epilepsy among others.  Nevertheless, the pharmacokinetics of CBD is poorly understood and the limited pharmacokinetics/pharmacodynamics studies in humans have revealed the variability in CBD pharmacokinetics1. This study aims to summaries CBD pharmacokinetics in healthy subjects by using mixed-effect meta-analysis and published clinical PK data.

Methods: We carried a systematic literature search in September 2021 and identified 12 pharmacokinetic studies of CBD formulations, containing CBD only, conducted in healthy adult subjects. Overall, summary NCA data from thirty-nine scenarios following single oral, oromucosal, inhalation or intravenous dosing (dose range 2.1 to 6000 mg) were collated. The summary metrics for NCA data were turned into mean and standard deviation (SD) for each scenario, as described by Abuhelwa et al2.  The models regressed log mean AUC against log dose and looked for covariates affecting exposure using the R statistical software and metafor package.  Only one dose scenario with IV data was available.

Results:  Following single CBD doses, log dose was a significant predictor of exposure, as expected, but route of administration (IV or not IV) was not a significant covariate. Significant inter-study variability was noted (I2=78.8%). Noteworthy, significant (100-fold) difference was observed between observed and predicted mean AUC for two studies which might be due to reporting errors.

Conclusion: Overall, the available CBD pharmacokinetic data are heterogenous with high inter-study variability and outliers. Lack of IV data confounds reliable estimation of bioavailability for the other routes.  As a result, drawing meaningful general inferences about the determinants of CBD exposure using this method was challenging. Further studies that evaluate the PK profile of different drug delivery systems by different routes of administration are required.


  1. Sophie A. Millar et al. Front. Pharmacol. (2018)
  2. Ahmad Y. Abuhelwa et al. The AAPS Journal (2016)