Early Abstinence Research Articles

Fatty acid amide hydrolase is lower in young cannabis users.

We have recently shown that levels of fatty acid amide hydrolase (FAAH), the enzyme that metabolizes the endocannabinoid anandamide, are lower in the brains of adult cannabis users (CUs) (34 ± 11 years of age), tested during early abstinence. Here, we examine replication of the lower FAAH levels in a separate, younger cohort (23 ± 5 years of age). Eighteen healthy volunteers (HVs) and fourteen CUs underwent a positron emission tomography scan using the FAAH radioligand [11 C]CURB. Regional [11 C]CURB binding was calculated using an irreversible two-tissue compartment model with a metabolite-corrected arterial plasma input function. The FAAH C385A genetic polymorphism (rs324420) was included as a covariate. All CUs underwent a urine screen to confirm recent cannabis use and had serum cannabinoids measured. One CU screened negative for cannabinoids via serum and was removed from analysis. All HVs reported less than five lifetime cannabis exposures more than a month prior to study initiation. There was a significant effect of group (F1,26 = 4.31; P = .048) when two A/A (rs324420) HVs were removed from analysis to match the genotype of the CU group (n = 16 HVs, n = 13 CUs). Overall, [11 C]CURB λk3 was 12% lower in CU compared with HV. Exploratory correlations showed that lower brain [11 C]CURB binding was related to greater use of cannabis throughout the past year. We confirmed our previous report and extended these findings by detecting lower [11 C]CURB binding in a younger cohort with less cumulative cannabis exposure.

Association Between Recent Cannabis Consumption and Withdrawal-Related Symptoms During Early Abstinence Among Females With Smoked Cocaine Use Disorder.

The effects of cannabis on clinical outcomes of treatment services for other drug use disorders remains unclear. The primary aim of the current study was to investigate the effects of recent cannabis consumption on the severity of cocaine withdrawal and depressive symptoms during a 3-week inpatient treatment program for women with cocaine use disorder. The second goal of this study was to test the effect of recent alcohol or tobacco use on the aforementioned outcomes. This was a longitudinal study with 2 assessment time points: at enrollment and upon discharge from a medically managed intensive inpatient unit. The sample was composed of 214 early abstinence females with cocaine use disorder. Cocaine withdrawal and depressive symptoms were measured using the Cocaine Selective Severity Assessment (CSSA) and the Beck Depressive Inventory (BDI-II). Recent substance use was evaluated using the Addiction Severity Index (ASI-6). Patients with cocaine use disorder and with frequent recent cannabis use reported higher severity of cocaine withdrawal and depressive symptoms after 3 weeks of inpatient treatment. Neither recent alcohol nor tobacco use was associated with increased CSSA or BDI outcomes, suggesting these substances play a minor role compared to recent cannabis use in affecting withdrawal-related symptoms. The assessment of recent cannabis use may help identify patients in need of additional treatment to manage severe cocaine withdrawal symptoms and depressive symptoms during early abstinence.

The neural interface between negative emotion regulation and motivation for change in cocaine dependent individuals under treatment

BackgroundEmotion regulation is important for cocaine addiction treatment success, particularly during early abstinence. In addition, the neural underpinnings of emotion processing overlap with those of motivation and goal-directed behavior. We examined if the neural underpinnings of emotion maintenance and its regulation correlate with cocaine treatment motivation. MethodsForty-five cocaine dependent individuals (CDIs) starting outpatient treatment in a public specialized addiction treatment clinic in Granada (Spain) underwent fMRI scans while performing a Reappraisal task, and completed the University of Rhode Island Change Assessment Scale (URICA), to measure treatment motivation. We conducted correlation analyses to examine the association between emotion maintenance and regulation related brain activation and URICA’s Readiness to Change scores. We also explored links between Emotional reports during the fMRI reappraisal task, duration of abstinence, and anxiety and depression symptoms. ResultsReadiness to Change scores were positively correlated with activations in the right dorsolateral prefrontal and right parietal cortices, the midbrain (p ≤ 0.001, cluster extents ≥109 voxels), and basolateral amygdala (PFWE-SVC<0.05), while negatively with emotion maintenance related activation in the same cortical areas and activations in the dorsomedial frontal cortex, the nucleus accumbens and the left fusiform gyrus. Emotional reactivity negatively correlated with right dorsolateral prefrontal cortex reappraisal related activation (r= -0.40, p = 0.007), and the Regulate score positively correlated with the left fusiform gyrus emotion maintenance related activation (r = 0.31, p = 0.04). ConclusionsEmotional related activation in frontoparietal, accumbens, fusiform, amygdala and midbrain regions engaged during emotion regulation and its maintenance correlate with early treatment motivation in CDIs.

Lower brain fatty acid amide hydrolase in treatment-seeking patients with alcohol use disorder: a positron emission tomography study with [C-11]CURB.

The endocannabinoid enzyme, fatty acid amide hydrolase (FAAH), has been proposed as a therapeutic target for alcohol use disorder (AUD) and co-morbid psychiatric illnesses. Investigating this target in the living human brain and its relationship to clinical outcome is a critical step of informed drug development. Our objective was to establish whether brain FAAH levels are low in individuals with AUD and related to drinking behavior. In this pilot study, treatment-seeking patients with AUD completed two PET scans with the FAAH radiotracer [C-11]CURB after 3-7 days (n = 14) and 2-4 weeks (n = 9) of monitored abstinence. Healthy controls (n = 25) completed one scan. FAAH genetic polymorphism (rs324420) and blood concentrations of anandamide and other N-acylethanolamines metabolized by FAAH were determined and AUD symptoms assessed. In AUD, brain FAAH levels were globally lower than controls during early abstinence (F(1,36) = 5.447; p = 0.025)) and FAAH substrates (anandamide, oleoylethanolamide, and N-docosahexaenoylethanolamide) were significantly elevated (30-67%). No significant differences in FAAH or FAAH substrates were noted after 2-4 weeks abstinence. FAAH levels negatively correlated with drinks per week (r = -0.57, p = 0.032) and plasma concentrations of the three FAAH substrates (r > 0.57; p < 0.04)). Our findings suggest that early abstinence from alcohol in AUD is associated with transiently low brain FAAH levels, which are inversely related to heavier alcohol use and elevated plasma levels of FAAH substrates. Whether low FAAH is an adaptive beneficial response to chronic alcohol is unknown. Therapeutic strategies focusing on FAAH inhibition should consider the possibility that low FAAH during early abstinence may be related to drinking.

Gabapentin for alcohol use disorder: A good option, or cause for concern?

The anticonvulsant drug gabapentin is used off-label to treat alcohol-related withdrawal, cravings, anxiety, and insomnia. Although it is well tolerated and has demonstrated efficacy for mild alcohol withdrawal and early abstinence, there is concern about its potential for abuse. Gabapentin should be prescribed only as a second-line alternative to standard therapies, and only after screening for opioid or other prescription drug abuse to determine if heightened monitoring is warranted. Clinicians should be aware of gabapentin's limitations for treating alcohol use disorder and be attentive to emerging data on risks and benefits.

Effects of smoking cessation treatment attendance on abstinence: The moderating role of psychologically based behavioral health conditions

Available smoking cessation treatments have shown only modest quit success. Presence of a psychologically based behavioral health condition (PBHC), such as depression, anxiety, or addiction, can impact smoking cessation treatment engagement and quit success; however, the differential effect of treatment engagement on smoking cessation outcomes across smokers with and without a PBHC is unknown. The current study examined the moderating effect presence (versus absence) of a PBHC on the relation between treatment attendance and early smoking abstinence following a 4-session smoking cessation treatment. Participants included 529 (45.9% male; Mage = 38.23 years, SD = 13.56; 75.4% White) smokers enrolled in a large randomized controlled trial evaluating the efficacy of a transdiagnostic smoking cessation treatment. A repeated-measures latent class analysis (RMLCA) was conducted to examine treatment attendance. The effects of treatment attendance, PBHC (present/absent), and their interaction were modeled on biochemically-verified point prevalence abstinence using a latent growth curve from 1-week to 1-month post-quit. The RMLCA provided evidence for three classes: Drop-outs (n = 197), Titrators (n = 89), and Completers (n = 243). A significant interaction emerged such that Completers without a PBHC were significantly more likely to be abstinent relative to Completers with a PBHC (b = 2.69, SE = 0.67, p < .001) and Titrators without a PBHC (b = 3.36, SE = 0.80, p < .001). These results provide novel data that implicate the clinical importance of treatment attendance and PBHC status on smoking abstinence.

Neuro-Immuno-Endocrine Interactions in Early Life Stress and Heroin Withdrawal Timeline

Both heroin abuse and early life stress (ELS) affect the immune system and the hypothalamic-pituitary-adrenal (HPA) axis. Additionally, accelerated aging due to mild inflammation has been indicated in these conditions. The present study aims to compare plasma levels of apoptosis markers, inflammatory markers, and stress hormones during early heroin abstinence period. Thirty-one individuals with heroin/opioid use disorder who had heroin-ELS and 26 of their siblings who were not abusing substances (ELS), and 32 individuals with heroin/opioid use disorder without a history of ELS (heroin-no ELS) were included in the study. The levels of interleukin-6, C-reactive protein, erythrocyte sedimentation rate, albumin, alanine transaminase, aspartate transaminase, and white blood cell count were assessed as the inflammatory and biochemistry markers. Also, apoptosis markers including tumor necrosis factor (TNF)-related weak inducer of apoptosis, TNF-related apoptosis-inducing ligand, soluble tumor necrosis factor receptor type I as apoptosis markers were detected by enzyme-linked immunosorbent assay. ELS was simultaneously evaluated using the Childhood Trauma Questionnaire, Minnesota Multiphasic Personality Inventory, and beck depression inventory scales. Besides, heroin craving was assessed by Daily Drinking/Drug Questionnaire score in individuals with heroin use disorder. This is the first study to evaluate the inflammatory, stress, and apoptosis markers during heroin abstinence, supporting the association between ELS and peripheral pro-inflammatory markers’ levels and HPA axis.

Difficulties In Emotion Regulation During Rehabilitation For Alcohol Addiction: Correlations With Metacognitive Beliefs About Alcohol Use And Relapse Risk.

PurposeUnderstanding how difficulties in emotion regulation can be related to metacognitive beliefs during early abstinence, identifying which factors are associated with craving and relapse risk may be useful in residential rehabilitation treatment of alcohol addiction.MethodsSixty-five patients underwent a 28-day rehabilitation program for alcohol addiction. They underwent a brief semi-structured interview at admission and completed a battery of five self-report questionnaires between days 7 and 10 of alcohol abstinence (T0) and 3 days prior to discharge (T1).ResultsAfter rehabilitation program, all symptoms of psychological distress decreased. We found a significant improvement in all emotional, cognitive and metacognitive scales except for “Cognitive harm” (NAM), “Awareness” (DERS) and a small effect size (low statistical power) for “Emotional clarity” (DERS). Compared to those still abstinent at 1 month from discharge, we found more difficulties in “Emotional clarity” in those who had an early relapse. Difficulties in “Emotional clarity” were observed also in patients with a high level of craving at discharge.ConclusionSignificant differences were observed between the groups “abstinence vs non-abstinence” at 1 month from discharge concerning difficulties in emotion regulation. In particular, we found difficulty in the awareness and understanding of emotion, precisely to identify correctly the emotions. The “Emotional Clarity” seems to be the emotional difficulty that characterized also the group with a high level of craving at discharge and the individuals with early relapse, suggesting the importance of this function as a preliminary factor in emotion regulation.

Positron Emission Tomography: Updates on Imaging of Addiction.

Positron Emission Tomography: Updates on Imaging of Addiction.

Detecting Alcohol-Induced Brain Damage Noninvasively Using Diffusion Tensor Imaging.

While alcohol's detrimental effects on the brain are widely acknowledged, diagnostic markers for detection and monitoring alcohol-induced brain damage are lacking. A recent study showed that diffusion tensor imaging can be used to monitor this damage and characterized the progression of the observed changes into early abstinence. Here, we discuss the main findings of that study and highlight current technical limitations which, once addressed, can pave the way to the development of new powerful diagnostic markers for alcohol-induced brain damage.

Absolute Abstinence as a Treatment Outcome in Servicemen with Alcohol Dependence: A Retrospective Cohort Study

Background: Within India’s military medical framework, alcohol dependence syndrome (ADS) is deemed a treatable medical illness incompatible with military service, and complete abstinence is the only acceptable successful treatment outcome. Objective: This study was designed to identify factors which were able to differentiate treatment outcomes of abstinence and relapse among ADS patients in a military framework. Method: Recognizing personal incentives to misrepresent alcohol consumption, abstinence, and relapse outcomes were established using official reports from a patient’s parent unit, in combination with biochemical parameters and clinical examination. Patients serially admitted for ADS treatment or follow-up review were surveyed, and their socio-demographic and alcohol consumption profiles, coping styles, life events and specific relapse precipitants were recorded and compared as contributory variables in a cognitive-behavioral model of ADS. From this survey of 140 patients, membership to abstainer or relapser groups was then predicted using a discriminant analysis. Results: 34% of patients achieved early absolute abstinence. No baseline socio-demographic or drinking profile distinctions existed between abstainers and relapsers. Differences were forthcoming on coping styles, life-event, and relapse-precipitant exposure measures. Stepwise discriminant analysis produced a final equation comprising 10 independent variables (including two positive life event measures), which predicted an abstinence/relapse outcome with an 86% and 79% hit-rate (original and cross-validated). Conclusion: Using prevailing cognitive-behavioral constructs, early absolute abstinence emerged as an actionable objective and an achievable goal without any contributory socio-demographic predilections. This preliminary evaluation suggests it is a tenable and realistic target of current ADS treatment programs.

Chronic ketamine abuse is associated with orexin-A reduction and ACTH elevation.

Ketamine has emerged as a major substance of abuse worldwide. Evidence suggests a role of orexin system in reward processing, withdrawal, and stress response. It also interacts with the stress mechanisms of hypothalamic-pituitary-adrenal (HPA) axis to regulate drug-taking behavior. The study aimed to explore the relevance of orexin and stress hormones to chronic ketamine abuse. We enrolled 67 ketamine-dependent (KD) patients and 64 controls. The levels of orexin-A, adrenocorticotropic hormone (ACTH), and cortisol were measured at baseline, 1week, and 2weeks after ketamine discontinuation. KD patients were assessed by Beck Depression Inventory, Beck Anxiety Inventory, and Visual Analogue Scale for ketamine craving at baseline. Compared with the controls, KD patients had significantly lower orexin-A (0.65 ± 0.12 vs. 0.74 ± 0.10ng/mL, p < 0.001) and increased ACTH (32.3 ± 16.3 vs. 22.3 ± 11.0pg/mL, p = 0.008) levels at baseline, whereas cortisol levels were similar between two groups. Levels of the three markers did not correlate with ketamine use variables, craving, depression, or anxiety symptoms. The levels did not alter after 1 or 2weeks of ketamine discontinuation. Notably, those with higher anxiety had lower orexin-A but increased cortisol levels than did those with lower anxiety. This study showed that KD patients had persistent orexin-A reduction and stress hormone dysregulation in early abstinence. The anxious phenotype of KD might be associated with a lower orexin-A expression. These results point to a promising pathway to investigate the neurochemical mechanisms of ketamine addiction.

Intraindividual changes in brain GABA, glutamate, and glutamine during monitored abstinence from alcohol in treatment-naive individuals with alcohol use disorder.

Proton magnetic resonance spectroscopy (1 H-MRS) studies have demonstrated abnormal levels of a variety of neurometabolites in treatment-seeking individuals with moderate-severe alcohol use disorder (AUD) following acute withdrawal. In contrast, few studies have investigated neurochemical changes across early abstinence in less severe, treatment-naïve AUD. The present study, which represents the primary report of a research grant from ABMRF/The Alcohol Research Fund, measured dorsal anterior cingulate cortex (dACC) GABA, glutamate, and glutamine levels in treatment-naïve AUD (n = 23) via three 1 H-MRS scans spaced across a planned week of abstinence from alcohol. In addition to AUD participants, 12 light drinkers completed two scans, separated by 48 hours, to ensure that results in AUD were not produced by between-scan differences other than abstinence from alcohol. 1 H-MRS spectra were acquired in dACC at each scan using 2D J-resolved point-resolved spectroscopy. Linear mixed modeling results demonstrated a significant increase in GABA, but not glutamate or glutamine (Ps = .237-.626), levels between scans 1 and 2 (+8.88%, .041), with no difference between scans 2 and 3 (+1.00%, .836), in AUD but not LD (F = 1.24, .290) participants. Exploratory regression analyses tentatively revealed a number of significant prospective associations between changes in glutamine levels and heavy drinking, craving, and withdrawal symptoms. Most notably, the present study demonstrated return from abnormally low to normal GABA levels in treatment-naïve AUD within 3 days of their last drink; the pattern of results was consistent with glutamate and glutamine disturbances being exclusive to relatively more severe AUD.

Students’ Smoking Abstinence Self-efficacy toward Early Maladaptive Schemas

Introduction: Smoking abstinence self-efficacy is a factor that plays a key role in preventing addiction or its revival tendency after quitting. This study attempted to analyze the relationship between the early maladaptive schemas and smoking abstinence self-efficacy among the sophomore high school students in the city of Gorgan, Iran. Methods: This was a descriptive study and its population (n= 9955) included all second grade high school students in the city of Gorgan in the school year 2015-2016. The multi- stage cluster sampling method was used to select 369 participants. The required data were collected using the maladaptive schema questioners and the smoking abstinence self-efficacy questionnaire. Pearson correlation and Multi- variable regression methods were also used to analyze data. Results: The results of the current study indicated a significant, yet reverse relationship of the early maladaptive schemas with smoking abstinence self-efficacy. Furthermore, 51 percent change in self-efficacy variance is derived from the components of early maladaptive schemas. Among components of the early maladaptive schemas, components of the abandonment / alienation, the strongest predictor was students smoking abstinence self-efficacy. Conclusion: Early self- efficacy schemas are among the individual and psychological causes with especial importance in studies on smoking dependency and its consumption. Such early schemas lead to biases in an individual’s interpretation of the events. These biases are represented as distorted attitudes, false speculations, unrealistic aims and perspectives, and high- risk behaviors such as smoking.

Sex-based differences in multidimensional clinical assessments of early-abstinence crack cocaine users.

Crack cocaine use disorder (CUD) has been related to sex differences. This work aimed to compare the severity of drug use and the severity of other negative related outcomes in males and females with CUD. A total of 1344 inpatients (798 males and 546 females) with crack cocaine use disorder (CUD) were evaluated by a detailed multidimensional clinical assessment, including addiction severity and trauma exposure. Linear regression predicted higher drug use severity (β = 0.273, p < 0.001) and more problems in domains related to childcare issues (β = 0.321), criminal involvement (β = 0.108), work-related problems (β = 0.281) and social support impairments (β = 0.142) for females, all with p < 0.001. Alcohol problems were predicted to be higher in males (β = -0.206, P < 0.001). Females had higher rates of other mental disorders, particularly trauma and stress-related disorders (OR: 3.206, CI: 2.22, 4.61). Important sex differences also emerged in trauma history and HIV infection prevalence. CUD has a more severe clinical presentation among females facing early abstinence. Sex differences in the CUD course indicate the need for consideration of sex-specific interventions and research.

Changes of frontal cortical subregion volumes in alcohol dependent individuals during early abstinence: associations with treatment outcome.

We previously reported that at 1-and-4weeks of sobriety, those who relapsed after treatment demonstrated significantly smaller total frontal cortical volume than individuals who maintained abstinence for at least 12months post treatment. The segmentation method employed did not permit examination of frontal subregions that serve as nodes of the executive, salience and emotional regulation networks; structural abnormalities in these circuits are associated with relapse in those seeking treatment for alcohol use disorders (AUD). The primary goal of this study was to determine if frontal cortical subregion volume recovery during early abstinence is associated with long-term abstinence from alcohol. We compared bilateral components of the dorsal prefrontal cortex, orbitofrontal cortex, anterior cingulate cortex and insula volumes, at 1 and 4weeks of abstinence, between individuals who resumed drinking within 12months of treatment (Relapsers) those who showed sustained abstinence over 12months following treatment (Abstainers) and healthy Controls. At 1 and 4weeks of sobriety, Relapsers demonstrated significantly smaller volumes than Controls in 15 of 20 regions of interest, while Abstainers only had smaller volumes than Controls in 5 of 20 regions. In Relapsers, increasing volumes over 1month in multiple frontal subregions and the insula were associated with longer duration of abstinence after treatment. The persistent bilateral frontal and insula volume deficits in Relapsers over 4weeks from last alcohol use may have implications for neurostimulation methods targeting anterior frontal/insula regions, and represent an endophenotype that differentiates those who respond more favorably to available psychosocial and pharmacological interventions.

Insomnia severity during early abstinence is related to substance use treatment completion in adults enrolled in an intensive outpatient program

BackgroundInsomnia and other types of sleep disturbance are highly prevalent during withdrawal across many different types of substance use disorders (SUDs). It is largely unknown how sleep impacts SUD treatment outcomes, including treatment completion. MethodsA retrospective chart review was conducted to obtain information about sleep disturbance and treatment completion in individuals beginning an intensive outpatient (IOP) SUD treatment program. Demographic data were collected along with number of sessions completed, treatment completion, comorbid psychiatric diagnosis, pertinent lab results, and scores on three self-reported measures of sleep: the Insomnia Severity Index (ISI), Pittsburgh Sleep Quality Index (PSQI), and Epworth Sleepiness Scale (ESS). ResultsPertinent information was available for 110 individuals. The majority had clinically significant scores on the ISI and PSQI but not the ESS. ISI, but not PSQI or ESS, was associated with treatment completion, such that those with more insomnia were less likely to complete treatment. ConclusionThe high prevalence of insomnia symptoms and poor sleep quality coupled with the relationship between insomnia severity and treatment completion may indicate that more severe symptoms of insomnia are a risk factor for treatment completion and subsequent relapse across many substance types. Applying evidence-based insomnia interventions in SUD treatment programs may have meaningful implications for outcomes.

Mechanisms underlying the efficacy of exercise as an intervention for cocaine relapse: a focus on mGlu5 in the dorsal medial prefrontal cortex.

Exercise shows promise as a treatment option for addiction; but in order to prevent relapse, it may need to be introduced early in the course of treatment. We propose that exercise, by upregulating dorsal medial prefrontal cortex (dmPFC)-nucleus accumbens (NAc) transmission, offsets deficits in pathways targeting glutamate, BDNF, and dopamine during early abstinence, and in doing so, normalizes neuroadaptations that underlie relapse. We compared the effects of exercise (wheel running, 2-h/day) during early (days 1-7), late (days 8-14), and throughout abstinence (days 1-14) to sedentary conditions on cocaine-seeking and gene expression in the dmPFC and NAc core of male rats tested following 24-h/day extended-access cocaine (up to 96 infusions/day) or saline self-administration and protracted abstinence (15 days). Based on these data, we then used site-specific manipulation to determine whether dmPFC metabotropic glutamate receptor5 (mGlu5) underlies the efficacy of exercise. Exercise initiated during early, but not late abstinence, reduced cocaine-seeking; this effect was strongly associated with dmPFC Grm5 expression (gene encoding mGlu5), and modestly associated with dmPFC Grin1 and Bdnf-IV expression. Activation of mGlu5 in the dmPFC during early abstinence mimicked the efficacy of early-initiated exercise; however, inhibition of these receptors prior to the exercise sessions did not block its efficacy indicating that there may be redundancy in the mechanisms through which exercise reduces cocaine-seeking. These findings indicate that addiction treatments, including exercise, should be tailored for early versus late phases of abstinence since their effectiveness will vary over abstinence due to the dynamic nature of the underlying neuroadaptations.

Brain Marker Links Stress and Nicotine Abstinence.

Subjective stress is a well-documented predictor of early smoking relapse, yet our understanding of stress and tobacco use is limited by reliance on self-reported measures of stress. We utilized a validated functional neuroimaging paradigm to examine whether stress exposure during early abstinence alters objective measures of brain function. Seventy-five participants underwent blood oxygen level dependent (BOLD) functional magnetic resonance imaging (fMRI) during the Montreal Imaging Stress Task (MIST) on two occasions: once during smoking satiety and once following biochemically confirmed 24-hour abstinence (order counterbalanced). The primary outcome measure was brain response during stress (vs. control) blocks of the MIST, assessed using whole-brain analysis corrected for multiple comparisons using clusters determined by Z ≥ 3.1. Abstinence (vs. satiety) was associated with significantly increased activation in the left inferior frontal gyrus, a brain region associated with inhibitory control. Abstinence-induced change in brain response to stress was positively associated with change in self-reported stress. This study provides objective evidence that the brain response to stress is altered during the first 24 hours of a quit attempt compared to smoking satiety. These results point to the potential value of inoculating smokers with stress management training prior to a quit attempt.

Anxiety Sensitivity and Distress Tolerance in Smokers: Relations With Tobacco Dependence, Withdrawal, and Quitting Success†.

This study examined relations of two affective vulnerabilities, high anxiety sensitivity (AS) and low distress tolerance (DT), with tobacco dependence, withdrawal, smoking cessation, and pharmacotherapy response. Smokers interested in quitting (N = 1067; 52.2% female, 28.1% African American) were randomized to 12 weeks of nicotine patch, nicotine patch plus nicotine lozenge, or varenicline. Baseline questionnaires assessed AS, DT, negative affect, anxiety, and dependence. Withdrawal was assessed the first-week post-quit via ecological momentary assessment. DT, but not AS, predicted biochemically confirmed point-prevalence abstinence at multiple endpoints: weeks 4, 12, 26, and 52 post-quit (ps < .05); relations remained after controlling for pharmacotherapy treatment, AS, baseline negative affect, anxiety, and anxiety disorder history (ps < .05). Additional exploratory analyses examining week 4 abstinence showed DT predicted abstinence (p = .004) even after controlling for baseline dependence, post-quit withdrawal (craving and negative affect), and treatment. DT moderated treatment effects on abstinence in exploratory analyses (interaction p = .025); those with high DT were especially likely to be abstinent at week 4 with patch plus lozenge versus patch alone. DT, but not AS, predicted abstinence over 1 year post-quit (higher DT was associated with higher quit rates), with little overlap with other affective measures. DT also predicted early abstinence independent of dependence and withdrawal symptoms. Results suggest low DT may play a meaningful role in motivation to use tobacco and constitute an additional affective risk factor for tobacco cessation failure beyond negative affect or clinical affective disorders. People in a stop-smoking study who reported a greater ability to tolerate distress were more likely to quit smoking and remain smoke-free 1 year later. Smokers with high DT were more likely to be smoke-free 4 weeks after their target quit day if they received nicotine patch plus nicotine lozenge rather than nicotine patch alone. NCT01553084.