Figure 3. Maladaptive alterations to the adaptive stress response.

Model showing the interactive effects of (i) stress, trauma and adversity, (ii) increased drug use, binge/chronic use, and (iii) acute withdrawal and abstinence-related distress,as the three stress factors presented in the section entitled “Factors affecting stress response, learning, and motivation.” With increasing cumulative aggregation of each of these factors, the natural adaptive processes involved become altered, which results in greater multilevel disruptions in stress, reward, and motivation pathways. Drug-related processes of tolerance, sensitization and withdrawal further facilitate the feed-forward disruptions in emotion, pain, and reward pathways to promote increased craving and risk of drug use escalation, relapse, and treatment failure.