Nevertheless the hypothesis outlined here is that a core component of alcoholism involves hyperactivity of the negative emotional state/extended amygdala system that is associated with increased emotional pain and stress and might be a risk factor for drug use as self-medication for emotional pain, dysphoria, and stress (Khantzian 1997). A subhypothesis is that vulnerability in the emotional pain parabrachial-amygdala system (Besson 1999; Shurman et al. 2010) may lead to increased emotional pain during withdrawal and intense craving-type 2 (or withdrawal relief craving), which is conceptualized as an excessive motivation for the drug to obtain relief from a state change characterized by anxiety and dysphoria after protracted abstinence (Heinz et al. 2003), thus contributing to the preponderant role of the withdrawal/negative affect stage that characterizes alcoholism. Increased reactivity of the stress/hypothalamic-pituitary-adrenal axis module may be critical in the initiation of alcohol intake and for the maintenance of drug intake which have little initial rewarding value, such as nicotine. Activation of the hypothalamic-pituitary-adrenal axis can potentiate the reinforcing effects of drugs (Piazza and Le Moal 1998). However, this activation can in turn
