We have introduced cognitive behavior therapy (CBT) into the treatment of substance dependence patients, which involves disease education and focused group therapy to obtain insight into the taking behavior and to establish concrete countermeasures to prevent relapse. We have created a bio-cognitive model based on biological aspects to explain the pathology of substance dependence. 'Dependence' is a term in behavioral pharmacology defined as reinforced drug seeking and taking behavior. Changes in taking behavior are thought to occur due to the repetition of the reinforcement action of psychoactive substances in the reward system of the brain. Therefore, when intake desire is strong, it is hard for patients to control themselves, and there is a feature of difficulties considering the process of thinking in CBT. In other words, when craving becomes strong, a chain of behavior happens spontaneously, without schema, involving automatic thoughts. We think that the improvement of protracted withdrawal syndrome (PWS) and entire frontal lobe function are important in learning to discern distortion of cognition. When PWS is improved, a conflict is easy to bring about in the process of drug seeking and taking behavior. And, it is easy to execute avoidance plans (coping skills) which are established to cope with craving in advance. We think that a goal for treatment is to discern drug seeking and taking behavior with natural emotion. The recovery of PWS and frontal lobe dysfunction takes a long time with a serious dependence, so we must perform repetition of CBT. As the treatment introduction of involuntary admission cases is adequate or cases of 1 to 3 months of admission treatment based on voluntary admission are hard to treat, treatment to obtain insights into patients while carrying out repeated CBT using a bio-cognitive model and to improve PWS could be a possibility as one treatment for the pathology of diversified substance dependence.