Tai Sherrica, Fantegrossi William E
Department of Pharmacology and Toxicology, University of Arkansas for Medical Sciences, College of Medicine, Little Rock, AR.
Curr Addict Rep. 2014 Jun 1;1(2):129-136. doi: 10.1007/s40429-014-0014-y.
Cannabis has been used throughout the world for centuries. The psychoactive effects of cannabis are largely attributable to Δ-tetrahydrocannabinol (Δ-THC), the prototypical cannabinoid that occurs naturally in the plant. More recently, chemically- and pharmacologically-distinct synthetic cannabinoids (SCBs) have emerged as drugs of abuse. As compared to Δ-THC, the distinct structures of these compounds allow them to avoid legal restrictions (at least initially) and detection in standard drug screens. This has contributed to the popularity of SCBs among drug users who seek to avoid positive drug screens. Importantly, the distinct structures of the SCBs also typically result in increased affinity for and efficacy at cannabinoid CB1 receptors, which are thought to be responsible for the psychoactive effects of Δ-THC and its analogues. Accordingly, it seems likely that these more powerful cannabimimetic effects could result in increased adverse reactions and toxicities not elicited by Δ-THC in cannabis. Animal models useful for the study of emerging SCBs include the cannabinoid tetrad, drug discrimination, and assays of tolerance, dependence, and withdrawal. However, these procedures have not been particularly informative with regards to drug efficacy, where the majority of SCB effects are comparable to those of Δ-THC. In contrast, essentially all measures of drug efficacy confirm Δ-THC as a relatively weak CB1 partial agonist, while the majority of the SCBs detected in commercial preparations are full agonists at the CB1 receptor. As use of these emerging SCBs continues to rise, there is an urgent need to better understand the pharmacology and toxicology of these novel compounds.
几个世纪以来，大麻在世界各地都有使用。大麻的精神活性作用主要归因于Δ-四氢大麻酚（Δ-THC），它是该植物中天然存在的典型大麻素。最近，化学和药理性质不同的合成大麻素（SCBs）已成为滥用药物。与Δ-THC相比，这些化合物独特的结构使它们能够避免法律限制（至少在最初阶段），并在标准药物筛查中不被检测到。这促使SCBs在试图避免药物筛查呈阳性的吸毒者中流行起来。重要的是，SCBs独特的结构通常还会导致对大麻素CB1受体的亲和力和效力增加，而CB1受体被认为是Δ-THC及其类似物产生精神活性作用的原因。因此，这些更强的拟大麻效应可能会导致更多由大麻中的Δ-THC未引发的不良反应和毒性。用于研究新兴SCBs的动物模型包括大麻素四联试验、药物辨别试验以及耐受性、依赖性和戒断试验。然而，就药物效力而言，这些程序并没有提供特别有用的信息，因为大多数SCB的作用与Δ-THC的作用相当。相比之下，基本上所有药物效力的测量都证实Δ-THC是一种相对较弱的CB1部分激动剂，而在商业制剂中检测到的大多数SCBs是CB1受体的完全激动剂。随着这些新兴SCBs的使用持续增加，迫切需要更好地了解这些新型化合物的药理学和毒理学。
