A Systematic Review on the Pharmacokinetics of Cannabidiol in Humans

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.

A systematic review of cannabidiol dosing in clinical populations

“…Within this review, 51% of studies have been published in the last 5 years (since 2013); however, the included articles span over decades, with prominent publications first appearing in the 1980s and early 1990s . Despite its long history of sole administration to patients, there is surprisingly little published about the pharmacokinetic properties of CBD, particularly its bioavailability, making it difficult to estimate true effective doses . Historically, there is a striking lack of dose‐ranging studies and, looking forward, there are no registered trials on http://clinicaltrials.gov including specific dose‐ranging investigations in their study design.…”

Model‐Based Analysis of Cannabidiol Dose‐Exposure Relationship and Bioavailability

“…There are, however, limited pharmacokinetics (PK) and/or pharmacodynamics (PD) studies of CBD in humans. As a result, the dosing of CBD used outside of the FDA‐approved indications remains unclear . Few descriptive PK parameters of CBD, such as area under the concentration‐time curve (AUC), maximum concentration (Cmax), and time of Cmax (Tmax), have been reported, and a large variation in PK parameters was found among the study subjects .…”

“…As a result, the dosing of CBD used outside of the FDA‐approved indications remains unclear . Few descriptive PK parameters of CBD, such as area under the concentration‐time curve (AUC), maximum concentration (Cmax), and time of Cmax (Tmax), have been reported, and a large variation in PK parameters was found among the study subjects . The large variability was partly explained by feeding status, as food intake has been shown to delay Tmax and increase AUC and Cmax .…”

“…The large variability was partly explained by feeding status, as food intake has been shown to delay Tmax and increase AUC and Cmax . The various dosage forms also resulted in different PK profiles; for example, smoking or vaping CBD results in a shorter Tmax compared with other dosage forms . Additionally, other studies reported a less than proportional dose‐exposure relationship .…”

Cannabidiol: A budding industry!

“…The shortest half‐life of CBD was observed when given as an oromucosal spray (1.4–10.9 hours), with slower clearance following chronic ingestion (2–5 days), intravenous administration (24 hours) and inhalation by smoking (31 hours) (Millar et al . ).…”