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 HsCB_{1} and RnCB_{1} (25.1 and 42.6nM, respectively) but not between HsCB_{1} and HsCB_{2} (25.1 and 35.2). Mean K_{d} values for HsCB_{1}, RnCB_{1} and HsCB_{2} of CP55,940 (2.5, 0.98, 0.92) and WIN55,212-2 (16.7, 2.4, 3.7) differed between HsCB_{1} and RnCB_{1} and between HsCB_{1} and HsCB_{2}. SR141716A differed between HsCB_{1} and RnCB_{1} (2.9 and 1.0nM). Anandamide at HsCB_{1}, RnCB_{1} and HsCB_{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 RnCB_{2}. Aggregate rank order analysis of CB_{1} distribution in the brain (pooled from 119 autoradiographic, immunohistochemical and in situ hybridization studies) showed denser HsCB_{1} expression in cognitive regions (cerebral cortex) compared to RnCB_{1}, which was relatively richer in movement-associated areas (cerebellum, caudate-putamen). Implications of interspecies differences are discussed