Abstract
Background: Cannabidiol is being pursued as a therapeutic treatment for multiple conditions, usually by oral delivery. Animal studies suggest oral bioavailability is low, but literature in humans is not sufficient. The aim of this review was to collate published data in this area.Methods: A systematic search of PubMed and EMBASE (including MEDLINE) was conducted to retrieve all articles reporting pharmacokinetic data of CBD in humans.Results: Of 792 articles retireved, 24 included pharmacokinetic parameters in humans. The half-life of cannabidiol was reported between 1.4 and 10.9 h after oromucosal spray, 2–5 days after chronic oral administration, 24 h after i.v., and 31 h after smoking. Bioavailability following smoking was 31% however no other studies attempted to report the absolute bioavailability of CBD following other routes in humans, despite i.v formulations being available. The area-under-the-curve and Cmax increase in dose-dependent manners and are reached quicker following smoking/inhalation compared to oral/oromucosal routes. Cmax is increased during fed states and in lipid formulations. Tmax is reached between 0 and 4 h.Conclusions: This review highlights the paucity in data and some discrepancy in the pharmacokinetics of cannabidiol, despite its widespread use in humans. Analysis and understanding of properties such as bioavailability and half-life is critical to future therapeutic success, and robust data from a variety of formulations is required.
Highlights
The Cannabis sativa plant contains more than a hundred phytocannabinoid compounds, including the non-psychotomimetic compound cannabidiol (CBD) (Izzo et al, 2009)
GW pharmaceuticals have developed an oral solution of pure CBD (Epidiolex R ) for the treatment of severe, orphan, early-onset, treatment-resistant epilepsy syndromes, showing significant reductions in seizure frequency compared to placebo in several trials (Devinsky et al, 2017, 2018a; Thiele et al, 2018)
One study was conducted in children with Dravet syndrome, while the remainder were conducted in healthy adult volunteers (Devinsky et al, 2018b)
Summary
The Cannabis sativa plant contains more than a hundred phytocannabinoid compounds, including the non-psychotomimetic compound cannabidiol (CBD) (Izzo et al, 2009). CBD has attracted significant interest due to its anti-inflammatory, anti-oxidative and anti-necrotic protective effects, as well as displaying a favorable safety and tolerability profile in humans (Bergamaschi et al, 2011), making it a promising candidate in many therapeutic avenues including epilepsy, Alzheimer’s disease, Parkinson’s disease, and multiple sclerosis. GW pharmaceuticals have developed an oral solution of pure CBD (Epidiolex R ) for the treatment of severe, orphan, early-onset, treatment-resistant epilepsy syndromes, showing significant reductions in seizure frequency compared to placebo in several trials (Devinsky et al, 2017, 2018a; Thiele et al, 2018). CBD is being pursued in clinical trials in Parkinson’s disease, Crohn’s disease, society anxiety disorder, and schizophrenia (Crippa et al, 2011; Leweke et al, 2012; Chagas et al, 2014; Naftali et al, 2017), showing promise in these areas. The aim of this review was to collate published data in this area
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