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This book originally and progressively connects the opioid system and benzodiazepines from pharmacokinetic and pharmacodynamic point of view, so that their interaction and mechanisms result in a concrete discussion in the development of opioid tolerance and dependence, which in turn develops addiction. It is written in a sequential precise manner from its abstract to the details of its findings and mechanisms for treating dependence. This work is not a mere explanation of these systems. In fact, it is for those who want to understand the physical pathway and psychological explanation for craving of drugs and its relative phenomena. For pharmacologists and researchers, it provides an in vitro model and methodology to develop physical opioid dependence and determine the effect of benzodiazepines in it. Assessed in this method, benzodiazepines ability to reduce opioid withdrawal responses expresses the very essence of the discussed topic.