Document Detail


Cannabidiolic acid as a selective cyclooxygenase-2 inhibitory component in cannabis.
MedLine Citation:
PMID:  18556441     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
In the present study it was revealed that cannabidiolic acid (CBDA) selectively inhibited cyclooxygenase (COX)-2 activity with an IC(50) value (50% inhibition concentration) around 2 microM, having 9-fold higher selectivity than COX-1 inhibition. In contrast, Delta(9)-tetrahydrocannabinolic acid (Delta(9)-THCA) was a much less potent inhibitor of COX-2 (IC(50) > 100 microM). Nonsteroidal anti-inflammatory drugs containing a carboxyl group in their chemical structures such as salicylic acid are known to inhibit nonselectively both COX-1 and COX-2. CBDA and Delta(9)-THCA have a salicylic acid moiety in their structures. Thus, the structural requirements for the CBDA-mediated COX-2 inhibition were next studied. There is a structural difference between CBDA and Delta(9)-THCA; phenolic hydroxyl groups of CBDA are freed from the ring formation with the terpene moiety, although Delta(9)-THCA has dibenzopyran ring structure. It was assumed that the whole structure of CBDA is important for COX-2 selective inhibition because beta-resorcylic acid itself did not inhibit COX-2 activity. Methylation of the carboxylic acid moiety of CBDA led to disappearance of COX-2 selectivity. Thus, it was suggested that the carboxylic acid moiety in CBDA is a key determinant for the inhibition. Furthermore, the crude extract of cannabis containing mainly CBDA was shown to have a selective inhibitory effect on COX-2. Taken together, these lines of evidence in this study suggest that naturally occurring CBDA in cannabis is a selective inhibitor for COX-2.
Authors:
Shuso Takeda; Koichiro Misawa; Ikuo Yamamoto; Kazuhito Watanabe
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2008-06-12
Journal Detail:
Title:  Drug metabolism and disposition: the biological fate of chemicals     Volume:  36     ISSN:  1521-009X     ISO Abbreviation:  Drug Metab. Dispos.     Publication Date:  2008 Sep 
Date Detail:
Created Date:  2008-08-21     Completed Date:  2008-11-07     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9421550     Medline TA:  Drug Metab Dispos     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1917-21     Citation Subset:  IM    
Affiliation:
Organization for Frontier Research in Preventive Pharmaceutical Sciences, Hokuriku University, Kanazawa, Japan.
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MeSH Terms
Descriptor/Qualifier:
Cannabinoids / chemistry,  pharmacology*
Cannabis / chemistry*
Cyclooxygenase 2 / drug effects*
Cyclooxygenase Inhibitors / chemistry,  pharmacology*
Dose-Response Relationship, Drug
Molecular Structure
Chemical
Reg. No./Substance:
0/Cannabinoids; 0/Cyclooxygenase Inhibitors; 1244-58-2/cannabidiolic acid; EC 1.14.99.1/Cyclooxygenase 2

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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