Molecular mechanisms involved in alcohol craving, IRF3, and endoplasmic reticulum stress: a multi-omics study.

Alcohol use disorder (AUD) is the most prevalent substance use disorder worldwide. Acamprosate and naltrexone are anti-craving drugs used in AUD pharmacotherapy. However, molecular mechanisms underlying their anti-craving effect remain unclear. This study utilized a patient-derived induced pluripotent stem cell (iPSC)-based model system and anti-craving drugs that are used to treat AUD as "molecular probes" to identify possible mechanisms associated with alcohol craving. We examined the pathophysiology of craving and anti-craving drugs by performing functional genomics studies using iPSC-derived astrocytes and next-generation sequencing. Specifically, RNA sequencing performed using peripheral blood mononuclear cells from AUD patients with extreme values for alcohol craving intensity prior to treatment showed that inflammation-related pathways were highly associated with alcohol cravings. We then performed a genome-wide assessment of chromatin accessibility and gene expression profiles of induced iPSC-derived astrocytes in response to ethanol or anti-craving drugs. Those experiments identified drug-dependent epigenomic signatures, with IRF3 as the most significantly enriched motif in chromatin accessible regions. Furthermore, the activation of IRF3 was associated with ethanol-induced endoplasmic reticulum (ER) stress which could be attenuated by anti-craving drugs, suggesting that ER stress attenuation might be a target for anti-craving agents. In conclusion, we found that craving intensity was associated with alcohol consumption and treatment outcomes. Our functional genomic studies suggest possible relationships among craving, ER stress, IRF3 and the actions of anti-craving drugs.

Predictive utility of the P3 event-related potential (ERP) response to alcohol cues for ecologically assessed alcohol craving and use.

Neural measures of alcohol cue incentive salience have been associated with retrospective reports of riskier alcohol use behaviour and subjective response profiles. This study tested whether the P3 event-related potential (ERP) elicited by alcohol-related cues (ACR-P3) can forecast alcohol use and craving during real-world drinking episodes. Participants (N = 262; Mage = 19.53; 56% female) completed a laboratory task in which they viewed images of everyday objects (Neutral), non-alcohol drinks (NonAlc) and alcohol beverages (Alc) while EEG was recorded and then completed a 21-day ecological momentary assessment (EMA) protocol in which they recorded alcohol craving and consumption. Anthropometrics were used to derive estimated blood alcohol concentration (eBAC) throughout drinking episodes. Multilevel modelling indicated positive associations between P3 amplitudes elicited by all stimuli and within-episode alcohol use measures (e.g., eBAC, cumulative drinks). Focal follow-up analyses indicated a positive association between AlcP3 amplitude and eBAC within episodes: Larger AlcP3 was associated with a steeper rise in eBAC. This association was robust to controlling for the association between NonAlcP3 and eBAC. AlcP3 also was positively associated with episode-level measures (e.g., max drinks, max eBAC). There were no associations between any P3 variables and EMA-based craving measures. Thus, individual differences in neural measures of alcohol cue incentive salience appear to predict the speed and intensity of alcohol consumption but not reports of craving during real-world alcohol use episodes.

Systematic review and meta-analysis: Combining transcranial magnetic stimulation or direct current stimulation with pharmacotherapy for treatment of substance use disorders.

BACKGROUND AND OBJECTIVES: Transcranial magnetic stimulation (TMS) and transcranial direct current stimulation (tDCS) have evidence for their potential in the treatment of substance use disorders (SUD). Medication for addiction treatment (MAT) is underutilized and not always effective. We identified randomized controlled trials (RCTs) and case studies that evaluated the effectiveness of TMS or tDCS used concurrently with MAT in SUD treatment. METHODS: A systematic review of published literature following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines was conducted on 6/1/2023 by a medical librarian. Craving-related scales were extracted for an effect size calculation. The Physiotherapy Evidence Database (PEDro) scale assessed study quality. RESULTS: Eight studies (7 RCT, 1 case) including 253 individuals were published from 2015 to 2022, 5 of which had available data for meta-analysis. TMS or tDCS combined with MAT significantly reduced craving-related measures relative to sham stimulation (Hedges' g = -0.42, confidence interval: -0.73 to -0.11, p < .01). Opioid use disorder, methadone, and the dorsolateral prefrontal cortex were the most commonly studied SUD, MAT, and target region. DISCUSSION AND CONCLUSIONS: Our results show a significant effect; however, is limited by a small number of studies with heterogeneous methodology across intervention methods and SUDs. Additional trials are needed to fully assess the clinical impact and mechanisms of combined brain stimulation and pharmacotherapy. We discuss a possible mechanism for synergism from these treatment combinations. SCIENTIFIC SIGNIFICANCE: Adds the first systematic review of combination treatment with TMS or tDCS and MAT in SUD patients to the literature and estimates its overall effect size.

Data-driven connectivity profiles relate to smoking cessation outcomes.

At a group level, nicotine dependence is linked to differences in resting-state functional connectivity (rs-FC) within and between three large-scale brain networks: the salience network (SN), default mode network (DMN), and frontoparietal network (FPN). Yet, individuals may display distinct patterns of rs-FC that impact treatment outcomes. This study used a data-driven approach, Group Iterative Multiple Model Estimation (GIMME), to characterize shared and person-specific rs-FC features linked with clinically-relevant treatment outcomes. 49 nicotine-dependent adults completed a resting-state fMRI scan prior to a two-week smoking cessation attempt. We used GIMME to identify group, subgroup, and individual-level networks of SN, DMN, and FPN connectivity. Regression models assessed whether within- and between-network connectivity of individual rs-FC models was associated with baseline cue-induced craving, and craving and use of regular cigarettes (i.e., "slips") during cessation. As a group, participants displayed shared patterns of connectivity within all three networks, and connectivity between the SN-FPN and DMN-SN. However, there was substantial heterogeneity across individuals. Individuals with greater within-network SN connectivity experienced more slips during treatment, while individuals with greater DMN-FPN connectivity experienced fewer slips. Individuals with more anticorrelated DMN-SN connectivity reported lower craving during treatment, while SN-FPN connectivity was linked to higher craving. In conclusion, in nicotine-dependent adults, GIMME identified substantial heterogeneity within and between the large-scale brain networks. Individuals with greater SN connectivity may be at increased risk for relapse during treatment, while a greater positive DMN-FPN and negative DMN-SN connectivity may be protective for individuals during smoking cessation treatment.

Cannabis cravings predict cigarette use in schizophrenia: a secondary analysis from two cannabis abstinence studies.

CLINICAL TRIAL NAME: Effects of Repetitive Transcranial Magnetic Stimulation (rTMS) on Cannabis Use and Cognitive Outcomes in SchizophreniaURL: www.clinicaltrials.gov; Registration Number: NCT03189810.

The Role of Emotion Dysregulation in Heightened Alcohol Craving Related to Posttraumatic Stress Disorder and Depression Symptoms.

Objective: Compared to their male counterparts, women with alcohol use disorders (AUD) alone and those with symptoms of co-occurring emotional disorders (posttraumatic stress disorder, PTSD, and depression) are particularly likely to have increased alcohol craving in response to negative affect and daily stressors. Emotion dysregulation is one transdiagnostic construct that may underlie heightened craving in response to stress within this population. In a secondary data analysis, the current study examined emotion dysregulation as a mediator of the associations of posttraumatic stress symptoms (PTSS) and depression symptoms with heightened stress-induced alcohol craving, as measured in the lab. Given the overlap in symptoms, the relative associations of PTSD and depression symptom clusters with stress-induced craving were explored. Method: 50 women Veterans (84% White, 88% Non-Hispanic, Mage=45.68) attended two in-lab sessions. Self-report measures of emotion dysregulation, PTSD, and depression symptoms were administered at baseline. During session two, participants reported on alcohol craving and negative affect at baseline and again after a personalized stress induction procedure. Results: Emotion dysregulation mediated the association of greater PTSS with heightened stress-induced craving, although emotion dysregulation was not a mediator of the association between depression and stress-induced craving. Greater alcohol craving after the stress induction was positively associated with cognitive-affective symptoms in PTSD and depression (and not with other symptom clusters of these diagnoses, e.g., avoidance, somatic-vegetative symptoms). Conclusions: Emotion dysregulation may be a transdiagnostic factor that helps to explain greater alcohol cravings and drinking in stressful contexts among women Veterans with heightened symptoms of co-occurring emotional disorders.

rTMS effects on urges and severity of tobacco use disorder operate independently of a retrieval-extinction component and involve frontal-striatal pathways.

BACKGROUND: Although smoking remains a leading cause of preventable disease, the treatment options for smoking are limited. The present study evaluated the neural features underlying effects of repetitive transcranial magnetic stimulation (rTMS) for reducing smoking cravings. In addition, the efficacy of a simulated retrieval-extinction procedure to augment rTMS efficacy was examined. METHODS: Sixty-one individuals with tobacco use disorder (TUD) were randomized into three groups: classic rTMS, retrieval rTMS (viewed smoking videos before rTMS), and sham rTMS. rTMS was performed on the left dorsolateral prefrontal cortex (DLPFC) over 5 days using a standard figure-8 coil. Smoking cravings and brain responses to smoking cues were measured before and after rTMS treatment. Changes in functional connectivity (FC) among different brain regions were calculated. RESULTS: rTMS reduced smoking urges in TUD. Both active-rTMS groups demonstrated greater activations of the DLPFC, caudate, and bilateral insula relative to the sham group. Increased FC was observed between executive and reward network brain regions, and decreased FC was observed within reward network regions. Compared with standard rTMS, retrieval-extinction rTMS demonstrated similar outcomes and was associated with less activation of the medial frontal gyrus. CONCLUSIONS: rTMS increased activations in brain regions implicated in executive control and reward processing. Strengthened prefrontal-striatal pathway suggests that rTMS enhanced top-down control over smoking cravings. The retrieval-extinction process, although associated with some different and multiple similar neural correlates as the standard rTMS, did not enhance cessation outcomes.

Targeting cravings in substance addiction with transcranial direct current stimulation: insights from a meta-analysis of sham-controlled trials.

Addiction is a substantial health concern; craving-the core symptom of addiction-is strongly associated with relapse. Transcranial direct current stimulation (tDCS) is a noninvasive brain stimulation technique that reduces cravings by altering cortical excitability and connectivity in brain regions. This systematic review and meta-analysis was conducted (following the PRISMA guidelines) to evaluate the efficacy of tDCS in reducing cravings for substances. Our analysis included 43 randomized, sham-controlled trials involving 1,095 and 913 participants receiving tDCS and sham stimulation, respectively. We analyzed the changes in craving scores and found that tDCS led to a moderate reduction in cravings compared with the sham effects. This effect was particularly pronounced when bilateral stimulation was used, the anodal electrode was placed on the right dorsolateral prefrontal cortex, current intensities ranged from 1.5 to 2 mA, stimulation sessions lasted 20 minutes, and the electrodes size was ≥35 cm². Notably, tDCS effectively reduced cravings for opioids, methamphetamine, cocaine, and tobacco but not for alcohol or cannabis. Our findings indicate tDCS as a promising, noninvasive, and low-risk intervention for reducing cravings for opioids, methamphetamine, cocaine, and tobacco. Additional studies are warranted to refine stimulation parameters and evaluate the long-term efficacy of tDCS in managing substance cravings.

The effect of cognitive reappraisal on food craving and consumption: Does working memory capacity influence reappraisal ability? An event-related potential study.

Regulating cravings for unhealthy foods in favour of healthier options is essential for weight management. Cognitive reappraisal, which involves changing the meaning of a stimulus to modify its emotional impact, has shown promise for regulating food craving and consumption. Eighty participants were presented with high-calorie (HC) and low-calorie (LC) food pictures preceded by cues signalling instructions to naturally view the food (i.e., passive viewing; LOOK) or to imagine the future consequences of consuming that food (i.e., cognitive reappraisal; REGULATE). Participants' subjective craving and event-related potentials (ERPs) were measured, and food consumption after the task was assessed. Participants' working memory capacity (WMC) was measured with the automated Operation Span task. During cognitive reappraisal, cravings for HC foods decreased, whereas cravings for LC foods increased, compared to passive viewing. Cravings for LC and HC foods were correlated with consumptions of LC and HC foods, respectively. Occipital N1 (100-200ms) amplitudes were more negative for LC than for HC pictures, but were not modulated by strategy (LOOK or REGULATE), whereas early posterior negativity (EPN; 200-300ms) was not sensitive to food type (HC or LC) or strategy. Late positive potential (LPP; 400-1000ms) ERPs were largest in the HC-REGULATE condition, possibly due to cognitive processes induced by focusing on the consequences of unhealthy foods. Late LPP (1000-3000ms) was not affected by food type or strategy. LPP amplitudes were not correlated with cravings. WMC was weakly correlated with cravings for LC following reappraisal, suggesting that WMC may influence reappraisal ability. In sum, focusing on future consequences of eating may promote healthier food choices through craving regulation. Further research is needed to examine how regulatory effects evolve over time and how they relate to WMC and brain activity.

The Application of the Metacognitive Model of Desire Thinking and Craving in Problematic Social Networking Sites Use.

Cognitive models of addictive behaviours have highlighted the central role of Desire Thinking (DT) - a conscious and voluntary cognitive process orienting to prefigure images and information about a positive target-related experience - in increasing craving and maintaining addictive behaviors. The metacognitive model of DT and craving posits that metacognition plays a central role in understanding dysregulation in DT. The current study aims to test the role of metacognitions about DT, DT, and craving in the relationship between Fear of Missing Out (FoMo), boredom proneness, negative emotional reactivity and Problematic Social Network Sites Use (PSNSU). A sample of 529 participants (Mage= 32.45 ± 13.33; F = 62.9%) completed an online survey. The hypothesised model produced an adequate fit to the data and accounted for 86% of PSNSU variance. FoMO predicted positive metacognitions about DT (PMDT), which predicted DT that, in association with craving, predicted PSNSU. Boredom proneness positively predicted PSNSU directly and indirectly through the serial mediation of PMDT, DT, and craving. A direct path between negative emotional reactivity and PSNSU was found. The current findings provide preliminary evidence for applying the metacognitive model of DT and craving in PSNSU. PMDT and DT may be central cognitive processes in craving and PSNSU for individuals who experience boredom proneness and FoMo.

Effects of Ovarian Hormone Levels on Stress, Cigarette Craving, and Smoking in a Laboratory Relapse Paradigm Among Females Who Smoke Daily.

INTRODUCTION: Females, versus males, have shown a slower decline in smoking prevalence, greater smoking-related mortality and morbidity, and tend to have more difficulty achieving and maintaining abstinence. Identifying sex-specific risk factors is needed to improve outcomes. Though ovarian hormones have been evaluated for their role in smoking and relapse, measures tend to be static and infrequent, failing to capture the influence of increasing or decreasing levels. AIMS AND METHODS: The present study evaluated the effect of static and fluctuating levels of ovarian hormones (ie, progesterone, estradiol, and estrogen to progesterone [E/P] ratio) on stress reactivity, cigarette craving, and smoking during a laboratory relapse paradigm. Female participants (assigned female at birth) reporting daily cigarette smoking (N = 91, ages 18-45) were recruited from the community. Participants provided daily salivary ovarian hormone levels leading up to a laboratory session, in which stress was induced and stress reactivity, cigarette craving, latency to smoke, and ad-libitum smoking were measured. RESULTS: Static levels of estradiol were associated with stress reactivity (ß = 0.28, SE = 0.13) and static E/P ratio was associated with smoking in the laboratory (HR = 1.4). Preceding 3-day changes in estradiol and E/P ratio, but neither static levels nor preceding 3-day changes in progesterone were associated with stress reactivity, cigarette craving, or smoking in a relapse paradigm. CONCLUSIONS: Ovarian hormones are among several sex-specific factors involved in the complex neuroendocrine response to stress, and their interaction with other biological, social, and psychological factors in the real-world environment is not yet fully understood. IMPLICATIONS: Findings of the present study provide novel information regarding the role of ovarian hormones among female participants who smoke daily in stress reactivity and smoking in the context of a laboratory relapse paradigm and highlight several avenues for future research. We found that same-day estradiol levels were associated with increased subjective stress reactivity and same-day estrogen to progesterone ratio was associated with increased likelihood of smoking in a relapse paradigm. Ovarian hormones are among several sex-specific factors contributing to the complex neuroendocrine response to stress, and their interaction with other biological, social, and psychological factors in the real-world environment is not yet fully understood.

Craving modulates attentional bias towards alcohol in severe alcohol use disorder: An eye-tracking study.

BACKGROUND AND AIMS: Competing models disagree on three theoretical questions regarding alcohol-related attentional bias (AB), a key process in severe alcohol use disorder (SAUD): (1) is AB more of a trait (fixed, associated with alcohol use severity) or state (fluid, associated with momentary craving states) characteristic of SAUD; (2) does AB purely reflect the over-activation of the reflexive/reward system or is it also influenced by the activity of the reflective/control system and (3) does AB rely upon early or later processing stages? We addressed these issues by investigating the time-course of AB and its modulation by subjective craving and cognitive load in SAUD. DESIGN: A free-viewing eye-tracking task, presenting pictures of alcoholic and non-alcoholic beverages, combined with a concurrent cognitive task with three difficulty levels. SETTING: A laboratory setting in the detoxification units of three Belgian hospitals. PARTICIPANTS: We included 30 patients with SAUD self-reporting craving at testing time, 30 patients with SAUD reporting a total absence of craving and 30 controls matched on sex and age. All participants from SAUD groups met the DSM-5 criteria for SAUD. MEASUREMENTS: We assessed AB through early and late eye-tracking indices. We evaluated the modulation of AB by craving (comparison between patients with/without craving) and cognitive load (variation of AB with the difficulty level of the concurrent task). FINDINGS: Dwell time measure indicated that SAUD patients with craving allocated more attention towards alcohol-related stimuli than patients without craving (P < 0.001, d = 1.093), resulting in opposite approach/avoidance AB according to craving presence/absence. SAUD patients without craving showed a stronger avoidance AB than controls (P = 0.003, d = 0.806). AB did not vary according to cognitive load (P = 0.962, η2 p = 0.004). CONCLUSIONS: The direction of alcohol-related attentional bias (approach/avoidance) appears to be determined by patients' subjective craving at testing time and does not function as a stable trait of severe alcohol use disorder. Alcohol-related attentional bias appears to rely on later/controlled attentional stages but is not modulated by the saturation of the reflective/control system.

A systematic review and meta-analysis of neuromodulation therapies for substance use disorders.

While pharmacological, behavioral and psychosocial treatments are available for substance use disorders (SUDs), they are not always effective or well-tolerated. Neuromodulation (NM) methods, including repetitive transcranial magnetic stimulation (rTMS), transcranial direct current stimulation (tDCS) and deep brain stimulation (DBS) may address SUDs by targeting addiction neurocircuitry. We evaluated the efficacy of NM to improve behavioral outcomes in SUDs. A systematic literature search was performed on MEDLINE, PsychINFO, and PubMed databases and a list of search terms for four key concepts (SUD, rTMS, tDCS, DBS) was applied. Ninety-four studies were identified that examined the effects of rTMS, tDCS, and DBS on substance use outcomes (e.g., craving, consumption, and relapse) amongst individuals with SUDs including alcohol, tobacco, cannabis, stimulants, and opioids. Meta-analyses were performed for alcohol and tobacco studies using rTMS and tDCS. We found that rTMS reduced substance use and craving, as indicated by medium to large effect sizes (Hedge's g > 0.5). Results were most encouraging when multiple stimulation sessions were applied, and the left dorsolateral prefrontal cortex (DLPFC) was targeted. tDCS also produced medium effect sizes for drug use and craving, though they were highly variable and less robust than rTMS; right anodal DLPFC stimulation appeared to be most efficacious. DBS studies were typically small, uncontrolled studies, but showed promise in reducing misuse of multiple substances. NM may be promising for the treatment of SUDs. Future studies should determine underlying neural mechanisms of NM, and further evaluate extended treatment durations, accelerated administration protocols and long-term outcomes with biochemical verification of substance use.

An electroencephalographic signature predicts craving for methamphetamine.

Craving is central to methamphetamine use disorder (MUD) and both characterizes the disease and predicts relapse. However, there is currently a lack of robust and reliable biomarkers for monitoring craving and diagnosing MUD. Here, we seek to identify a neurobiological signature of craving based on individual-level functional connectivity pattern differences between healthy control and MUD subjects. We train high-density electroencephalography (EEG)-based models using data recorded during the resting state and then calculate imaginary coherence features between the band-limited time series across different brain regions of interest. Our prediction model demonstrates that eyes-open beta functional connectivity networks have significant predictive value for craving at the individual level and can also identify individuals with MUD. These findings advance the neurobiological understanding of craving through an EEG-tailored computational model of the brain connectome. Dissecting neurophysiological features provides a clinical avenue for personalized treatment of MUD.

Cognitive reappraisal of food craving and emotions: a coordinate-based meta-analysis of fMRI studies.

Growing evidence supports the effectiveness of cognitive reappraisal in down-regulating food desire. Still, the neural bases of food craving down-regulation via reappraisal, as well as their degree of overlap vs specificity compared with emotion down-regulation, remain unclear. We addressed this gap through activation likelihood estimation meta-analyses of neuroimaging studies on the neural bases of (i) food craving down-regulation and (ii) emotion down-regulation, alongside conjunction and subtraction analyses among the resulting maps. Exploratory meta-analyses on activations related to food viewing compared with active regulation and up-regulation of food craving have also been performed. Food and emotion down-regulation via reappraisal consistently engaged overlapping activations in dorsolateral and ventrolateral prefrontal, posterior parietal, pre-supplementary motor and lateral posterior temporal cortices, mainly in the left hemisphere. Its distinctive association with the right anterior/posterior insula and left inferior frontal gyrus suggests that food craving down-regulation entails a more extensive integration of interoceptive information about bodily states and greater inhibitory control over the appetitive urge towards food compared with emotion down-regulation. This evidence is suggestive of unique interoceptive and motivational components elicited by food craving reappraisal, associated with distinctive patterns of fronto-insular activity. These results might inform theoretical models of food craving regulation and prompt novel therapeutic interventions for obesity and eating disorders.

Progesterone Attenuates the Stress Response in Individuals with Alcohol Dependence and Post-Traumatic Stress Disorder - A Pilot Study.

OBJECTIVE: Evidence from laboratory studies suggests that progesterone may be effective in reducing stress and craving, and may improve cognitive performance in smokers and individuals with cocaine dependence. The objective of this study was to examine if progesterone would attenuate stress-induced craving, anxiety, affect and physiological measures, as well as improve stress-induced cognitive performance (processing speed and selective attention) in individuals diagnosed with alcohol use disorder (AUD) and post traumatic stress disorder (PTSD). METHODS: This laboratory study included (n = 13) participants who were diagnosed with current AUD and PTSD who were randomly assigned to recive either progesterone (200mg bid) or placebo in identical looking capsules for 3 days. On the fourth day they completed a laboratory session. In the morning of the test session, they received the last dose of medication and completed the rest of the laboratory procedures. The procedures included presentation in random order of personalized trauma and neutral scripts with relaxation in between. Main outcomes included measure of craving, anxiety, affect and cognitive performance. RESULTS: Consistent with other research, trauma scripts produced significantly greater increases in craving, anxiety and negative affect when compared with neutral scripts. Progesterone significantly reduced stress-induced symptoms of craving, anxiety, fear, anger and sadness but had no effect on positive emotions (joy, relaxation). Progesterone was effective in ameliorating stress-induced decreases in cognitive performance. CONCLUSIONS: The findings from this study demonstrate that progesterone can be effective in reducing stress-induced craving, anxiety and negative affect in a laboratory setting in individuals with comorbid AUD and PTSD. Interestingly, progesterone also improved cognitive performance. These findings require replication in a larger clinical trial and may have implications for treatment among individuals with AUD and PTSD.This study was registered as NCT02187224, at www.clinicaltrials.gov.

Effects of virtual reality-based cue exposure therapy on craving and physiological responses in alcohol-dependent patients-a randomised controlled trial.

BACKGROUND: Cue exposure therapy is used to treat alcohol dependence. However, its effectiveness is controversial due to the limitations of the clinical treatment setting. Virtual reality technology may improve the therapeutic effect. The aim of this study is to explore whether virtual reality-based cue exposure therapy can reduce the psychological craving and physiological responses of patients with alcohol dependence. METHODS: Forty-four male alcohol-dependent patients were recruited and divided into the study group (n = 23) and the control group (n = 21) according to a random number table. The control group received only conventional clinical treatment for alcohol dependence. The study group received conventional clinical treatment with the addition of VR cue exposure (treatment). The primary outcome was to assess psychological craving and physiological responses to cues of patients before and after treatment. RESULTS: After virtual reality-based cue exposure therapy, the changes in VAS and heart rate before and after cue exposure in the study group were significantly lower than those in the control group (P < 0.05), while the changes in skin conductance and respiration between the study group and the control group were not significantly different (P > 0.05). The changes in VAS and heart rate before and after cue exposure in the study group were significantly lower than those before treatment (P < 0.05), while the changes in skin conductance and respiration were not significantly different from those before treatment (P > 0.05). The changes in VAS, heart rate, skin conductance and respiration before and after cue exposure in the control group were not significantly different from those before treatment (P > 0.05). CONCLUSION: Virtual reality-based cue exposure therapy can reduce the psychological craving and part of the physiological responses of alcohol-dependent patients during cue exposure in the short term and may be helpful in the treatment of alcohol dependence. TRIAL REGISTRATION: The study protocol was registered at the China Clinical Trial Registry on 26/02/2021 ( www.chictr.org.cn ; ChiCTR ID: ChiCTR2100043680).

Intense craving for eat: standardization of the Food Cravings Questionnaire-State in Mexico.

BACKGROUND: Food craving is an intense-compulsive response to eating highly appetizing foods. The Food Cravings Questionnaire-State (FCQ-S) is the most used instrument for its diagnosis. It is a multidimensional instrument, sensitive and adaptable to contextual and cultural changes. OBJECTIVE: To standardize the FCQ-S in the adult population of Mexico City. METHOD: Non-experimental, cross-sectional, at convenience design, with 1059 adults of both sexes, aged 18-84 years. It is highlighted that 71.9% of the participants were women. RESULTS: A reliability coefficient of 0.95 was obtained, the correlations between the items were from r = 0.598 to r = 0.793. With the exploratory factorial analysis, an MKO of sampling adequacy of 0.943 was obtained, and with the Bartlett sphericity test a p = 0.000. The factors explain 78.61% of the total variation of the data. The RMSEA was 0.068, which indicates an acceptable fit. The CFI was 0.974, considered good, and NNFI was 0.969, good fit. The correlations ranged from p < 0.05 to p < 0.01, showing a connection between the different dimensions. CONCLUSIONS: The FCQ-S is valid and adaptable in the Mexican population.

ANTECEDENTES: El food craving es un deseo intenso y compulsivo de comer alimentos altamente apetecibles. El Food Cravings Questionnaire-State (FCQ-S) es el instrumento más utilizado para su diagnóstico. Es un instrumento multidimensional, sensible y adaptable a cambios contextuales y culturales. OBJETIVO: estandarizar el FCQ-S en población adulta de la Ciudad de México. MÉTODO: Diseño no experimental, transversal y a conveniencia por método de bola de nieve, con 1059 adultos ambos sexos y de 18-84 años. Se destaca que el 71.9% de los participantes fueron mujeres. RESULTADOS: Se obtuvo un coeficiente de fiabilidad de 0.95 y las correlaciones entre los ítems fueron de r = 0.598 a r = 0.793. Con el análisis factorial exploratorio se obtuvo una MKO de adecuación de muestreo de 0.943, y con la prueba de esfericidad de Bartlett una p = 0.000. Los factores explican el 78.61% de la variación total de los datos. La RMSEA fue 0.068, lo cual indica ajuste aceptable. El CFI fue 0.974, considerado bueno, y el NNFI fue 0.969 (buen ajuste). Las correlaciones fueron de p < 0.05 a p < 0.01, lo que muestra una conexión entre las diferentes dimensiones. CONCLUSIONES: El FCQ-S es válido y adaptable en población mexicana.

Effects of transcranial magnetic stimulation on cocaine addiction: A systematic review of randomized controlled trials.

OBJECTIVE: While pharmacological strategies appear to be ineffective in treating long-term addiction, repetitive transcranial magnetic stimulation (rTMS) is emerging as a promising new tool for the attenuation of craving among multiple substance dependent populations. METHOD: A systematic review of randomized controlled trials (RCTs) was conducted on the efficacy and tolerability of rTMS in treating cocaine use disorder (CUD). Relevant papers published in English through November 30th 2022 were identified, searching the electronic databases MEDLINE, Embase, PsycINFO and the Cochrane Library. RESULTS: Eight studies matched inclusion criteria. The best findings were reported by the RCTs conducted at high-frequency (≥5 Hz) multiple sessions of rTMS delivered over the left dorsolateral prefrontal cortex (DLPFC): a significant decrease in self-reported cue-induced cocaine craving and lower cocaine craving scores and a considerable amelioration in the tendency to act rashly under extreme negative emotions (impulsivity) were found in the active group compared to controls. CONCLUSION: Although still scant and heterogeneous, the strongest evidence so far on the use of rTMS on individuals with CUD support the high frequency stimulation over the left DLPFC as a well tolerated treatment of cocaine craving and impulsivity.