Meta‐analysis of cannabinoid ligand binding affinity and receptor distribution: interspecies differences

Abstract

A meta‐analysis, unlike a literature review, synthesizes previous studies into new results. Pooled data from 211 studies measured ligand binding affinities at human (Hs) or rat (Rn) cannabinoid receptors CB 1 and CB 2. Cochrane methods were modified for this non‐clinical analysis. Meta‐regression detected data heterogeneity arising from methodological factors: use of sectioned tissues, lack of PMSF and choice of radioligand. Native brain tissues exhibited greater affinity (lower nM) than transfected cells, but the trend fell short of significance, as did the trend between centrifugation and filtration methods. Correcting for heterogeneity, mean K i values for Δ 9‐tetrahydrocannabinol differed significantly between Hs CB 1 and Rn CB 1(25.1 and 42.6 nM, respectively) but not between Hs CB 1 and Hs CB 2(25.1 and 35.2). Mean K d values for Hs CB 1,Rn CB 1 and Hs CB 2 of CP55,940 (2.5, 0.98, 0.92) and WIN55,212‐2 (16.7, 2.4, 3.7) differed between Hs CB 1 and Rn CB 1 and between Hs CB 1 and Hs CB 2. SR141716A differed between Hs CB 1 and Rn CB 1(2.9 and 1.0 nM). Anandamide at Hs CB 1,Rn CB 1 and Hs CB 2(239.2, 87.7, 439.5) fell short of statistical differences due to heterogeneity. We consider these K d and K i values to be the most valid estimates in the literature. Sensitivity analyses did not support the numerical validity of cannabidiol, cannabinol, 2‐arachidonoyl glycerol and all ligands at Rn CB 2. Aggregate rank order analysis of CB 1 distribution in the brain (pooled from 119 autoradiographic, immunohistochemical and in situ hybridization studies) showed denser Hs CB 1 expression in cognitive regions (cerebral cortex) compared to Rn CB 1, which was relatively richer in movement‐associated areas (cerebellum, caudate‐putamen). Implications of interspecies differences are discussed. British Journal of Pharmacology(2007)152, 583–593; doi:10.1038/sj.bjp.0707399; published online 16 July 2007