Reduced executive and reward connectivity is associated with smoking cessation response to repetitive transcranial magnetic stimulation: A double-blind, randomized, sham-controlled trial.

Repetitive transcranial magnetic stimulation (rTMS) can reduce cue-elicited craving, decrease cigarette consumption, and increase the abstinence rate in tobacco use disorders (TUDs). We used functional magnetic resonance imaging (fMRI) to investigate the effect of 10 sessions of rTMS on cortical activity and neural networks in treatment-seeking smokers. Smoking cue exposure fMRI scans were acquired before and after the 10 sessions of active or sham rTMS (10 Hz, 3000 pulses per session) to the left dorsal lateral prefrontal cortex (DLPFC) in 42 treatment-seeking smokers (≥ 10 cigarettes per day). Brain activity and functional connectivity were compared before and after 10 sessions of rTMS. Ten sessions of rTMS significantly reduced the number of cigarettes consumed per day (62.93%) compared to sham treatment (39.43%) at the end of treatment (p = 0.027). fMRI results showed that the rTMS treatment increased brain activity in the dorsal anterior cingulate cortex (dACC) and DLPFC, but decreased brain activity in the bilateral medial orbitofrontal cortex (mOFC). The lower strength of dACC and mOFC connectivity was associated with quitting smoking (Wald score = 5.00, p = 0.025). The reduction of cigarette consumption significantly correlated with the increased brain activation in the dACC (r = 0.76, p = 0.0001). By increasing the brain activity in the dACC and prefrontal cortex and decreasing brain activity in the mOFC, 10 sessions of rTMS significantly reduced cigarette consumption and increased quit rate. Reduced drive-reward and executive control functional connectivity was associated with the smoking cessation effect from rTMS. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT02401672.

Two weeks of image-guided left dorsolateral prefrontal cortex repetitive transcranial magnetic stimulation improves smoking cessation: A double-blind, sham-controlled, randomized clinical trial.

BACKGROUND: Previous studies have found that repetitive transcranial magnetic stimulation (rTMS) to the left dorsal lateral prefrontal cortex (LDLPFC) transiently reduces smoking craving, decreases cigarette consumption, and increases abstinence rates. OBJECTIVE: We investigated whether 10 daily MRI-guided rTMS sessions over two weeks to the LDLPFC paired with craving cues could reduce cigarette consumption and induce smoking cessation. METHODS: We enrolled 42 treatment-seeking nicotine-dependent smokers (≥10 cigarettes per day) in a randomized, double-blind, sham-controlled trial. Participants received 10 daily sessions over 2 weeks of either active or sham MRI-guided rTMS (10Hz, 3000 pulses each session) to the LDLPFC concurrently with video smoking cues. The primary outcome was a reduction in biochemically confirmed cigarette consumption with a secondary outcome of abstinence on the target quit date. We also recorded cue-induced craving and withdrawal symptoms. RESULTS: Compared to sham (n = 17), participants receiving active rTMS (n = 21) smoked significantly fewer cigarettes per day during the 2-week treatment (mean [SD], 13.73[9.18] vs. 11.06[9.29], P < .005) and at 1-month follow-up (12.78[9.53] vs. 7.93[7.24], P < .001). Active rTMS participants were also more likely to quit by their target quit rate (23.81%vs. 0%, OR 11.67, 90% CL, 0.96-141.32, x2 = 4.66, P = .031). Furthermore, rTMS significantly reduced mean craving throughout the treatments and at follow-up (29.93[13.12] vs. 25.01[14.45], P < .001). Interestingly across the active treatment sample, more lateral coil location was associated with more success in quitting (-43.43[0.40] vs. -41.79[2.24], P < .013). CONCLUSIONS: Daily MRI-guided rTMS to the LDLPFC for 10 days reduces cigarette consumption and cued craving for up to one month and also increases the likelihood of smoking cessation. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT02401672.

Rates of substance use disorder treatment seeking visits after emergency department-initiated buprenorphine.

BACKGROUND: Emergency department-initiated buprenorphine (EDIB) programs have been shown to improve treatment outcomes for patients with opioid use disorders (OUD); however, little is known about how EDIB implementation impacts the patient census at participating hospitals. OBJECTIVES: To determine if implementation of an EDIB program was associated with changes in the number of patients presenting to the ED seeking treatment for substance use disorder (SUD). METHODS: We conducted a retrospective evaluation at a single academic ED that began offering EDIB in December 2017. Data span the period of December 2016 to April 2019, All ED visits with a chief complaint of addiction problem, detoxification, drug/alcohol assessment, drug problem, or withdrawal charted by nursing at the time of triage were eligible for inclusion. Charts were reviewed to determine: (1) treatment status and (2) substance(s) for which the patient was seeking treatment. An interrupted time series analysis was used to compare the pre- and post-EDIB rates for all-substance, as well as opioid-specific, treatment-seeking visits. RESULTS: For all-substance visits, the predicted level change in the treatment-seeking rate after EDIB was implemented was positive but not significant (0.000497, p = 0.53); the trend change after EDIB was also not significant (-0.00004, p = 0.73). For visits involving opioids, the predicted level change was (0.000638, p = 0.21); and the trend change was (0.000047, p = 0.49). CONCLUSION: Implementation of an EDIB program was not associated with increased rates of presentation by patients requesting treatment for a substance use disorder in the participating ED setting.

Adherence Across FDA-Approved Medications for Alcohol Use Disorder in a Veterans Administration Population.

OBJECTIVE: U.S. Food and Drug Administration (FDA)-approved medications exist for the treatment of alcohol use disorders. However, their effectiveness depends on proper adherence to the prescribed regimen. Differences in adherence across medications may have implications for clinical outcomes and may provide helpful information in considering treatment options. This study aims to identify significant differences in adherence if present. METHOD: A retrospective chart review was conducted in the Veterans Integrated Service Networks (VISN)-7 region of Veterans Affairs hospital and community-based outpatient clinics within South Carolina and Georgia. Prescriptions of FDA-approved alcohol use disorder medications from 2010 through 2015 were reviewed. Adherence was determined by the proportion of days the veteran had oral or injectable medication available over a 6-month period as noted by medication fills (reported as 0%-100% medication availability). We compared adherence for specific medications using chi-square, t test, logistic regression for dichotomous outcomes, and linear regression for continuous outcomes. RESULTS: A total of 715 subjects and 807 medication trials were included. Mean adherence (percentage of days that medication was available) was 41.3% for disulfiram, 44.7% for acamprosate, 49.8% for oral naltrexone, and 54.6% for extended-release injectable naltrexone. The mean adherence was significantly different between disulfiram and oral naltrexone (p = .002) as well as disulfiram and extended-release injectable naltrexone (p = .004). Adherence of 80% was achieved in 11.9%, 19.4%, 22.7%, and 24.4% of treatment courses with disulfiram, acamprosate, naltrexone, and extended-release injectable naltrexone, respectively. These differences were significant for disulfiram versus oral naltrexone (p = .004) and disulfiram versus extended-release injectable naltrexone (p = .05). CONCLUSIONS: These results demonstrate that overall adherence to medication-assisted treatment for alcohol use disorder is low across all medications. When directly compared, disulfiram had significantly lower adherence than both oral and extended-release injectable naltrexone.

Impact of Oxytocin on the neural correlates of fearful face processing in PTSD related to childhood Trauma.

Background: Posttraumatic stress disorder (PTSD) related to exposure to abuse and neglect during childhood is associated with particularly severe and persistent deleterious outcomes. Amygdala hyperreactivity has been observed in childhood trauma survivors and implicated in symptoms of PTSD. Objective: The neuropeptide oxytocin holds promise as a potential treatment for PTSD due to its ability to attenuate amygdala response to threat cues. However, the effect of oxytocin on amygdala reactivity in individuals with childhood trauma-related PTSD has not been investigated. Method: We employed a double-blind, randomized, placebo-controlled crossover design to examine the effects of intranasal oxytocin (24 IU) versus placebo on amygdala reactivity to fearful faces among childhood-trauma exposed individuals with PTSD (n = 17) and without PTSD (control group; n = 16). Results: Region-of-interest based amygdala fMRI signal magnitude did not differ by group, drug, or group x drug interaction. Self-report of childhood trauma exposure severity was negatively associated with the oxytocin-related change in left amygdala response in the PTSD group, but not in the control group. Supplementary and exploratory whole-brain analyses conducted separately in each group revealed that left amygdala reactivity to fearful faces was absent on placebo but increased on oxytocin in the control group. The PTSD group showed right amygdala activation to fearful faces in both the oxytocin and placebo conditions, but the left amygdala response observed in the placebo condition was diminished on oxytocin. Conclusions: Findings extend the literature pertaining to the potential for oxytocin to attenuate neural correlates of PTSD to a childhood trauma-related PTSD sample.

Antecedentes: El trastorno de Estrés Postraumático (TEPT) relacionado con exposición a abuso y negligencia durante la infancia se asocia con consecuencias deletéreas particularmente persistentes y severas. Se ha observado una hiperreactividad de la amígdala en sobrevivientes de trauma infantil y también se ha implicado en los síntomas de TEPT. Objetivo: El neuropéptido oxitocina es prometedor como un potencial tratamiento para el TEPT debido a su habilidad de atenuar la respuesta de la amígdala frente a señales de amenaza. Sin embargo, el efecto de la oxitocina en la reactividad de la amígdala en individuos con TEPT relacionado a trauma infantil no ha sido investigado. Método: Empleamos un diseño doble ciego, aleatorizado, cruzado placebo-control para examinar los efectos de la oxitocina intranasal (24 IU) versus placebo en la reactividad de la amígdala a las caras de miedo entre individuos expuestos a trauma infantil con TEPT (n=17) y sin TEPT (grupo control; n=16). Resultados: La magnitud de la señal por IRMf de la amígdala basada en la región de interés no difirió por grupo, droga, o interacción droga x grupo. El auto-reporte de la severidad de la exposición a trauma infantil se asoció negativamente con el cambio asociado a oxitocina en la respuesta de la amígdala izquierda en el grupo con TEPT, pero no en el grupo control. Los análisis suplementarios de todo el cerebro revelaron que la reactividad de la amígdala izquierda a caras de miedo estuvo ausente con placebo, pero aumentó con la oxitocina en el grupo control. El grupo con TEPT mostró una activación de la amígdala derecha a caras de miedo en ambas condiciones, con oxitocina y con placebo, pero la respuesta de la amígdala izquierda observada en la condición de placebo estuvo disminuida con la oxitocina. Conclusiones: Los hallazgos amplían la literatura sobre el potencial de la oxitocina para atenuar los correlatos neurales del TEPT a una muestra de TEPT relacionado con trauma infantil.

Cannabis Withdrawal in Adults With Attention-Deficit/Hyperactivity Disorder.

OBJECTIVE: Cannabis withdrawal has not been studied in adults with attention-deficit/hyperactivity disorder (ADHD) who have high rates of cannabis use. We aimed to describe cannabis withdrawal, motivations to quit, and strategies to quit cannabis use in cannabis-dependent adults with ADHD. METHODS: Twenty-three adults with ADHD enrolled in a controlled clinical trial of pharmacotherapy (atomoxetine) for cannabis dependence (DSM-IV criteria) completed the Marijuana Quit Questionnaire (MJQQ) to provide information on their "most serious" quit attempt made without formal treatment. The study was conducted between November 2005 and June 2008. RESULTS: Participants were predominantly male (82.6%, n = 19), with a mean (SD) age of 27.4 (8.5) years (range, 18-53) at the start of their index quit attempt. The most common motive for quitting cannabis was "to save money" (87%, n = 20); the most common strategy to maintain abstinence was "stopped associating with people who smoke marijuana" (43%, n = 10). Almost all (96%, n = 22) subjects reported ≥ 1 cannabis withdrawal symptom; 7 (30%) met DSM-5 diagnostic criteria for cannabis withdrawal syndrome. CONCLUSIONS: Participants with comorbid ADHD and cannabis dependence reported withdrawal symptoms similar to other samples of non-treatment-seeking cannabis-dependent adults with no psychiatric comorbidity. These findings suggest that ADHD does not influence cannabis withdrawal in the way that it does tobacco (nicotine) withdrawal. TRIAL REGISTRATION: Data used in this secondary analysis came from ClinicalTrials.gov identifier: NCT00360269.

Network Analysis of Intrinsic Functional Brain Connectivity in Male and Female Adult Smokers: A Preliminary Study.

Background: The goal of this study was to conduct a preliminary network analysis (using graph-theory measures) of intrinsic functional connectivity in adult smokers, with an exploration of sex differences in smokers. Methods: Twenty-seven adult smokers (13 males; mean age = 35) and 17 sex and age-matched controls (11 males; mean age = 35) completed a blood oxygen level-dependent resting state functional magnetic resonance imaging experiment. Data analysis involved preprocessing, creation of connectivity matrices using partial correlation, and computation of graph-theory measures using the Brain Connectivity Toolbox. Connector hubs and additional graph-theory measures were examined for differences between smokers and controls and correlations with nicotine dependence. Sex differences were examined in a priori regions of interest based on prior literature. Results: Compared to nonsmokers, connector hubs in smokers emerged primarily in limbic (parahippocampus) and salience network (cingulate cortex) regions. In addition, global influence of the right insula and left nucleus accumbens was associated with higher nicotine dependence. These trends were present in male but not female smokers. Conclusions: Network communication was altered in smokers, primarily in limbic and salience network regions. Network topology was associated with nicotine dependence in male but not female smokers in regions associated with reinforcement (nucleus accumbens) and craving (insula), consistent with the idea that male smokers are more sensitive to the reinforcing aspects of nicotine than female smokers. Implications: Identifying alterations in brain network communication in male and female smokers can help tailor future behavioral and pharmacological smoking interventions. Male smokers showed alterations in brain networks associated with the reinforcing effects of nicotine more so than females, suggesting that pharmacotherapies targeting reinforcement and craving may be more efficacious in male smokers.

Transcranial magnetic stimulation of the dorsal lateral prefrontal cortex inhibits medial orbitofrontal activity in smokers.

BACKGROUND AND OBJECTIVE: Several studies have shown that repetitive transcranial magnetic stimulation (rTMS), applied to the dorsolateral prefrontal cortex (DLPFC), can reduce cue-elicited craving in smokers. Currently, the mechanism of this effect is unknown. We used functional magnetic resonance imaging (fMRI) to explore the effect of a single treatment of rTMS on cortical and sub-cortical neural activity in non-treatment seeking nicotine-dependent participants. METHODS: We conducted a randomized, counterbalanced, crossover trial in which participants attended two experimental visits separated by at least 1 week. On the first visit, participants received either active, or sham rTMS (10 Hz, 5 s-on, 10 s-off, 100% motor threshold, 3,000 pulses) over the left DLPFC, and on the second visit they received the opposite condition (active or sham). Cue craving fMRI scans were completed before and after each rTMS session. RESULTS: A total of 11 non-treatment seeking nicotine-dependent cigarette smokers were enrolled in the study [six female, average age 39.7 ± 13.2, average cigarettes per day 17.3 ± 5.9]. Active rTMS decreased activity in the contralateral medial orbitofrontal cortex (mOFC) and ipsilateral nucleus accumbens (NAc) compared to sham rTMS. CONCLUSIONS: This preliminary data suggests that one session of rTMS applied to the DLPFC decreases brain activity in the NAc and mOFC in smokers. SCIENTIFIC SIGNIFICANCE: rTMS may exert its anti-craving effect by decreasing activity in the NAc and mOFC in smokers. Despite a small sample size, these findings warrant future rTMS/fMRI studies in addictions. (Am J Addict 2017;26:788-794).

Individualized real-time fMRI neurofeedback to attenuate craving in nicotine-dependent smokers.

BACKGROUND: Cue-induced craving plays an important role in relapse, and the neural correlates of cue-induced craving have been elucidated using fMRI. This study examined the utility of real-time fMRI (rtfMRI) neurofeedback to strengthen self-regulation of craving-related neural activation and cue-reactivity in cigarette smokers. METHODS: Nicotine-dependent smokers were randomized to rtfMRI neurofeedback or to a no-feedback control group. Participants completed 3 neuroimaging visits. Within each visit, an initial run during which smoking-related cues were used to provoke craving, an individualized craving-related region of interest (ROI) in the prefrontal cortex or anterior cingulate cortex was identified. In the rtfMRI group, activity from the ROI was fed back via a visual display during 3 subsequent runs while participants were instructed to reduce craving during cue exposure. The control group had an identical experience with no feedback provided. RESULTS: Forty-four nicotine-dependent smokers were recruited to participate in our study; data from the 33 participants who completed a 1-week follow-up visit were included in the analysis. Subjective craving ratings and cue-induced brain activation were lower in the rtfMRI group than in the control group. LIMITATIONS: As participants were not seeking treatment, clinical outcomes are lacking. CONCLUSION: Nicotine-dependent smokers receiving rtfMRI feedback from an individualized ROI attenuated smoking cue-elicited neural activation and craving, relative to a control group. Further studies are needed in treatment-seeking smokers to determine if this intervention can translate into a clinically meaningful treatment modality.

Vilazodone for cannabis dependence: A randomized, controlled pilot trial.

BACKGROUND AND OBJECTIVES: The purpose of this study was to evaluate the efficacy of vilazodone, a selective serotonin receptor inhibitor and partial 5-HT1A agonist, for treatment of cannabis dependence. METHODS: Seventy-six cannabis-dependent adults were randomized to receive either up to 40 mg/day of vilazodone (n = 41) or placebo (n = 35) for 8 weeks combined with a brief motivational enhancement therapy intervention and contingency management to encourage study retention. Cannabis use outcomes were assessed via weekly urine cannabinoid tests; secondary outcomes included cannabis use self-report and cannabis craving. RESULTS: Participants in both groups reported reduced self-reported cannabis use over the course of the study; however, vilazodone provided no advantage over placebo in reducing cannabis use. Men had significantly lower creatinine-adjusted cannabinoid levels and a trend for increased negative urine cannabinoid tests than women. DISCUSSION AND CONCLUSIONS: Vilazodone was not more efficacious than placebo in reducing cannabis use. Important gender differences were noted, with women having worse cannabis use outcomes than men. SCIENTIFIC SIGNIFICANCE: Further medication development efforts for cannabis use disorders are needed, and gender should be considered as an important variable in future trials.

Lower subcortical gray matter volume in both younger smokers and established smokers relative to non-smokers.

Although established adult smokers with long histories of nicotine dependence have lower neural tissue volume than non-smokers, it is not clear if lower regional brain volume is also observed in younger, less established smokers. The primary goal of this study was to investigate neural tissue volume in a large group of smokers and non-smokers, with a secondary goal of measuring the impact of age on these effects. We used voxel-based morphometry to compare regional gray matter volume in 118 individuals (59 smokers, 59 age- and gender-matched non-smokers). Younger smokers had significantly lower gray matter volume in the left thalamus and the left amygdala than their non-smoking peers (family-wise error-corrected clusters, P < 0.05). There was no correlation between smoking use variables and tissue volume among younger smokers. Established smokers had significantly lower gray matter volume than age-matched non-smokers in the insula, parahippocampal gyrus and pallidum. Medial prefrontal cortex gray matter volume was negatively correlated with pack-years of smoking among the established smokers, but not the younger smokers. These data reveal that regional tissue volume differences are not limited exclusively to established smokers. Deficits in young adults indicate that cigarette smoking may either be deleterious to the thalamus and amygdala at an earlier age than previously reported, or that pre-existing differences in these areas may predispose individuals to the development of nicotine dependence.

The fMRI BOLD response to unisensory and multisensory smoking cues in nicotine-dependent adults.

Given that the vast majority of functional magnetic resonance imaging (fMRI) studies of drug cue reactivity use unisensory visual cues, but that multisensory cues may elicit greater craving-related brain responses, the current study sought to compare the fMRI BOLD response to unisensory visual and multisensory, visual plus odor, smoking cues in 17 nicotine-dependent adult cigarette smokers. Brain activation to smoking-related, compared to neutral, pictures was assessed under cigarette smoke and odorless odor conditions. While smoking pictures elicited a pattern of activation consistent with the addiction literature, the multisensory (odor+picture) smoking cues elicited significantly greater and more widespread activation in mainly frontal and temporal regions. BOLD signal elicited by the multisensory, but not unisensory cues, was significantly related to participants' level of control over craving as well. Results demonstrated that the co-presentation of cigarette smoke odor with smoking-related visual cues, compared to the visual cues alone, elicited greater levels of craving-related brain activation in key regions implicated in reward. These preliminary findings support future research aimed at a better understanding of multisensory integration of drug cues and craving.

An exploratory short-term double-blind randomized trial of varenicline versus nicotine patch for smoking cessation in women.

AIMS: Within a parent study examining ovarian hormone effects on smoking cessation in women, we conducted an exploratory short-term trial of varenicline versus transdermal nicotine patch. DESIGN: Double-blind double-dummy randomized trial. SETTING: Single-site out-patient research clinic in the United States. PARTICIPANTS: Female smokers, ages 18-45 years and averaging ≥10 cigarettes per day for at least 6 months (n=140). INTERVENTIONS: Participants were randomized to receive a 4-week course of (a) varenicline tablets and placebo patches (n = 67) or (b) placebo tablets and nicotine patches (n=73). Two brief cessation counseling sessions were provided for all participants. MEASUREMENTS: The outcome of primary clinical interest was 2-week end-of-treatment abstinence. Secondary outcomes included 1- and 4-week end-of treatment abstinence and abstinence at a post-treatment follow-up visit occurring 4 weeks after treatment conclusion. Breath carbon monoxide (≤ 10 parts per million) was used to confirm biochemically self-reported abstinence. FINDINGS: Two-week end-of-treatment abstinence was achieved by 37.3% (25 of 67) of varenicline participants and by 17.8% (13 of 73) of nicotine patch participants [odds ratio (OR) = 2.7, 95% confidence interval (CI)=1.3-6.0, P=0.011]. One-week (44.8 versus 20.6%, OR=3.1, 95% CI=1.5-6.6, P=0.003) and 4-week (22.4 versus 9.6%, OR=2.7, 95% CI=1.0-7.2, P=0.043) end-of-treatment abstinence similarly favored varenicline, although post-treatment follow-up Russell Standard abstinence was not significantly different between groups (23.9 versus 13.7%, OR=2.0, 95% CI=0.8-4.7, P=0.126). CONCLUSION: In an exploratory 4-week head-to-head trial in female smokers, varenicline, compared with nicotine patch, more than doubled the odds of end-of-treatment abstinence, although this diminished somewhat at post-treatment follow-up.

Increasing progesterone levels are associated with smoking abstinence among free-cycling women smokers who receive brief pharmacotherapy.

INTRODUCTION: Preclinical and human laboratory research suggests that (a) progesterone may decrease drug reward, craving, and smoking behavior, and (b) estradiol may enhance drug reward and smoking behavior. A modest majority of treatment research examining the relationship between menstrual cycle phase and outcomes suggests that the luteal menstrual phase, with its uniquely higher progesterone levels, is associated with better cessation outcomes. However, no studies to date have examined the effects of naturally occurring variation in progesterone and estradiol levels on medication-assisted smoking cessation. The present study sought to fill this notable gap in the treatment literature. METHODS: Weekly plasma progesterone and estradiol levels were obtained from nicotine-dependent female smokers enrolled in a 4-week cessation trial. Participants (N = 108) were randomized to receive a 4-week course of either varenicline (VAR) tablets and placebo patches or placebo tablets and nicotine patches. Plasma samples were obtained 1 week before their cessation attempt and weekly during medication administration. Abstinence was assessed weekly. RESULTS: Weekly hormone data replicated commonly observed menstrual cycle patterns of progesterone and estradiol levels. Importantly, increases in progesterone level were associated with a 23% increase in the odds for being abstinent within each week of treatment. This effect was driven primarily by nicotine patch-treated versus VAR-treated females. CONCLUSIONS: This study was the first to identify an association between progesterone level (increasing) and abstinence outcomes in free-cycling women smokers who participated in a medication-based treatment. Furthermore, the potential benefits of progesterone may vary across different pharmacotherapies. Implications of these findings for smoking cessation intervention are discussed.

Olfactory cue reactivity in nicotine-dependent adult smokers.

Cue-elicited reactivity is a significant factor in relapse during smoking quit attempts. Previous research has focused primarily on visual smoking cues, with very limited research examining reactivity to olfactory triggers. Twenty-six adult non-treatment-seeking, nicotine-dependent smokers were exposed to 7 odorants during a cue-reactivity session measuring heart rate, skin conductance, and subjective craving. Cues included 2 cigarette odors (fresh tobacco and cigarette smoke), 2 odors previously identified as smoking-related (freshly mowed grass and coffee), 2 odors previously identified as unrelated to smoking (lavender and burned rubber), and 1 odorless control (propylene glycol). Pairwise comparisons demonstrated that subjective intensity of craving was significantly higher following exposure to the fresh tobacco odor compared with the odorless control (p < .01). A significant main effect for cue type on a physiological measure of arousal was also revealed, with a fresh tobacco odor-elicited significant increase in skin conductance level compared with the odorless control. However, no main effect of cue type on heart rate was found (p = .25). The results of the present study indicate that cigarette odor is an effective olfactory cue that heightens both subjective craving and increases skin conductance in smokers. Future research is needed to evaluate whether avoidance of these odors, or extinction of responses to them, can reduce relapse risk during smoking quit attempts.

Right anterior insula connectivity is important for cue-induced craving in nicotine-dependent smokers.

The insula has been implicated in cue-induced craving and relapse in nicotine-dependent tobacco cigarette smokers. The aims of the present study were to identify brain regions that exhibit greater functional connectivity with the right anterior insula in response to smoking cues than to neutral cues and the role of functional connectivity between these regions in mediating cue-induced craving in healthy (free of axis I psychiatric disorders) nicotine-dependent tobacco cigarette smokers. Functional magnetic resonance imaging data were collected from 63 healthy nicotine-dependent smokers viewing blocks of smoking and neutral cues. Craving ratings were obtained after each block. A psychophysiologic interaction approach was used to identify regions that exhibited significantly greater functional connectivity with the right anterior insula (seed) during the smoking cues than during the neutral (corrected cluster thresholding, Z > 2.3, P = 0.05). Parameter estimates of the interaction effects from each region were regressed against the mean cue-induced craving scores. Significant task by seed interactions were observed in two clusters centered in the bilateral precuneus and left angular gyrus. The strength of connectivity between the right anterior insula and the precuneus, which is involved interoceptive processing and self-awareness, was positively correlated with the magnitude of the craving response to the smoking cues (r(2) = 0.15; P < 0.01). These data suggest that among smokers, cue-induced craving may be a function of connectivity between two regions involved in interoception and self-awareness. Moreover, treatment strategies that incorporate mindful attention may be effective in attenuating cue-induced craving and relapse in nicotine-dependent smokers.

Sustained reduction of nicotine craving with real-time neurofeedback: exploring the role of severity of dependence.

BACKGROUND: Neurofeedback delivered via real-time functional magnetic resonance imaging (rtfMRI) is a promising therapeutic technique being explored to facilitate self-regulation of craving in nicotine-dependent cigarette smokers. The current study examined the role of nicotine-dependence severity and the efficacy of multiple visits of neurofeedback from a single region of interest (ROI) in the anterior cingulate cortex (ACC) on craving reduction. METHODS: Nine nicotine-dependent cigarette smokers participated in three rtfMRI visits that examined cue-induced craving and brain activation. Severity of nicotine dependence was assessed with the Fagerström Test for Nicotine Dependence. When viewing smoking-related images with instructions to "crave," patient-tailored ROIs were generated in the vicinity of the ACC. Activity levels from the ROI were fed back while participants viewed smoking cues with the instruction to reduce craving. RESULTS: Neurofeedback from a single ROI in the ACC led to consistent decreases in self-reported craving and activation in the ACC across the three visits. Dependence severity predicted response to neurofeedback at Visit 3. CONCLUSIONS: This study builds upon previous rtfMRI studies on the regulation of nicotine craving in demonstrating that feedback from the ACC can reduce activation to smoking cues across three separate visits. Individuals with lower nicotine-dependence severity were more successful in reducing ACC activation over time. These data highlight the need to consider dependence severity in developing more individualized neurofeedback methods.

Substance use disorders and anxiety: a treatment challenge for social workers.

Converging evidence from epidemiologic and treatment studies indicate that anxiety disorders and substance use disorders commonly co-occur, and the interaction is multifaceted and variable. Epidemiological studies and investigations within clinical substance abuse populations have found an association between anxiety disorders and substance use disorders. Specific anxiety disorders including generalized anxiety disorder, panic disorder, and post traumatic stress disorder have all been associated with substance use. The association with obsessive-compulsive disorder is less robust, and some research has found a negative association. The risk of nicotine dependence is significantly higher among individuals with an anxiety disorder, and conversely, smoking has been found to be associated with trait anxiety and anxiety disorders. A review of the current literature and the relationship between specific anxiety disorders and alcohol and substance use disorders is discussed in detail. This article, written for social workers in a variety of practice settings, reviews the prevalence, diagnostic, and treatment issues at the interface of substance use disorders and anxiety disorders.

Reduction of cue-induced craving through realtime neurofeedback in nicotine users: the role of region of interest selection and multiple visits.

This multi-visit, real-time functional magnetic resonance imaging feedback study demonstrates that treatment-seeking smokers can effectively modulate their behavioral and brain responses to smoking cues. They are more effective at decreasing activity in functionally defined regions involved in "craving" (e.g. ventral anterior cingulate cortex (vACC)) rather than increasing activity in regions involved in "resisting" (e.g. dorsal medial prefrontal cortex (dmPFC)).