Search Results (225)

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: Research on sex differences in personality disorders profiles among individuals with Alcohol Use Disorder (AUD) remains limited. This study aimed to examine sex differences in personality disorders in AUD individuals attending to an outpatient alcohol and drugs treatment unit. Methods: Persons seeking alcohol detoxification treatment were assessed with the Millon Clinical Multiaxial Inventory-III (MCMI-III) after abstinence. Both dimensional trait scores and cluster personality disorders types distribution were analyzed. A total of 216 subjects, 114 women (53%) and 102 men (47%), participated in the study. Results: No sex differences were found for paranoid, schizoid or schizotypal traits scores of Cluster A types. Women exhibited higher scores on the Cluster B histrionic trait (48 ± 22 vs. 39 ± 23, p = 0.012), with no differences in antisocial, borderline, or narcissistic trait scores. Narcissistic personality disorder was more prevalent in men than women (44% vs. 20%, p = 0.012). Cluster C dependent (52 ± 24 vs. 46 ± 20, p = 0.025) and obsessive-compulsive (54 ± 20 vs. 43 ± 19, p = 0.012) traits scores were elevated in women, but only dependent personality disorder prevalence differed categorically (38% women vs. 15% men, p = 0.012). Conclusions: Employing both dimensional and cluster approaches enriches personality disorder research in AUD. Dependent personality disorder in Cluster C robustly differentiates sexes, while personality disorder patterns in Clusters A and B show minimal sex differences when both approaches are considered. Full article

Alcohol is a prevalent psychoactive substance and a risk factor for developing injuries and non-communicable diseases, representing a significant health and economic burden. Alcohol involves numerous molecular pathways. Its metabolism is regulated by alcohol dehydrogenases and aldehyde dehydrogenases; it also stimulates cholinergic interneurons, increasing the sensitivity of 5-HT3 receptors, while chronic alcohol consumption alters the mesolimbic dopaminergic system involved in reward processing. The treatment of alcohol use disorder (AUD) is essential to manage complex patients, following an evidence-based approach. The aim of this narrative review is to provide a clear and practical summary to support and assist healthcare professionals in the Italian context. Approved pharmacological treatments for AUD include oral naltrexone and acamprosate, sodium oxybate, disulfiram, and nalmefene. Off-label therapies include baclofen, topiramate, gabapentin, pregabalin, ondansetron, and cytisine. A more informed clinical and practical approach that understands the altered neuronal signaling pathways is essential for offering effective, efficient, appropriate, and safe therapeutic algorithms for complex patients with alcohol use disorder. A comprehensive framework should include integrated treatments with a personalized approach. Full article

Introduction: Chronic alcohol use is a complex condition influenced by psychological, behavioral, and socio-demographic factors. This study aimed to develop a comprehensive psychosocial profile of individuals with alcohol use disorder (AUD) by examining associations between psychometric variables and relapse risk including repeated psychiatric hospitalizations. Methodology: A cross-sectional observational analytical study was conducted on a sample of 104 patients admitted for alcohol withdrawal management at the “Prof. Dr. Al. Obregia” Psychiatric Clinical Hospital in Bucharest between March 2023 and September 2024. Participants completed a set of validated psychometric tools: the Drinker Inventory of Consequences—Lifetime Version (DrInC), Readiness to Change Questionnaire—Treatment Version (RTCQ), Drinking Expectancy Questionnaire (DEQ), and Drinking Refusal Self-Efficacy Questionnaire (DRSEQ). Additional data were collected on the socio-demographic (education level, socio-professional category), genetic (family history of alcohol use), and behavioral factors (length of abstinence, tobacco use, co-occurring substance use disorders). Results: Higher alcohol-related consequence scores (DrInC) were significantly associated with lower education (p < 0.001, η² = 0.483), disadvantaged socio-professional status (p < 0.001, η² = 0.514), and family history of alcohol use (p < 0.001, η² = 0.226). Self-efficacy (DRSEQ) was significantly lower among individuals with co-occurring substance use (p < 0.001) and nicotine dependence (p < 0.001). Logistic regression showed that the DrInC scores significantly predicted readmission within three months (OR = 1.09, p = 0.001). Conclusions: Psychometric tools are effective in identifying individuals at high risk. Personalized, evidence-based interventions tailored to both psychological and socio-professional profiles, combined with structured post-discharge support, are essential for improving long-term recovery and reducing the readmission rates. Full article

Despite the growing morbidity associated with alcohol use disorder (AUD), current FDA-approved therapeutics fail to adequately address the condition. This is in part due to the complex systemic effects of ethanol (EtOH), which have particularly negative consequences on the gut–liver–brain axis. Importantly, two systemic mechanisms underlying the progression of AUD remain underemphasized in therapeutic development: thiamine deficiency and neuroinflammation. Alcohol-induced thiamine deficiency leads to reduced activity of key metabolic enzymes, thereby resulting in energy deficits, oxidative stress, and severe clinical implications. EtOH also activates TLR4 and NLRP3, both of which play critical roles in the regulation of neuroimmune responses. While research directly investigating the relationship between thiamine deficiency and neuroinflammation is still in its early stages, our review highlights the emerging connections between these two seemingly distinct pathomechanisms. Additionally, potential therapeutic approaches and targets for addressing AUD at a systemic level are discussed. 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

This paper presents an analysis of the severity of alcohol use disorder (AUD) based on electroencephalogram (EEG) signals and alcohol drinking experiments by utilizing power spectral density (PSD) and the transitions that occur as individuals drink alcohol in increasing amounts. We use data from brain—computer interface (BCI) experiments using alcohol as a stimulus recorded from a group of seventeen alcohol-drinking male participants and the assessment scores of the alcohol use disorders identification test (AUDIT). This method investigates the mild, moderate, and severe symptoms of AUD using the three key domains of AUDIT, which are hazardous alcohol use, dependence symptoms, and severe alcohol use. We utilize the EEG spectral power of the theta, alpha, and beta frequency bands by observing the transitions from the initial to the final phase of alcohol consumption. Our results are compared for people with low-risk alcohol consumption, harmful or hazardous alcohol consumption, and lastly a likelihood of AUD based on the individual assessment scores of the AUDIT. We use Balanced Iterative Reducing and Clustering using Hierarchies (BIRCH) to cluster the results of the transitions in EEG signals and the overall brain activity of all the participants for the entire duration of the alcohol-drinking experiments. This study can be useful in creating an automatic AUD severity level detection tool for alcoholics to aid in early intervention and supplement evaluations by mental health professionals. Full article

Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are long-acting drugs that have gathered a lot of attention worldwide for their utility in the treatment landscape of type 2 diabetes mellitus and obesity. Their widespread global use has been accompanied by an additional observation related to a potential reduction in alcohol consumption. Preclinical studies in animal models, along with preliminary clinical findings, suggest that GLP-1 RAs may exert beneficial effects on alcohol use disorder (AUD). The latter represents a significant public health challenge, contributing to a broad spectrum of health, social, and economic burdens. Concurrently, the use of GLP-1 RAs in patients with metabolic dysfunction-associated steatotic liver disease (MASLD) has been associated with a clinically meaningful reduction in all-cause mortality, major cardiovascular events, and progression to metabolic dysfunction-associated steatohepatitis (MASH). In this current opinion article, we firstly summarize the current literature dealing with the effect of GLP-1 RAs on AUD based on findings from experimental and human clinical studies. Additionally, beyond their role in MASLD, we explore in detail the potential impact of GLP-1 RAs on patients with alcoholic liver disease (ALD) and metabolic and alcohol-related/associated liver disease (MetALD). Finally, we highlight current challenges and unresolved issues, including concerns related to safety, accessibility, cost, and limitations in the clinical application of GLP-1 RAs. 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

Background/Objectives: D-lysergic acid diethylamide (D-LSD) is under investigation as a potential therapeutic strategy for alcohol use disorder (AUD). However, the extreme light sensitivity of D-LSD presents a significant challenge in developing suitable pharmaceutical forms, particularly for clinical trial settings. This study proposes a liquid-filled capsule formulation designed to provide accurate dosing while protecting D-LSD from photodegradation. Methods: To support formulation development and ensure its suitability as an investigational medicinal product, a multi-tiered analytical strategy was employed. This included liquid chromatography coupled with ion mobility spectrometry and mass spectrometry (LC-IM-MS), along with quantum chemical calculations (density functional theory (DFT) and time dependent-DFT (TD-DFT)), to ensure robust and orthogonal structural characterization of degradation products. Results: Photostress studies demonstrated that while D-LSD in solution rapidly degrades into photoisomers and photooxidative byproducts, the capsule formulation markedly mitigates these transformations under ICH-compliant conditions. Conclusions: These findings highlight the essential role of orthogonal stability profiling in guiding formulation development and demonstrate that this approach may offer a viable, photostable platform for future clinical investigation of D-LSD in the treatment of AUD. Full article

With increasing substance misuse among older adults, we examined the question of whether older adults may be less likely to endorse certain DSM-5 criteria for alcohol and cannabis use disorders (AUD and CUD). We used the 2021–2023 National Surveys on Drug Use and Health (N = 17,494 for AUD and N = 12,264 for CUD) and descriptive statistics to compare the 65+ and under 65 age groups in their endorsements of 11 DSM-5 criteria. A multivariable logistic regression model was fitted for each criterion as the dependent variable with the age group as the independent variable and other characteristics as covariates. For AUD, the 65+ age group was associated with lower odds of endorsing seven out of eleven DSM-5 criteria, including social impairments (e.g., failure to fulfill role obligations (aOR = 0.30, 95% CI = 0.16–0.56); social problems (aOR = 0.46, 95% CI = 0.30–0.71); given-up activities (aOR = 0.66, 95% CI = 0.47–0.94); hazardous use (aOR = 0.53, 95% Yes CI = 0.34–0.81); and physical/psychological problems (aOR = 0.51, 95% CI = 0.37–0.70). For CUD, the 65+ age group was less likely than the under 65 age group to endorse hazardous use (aOR = 0.04, 95% CI = 0.01–0.17) and withdrawal (aOR = 0.39, 95% CI = 0.20–0.73 for criterion A and aOR = 0.16, 95% CI = 0.05–0.48 for criterion B). Clinicians should be aware that older adults might not express the full range of symptoms in the same way as the younger age groups. A more nuanced understanding of older adults’ social context may be needed for accurate diagnosis. Full article

Background: Alcohol Use Disorder (AUD) is highly prevalent among substance use disorders worldwide and is characterized by a multifactorial pathophysiology. AUD treatment is mostly based on combined pharmacotherapy and multidisciplinary clinical approaches. Nonetheless, meta-analytical studies assessing the efficacy of combination therapy are scarcely available. Methods: We searched for randomized clinical trials through PubMed, ClinicalTrials.gov, Cochrane Library, SciELO, Biblioteca Virtual em Saúde, and Google Scholar databases. Original clinical trials published in English and Portuguese were selected. Data collection followed the PRISMA and MOOSE guidelines and was assessed using the Risk of Bias Tool (RoB 2). Heterogeneity was assessed using the Q test. Meta-regression was conducted using Egger’s regression method. Twelve articles were finally included in the analysis, and random-effects models were applied on aggregate trial results. Results: The meta-analysis found that combination therapies led to an average 4.045% increase in abstinence rates (95% CI: 0.415% to 7.675%) compared to monotherapies. Meta-regression showed a strong positive association between the use of naltrexone, acamprosate, and sertraline—either alone or in combination—and treatment success in AUD. The meta-regression also highlighted the impact of patients’ variables, such as gender, age, country, and psychiatric comorbidities, on their treatment outcomes. These findings may identify a potential therapeutic pathway promoting alcohol abstinence, further supported by a Number Needed to Treat (NNT) of 25, as an acceptable value for substance use disorder treatments. Conclusions: Combined pharmacotherapies are more effective than monotherapy in enhancing abstinence rates in AUD treatment, with naltrexone, acamprosate, and sertraline emerging as key adjunctive agents promoting these outcomes. These findings underscore the complexity of AUD as a multifactorial psychiatric condition and highlight the potential of combined pharmacotherapy as a promising strategy for achieving better treatment outcomes, particularly in terms of abstinence rates. Full article

Substance Use Disorders (SUDs) are frequently associated with impairments in emotional regulation and behavioural control. Among the most prevalent substances of abuse, alcohol and cocaine are known to exert distinct effects on neuropsychological functioning. This study aimed to compare individuals with Alcohol Use Disorder (AUD) and Cocaine Use Disorder (CUD) in terms of impulsivity and alexithymia, and to examine the clinical implications of poly-substance use involving both alcohol and cocaine. Participants completed standardized psychometric assessments, including the Barratt Impulsiveness Scale (BIS-11), the Brief Psychiatric Rating Scale (BPRS), and the Toronto Alexithymia Scale (TAS-20). Group comparisons were conducted using non-parametric tests, and logistic regression models were applied to control for demographic covariates. The findings showed that impulsivity levels were comparable across groups, whereas alexithymia scores were significantly higher in individuals with AUD and in those with poly-substance use, relative to CUD-only participants. These findings underscore the relevance of targeting emotional regulation difficulties, particularly alexithymia, in the assessment and treatment of SUDs. Integrating emotion-focused interventions may enhance treatment outcomes, especially for individuals with co-occurring substance use patterns. Future research is needed to clarify the underlying neuropsychological mechanisms contributing to these differences and to inform more personalized approaches to addiction care. Full article

The dysregulation of the serotonin system has been implicated in the pathophysiology of alcohol use disorders. Meta-analytic evidence suggests a significant correlation between genetic variation in the serotonin transporter gene and the risk of alcohol dependence. Hence, we aimed to analyse the association between 5-HTTLPR polymorphism and alcohol use disorder in a group of women and to perform an interaction analysis of 5-HTTLPR variants, personality traits, and AUD. The study group comprised 213 female volunteers; 101 were diagnosed with alcohol addiction, and 112 were not dependent on any substance or behaviour. The 5-HTTLPR variants were identified by PCR, and the resulting products were separated electrophoretically. When comparing the AUD group with the controls, we observed significant differences in the distribution of 5-HTTLPR genotypes (p = 0.0230) and alleles (p = 0.0046). We also observed a significant impact of the 5-HTTLPR genotype (p = 0.0001) on the Neuroticism and Extraversion (p = 0.0037) scales. Additionally, there was a statistically significant impact of 5-HTTLPR genotype interaction and alcohol dependency or lack of it on the Neuroticism scale (p < 0.0001). The observed interaction suggests that the effect of the 5-HTTLPR on neuroticism may be exacerbated or attenuated in the presence of alcohol addiction. Further investigation is needed to elucidate the precise nature of this interaction. Still, it potentially indicates a gene–environment interaction where the genetic predisposition conferred by the 5-HTTLPR polymorphism interacts with the environmental stressor of alcohol dependence to influence neuroticism. Full article

Using data from the 2022 and 2023 National Survey on Drug Use and Health, we examined factors associated with treatment use for substance use disorder (SUD), perceived SUD treatment needs, and reasons for treatment non-use. Of U.S. adults, 18.1% had any past-year SUD (alcohol use disorder [AUD] and/or any drug use disorder [DUD]), 14.4% of those with SUD received SUD treatment in the past year, and 5.5% of those who did not receive treatment had a perceived need for treatment. Treatment use was significantly associated with AUD and DUD severities (aOR = 3.85, 95% CI = 2.82–5.26 for severe AUD; aOR = 2.82, 95% CI = 2.27–3.47 for severe DUD), problem self-perception (aOR = 2.12, 95% CI = 1.74–2.58), and mental health treatment use (aOR = 6.07, 95% CI = 4.73–7.78). Perceived treatment needs among those who did not use treatment were also significantly associated with AUD and DUD severities, problem self-perception, and any mental illness. The most frequently reported reasons for treatment non-use among those with perceived need were self-sufficiency beliefs, lack of readiness to stop using or start treatment, stigma-related concerns, and health insurance/cost problems. The findings underscore the importance of screening SUD and educating about the harms of untreated SUD in increasing motivation and readiness for treatment use among people with SUD. Full article