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Review
. 2016 Mar 1;1(1):90-101.
doi: 10.1089/can.2015.0012. eCollection 2016.

Human Metabolites of Cannabidiol: A Review on Their Formation, Biological Activity, and Relevance in Therapy

István Ujváry  1 , Lumír Hanuš  2
Affiliations
Review

Human Metabolites of Cannabidiol: A Review on Their Formation, Biological Activity, and Relevance in Therapy

István Ujváry et al. Cannabis Cannabinoid Res. .

Abstract

Cannabidiol (CBD), the main nonpsychoactive constituent of Cannabis sativa, has shown a wide range of therapeutically promising pharmacological effects either as a sole drug or in combination with other drugs in adjunctive therapy. However, the targets involved in the therapeutic effects of CBD appear to be elusive. Furthermore, scarce information is available on the biological activity of its human metabolites which, when formed in pharmacologically relevant concentration, might contribute to or even account for the observed therapeutic effects. The present overview summarizes our current knowledge on the pharmacokinetics and metabolic fate of CBD in humans, reviews studies on the biological activity of CBD metabolites either in vitro or in vivo, and discusses relevant drug-drug interactions. To facilitate further research in the area, the reported syntheses of CBD metabolites are also catalogued.

Keywords: biological activity; cannabidiol; metabolites; pharmacokinetics; synthesis.

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Conflict of interest statement

No competing financial interest.

Figures

<b>FIG. 1.</b>
FIG. 1.
Chemical structures and numbering system for CBD and Δ9- THC type cannabinoids. CBD, cannabidiol; THC, tetrahydrocannabinol.
<b>FIG. 2.</b>
FIG. 2.
(a) Chemical structures of major (>1%) metabolites of CBD identified by GC-MS in anhydrolyzed urine of a dystonic patient treated chronically with the drug. The compounds are listed according to their relative amounts (decreasing from upper left to lower right) based on peak areas of the gas chromatogram. Additional major metabolite was Δ8-THC (1.97%; structure not shown). In the structural diagrams, wavy bonds indicate stereogenic center with R+S indicating that the two epimers were chromatographically separated; otherwise, stereochemistry is unknown. (b) List of minor (<1%) urinary metabolites present in the urine of the same patient; additional excreted compound present was Δ9-THC (0.69%), which has also been identified in artificial gastric juice. For numbering, see Figure 1. The chemical structures of the minor metabolites are given in Supplementary Figure S1. (c) CBD metabolites identified in human liver microsomal preparation. Their chemical structures are given in Supplementary Figure S1. For convenience, the shorthand notation adopted here indicates only the newly formed functional group(s) present in the metabolite of CBD.
<b>FIG. 3.</b>
FIG. 3.
Chemical structures of CBD-derived substances of biological interest.
See this image and copyright information in PMC

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