1. ¹Department of Molecular Biology, GW Pharmaceuticals, Salisbury, Wiltshire, UK
2. ²Department of Pharmacology, University of Auckland, Auckland, New Zealand
3. ³School of Medical Sciences, University of Aberdeen, Aberdeen, UK

Correspondence: Dr JM McPartland, GW Pharmaceuticals, 53 Washington Street, Middlebury, VT 05753, USA. E-mail: mcpruitt@verizon.net

Received 15 May 2007; Revised 18 June 2007; Accepted 21 June 2007; Published online 16 July 2007.

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 CB₁ and CB₂. 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 ⁹-tetrahydrocannabinol differed significantly between HsCB₁ and RnCB₁ (25.1 and 42.6 nM, respectively) but not between HsCB₁ and HsCB₂ (25.1 and 35.2). Mean K_d values for HsCB₁, RnCB₁ and HsCB₂ of CP55,940 (2.5, 0.98, 0.92) and WIN55,212-2 (16.7, 2.4, 3.7) differed between HsCB₁ and RnCB₁ and between HsCB₁ and HsCB₂. SR141716A differed between HsCB₁ and RnCB₁ (2.9 and 1.0 nM). Anandamide at HsCB₁, RnCB₁ and HsCB₂ (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 RnCB₂. Aggregate rank order analysis of CB₁ distribution in the brain (pooled from 119 autoradiographic, immunohistochemical and in situ hybridization studies) showed denser HsCB₁ expression in cognitive regions (cerebral cortex) compared to RnCB₁, which was relatively richer in movement-associated areas (cerebellum, caudate-putamen). Implications of interspecies differences are discussed.