About this pathway
Cannabidiol, CBD, a phytocannabinoid found in the Cannabis sativa plant, possesses a wide-range of therapeutic benefits, including anticonvulsant, antiemetic, and anti-inflammatory properties. In the United States, cannabidiol is FDA approved under the brand name Epidiolex® to treat two rare forms of epilepsy, Lennox-Gastaut syndrome and Dravet syndrome.
Pharmacokinetics
The overall bioavailability of cannabidiol is low (11-45%), due in part to poor absorption and a significant first-pass effect [Article:2937482]. To date, cannabidiol has not been identified as a substrate for any drug transporters; however, it inhibits SLC29A1 [Article:16672367] and ABCC1 [Article:18619955]. The inhibitory effect of cannabidiol on ABCB1 and ABCG2 is less clear and may depend on the length of CBD exposure and the cell type [Articles:16458258, 16439618, 32256321, 24058883, 17906686, 23933222]. Cannabidiol is extensively metabolized in the liver by a variety of cytochrome P450 enzymes, CYP450, to approximately 40 metabolites [Articles:2336840, 21704641]. The primary metabolic pathways of cannabidiol are hydroxylation at the 4, 6, and 7 positions. CYP2C19 catalyzes the formation of the major metabolites 7-hydroxycannabidiol (7-OH-CBD) and 6alpha-hydroxycannabidiol, whereas CYP3A4 carries out the hydroxylation of cannabidiol to 6beta-hydroxycannabidiol and 4”-hydroxycannabidiol [Article:21704641]. Glucuronidation of cannabidiol at the phenolic oxygen by UGT1A7, UGT1A9, and UGT2B7 has been described as an additional route of biotransformation ([Article:19339377]; Epidiolex® package insert; Radominska-Pandya et al. 2008 Human hepatic and extrahepatic UDP-glucuronosyltransferase (UGTs) enzymes involved in the metabolism of cannabinoids. FASEB J, 2008. Volume 22, Issue S1 page 711.4). The major metabolite 7-OH-CBD is slightly less active than cannabidiol, whereas 7-carboxycannabidiol is not active ([Article:2993595], Epidiolex®package insert). In vitro data suggests cannabidiol inhibits a number of CYP450 enzymes, including CYP1A1, CYP1A2, CYP1B1, CYP2B6, CYP2C9, CYP2C19, CYP2D6, CYP3A4, CYP3A5, and CYP3A7, as well as the phase II metabolizing enzymes UGT1A9 and UGT2B7 [Articles:26187180, 20117100, 22166891, 23318708, 21356216, 21821735, 23230132]. Elimination of cannabidiol is primarily via the feces, with minimal renal clearance occurring (Epidiolex®package insert).
Reactions & interactions (62)
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Biochemical Reaction
cannabidiol → 7-hydroxycannabidiol
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Biochemical Reaction
7-hydroxycannabidiol → 7-carboxy cannabidiol
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Biochemical Reaction
cannabidiol → 2''-hydroxycannabidiol
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Biochemical Reaction
cannabidiol → 5''-hydroxycannabidiol
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Biochemical Reaction
cannabidiol → 4''-hydroxycannabidiol
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Biochemical Reaction
cannabidiol → cannabidiol-O-glucuronide
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Biochemical Reaction
cannabidiol → 6alpha-hydroxycannabidiol
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Biochemical Reaction
cannabidiol → 6beta-hydroxycannabidiol
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Biochemical Reaction
cannabidiol → 3''-hydroxycannabidiol
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Biochemical Reaction
cannabidiol → 1''-hydroxycannabidiol
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Catalysis
CYP1A2 → Biochemical Reaction
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Catalysis
CYP3A5 → Biochemical Reaction
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Catalysis
CYP2C9 → Biochemical Reaction
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Catalysis
CYP2C19 → Biochemical Reaction
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Catalysis
CYP2D6 → Biochemical Reaction
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Catalysis
CYP1A1 → Biochemical Reaction
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Catalysis
CYP3A4 → Biochemical Reaction
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Catalysis
CYP3A4 → Biochemical Reaction
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Catalysis
CYP2D6 → Biochemical Reaction
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Catalysis
CYP1A2 → Biochemical Reaction
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Catalysis
CYP3A5 → Biochemical Reaction
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Catalysis
CYP3A4 → Biochemical Reaction
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Catalysis
CYP2D6 → Biochemical Reaction
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Catalysis
CYP1A2 → Biochemical Reaction
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Catalysis
CYP2C9 → Biochemical Reaction
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Catalysis
CYP3A4 → Biochemical Reaction
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Catalysis
CYP1A2 → Biochemical Reaction
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Catalysis
CYP2C9 → Biochemical Reaction
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Catalysis
CYP3A5 → Biochemical Reaction
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Catalysis
CYP2C19 → Biochemical Reaction
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Catalysis
CYP2D6 → Biochemical Reaction
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Catalysis
UGT1A7 → Biochemical Reaction
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Catalysis
UGT2B7 → Biochemical Reaction
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Catalysis
UGT1A9 → Biochemical Reaction
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Catalysis
CYP2C9 → Biochemical Reaction
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Catalysis
CYP3A5 → Biochemical Reaction
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Catalysis
CYP2C19 → Biochemical Reaction
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Catalysis
CYP1A1 → Biochemical Reaction
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Catalysis
CYP1A2 → Biochemical Reaction
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Catalysis
CYP3A4 → Biochemical Reaction
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Catalysis
CYP2D6 → Biochemical Reaction
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Catalysis
CYP2D6 → Biochemical Reaction
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Catalysis
CYP3A5 → Biochemical Reaction
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Catalysis
CYP2C19 → Biochemical Reaction
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Catalysis
CYP1A1 → Biochemical Reaction
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Catalysis
CYP1A2 → Biochemical Reaction
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Catalysis
CYP3A4 → Biochemical Reaction
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Catalysis
CYP2C9 → Biochemical Reaction
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Catalysis
CYP3A5 → Biochemical Reaction
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Catalysis
CYP1A2 → Biochemical Reaction
- Showing first 50 of 62 reactions — full data preserved in database.
Edit history (1)
- 2020-12-01 Create