Search Results (347)

Substance use disorders (SUDs) remain a major public health challenge, with existing pharmacotherapies offering limited long-term efficacy. Traditional treatments focus on dopaminergic systems but often overlook the complex interplay between metabolic signals, neuroplasticity, and conditioned behaviors that perpetuate addiction. Glucagon-like peptide-1 receptor agonists (GLP-1RAs), originally developed for type 2 diabetes and obesity, have recently emerged as promising modulators of reward-related brain circuits. This review synthesizes current evidence on the role of glucagon-like peptide-1 (GLP-1) and its receptor in modulating craving and substance-seeking behaviors. We highlight how GLP-1 receptors are expressed in addiction-relevant brain regions, including the ventral tegmental area (VTA), nucleus accumbens (NAc), and prefrontal cortex (PFC), where their activation influences dopaminergic, glutamatergic, and GABAergic neurotransmission. In addition, we explore how GLP-1 signaling affects reward processing through gut–brain vagal pathways, hormonal crosstalk, and neuroinflammatory mechanisms. Preclinical studies demonstrate that GLP-1RAs attenuate intake and relapse-like behavior across a range of substances, including alcohol, nicotine, and cocaine. Early-phase clinical trials support their safety and suggest potential efficacy in reducing craving. By integrating findings from molecular signaling, neurocircuitry, and behavioral models, this review provides a translational perspective on GLP-1RAs as an emerging treatment strategy in addiction medicine. We propose that targeting gut–brain metabolic signaling could provide a novel framework for understanding and treating SUDs. Full article

Background/Objectives: Food-related memory influences appetite regulation, with memory inhibition potentially reducing cravings. While obesity is linked to inhibitory deficits, how restrained eating affects memory suppression in healthy-weight individuals remains unclear. This study examined the cognitive and neural mechanisms of food-memory suppression in young women. Methods: Forty-two female participants completed a think/no-think task with high-/low-calorie food cues while an EEG was recorded. Event-related potentials (ERPs) were assessed and time–frequency analyses (theta/beta oscillations) were performed. Results: Restrained eaters showed reduced memory control for both food types. The ERP analysis revealed significant N200 amplitude differences between think/no-think conditions (p = 0.03) and a significant interaction between food calories and think/no-think conditions (p = 0.032). Theta oscillations differed by group, food calories, and conditions (p = 0.038), while beta oscillations reflected food-cue processing variations. Conclusions: In conclusion, restrained eaters exhibit distinct neural processing and attenuated food-memory suppression. These results elucidate the neurocognitive mechanisms underlying dietary behavior, suggesting that targeted interventions for maladaptive eating could strengthen memory inhibition. Full article

Background/Objectives: We examined maternal perceptions of infant cries as a mediator between maternal tobacco/cannabis use, psychological distress (depression/anger/hostility) and reported cravings for cigarettes and/or cannabis across two time points. Methods: A total of 96 substance-using mothers (35 tobacco-only and 61 tobacco/cannabis) were recruited in pregnancy. Maternal substance use and psychological distress were measured when their children were school age (5–6 years, T1). At the middle childhood assessment (9–12 years, T2), mothers listened to a standardized set of newborn cries and, afterwards, rated their aversiveness, impact on negative affect, and their tobacco/cannabis cravings. Results: Higher levels of maternal depressive symptoms at T1 were associated with perceptions of cries as being more aversive at T2, which, in turn, were associated with increased cannabis cravings at T2. At T1, higher depressive symptoms predicted increased tobacco cravings and higher maternal anger/hostility predicted increased cannabis cravings. Conclusions: Results highlight the role that infant cries and psychological distress play in cravings among tobacco/cannabis-using mothers. Full article

Background/Objectives: Digital food-related videos significantly influence cravings, appetite, and weight outcomes; however, the dynamic neural mechanisms underlying appetite fluctuations during naturalistic viewing remain unclear. This study aimed to identify neural activity patterns associated with moment-to-moment appetite changes during naturalistic food-cue video viewing and to examine their relationships with cravings and weight-related outcomes. Methods: Functional magnetic resonance imaging (fMRI) data were collected from 58 healthy female participants as they viewed naturalistic food-cue videos. Participants concurrently provided continuous ratings of their appetite levels throughout video viewing. Hidden Markov Modeling (HMM), combined with machine learning regression techniques, was employed to identify distinct neural states reflecting dynamic appetite fluctuations. Findings were independently validated using a shorter-duration food-cue video viewing task. Results: Distinct neural states characterized by heightened activation in default mode and frontoparietal networks consistently corresponded with increases in appetite ratings. Importantly, the higher expression of these appetite-related neural states correlated positively with participants’ Body Mass Index (BMI) and post-viewing food cravings. Furthermore, these neural states mediated the relationship between BMI and food craving levels. Longitudinal analyses revealed that the expression levels of appetite-related neural states predicted participants’ BMI trajectories over a subsequent six-month period. Participants experiencing BMI increases exhibited a significantly greater expression of these neural states compared to those whose BMI remained stable. Conclusions: Our findings elucidate how digital food cues dynamically modulate neural processes associated with appetite. These neural markers may serve as early indicators of obesity risk, offering valuable insights into the psychological and neurobiological mechanisms linking everyday media exposure to food cravings and weight management. Full article

Brain-derived neurotrophic factor (BDNF) is associated with nicotine use behaviours, the intensity of nicotine cravings, and the experience of withdrawal symptoms. Given the established influence of sex, brain-derived neurotrophic factor variants, personality traits and anxiety levels on nicotine use, this study aimed to conduct a comprehensive association analysis of these factors within a cohort of women who use nicotine. The study included 239 female participants: 112 cigarette users (mean age = 29.19, SD = 13.18) and 127 never-smokers (mean age = 28.1, SD =10.65). Study participants were examined using the NEO Five-Factor Inventory and the State–Trait Anxiety Inventory. Genotyping of rs6265, rs10767664, and rs2030323 was performed by real-time PCR using an oligonucleotide assay. We did not observe significant differences in the distribution of either genotype or allele of rs6265, rs10767664 and rs2030323 between groups. However, compared to the never-smokers, cigarette users scored significantly lower on the Agreeableness (5.446 vs. 6.315; p = 0.005767; d_Cohen’s = 0.363; η² = 0.032) and the Conscientiousness (5.571 vs. 6.882; p = 0.000012; d_Cohen’s = 0.591; η²= 0.08) scales. There was significant linkage disequilibrium between all three analysed polymorphic variants—between rs6265 and rs10767664 (D′ = 0.9994962; p < 2.2204 × 10⁻¹⁶), between rs6265 and rs2030323 (D′ = 0.9994935; p < 2.2204 × 10⁻¹⁶) and between rs10767664 and rs20330323 (D′ = 0.9838157; p < 2.2204 × 10⁻¹⁶), but the haplotype association analysis revealed no significant differences. While our study did not reveal an association between the investigated brain-derived neurotrophic factor polymorphisms (rs6265, rs10767664 and rs2030323) and nicotine use, it is essential to acknowledge that nicotine dependence is a complex, multifactorial phenotype. Our study expands the current knowledge of BDNF ’s potential role in addictive behaviours by exploring the understudied variants (rs10767664 and rs2030323), offering a novel contribution to the field and paving the way for future research into their functional relevance in addiction-related phenotypes. The lower Agreeableness and Conscientiousness scores observed in women who use nicotine compared to never-smokers suggest that personality traits play a significant role in nicotine use in women. The observed relationship between personality traits and nicotine use lends support to the self-medication hypothesis, suggesting that some women may initiate or maintain nicotine use as a coping mechanism for stress and negative affect. Public health initiatives targeting women should consider personality and psychological risk factors in addition to biological risks. Full article

Posttraumatic stress disorder (PTSD) and alcohol use disorder (AUD) often co-occur and present significant treatment challenges. Cognitive Processing Therapy (CPT) is a widely used, efficacious treatment for PTSD, but the application of CPT among individuals with co-occurring PTSD/AUD has been limited. To address this gap, we developed a novel, 12-session trauma-focused treatment that combines CPT with Relapse Prevention (RP) for AUD (CPT+RP). This paper describes CPT+RP and presents preliminary outcomes from the first six participants enrolled in a larger, ongoing multisite clinical trial of CPT+RP. PTSD symptoms were assessed using the Clinician-Administered PTSD Scale for DSM-5 (CAPS-5) and PTSD Checklist for DSM-5 (PCL-5). The Timeline Follow-Back (TLFB) assessed frequency (percent days drinking; PDD) and quantity (drinks per drinking day; DDD) of alcohol use, and craving was measured using the Penn Alcohol Craving Scale (PACS). The Client Satisfaction Questionnaire measured acceptability. Pre- to post-treatment reductions were observed in PTSD symptoms (ΔMCAPS-5 = 14.00; ΔMPCL-5 = 20.50), frequency and quantity of alcohol use (ΔMPDD = 38.65; ΔMDDD = 6.24), and craving (ΔPACS = 6.17). Most participants achieved clinically significant improvement in their PTSD symptoms and acceptability was high. Although preliminary, the findings suggest the new CPT+RP intervention is feasible, acceptable, and a promising treatment innovation for co-occurring PTSD and AUD. Full article

Background and Objectives: Preliminary studies indicate that dihydrogen (H₂) may affect molecular pathways involved in appetite regulation; however, its role in influencing patient-reported appetite outcomes in individuals with obesity remains uncertain. This randomized, placebo-controlled, double-blind trial aimed to evaluate the effects of H₂ supplementation on appetite, body composition, sleep quality, obesity-specific quality of life, and related biomarkers in obese men and women. Materials and Methods: The study included 36 participants (24 females; age 42.1 ± 13.2 years; BMI 30.8 ± 4.2 kg/m²) randomized to receive either 1.0 L of hydrogen-rich water (15 mg of H₂) or 1.0 L of control water (0 mg of H₂) daily for eight weeks. Results: The results demonstrated that hydrogen-rich water significantly mitigated cravings (p = 0.05), improved subjective sleep quality (p = 0.05), reduced total cholesterol (p = 0.02) and LDL cholesterol (p = 0.04), and increased plasma glucagon-like peptide-1 levels (p = 0.05) compared to the control. No severe adverse effects were reported throughout the trial. Conclusions: These findings suggest that hydrogen-rich water may serve as a safe and effective dietary strategy to address appetite regulation and related metabolic indices in individuals with obesity. The study is registered at ClinicalTrials.gov (NCT06722326). Full article

Introduction: Substance use disorders (SUDs) pose a significant public health challenge, with current treatments often exhibiting limited effectiveness and high relapse rates. Transcranial direct current stimulation (tDCS), a noninvasive neuromodulation technique that delivers low-intensity direct current via scalp electrodes, has shown promise in various psychiatric and neurological conditions. In SUDs, tDCS may help to modulate key neurocircuits involved in craving, executive control, and reward processing, potentially mitigating compulsive drug use. However, the precise neurobiological mechanisms by which tDCS exerts its therapeutic effects in SUDs remain only partly understood. This review addresses that gap by synthesizing evidence from clinical studies that used neuroimaging (fMRI, fNIRS, EEG) and blood-based biomarkers to elucidate tDCS’s mechanisms in treating SUDs. Methods: A targeted literature search identified articles published between 2008 and 2024 investigating tDCS interventions in alcohol, nicotine, opioid, and stimulant use disorders, focusing specifically on physiological and neurobiological assessments rather than purely behavioral outcomes. Studies were included if they employed either neuroimaging (fMRI, fNIRS, EEG) or blood tests (neurotrophic and neuroinflammatory markers) to investigate changes induced by single- or multi-session tDCS. Two reviewers screened titles/abstracts, conducted full-text assessments, and extracted key data on participant characteristics, tDCS protocols, neurobiological measures, and clinical outcomes. Results: Twenty-seven studies met the inclusion criteria. Across fMRI studies, tDCS—especially targeting the dorsolateral prefrontal cortex—consistently modulated large-scale network activity and connectivity in the default mode, salience, and executive control networks. Many of these changes correlated with subjective craving, attentional bias, or extended time to relapse. EEG-based investigations found that tDCS can alter event-related potentials (e.g., P3, N2, LPP) linked to inhibitory control and salience processing, often preceding or accompanying changes in craving. One fNIRS study revealed enhanced connectivity in prefrontal regions under active tDCS. At the same time, two blood-based investigations reported the partial normalization of neurotrophic (BDNF) and proinflammatory markers (TNF-α, IL-6) in participants receiving tDCS. Multi-session protocols were more apt to drive clinically meaningful neuroplastic changes than single-session interventions. Conclusions: Although significant questions remain regarding optimal stimulation parameters, sample heterogeneity, and the translation of acute neural shifts into lasting behavioral benefits, this research confirms that tDCS can induce detectable neurobiological effects in SUD populations. By reshaping activity across prefrontal and reward-related circuits, modulating electrophysiological indices, and altering relevant biomarkers, tDCS holds promise as a viable, mechanism-based adjunctive therapy for SUDs. Rigorous, large-scale studies with longer follow-up durations and attention to individual differences will be essential to establish how best to harness these neuromodulatory effects for durable clinical outcomes. Full article

Background: Invasive and non-invasive neuromodulation in psychiatry represents a burgeoning field that leverages advanced neuromodulation techniques to address substance use disorders (SUDs). Aims: This narrative review synthesizes findings from multiple reviews to evaluate the efficacy of neuromodulation in treating SUDs. Methods: A comprehensive literature search was conducted between December 2024 and April 2025, focusing on systematic reviews and meta-analyses that examined various neuromodulation modalities, including repetitive transcranial magnetic stimulation (rTMS), transcranial direct current stimulation (tDCS), and deep brain stimulation (DBS). The selected reviews were analyzed to identify common themes, outcomes, and gaps in the current understanding of these treatments for SUDs. Results: 11 reviews met the final inclusion criteria; 5 focused on non-invasive neuromodulation (rTMS, tDCS) and 6 on invasive neuromodulation (DBS). Non-invasive neurostimulation was associated with modest improvements in craving and cognitive dysfunction in individuals with SUDs. Similarly, invasive neuromodulation (DBS), through high-frequency stimulation of the bilateral nucleus accumbens, appeared to reduce cravings and improve comorbid psychiatric symptoms in both preclinical and human studies. Importantly, small sample sizes, heterogeneity in targets and stimulation protocols, and short follow-up periods significantly limit the generalizability of current findings from both non-invasive and invasive neuromodulation studies. Conclusions: As novel and more effective therapies for the treatment of SUD are desperately needed, procedural interventional psychiatry holds promise. However, despite encouraging results, existing evidence is still preliminary, and larger, rigorously designed studies are warranted to further establish the safety and efficacy of neuromodulatory interventions for SUD treatment. Full article

Introduction: The introduction of the transdiagnostic approach in psychiatry shifts the focus from discrete diagnoses to shared symptoms across various disorders. The Transdiagnostic Global Impression—Psychopathology (TGI-P) scale is a newly developed tool designed to assess psychiatric symptoms across diagnostic boundaries. It evaluates ten core symptom domains—positive, negative, cognitive, manic, depressive, addiction, anxiety, sleep, hostility, and self-harm—regardless of specific diagnoses. Objective: This study aims to evaluate the efficacy of cariprazine across these ten transdiagnostic symptom domains. Methods: A systematic literature review and meta-analysis were conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Searches were performed on EMBASE and clinicaltrials.gov. Efficacy measures such as the Positive and Negative Syndrome Scale (PANSS), Montgomery–Åsberg Depression Rating Scale (MADRS), Young Mania Rating Scale (YMRS), Hamilton Anxiety Rating Scale (HAM-A), and Columbia-Suicide Severity Rating Scale (C-SSRS) were used to assess cariprazine’s effect on the ten transdiagnostic symptoms. Multilevel random-effects meta-analyses were conducted to evaluate the efficacy of cariprazine versus placebo in alleviating depressive and anxiety symptoms across clinical trials. Results: A total of 30 studies were included in the review. Cariprazine showed therapeutic benefits on positive, negative, manic, and depressive symptoms in specifically designed trials. Preliminary positive effects were seen on anxiety, hostility, and cognitive symptoms across disorders. However, specific trials have not been conducted for anxiety disorders or cognitive impairment. Meta-analyses demonstrated that cariprazine significantly reduces both depressive and anxiety symptoms compared to placebo. Cariprazine significantly improved sleep-related symptoms in both mania and depression trials. Suicidality was evaluated in non-suicidal populations, and no increase was observed. Addiction symptoms were part of the exclusion criteria in the RCTs, so they could not be assessed. Previous reports of cariprazine’s anti-craving and anti-abuse effects come from real-world evidence rather than RCT data. Conclusions: Cariprazine appears to be promising in addressing a broad range of symptom domains across psychiatric conditions. Full article

Background/Objectives: Glucagon-like peptide-1 receptor agonists (GLP-1RAs), which were originally developed for managing type 2 diabetes by enhancing insulin secretion and reducing appetite, have emerged as promising candidates in alcohol use disorder (AUD). These medications offer a dual mechanism of action that aligns with the multifaceted nature of addiction by targeting both peripheral metabolic and central reward pathways. This review focused on the current clinical trials and real-world evidence regarding the effects of GLP-1RAs as novel therapeutics for AUD. We also discussed early but encouraging results from clinical trials in AUD, observational and real-world evidence, safety profiles, psychiatric considerations, and future directions leading beyond GLP-1RAs. Methods: A comprehensive English-language literature search was conducted per PRISMA guidelines across PubMed, Medline, Google Scholar, Web of Science, and trial registries. Using targeted keywords, we identified relevant clinical and observational studies on GLP-1RAs for alcohol use disorder, excluding off-topic or non-English works and assessing all studies for eligibility. Results: Out of 1080 records identified, seven studies met the inclusion criteria. The findings from recent clinical trials, large-scale observational studies, and real-world evidence suggest that GLP-1RAs may significantly reduce alcohol consumption, cravings, and alcohol-related hospitalizations. Their central effect on reward processing, coupled with a generally favorable safety profile, supports their potential therapeutic role beyond metabolic disorders. Conclusions: Emerging evidence positions GLP-1RAs as a promising new pharmacologic approach for managing AUD. Ongoing and future research should prioritize larger, longer-duration randomized controlled trials that include diverse populations, with specific attention to treatment motivation, co-occurring psychiatric conditions, and long-term outcomes. Full article

Background and aims: Opioid maintenance therapy (OMT) is the first-line treatment for opioid use disorder (OUD), reducing opioid use and mortality while improving physical and mental health. However, concomitant substance use remains common, with cannabis being the most frequently used substance. This study assessed the prevalence and clinical correlates of cannabis use in OMT patients, as well as individual motivations. Methods: In this cross-sectional, single-center study, 128 OUD patients (96 male, 32 female) receiving OMT were assessed using standardized questionnaires: the Marijuana Smoking History Questionnaire (MSHQ), Cannabis Problems Questionnaire (CPQ) and the Severity of Dependence Scale (SDS). Cannabis users and non-users were compared regarding type (methadone vs. buprenorphine) and dosage of maintenance medication. Results: Cannabis use was reported by 41% of patients, 73% met criteria for cannabis dependence, 30% of the full sample. Of the patients, 85% reported cannabis-related legal issues. Common reasons for use included recreational motives (mood change, enhancement) and reduction in cravings for other substances. Cannabis dependence was significantly more common in patients receiving buprenorphine than methadone. Higher methadone doses were also associated with increased cannabis use. These results suggest a clinically relevant pattern. Conclusions: Cannabis use is highly prevalent and appears to be influenced by type and dosage of substitution medication. These findings highlight a complex interaction between opioid treatment and cannabis use, possibly involving behavioral coping or regulatory processes. Further longitudinal and placebo-controlled trials are needed to investigate the clinical and pharmacological interactions between cannabis and OMT, including effects on craving, withdrawal, and overall treatment outcomes. Full article

Food can help release and promote neurotransmitters. As a result, the food’s effect in this regard is of great interest to individuals who have experienced dysregulation of the brain reward circuit due to addiction to drugs or other substances. This is one of the chief reasons why dietary choices can influence the success of drug addiction programs. While the general importance of nutrition was known previously—although it has been applied on few occasions—this review provides new knowledge that has emerged in recent years, which reinforces earlier findings regarding food’s importance in overcoming addiction. In the last 15 years, there has been great progress in the understanding of the human intestinal microbiota, its importance for health, and its connections with the brain. However, since this area of nutrition is such a new field of study, it has rarely been applied to or considered in treatment programs. At the same time, it is important to avoid a diet based on ultra-processed foods, which deteriorate the microbiome and consequently harm the restoration of the natural reward system. Although ongoing research will undoubtedly provide a wealth of information in the coming years, the knowledge currently available is enough to confirm the importance of diet in a person’s addiction recovery process. For this reason, it is important for patients and programs to follow a diet that regulates the brain’s natural neurotransmitters through the microbiota and restores the natural functioning of the reward circuit, helping to overcome cravings. Full article

Background: Previous syntheses on the neural effects of alcohol have been restricted to tasks assessing craving, cognitive control, and reward processing. Despite extensive research, a comprehensive synthesis of functional magnetic resonance imaging (fMRI) findings on alcohol use disorder (AUD) remains lacking. This study aimed to identify consistent brain activation alterations across all cognitive and emotional tasks administered to individuals with AUD while distinguishing between short-term and long-term abstinence and using activation likelihood estimation meta-analysis. Sub-analyses on task types were performed. Methods: A systematic review identified 67 fMRI studies on participants with an AUD. Results: The meta-analysis revealed significant alterations in brain activity, including both hypo- and hyperactivation in the left putamen across all AUD participants. These alterations were observed more frequently during decision-making and reward tasks. Short-term abstinent individuals exhibited hypoactivation in the right middle frontal gyrus (MFG), corresponding to the dorsolateral prefrontal cortex. In contrast, long-term abstinent individuals displayed hypoactivation in the right superior frontal gyrus (SFG) and dorsal anterior cingulate cortex (dACC). This meta-analysis highlights critical neural alterations in AUD, particularly in regions associated with reward processing (putamen), executive functions (MFG and SFG), and attentional salience (dACC). Putamen changes were predominantly observed during short-term abstinence and in decision-making, as well as reward processing tasks. dACC and SFG hypoactivation were specific to long-term abstinence, while MFG hypoactivation was specific to short-term abstinence. Conclusions: These findings support prior research indicating a motivational imbalance and persistent executive dysfunctions in AUD. Standardizing consumption metrics and expanding task diversity in future research is essential to further refine our understanding of the neural effects of AUD. Full article