Overnight Abstinence, Ventrostriatal-Insular Connectivity, and Tridimensional Personality Traits in Cigarette Smokers.

BACKGROUND: Personality traits contribute to the risks of smoking. The striatum has been implicated in nicotine addiction and nicotine deprivation is associated with alterations in resting state functional connectivity (rsFC) of the ventral (VS) and dorsal (DS) striatum. However, it remains unclear how striatal rsFC may change following overnight abstinence or how these shorter-term changes in inter-regional connectivity relate to personality traits. METHODS: In the current study, 28 smokers completed assessments with Fagerström Test of Nicotine Dependence, Tridimensional Personality Questionnaire (TPQ), as well as resting state functional magnetic resonance imaging (fMRI) scans during satiety and after overnight abstinence. We processed imaging data with published routines and evaluated the results with a corrected threshold. RESULTS: Smokers showed increases in the VS-insula rsFC but no significant changes in the DS rsFC after overnight abstinence as compared to satiety. The difference in the VS-insula rsFC (abstinence minus satiety) was negatively correlated with harm avoidance. CONCLUSIONS: These findings highlighted striatal connectivity correlates of very short-term abstinence from smoking and how the VS-insula rsFC may vary with individual personality traits, interlinking neural markers and personality risk factors of cigarette smoking at the earliest stage of abstinence.

The Association Between Smoking Abstinence and Pain Trajectory Among Veterans Engaged in U.S. Department of Veterans Affairs Mental Health Care.

OBJECTIVE: To prospectively examine associations between smoking and nicotine abstinence and pain trajectory over 12 months among smokers with low, moderate, and severe pain and to assess whether these associations differ over time. DESIGN: A secondary analysis of the "Proactive Outreach for Smokers in VA Mental Health" study, a randomized controlled trial of proactive outreach for veteran smokers engaged in U.S. Department of Veterans Affairs (VA) mental health care. METHODS: Participants were categorized into "low" (n = 616), "moderate" (n = 479), and "severe" pain (n = 656) groups according to baseline pain score. Associations between self-reported abstinence from smoking and nicotine at 6 and 12 months and pain trajectory, measured via the PEG scale (Pain intensity, Enjoyment of life, General activity) composite score, were assessed through the use of general linear mixed models. Interaction tests assessed whether these associations differed at 6 and 12 months. Analyses were conducted within the overall sample and within the separate pain groups. RESULTS: There were significant interactions in the overall sample and the low and moderate pain groups, such that 7-day point prevalence smoking abstinence was associated with lower pain scores at 6 but not 12 months. In the severe pain group, 7-day abstinence from both smoking and nicotine was associated with lower pain scores across both time points. Six-month prolonged abstinence was not associated with pain scores. CONCLUSIONS: In this prospective analysis conducted among veteran smokers engaged in mental health services, 7-day abstinence from smoking and nicotine was associated with significantly lower levels of pain. Education efforts could help better inform smokers on the relationship between smoking and pain.

Use of Electronic Cigarettes to Aid Long-Term Smoking Cessation in the United States: Prospective Evidence From the PATH Cohort Study.

Electronic cigarettes (e-cigarettes) are the preferred smoking-cessation aid in the United States; however, there is little evidence regarding long-term effectiveness among those who use them. We used the Population Assessment of Tobacco and Health Study to compare long-term abstinence between matched US smokers who tried to quit with and without use of e-cigarettes as a cessation aid. We identified a nationally representative cohort of 2,535 adult US smokers in 2014-2015 (baseline assessment), who, in 2015-2016 (exposure assessment), reported a past-year attempt to quit and the cessation aids used, and reported smoking status in 2016-2017 (outcome assessment; self-reported ≥12 months continuous abstinence). We used propensity-score methods to match each e-cigarette user with similar nonusers. Among US smokers who used e-cigarettes to help quit, 12.9% (95% confidence interval (CI): 9.1%, 16.7%) successfully attained long-term abstinence. However, there was no difference compared with matched non-e-cigarette users (cigarette abstinence difference: 2%; 95% CI: -3%, 7%). Furthermore, fewer e-cigarette users were abstinent from nicotine products in the long term (nicotine abstinence difference: -4%; 95% CI: -7%, -1%); approximately two-thirds of e-cigarette users who successfully quit smoking continued to use e-cigarettes. These results suggest e-cigarettes may not be an effective cessation aid for adult smokers and, instead, may contribute to continuing nicotine dependence.

Greater externalizing personality traits predict less error-related insula and anterior cingulate cortex activity in acutely abstinent cigarette smokers.

Attenuated activity in performance-monitoring brain regions following erroneous actions may contribute to the repetition of maladaptive behaviors such as continued drug use. Externalizing is a broad personality construct characterized by deficient impulse control, vulnerability to addiction and reduced neurobiological indices of error processing. The insula and dorsal anterior cingulate cortex (dACC) are regions critically linked with error processing as well as the perpetuation of cigarette smoking. As such, we examined the interrelations between externalizing tendencies, erroneous task performance, and error-related insula and dACC activity in overnight-deprived smokers (n = 24) and non-smokers (n = 20). Participants completed a self-report measure assessing externalizing tendencies (Externalizing Spectrum Inventory) and a speeded Flanker task during functional magnetic resonance imaging scanning. We observed that higher externalizing tendencies correlated with the occurrence of more performance errors among smokers but not non-smokers. Suggesting a neurobiological contribution to such suboptimal performance among smokers, higher externalizing also predicted less recruitment of the right insula and dACC following error commission. Critically, this error-related activity fully mediated the relationship between externalizing traits and error rates. That is, higher externalizing scores predicted less error-related right insula and dACC activity and, in turn, less error-related activity predicted more errors. Relating such regional activity with a clinically relevant construct, less error-related right insula and dACC responses correlated with higher tobacco craving during abstinence. Given that inadequate error-related neuronal responses may contribute to continued drug use despite negative consequences, these results suggest that externalizing tendencies and/or compromised error processing among subsets of smokers may be relevant factors for smoking cessation success.

Effectiveness of Non-Nicotinic E-Cigarettes to Reduce Cue- and Abstinence-Induced Cigarette Craving in Non-Treatment Seeking Daily Dependent Smokers.

RATIONALE: Electronic cigarettes (e-cigarettes) are potential tools for smoking cessation because they deliver nicotine and simulate smoking behaviors. The contribution of sensorimotor versus pharmacological substitution is unknown. OBJECTIVES: To evaluate whether non-nicotinic e-cigarettes, used alone or with nicotine lozenges, can attenuate cigarette craving following visual cue presentation or acute (3 h post ad-lib use) abstinence in dependent daily smokers. METHODS: Following overnight (12 hours) abstinence, 41 daily smokers were exposed to 4 experimental conditions on separate days: (i) tobacco cigarettes (CIG); (ii) non-nicotinic e-cigarettes with placebo lozenges (EPL); (iii) non-nicotinic e-cigarettes with 4 mg nicotine lozenge (ENL); and (iv) 4 mg nicotine lozenge (NL). Cigarette craving was assessed following presentation of neutral and smoking cues at various time points using the Brief Questionnaire of Smoking Urges (QSU-B) and visual analog scales (VAS). RESULTS: All experimental conditions significantly reduced participants' baseline overnight abstinence cigarette craving. ENLs and NLs attenuated smoking-cue-induced cravings to a greater extent than CIGs, where cravings were significantly higher with CIGs compared to ENLs [mean difference (MD) ± standard error (SE) in QSU-B = 3.2 ± 0.84, P = 0.002; VAS = 12.7 ± 2.7, P < 0.0005] and NLs [MD ± SE in QSU-B = 2.7 ± 0.92, P = 0.031; VAS = 8.1 ± 2.3, P = 0.005]. Craving responses to cues after 3 h were higher after smoking CIGs compared to ENLs [MD ± SE in QSU-B = 3.9 ± 1.4, P = 0.047; VAS = 14.1 ± 3.6, P = 0.002] and NLs [MD ± SE in QSU-B = 3.2 ± 1.1, P = 0.046; VAS = 9.7 ± 3.1, P = 0.017]. CONCLUSIONS: Behavioral simulation of smoking with or without nicotine reduces nicotine craving. Compared to cigarettes, ENL with NL or NL alone attenuates cigarette craving over time. Future clinical trials should evaluate the combination of ENL and NL as a method for smoking reduction or cessation. TRIAL REGISTRATION: NCT02108626.

The effects of oral nicotine administration and abstinence on sleep in male C57BL/6J mice.

BACKGROUND: Sleep disturbances are common in smoking cessation attempts and are predictive of relapse. Despite this knowledge, there is no established animal model to study the effect of nicotine abstinence on sleep and EEG parameters. OBJECTIVES: The present study was conducted to characterize sleep and wakefulness in male C57BL/6J mice during periods of oral nicotine administration and abstinence. METHODS: Male C57BL/6J mice were implanted with EEG/EMG recording devices. EEG/EMG data were recorded continuously for a period of 4 weeks. At the beginning of week 2, 200 µg/ml of nicotine was added to the 0.2% saccharin vehicle drinking solution. Following a 2-week period of oral nicotine administration, abstinence was initiated by excluding the nicotine from the 0.2% saccharin vehicle drinking solution. EEG/EMG were analyzed at pre-nicotine baseline, during nicotine administration, and on days 1, 2, and 5 of abstinence from nicotine. RESULTS: Oral nicotine administration decreased total sleep time during the active phase, consistent with the stimulant actions of nicotine. In contrast, NREM sleep quantity was increased during the active phase on nicotine abstinence day 1 and REM sleep was decreased during days 2 and 5 of abstinence. Further, sleep fragmentation was increased during the inactive phase on all days of abstinence. Oral nicotine administration and abstinence from nicotine also altered EEG relative power frequencies during the inactive and active phase. CONCLUSIONS: Both oral nicotine administration and abstinence lead to sleep disturbances in mice. Similarities between this model and human reports on the effect of nicotine/nicotine withdrawal on sleep support its utility in examining the molecular mechanisms that modulate the relationship between sleep, nicotine, and nicotine abstinence/withdrawal.

Brain substrates of early (4h) cigarette abstinence: Identification of treatment targets.

INTRODUCTION: Research indicates that overnight nicotine abstinence disrupts neural activity in the mesocorticolimbic reward network; however, less is known about the time course of abstinence-induced brain changes. To examine the potential neural effects of early abstinence, we used arterial spin labeling perfusion fMRI, to measure regional cerebral blood flow (rCBF) changes in the resting brain induced by 4h of nicotine abstinence. METHODS: In a repeated measures design, 5min of resting perfusion fMRI data were acquired in awake nicotine-dependent individuals (eyes open) during 'smoking as usual' (SMK) and following 4h of monitored nicotine abstinence (ABS) conditions (N=20). Conditions were compared using a paired t test in SPM8. Craving was assessed prior to each condition. RESULTS: Compared to SMK, ABS significantly increased craving and reduced rCBF in select regions, including the hippocampus and ventral striatum (cluster corr, α=0.01, 943 contiguous voxels). The magnitude of the abstinence-induced change in rCBF correlated with the magnitude of the change in craving across conditions in select regions, including the medial and lateral orbitofrontal cortices and the anterior ventral insula (r values ranging from 0.59-0.74). CONCLUSIONS: Results show that as few as 4h of abstinence can reduce resting rCBF in multiple nodes of the brain's mesocorticolimbic network, disrupting neural processing. Identifying early withdrawal treatment targets has far-reaching implications, which include thwarting relapse proclivities. Results parallel those of the extant human literature and are in agreement with an extensive preclinical literature showing compromised mesolimbic dopaminergic function and impairments in reward function during nicotine withdrawal.