The Gill Center and Department of Psychological & Brain Sciences, Indiana University, 1101 E. 10th St, Bloomington, IN 47405, USA.
Eur J Pharmacol. 2011 Jun 1;659(2-3):139-45. doi: 10.1016/j.ejphar.2011.01.066. Epub 2011 Feb 16.
'Spice' is an herbal blend that has been reported to produce cannabis-like effects when smoked and is marketed as an alternative to marijuana. Synthetic additives have been identified in numerous 'Spice' preparations from different sources. Common among many of the preparations were the compounds JWH018 and a dimethyloctyl variant of CP47,497 (CP47,497-C8) and, more recently JWH073. The synaptic effects of each of these compounds were uncharacterized. We previously reported that JWH018 is a potent and efficacious CB(1) cannabinoid receptor agonist. In this study we have examined the abilities of CP47,497-C8 and JWH073 to inhibit neurotransmission in cultured autaptic hippocampal neurons. Each inhibited EPSCs with an efficacy and potency similar to JWH018. We also analyzed these compounds' effects on promoting internalization of CB(1) receptors in HEK293 cells stably expressing CB(1) receptors. Similar to our neurotransmission data, CP47,497-C8 internalized CB(1) in a fashion indistinguishable from JWH018. However, JWH073 was less potent and produced slower internalization than JWH018 and CP47,497-C8. It appears that 'Spice' contains a number of cannabinoid receptor agonists that activate CB(1) receptors to inhibit synaptic transmission with similar potencies and efficacies. It is highly probable that the cannabis-like effects of 'Spice' are due to the presence of these and analogous synthetic additives acting on CB(1) receptors.
“香料”是一种草药混合物，据报道，吸食后会产生类似大麻的效果，并作为大麻的替代品进行销售。从不同来源的多种“香料”制剂中已经鉴定出了合成添加剂。许多制剂中都含有 JWH018 和 CP47,497 的二甲辛基变体（CP47,497-C8），以及最近的 JWH073。这些化合物的突触效应尚未确定。我们之前报道过 JWH018 是一种有效的 CB(1) 大麻素受体激动剂。在这项研究中，我们研究了 CP47,497-C8 和 JWH073 抑制培养的自突触海马神经元神经传递的能力。这两种化合物的抑制功效和效力都与 JWH018 相似。我们还分析了这些化合物在促进稳定表达 CB(1)受体的 HEK293 细胞中 CB(1)受体内化的作用。与我们的神经传递数据相似，CP47,497-C8 以与 JWH018 相似的方式内化 CB(1)。然而，JWH073 的效力比 JWH018 和 CP47,497-C8 低，内化速度也较慢。“香料”中似乎含有多种大麻素受体激动剂，它们以相似的效力和功效激活 CB(1)受体，从而抑制突触传递。“香料”产生类似大麻的效果很可能是由于这些类似的合成添加剂与 CB(1)受体相互作用所致。
