ABSTRACT: In the present study it was revealed that cannabidiolic acid (CBDA) selectively inhibited cyclooxygenase (COX)-2 activity with an IC50 value (50% inhibition concentration) around 2 M, having 9-fold higher selectivity than COX-1 inhibition. In contrast, 9-tetrahydro- cannabinolic acid (9-THCA) was a much less potent inhibitor of COX-2 (IC50 > 100 M). Nonsteroidal anti-inflammatory drugs con- taining a carboxyl group in their chemical structures such as salicylic acid are known to inhibit nonselectively both COX-1 and COX-2. CBDA and 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...