Drug addiction is characterized by the inability to control drug use when it results in negative consequences or conflicts with more adaptive goals. Our previous work showed that damage to the insula disrupted addiction to cigarette smoking—the first time that the insula was shown to be a critical neural substrate for addiction. Here, we review those findings, as well as more recent studies that corroborate and extend them, demonstrating the role of the insula in (1) incentive motivational processes that drive addictive behavior, (2) control processes that moderate or inhibit addictive behavior, and (3) interoceptive processes that represent bodily states associated with drug use. We then describe a theoretical framework that attempts to integrate these seemingly disparate findings. In this framework, the insula functions in the recall of interoceptive drug effects during craving and drug seeking under specific conditions where drug taking is perceived as risky and/or where there is conflict between drug taking and more adaptive goals. We describe this framework in an evolutionary context and discuss its implications for understanding the mechanisms of behavior change in addiction treatments.

The findings show that damage to the BG alone can cause disruption of smoking addiction, and when BG damage is combined with INS damage, the disruption increases. The latter finding is consistent with the proposal that the INS has a key role in smoking addiction.

Patterns of smoking behavior vary between the sexes. There is evidence that decision-making, which is one of the key “executive functions” necessary for making life-style modifications such as smoking cessation, is relatively lateralized to the right hemisphere in males and left hemisphere in females. In the current study, we examined whether the side of brain lesion has a differential effect on smoking behavior between the sexes. We hypothesized sex differences in smoking cessation based on lesion side. Participants were 49 males and 50 females who were smoking at the time of lesion onset. The outcome variable was abstinence from smoking (quit rate) at least one year post lesion. We found that in patients with left hemisphere damage, quit rates were significantly higher in males than in females; however, in patients with right hemisphere damage, quit rates were not statistically different. The findings support previous cognitive neuroscience literature showing that components of behavior responsible for maintaining addiction tend to be more strongly lateralized in males, whereas in females there is a more bilateral distribution. Our study provides further evidence for differences in lateralization of complex behavior between the sexes, which has significant implications for differences in treatment strategies between the sexes.

Introduction Psychiatric and substance use disorders represent barriers to smoking cessation. We sought to identify correlates of psychiatric co-morbidity (2 diagnoses) and multi-morbidity (3+ diagnoses) among smokers attempting to quit and to evaluate whether these conditions predicted neuropsychiatric adverse events (NPSAEs), treatment adherence, or cessation efficacy (CE). Method Data were collected from November 2011 to January 2015 across sixteen countries and reflect the psychiatric cohort of the EAGLES trial. Participants were randomly assigned to receive varenicline, bupropion, nicotine replacement therapy, or placebo for 12 weeks and were followed for an additional 12 weeks post-treatment. NPSAE outcomes reflected sixteen moderate-to-severe neuropsychiatric symptom categories, and CE outcomes included continuous abstinence at weeks 9-12 and weeks 9-24. Results Of the 4103 participants included, 36.2% were diagnosed with multiple psychiatric conditions (20.9% co-morbidity, 15.3% multi-morbidity). Psychiatric co- and multi-morbidity were associated with several baseline factors, including male gender, non-white race/ethnicity, more previous quit attempts, and more severe mental health symptoms. The incidence of moderate-to-severe NPSAEs was significantly higher (p<0.01) in participants with multi-morbidity (11.9%) than those with co-morbidity (5.1%) or primary diagnosis only (4.6%). There were no significant (ps>0.05) main effects or interactions with treatment condition for diagnostic grouping on treatment adherence or CE outcomes. Conclusions While having multiple psychiatric diagnoses increased risk of developing moderate-to-severe NPSAEs during a quit attempt, neither co- nor multi-morbidity were associated with treatment adherence or odds of quitting. These findings reassure providers to advise smokers with multiple stable psychiatric conditions to consider using FDA-approved medications when trying to quit.

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