A Systematic Review on the Pharmacokinetics of Cannabidiol in Humans

Summary & key facts

This review collected human studies on how cannabidiol (CBD) is absorbed, distributed, and cleared. From 792 records, 24 studies reported pharmacokinetic (PK) data. Results varied by how CBD was given and by formulation. For example, smoking produced faster and higher blood levels than oral or oromucosal routes. The authors concluded the available human PK data are limited, often inconsistent, and many studies were small or used CBD together with THC or in extracts.

Key facts:

• The systematic search found 792 records and 24 studies that reported CBD pharmacokinetic data in humans.
• Half-life (t1/2) after oromucosal spray was reported between 1.4 and 10.9 hours.
• Half-life after chronic oral administration was reported as 2 to 5 days.
• Half-life after an intravenous (i.v.) dose was reported as about 24 hours, and after smoking about 31 hours.
• Estimated systemic availability (bioavailability) from smoking was 31% (±13%).
• No human study in the review reported the absolute bioavailability of CBD for oral or oromucosal routes, even though i.v. formulations exist.
• Peak concentration (Cmax) and area under the curve (AUC) increased with higher CBD doses (dose-dependent), and these peaks were reached faster after smoking/inhalation than after oral or oromucosal dosing.
• Cmax was reported to be higher when CBD was taken with food (fed state) and when given in lipid-containing formulations.
• Time to peak concentration (Tmax) was generally reported between 0 and 4 hours across studies.
• Many included studies had small sample sizes, often combined CBD with THC or used whole-plant extracts, and most were in healthy adults (only one study was in children with Dravet syndrome), so the results are heterogeneous and should be in

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.

Topics

Alcohol Consumption and Health Effects Cannabis and Cannabinoid Research Diet, Metabolism, and Disease

Categories

Health Sciences Medicine Pharmacology

Tags

Cannabidiol Cannabis Medicine Pharmacokinetics Pharmacology Psychiatry