Mesocorticolimbic system reactivity to alcohol use-related visual cues as a function of alcohol sensitivity phenotype: A pilot fMRI study.

Low sensitivity (LS) to alcohol is a risk factor for alcohol use disorder (AUD). Compared to peers with high sensitivity (HS), LS individuals drink more, report more problems, and exhibit potentiated alcohol cue reactivity (ACR). Heightened ACR suggests LS confers AUD risk via incentive sensitization, which is thought to take place in the mesocorticolimbic system. This study examined neural ACR in LS and HS individuals. Young adults (N = 32, M age=20.3) were recruited based on the Alcohol Sensitivity Questionnaire (HS: n = 16; LS: n = 16; 9 females/group). Participants completed an event-related fMRI ACR task. Group LS had higher ACR in left ventrolateral prefrontal cortex than group HS. In group LS, ACR in left caudomedial orbitofrontal cortex or left putamen was low at low alcohol use levels and high at heavier or more problematic alcohol use levels, whereas the opposite was true in group HS. Alcohol use level also was associated with the level of ACR in left substantia nigra among males in group LS. Taken together, results suggest elevated mesocorticolimbic ACR among LS individuals, especially those using alcohol at hazardous levels. Future studies with larger samples are warranted to determine the neurobiological loci underlying LS-based amplified ACR and AUD risk.

Virtual reality and neurofeedback as a supportive approach to managing cancer symptoms for patients receiving treatment: A brief report of a feasibility trial.

OBJECTIVES: Managing cancer symptoms while patients receive systemic treatment remains a challenge in oncology. The use of complementary and alternative medicine (CAM) approaches like virtual reality (VR) and neurofeedback (NF) in tandem with systemic treatment might reduce symptom burden for patients. The combination of VR + NF as a CAM intervention approach is novel and understudied, particularly as it relates to supportive cancer care. The purpose of this study is to summarize our VR + NF study protocol and share preliminary results regarding study retention (across 2 treatment sessions) and preliminary impact of VR or VR + NF on patient-reported outcomes such as anxiety and pain. METHODS: We utilized a parallel arm trial design to compare preliminary impact of VR only and VR + NF on cancer symptoms among patients who are actively receiving cancer treatment. RESULTS: Sixty-seven percent (n = 20) of participants returned to participate in a second VR session, and the rates of return were the same between the VR groups. Patients in the VR + NF group showed improvements in anxiety after both sessions, while patients in the VR only group showed significant improvements in pain and depression after both sessions. Patients in the VR + NF group showed improved pain after session 1. SIGNIFICANCE OF RESULTS: This study demonstrates that patients can be retained over multiple treatment sessions and that VR and NF remain promising treatment approaches with regard to impact on patient-reported outcomes like anxiety and pain.

A systematic review of cannabis health warning research.

Background: Cannabis legalization provides an opportunity to communicate with consumers through mandated health warnings on cannabis packaging. However, research on cannabis health warnings is a nascent field. Therefore, a review is needed to synthesize cannabis health warning research and inform ongoing policy discussions. Methods: This paper used systematic review guidelines to search online databases, including PubMed Central, Scopus, Web of Science, Jstor, Communication and Mass Media Complete, Medline, PsycINFO, and Google Scholar. Search strings combined the terms "cannabis" or "marijuana" with "health warning" or "health warning message" or "warning label" or "health warning label" or "health information label." Results were synthesized narratively. Results: The search identified 90 research articles. After screening, 17 studies on the impact of cannabis health warnings were retained. Retained studies focused on the hypothetical effects of cannabis health warnings (n = 11; 64.7 %) and "real world" effects of implementing warnings post-legalization (n = 6; 35.3 %). Evidence indicated mandated cannabis health warnings improved noticing and recall of health warning content. Cannabis health warnings describing risks of addiction were consistently rated the least effective. Pictorial cannabis health warnings generally outperformed text-only warnings when displayed on their own, while experiments with warnings on products had mixed results. Cannabis health warnings decreased product appeal, mainly when package branding was minimized. Conclusions: Health warnings on cannabis packaging are an important strategy to communicate risk to consumers. Mandating warnings increased notice, recall, and health knowledge. Warnings with pictures and describing specific risks were most effective, as was showing warnings without product branding.

Mindfulness-Oriented Recovery Enhancement for Veterans and Military Personnel on Long-Term Opioid Therapy for Chronic Pain: A Randomized Clinical Trial.

OBJECTIVE: This randomized clinical trial evaluated the efficacy of Mindfulness-Oriented Recovery Enhancement (MORE) among past and present U.S. military personnel with prescriptions for long-term opioid therapy for chronic pain. METHODS: In this clinical trial, 230 past and present military personnel with prescriptions for long-term opioid therapy were randomized in a 1:1 ratio to MORE or supportive psychotherapy (initially delivered in person and then via videoconferencing after the onset of the COVID-19 pandemic). Primary outcomes were chronic pain, measured by the Brief Pain Inventory, and aberrant drug-related behaviors, measured by the Current Opioid Misuse Measure, through 8 months of follow-up. Opioid dose was a key secondary outcome. Other outcomes included psychiatric symptoms, catastrophizing, positive affect, ecological momentary assessments of opioid craving, and opioid attentional bias. RESULTS: MORE was superior to supportive psychotherapy through the 8-month follow-up in reducing pain-related functional interference, pain severity, and opioid dose. MORE reduced daily opioid dose by 20.7%, compared with a dose reduction of 3.9% with supportive psychotherapy. Although there was no overall between-group difference in opioid misuse, the in-person MORE intervention outperformed supportive psychotherapy for reducing opioid misuse. MORE reduced anhedonia, pain catastrophizing, craving, and opioid attentional bias and increased positive affect to a greater extent than supportive psychotherapy. MORE also modulated therapeutic processes, including mindful reinterpretation of pain sensations, nonreactivity, savoring, positive attention, and reappraisal. CONCLUSIONS: Among past and present U.S. military personnel, MORE led to sustained decreases in chronic pain, opioid use, craving, and opioid cue reactivity. MORE facilitated opioid dose reduction while preserving adequate pain control and preventing mood disturbances, suggesting its utility for safe opioid tapering.

Development of two novel treatments to promote smoking cessation: Savor and retrieval-extinction training pilot clinical trial findings.

Despite decades of progress, cigarette smoking remains a significant contributor to disease burden. This effect is especially pronounced for specific priority populations, such as individuals who live in rural communities, in that the burden of tobacco smoking is greater among these groups than in urban areas and the general population. The present study aims to evaluate the feasibility and acceptability of two novel tobacco treatment interventions delivered through remote telehealth procedures to individuals who smoke in the state of South Carolina. Results also include exploratory analyses of smoking cessation outcomes. Study I evaluated savoring, a strategy based on mindfulness practices, alongside nicotine replacement therapy (NRT). Study II evaluated retrieval-extinction training (RET), a memory-modification paradigm alongside NRT. In Study I (savoring), recruitment and retention data showed high interest and engagement in the intervention components, and participants who received this intervention decreased cigarette smoking throughout the course of the treatment (ps < .05). In Study II (RET), results showed high interest and moderate engagement in treatment, although exploratory outcome analyses did not demonstrate significant treatment effects on smoking behaviors. Overall, both studies showed promise in generating interest among individuals who smoke in participating in remotely delivered, telehealth smoking cessation interventions with novel therapeutic targets. A brief savoring intervention appeared to have effects on cigarette smoking throughout treatment, whereas RET did not. Gaining insight from the present pilot study, future studies may improve the efficacy of these procedures and incorporate the treatment components into more robust available treatments. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Exploring the Utility of a Functional Magnetic Resonance Imaging (fMRI) Cannabis Cue-Reactivity Paradigm in Treatment Seeking Adults with Cannabis Use Disorder.

Introduction: Functional magnetic resonance imaging (fMRI) studies examining cue-reactivity in cannabis use disorder (CUD) to date have either involved non-treatment seeking participants or been small. We addressed this gap by administering an fMRI cue-reactivity task to CUD participants entering two separate clinical trials. Methods: Treatment-seeking participants with moderate or severe CUD had behavioral craving measured at baseline via the Marijuana Craving Questionnaire (MCQ-SF). They additionally completed a visual cannabis cue-reactivity paradigm during fMRI following 24-hours of abstinence from cannabis. During fMRI, the Blood Oxygen Level Dependent (BOLD) signal was acquired while participants viewed cannabis-images or matched-neutral-images. BOLD responses were correlated with the MCQ-SF using a General Linear Model. Results: N=65 participants (32% female; mean age 30.4±9.9SD) averaged 46.3±15.5SD on the MCQ-SF. When contrasting cannabis-images vs. matched-neutral-images, participants showed greater BOLD response in bilateral ventromedial prefrontal, dorsolateral prefrontal, anterior cingulate, and visual cortices, as well as the striatum. Similarly, there was stronger task-based functional-connectivity (tbFC) between the medial prefrontal cortex and both the amygdala and the visual cortex. There were no significant differences in either activation or tbFC between studies or between sexes. Craving negatively correlated with BOLD response in the left ventral striatum (R 2 =-0.25; p =0.01). Conclusions: We found that, among two separate treatment-seeking CUD groups, cannabis cue-reactivity was evidenced by greater activation and tbFC in regions related to executive function and reward processing, and craving was negatively associated with cue-reactivity in the ventral striatum. Future directions include examining if pharmacological, neuromodulatory, or psychosocial interventions can alter corticostriatal cue-reactivity.

Effects of Hyperdirect Pathway Theta Burst Transcranial Magnetic Stimulation on Inhibitory Control, Craving, and Smoking in Adults With Nicotine Dependence: A Double-Blind, Randomized Crossover Trial.

BACKGROUND: Nicotine dependence is associated with dysregulated hyperdirect pathway (HDP)-mediated inhibitory control (IC). However, there are currently no evidence-based treatments that have been shown to target the HDP to improve IC and reduce cigarette cravings and smoking. METHODS: Following a baseline nonstimulation control session, this study (N = 37; female: n = 17) used a double-blind, randomized crossover design to examine the behavioral and neural effects of intermittent theta burst stimulation (iTBS) and continuous TBS (cTBS) to the right inferior frontal gyrus (rIFG)-a key cortical node of the HDP. Associations between treatment effects were also explored. RESULTS: At baseline, HDP IC task-state functional connectivity was positively associated with IC task performance, which confirmed the association between HDP circuit function and IC. Compared with iTBS, rIFG cTBS improved IC task performance. Compared with the baseline nonstimulation control session, both TBS conditions reduced cigarette craving and smoking; however, although craving and smoking were lower for cTBS, no differences were found between the two active conditions. In addition, although HDP IC task-state functional connectivity was greater following cTBS than iTBS, there was no significant difference between conditions. Finally, cTBS-induced improvement in IC task performance was associated with reduced craving, and cTBS-induced reduction in craving was associated with reduced smoking. CONCLUSIONS: These findings warrant further investigation into the effects of rIFG cTBS for increasing IC and reducing craving and smoking among individuals with nicotine dependence. Future sham-controlled cTBS studies may help further elucidate the mechanisms by which rIFG cTBS mediates IC and smoking behavior.

Immersive virtual reality and neurofeedback for the management of cancer symptoms during treatment.

Millions of people are diagnosed with cancer each year in the USA and are living on systemic therapies designed to prolong their life. While these therapies are intended to treat the disease, most exacerbate cancer symptoms such as pain and anxiety. Oncologists and other healthcare providers are now challenged to deliver adjunctive therapies designed to improve quality of life of patients while they undergo cancer treatment, including minimizing already disruptive symptoms such as cancer pain and anxiety. Complementary and alternative medicines such as immersive virtual reality (VR) and neurofeedback (NF) are novel approaches to the management of cancer symptoms. While the evidence for combining VR and NF, specifically for management of cancer pain, while patients undergo systemic therapies, is still emerging; our preliminary findings suggest this treatment modality might offer relief of cancer symptoms. This paper briefly highlights the clinical need for supportive therapies such as VR and NF in the oncological setting and summarizes innovative research in this area.

Right inferior frontal gyrus theta-burst stimulation reduces smoking behaviors and strengthens fronto-striatal-limbic resting-state functional connectivity: a randomized crossover trial.

Introduction: Functional and anatomical irregularities in the right inferior frontal gyrus (rIFG), a ventrolateral prefrontal region that mediates top-down inhibitory control over prepotent behavioral responding, are implicated in the ongoing maintenance of nicotine dependence (ND). However, there is little research on the effects of neuromodulation of the rIFG on smoking behavior, inhibitory control, and resting-state functional connectivity (rsFC) among individuals with ND. Methods: In this double-blind, crossover, theta-burst stimulation (TBS) study, adults with ND (N = 31; female: n = 15) completed a baseline session and were then randomized to two counterbalanced sessions of functionally neuronavigated TBS to the rIFG: continuous TBS (cTBS) on 1 day and intermittent TBS (iTBS) on another. Differences in cigarette cravings, smoking, and fronto-striatal-limbic rsFC were assessed. Results: Relative to baseline, cTBS significantly reduced appetitive and withdrawal cravings immediately after treatment. The effects of cTBS on withdrawal craving persisted for 24 h, as well as produced a reduction in smoking. Furthermore, cTBS significantly strengthened rsFC between the rIFG pars opercularis and subcallosal cingulate (fronto-striatal circuit), and between the rIFG pars opercularis and the right posterior parahippocampal gyrus (fronto-limbic circuit). At post-24 h, cTBS-induced increase in fronto-striatal rsFC was significantly associated with less appetitive craving, while the increase in fronto-limbic rsFC was significantly associated with less withdrawal craving and smoking. Discussion: These findings warrant further investigation into the potential value of rIFG cTBS to attenuate smoking behavior among individuals with ND.

Associations Between the Wisconsin Inventory of Smoking Dependence Motives and Regional Brain Volumes in Adult Smokers.

INTRODUCTION: The Wisconsin Inventory of Smoking Dependence Motives (WISDM-68) is a 68-item questionnaire to assess nicotine dependence as a multifactorial construct based on 13 theoretically derived smoking motives. Chronic smoking is associated with structural changes in brain regions implicated in the maintenance of smoking behavior; however, associations between brain morphometry and the various reinforcing components of smoking behavior remain unexamined. The present study investigated the potential association between smoking dependence motives and regional brain volumes in a cohort of 254 adult smokers. AIMS AND METHODS: The WISDM-68 was administered to participants at the baseline session. Structural magnetic resonance brain imaging (MRI) data from 254 adult smokers (Mage = 42.7 ± 11.4) with moderate to severe nicotine dependence (MFTND = 5.4 ± 2.0) smoking for at least 2 years (Myears = 24.3 ± 11.8) were collected and analyzed with Freesurfer. RESULTS: Vertex-wise cluster analysis revealed that high scores on the WISDM-68 composite, secondary dependence motives (SDM) composite, and multiple SDM subscales were associated with lower cortical volume in the right lateral prefrontal cortex (cluster-wise p's < .035). Analysis of subcortical volumes (ie, nucleus accumbens, amygdala, caudate, and pallidum) revealed several significant associations with WISDM-68 subscales, dependence severity (Fagerström Test for Nicotine Dependence), and overall exposure (pack-years). No significant associations between cortical volume and other nicotine dependence measures or pack-years were observed. CONCLUSIONS: Results suggest that smoking motives may play a larger role in cortical abnormalities than addiction severity and smoking exposure per se, whereas subcortical volumes are associated with smoking motives, addiction severity, and smoking exposure. IMPLICATIONS: The present study reports novel associations between the various reinforcing components of smoking behavior assessed by the WISDM-68 and regional brain volumes. Results suggest that the underlying emotional, cognitive, and sensory processes that drive non-compulsive smoking behaviors may play a larger role in gray matter abnormalities of smokers than smoking exposure or addiction severity.

Restructuring reward: A pilot study to enhance natural reward response in adults with cannabis use disorder.

BACKGROUND: Hedonic dysregulation is a core mechanism of addiction. There is a dearth of research on hedonic dysregulation in cannabis use disorder (CUD). The current study tested whether personalized scripted imagery may be an efficacious approach to remediate reward functioning in adults with CUD. METHODS: Adults with CUD (n=10) and non-CUD controls (n=12) completed a single session personalized scripted imagery procedure. Non-drug (i.e. natural) reward and neutral scripts were transcribed and participants listened to the scripts in counterbalanced order. Primary outcomes included positive affect (PA), galvanic skin response (GSR), and cortisol and were assessed at four timepoints. Mixed effects models were used to compare between and within subject effects. RESULTS: Mixed effects models revealed a Condition (reward vs. neutral) X Group (CUD vs. control) interaction (p=0.01) on PA response, indicating blunted PA response to the neutral script relative to the reward script in CUD participants. Likewise, GSR response in CUD participants was decreased in response to the neutral script relative to the reward script (p=0.034; interaction n.s.). An interaction effect of Group X PA on cortisol response was found (p=.036) indicating that cortisol was positively correlated with PA in healthy control participants, but not CUD participants. CONCLUSIONS: Adults with CUD may demonstrate acute deficits in hedonic tone under neutral conditions relative to healthy controls. Personalized scripted imagery may be an efficacious tool to remediate hedonic dysregulation in CUD. Cortisol may play a role in healthy positive affect regulation warranting further investigation.

Mindfulness-Oriented Recovery Enhancement remediates anhedonia in chronic opioid use by enhancing neurophysiological responses during savoring of natural rewards.

BACKGROUND: Neuropsychopharmacologic effects of long-term opioid therapy (LTOT) in the context of chronic pain may result in subjective anhedonia coupled with decreased attention to natural rewards. Yet, there are no known efficacious treatments for anhedonia and reward deficits associated with chronic opioid use. Mindfulness-Oriented Recovery Enhancement (MORE), a novel behavioral intervention combining training in mindfulness with savoring of natural rewards, may hold promise for treating anhedonia in LTOT. METHODS: Veterans receiving LTOT (N = 63) for chronic pain were randomized to 8 weeks of MORE or a supportive group (SG) psychotherapy control. Before and after the 8-week treatment groups, we assessed the effects of MORE on the late positive potential (LPP) of the electroencephalogram and skin conductance level (SCL) during viewing and up-regulating responses (i.e. savoring) to natural reward cues. We then examined whether these neurophysiological effects were associated with reductions in subjective anhedonia by 4-month follow-up. RESULTS: Patients treated with MORE demonstrated significantly increased LPP and SCL to natural reward cues and greater decreases in subjective anhedonia relative to those in the SG. The effect of MORE on reducing anhedonia was statistically mediated by increases in LPP response during savoring. CONCLUSIONS: MORE enhances motivated attention to natural reward cues among chronic pain patients on LTOT, as evidenced by increased electrocortical and sympathetic nervous system responses. Given neurophysiological evidence of clinical target engagement, MORE may be an efficacious treatment for anhedonia among chronic opioid users, people with chronic pain, and those at risk for opioid use disorder.

Genetic Associations with Smoking Relapse and Proportion of Follow-up in Smoking Relapse throughout Adulthood in Pre- and Postmenopausal Women.

PREVENTION RELEVANCE: This study is the first to quantify genetic associations with smoking relapse among female smokers throughout adulthood. These findings could inform precision medicine approaches to improve long-term smoking relapse prevention to reduce smoking attributable cancer morbidity and mortality.

CHRNA5-A3-B4 and DRD2 Genes and Smoking Cessation Throughout Adulthood: A Longitudinal Study of Women.

INTRODUCTION: Smoking cessation is more than 50% heritable. Genetic studies of smoking cessation have been limited by short-term follow-up or cross-sectional design. AIMS AND METHODS: This study tests single nucleotide polymorphism (SNP) associations with cessation during long-term follow-up throughout adulthood in women. The secondary aim tests whether genetic associations differ by smoking intensity. Associations between 10 SNPs in CHRNA5, CHRNA3, CHRNB2, CHRNB4, DRD2, and COMT and the probability of smoking cessation over time were evaluated in two longitudinal cohort studies of female nurses, the Nurses' Health Study (NHS) (n = 10 017) and NHS-2 (n = 2793). Participant follow-up ranged from 2 to 38 years with data collected every 2 years. RESULTS: Women with the minor allele of either CHRNA5 SNP rs16969968 or CHRNA3 SNP rs1051730 had lower odds of cessation throughout adulthood [OR = 0.93, p-value = .003]. Women had increased odds of cessation if they had the minor allele of CHRNA3 SNP rs578776 [OR = 1.17, p-value = .002]. The minor allele of DRD2 SNP rs1800497 was associated with lower odds of cessation in moderate-to-heavy smokers [OR = 0.92, p-value = .0183] but increased odds in light smokers [OR = 1.24, p-value = .096]. CONCLUSIONS: Some SNP associations with short-term smoking abstinence observed in prior studies were shown in the present study to persist throughout adulthood over decades of follow-up. Other SNP associations with short-term abstinence did not persist long-term. The secondary aim findings suggest genetic associations may differ by smoking intensity. IMPLICATIONS: The results of the present study expand on previous studies of SNP associations in relation to short-term smoking cessation to demonstrate some of these SNPs were associated with smoking cessation throughout decades of follow-up, whereas other SNP associations with short-term abstinence did not persist long-term. The rate of relapse to smoking remains high for several years after quitting smoking, and many smokers experience multiple quit attempts and relapse episodes throughout adulthood. Understanding genetic associations with long-term cessation has potential importance for precision medicine approaches to long-term cessation management.

Associations between right inferior frontal gyrus morphometry and inhibitory control in individuals with nicotine dependence.

BACKGROUND: The hyperdirect pathway - a circuit involved in executing inhibitory control (IC) - is dysregulated among individuals with nicotine dependence. The right inferior frontal gyrus (rIFG), a cortical input to the hyperdirect circuit, has been shown to be functionally and structurally altered among nicotine-dependent people who smoke. The rIFG is composed of 3 cytoarchitecturally distinct subregions: The pars opercularis, pars triangularis, and pars orbitalis. The present study assessed the relationship between rIFG subregion morphometry and inhibitory control among individuals with nicotine dependence. METHODS: Behavioral and magnetic resonance brain imaging (MRI) data from 127 nicotine-dependent adults who smoke (MFTND = 5.4, ± 1.9; MCPD = 18.3, ± 7.0; Myears = 25.04, ± 11.97) (Mage = 42.9, ± 11.1) were assessed. Brain morphometry was assessed from T1-weighted MRIs using Freesurfer. IC was assessed with a response-inhibition Go/Go/No-Go (GGNG) task and a smoking relapse analog task (SRT). RESULTS AND CONCLUSIONS: Vertex-wise analyses revealed that GGNG task scores were positively associated with cortical thickness and volume in the right pars triangularis (cluster-wise p = 0.006, 90% CI = 0.003 - 0.009; cluster-wise p = 0.040, 90% CI = 0.032 - 0.048), and the ability to inhibit ad lib smoking during the SRT was positively associated with cortical thickness in the right pars orbitalis (cluster-wise p = 0.011, 90% CI = 0.007 - 0.015). Our results indicate that cortical thickness of distinct rIFG subregions may serve as biomarkers for unique forms of IC deficits.

Cognitive training and remediation interventions for substance use disorders: a Delphi consensus study.

AIMS: Substance use disorders (SUD) are associated with cognitive deficits that are not always addressed in current treatments, and this hampers recovery. Cognitive training and remediation interventions are well suited to fill the gap for managing cognitive deficits in SUD. We aimed to reach consensus on recommendations for developing and applying these interventions. DESIGN, SETTING AND PARTICIPANTS: We used a Delphi approach with two sequential phases: survey development and iterative surveying of experts. This was an on-line study. During survey development, we engaged a group of 15 experts from a working group of the International Society of Addiction Medicine (Steering Committee). During the surveying process, we engaged a larger pool of experts (n = 54) identified via recommendations from the Steering Committee and a systematic review. MEASUREMENTS: Survey with 67 items covering four key areas of intervention development: targets, intervention approaches, active ingredients and modes of delivery. FINDINGS: Across two iterative rounds (98% retention rate), the experts reached a consensus on 50 items including: (i) implicit biases, positive affect, arousal, executive functions and social processing as key targets of interventions; (ii) cognitive bias modification, contingency management, emotion regulation training and cognitive remediation as preferred approaches; (iii) practice, feedback, difficulty-titration, bias modification, goal-setting, strategy learning and meta-awareness as active ingredients; and (iv) both addiction treatment work-force and specialized neuropsychologists facilitating delivery, together with novel digital-based delivery modalities. CONCLUSIONS: Expert recommendations on cognitive training and remediation for substance use disorders highlight the relevance of targeting implicit biases, reward, emotion regulation and higher-order cognitive skills via well-validated intervention approaches qualified with mechanistic techniques and flexible delivery options.

Mindfulness-induced endogenous theta stimulation occasions self-transcendence and inhibits addictive behavior.

Self-regulation is instantiated by theta oscillations (4 to 8 Hz) in neurons of frontal midline brain regions. Frontal midline theta (FMΘ) is inversely associated with default mode network (DMN) activation, which subserves self-referential processing. Addiction involves impaired self-regulation and DMN dysfunction. Mindfulness is an efficacious self-regulatory practice for treating addiction, but little is known about the mechanisms by which mindfulness reduces addictive behavior. In this mechanistic study of long-term opioid users (N = 165), we assessed meditation-induced FMΘ as a mediator of changes in opioid misuse. Relative to a supportive psychotherapy control, participants treated with Mindfulness-Oriented Recovery Enhancement (MORE) exhibited increased FMΘ during a laboratory-based meditation session. FMΘ during meditation was associated with self-transcendent experiences characterized by ego dissolution, nondual awareness, and bliss. MORE's effects on decreasing opioid misuse were mediated by increased FMΘ. Given the role of aberrant self-referential processing in addiction, mindfulness-induced endogenous theta stimulation might "reset" DMN dysfunction to inhibit addictive behavior.

A systematic review of genetic variation within nicotinic acetylcholine receptor genes and cigarette smoking cessation.

BACKGROUND: Nicotine produces its effects by binding to nicotinic acetylcholine receptors (nAChRs). Variants of genes encoding properties of nAChRs are candidates for affecting likelihood of smoking cessation. METHODS: A systematic review was conducted summarizing evidence of associations between single nucleotide polymorphisms (SNPs) of nAChR genes and smoking cessation. From 24 articles meeting inclusion criteria, summary odds ratios (ORs) for associations between nine SNPs and smoking cessation were calculated from 26 studies (N = 233-29,072) stratified by gene, ancestry, study design, and pharmacotherapy; SNPs in linkage disequilibrium were pooled. Results for a tenth SNP from two GWAS were summarized. RESULTS: People of European ancestry with minor alleles of CHRNA5 rs16969968 and CHRNA3 rs1051730 had longer time to cessation [HR = 0.90, 95 % CI 0.88 - 0.92 (n = 2 studies)] and lower odds of cessation [OR = 0.88, 95 % CI 0.80 - 0.97 (n = 5 cohort studies), OR = 0.64, 95 % CI 0.45 - 0.90 (n = 4 placebo arms)]. Risk of persistent smoking associated with these alleles was attenuated in smokers receiving nicotine replacement therapy (NRT). Recipients of bupropion alone or with NRT with these alleles had higher, though not statistically significant, odds of cessation. Results for CHRNA5 rs588765 and rs680244 were similar to rs16969968/rs1051730 findings. Evidence was limited for other SNPs. CONCLUSION: Evidence consistently indicates the minor alleles of four SNPs within CHRNA3 or CHRNA5 are risk alleles for cessation failure. Analysis by pharmacotherapy revealed bupropion may be the most efficacious intervention for people with these alleles.

Insomnia as a moderator of alcohol use and blackout: Potential role in acute physiological consequences.

BACKGROUND: Alcohol-induced blackout is associated concurrently and prospectively with alcohol-related harm, including emergency room visits and sexual coercion. Although sleep has not been linked empirically to blackout, symptoms of insomnia have also been linked to memory impairment, in which case insomnia symptoms may compound alcohol's negative effects on memory. This study tested insomnia symptoms as a moderator of the association between heavy drinking and alcohol-induced blackout. METHODS: Heavy-drinking young adults in college (N = 461, 69% female) completed assessments online from remote locations. Hierarchical linear regression was used to test a moderation model predicting blackout frequency. Logistic regression was used to test post hoc hypotheses. RESULTS: In contrast to our main hypothesis, heavy drinking was more weakly (not more strongly) associated with blackout in the context of more severe insomnia. Post hoc analyses tested insomnia symptoms as a unique moderator of the association between heavy drinking and likelihood of acute physiological consequences of alcohol use (blackout, passing out, nausea/throwing up, and hangover). Insomnia severity at least marginally moderated the association between heavy drinking and 4 out of 5 physiological consequences of alcohol use, and only moderated the association between drinking and 1 of 19 remaining consequences. CONCLUSIONS: Symptoms of insomnia are associated with alcohol-related harm, but may buffer associations between drinking and acute physiological consequences of alcohol. Additional research is needed to determine if alcohol heightens sensitivity to the acute physiological effects of alcohol, in which case less alcohol may be required for young adults with insomnia to experience these effects.

Neurophysiological Deficits During Reappraisal of Negative Emotional Stimuli in Opioid Misuse.

BACKGROUND: Opioid misuse is hypothesized to compromise the ability to regulate negative emotions, as manifested through visceral and peripheral physiological signals. However, neurophysiological impairment of top-down cognitive emotion regulation in opioid misuse has not previously been shown. METHODS: Patients with chronic pain who had been taking opioids for 90 days or longer (N = 149; female, n = 98) underwent a negative emotion regulation task with electroencephalography. Participants were instructed to view or reappraise negative images presented for 3 seconds. Using a validated cutoff score on the Current Opioid Misuse Measure, participants were classified as exhibiting aberrant drug-related behavior consistent with opioid misuse (MISUSE+) or as being low risk for opioid misuse (MISUSE-). Participants reported their craving in response to negative emotions over the past week. RESULTS: We observed a group × condition interaction (p = .003) such that the MISUSE- group decreased the late positive potential of the electroencephalography during reappraisal, whereas the MISUSE+ group showed increased late positive potential during reappraisal. This deficit in negative emotion regulation remained significant after controlling for an array of potential confounding variables, including opioid dose, pain, and depression. Heightened late positive potential during reappraisal was associated with more severe opioid craving. CONCLUSIONS: Opioid misuse may occasion top-down deficits in emotional regulation that begin as early as 400 ms after presentation of negative stimuli. It remains unknown whether emotion dysregulation is the cause, correlate, or consequence of opioid misuse. Nonetheless, targeting emotion dysregulation in opioid misuse with reappraisal-focused interventions may represent an important treatment approach.