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中國醫藥大學附設醫院 洪崇傑醫師 Stages of drug addiction Criteria for Substance Dependence (DSM-IV) Koob GF and Le Moal M, Science, 1997 Criteria for Substance Dependence (DSM-V) Taking the substance in larger amounts or for longer than the you meant to Wanting to cut down or stop using the substance but not managing to Spending a lot of time getting, using, or recovering from use of the substance Cravings and urges to use the substance Not managing to do what you should at work, home or school, because of substance use Continuing to use, even when it causes problems in relationships Giving up important social, occupational or recreational activities because of substance use Using substances again and again, even when it puts the you in danger Continuing to use, even when the you know you have a physical or psychological problem that could have been caused or made worse by the substance Needing more of the substance to get the effect you want (tolerance) Development of withdrawal symptoms, which can be relieved by taking more of the substance. DSM-V 2~3 symptoms indicate a mild substance use disorder, 4~5 symptoms indicate a moderate substance use disorder, 6 or more symptoms indicate a severe substance use disorder. “in early remission,” “in sustained remission,” “on maintenance therapy,” and “in a controlled environment.” Drug-seeking Drug-taking behaviors What happens? Neural circuitry Genetics and molecular pathway A brief summary about the mechanism underlying drug addiction Reward Pathway 自我獎賞系 統 Natural reward Food 食物(美食!) Water 水 Sex 性 Nurturing 撫摸 Substance 所有的酒精跟成癮物質 Neural Circuitry Mediating the Activation of GoalDirected Behavior after rewarding Stahl’s essential psychopharmacology 5th E. Stahl’s essential psychopharmacology 5th E. How abused drugs act as temptation? Neural Circuitry Mediating Drug Seeking Repeated psychostimulant or opioids administration Prefrontal cortex Dysmorphism of pyramidal cells Nucleus accumbens adpatation Promote in presynaptic glutamate release Altering postsynaptic responsiveness to released glutamate Enduring change in postsynaptic receptor associated proteins like PSD-95 and Homer →dendritic and synaptic change Drug dependence is believed to be a result from the interaction between multiple genetic andenvironmental factors. (Imlah 1989; Duaux et al. 2000). Opioid receptor, dopamine and COMT genetic polyphormism well studied → lack the NMDA series gene reports in human drug abusers Discussion Thanks for your attention !