Addiction Biology

Chumin, Evgeny J.; Dzemidzic, Mario; Yoder, Karmen K.

doi: 10.1111/adb.70008pmid: 39576234

One of the neurobiological correlates of alcohol use disorder (AUD) is the disruption of striatal dopaminergic function. Although regional differences in dopamine (DA) tone/function have been well studied, interregional relationships (represented as inter‐subject covariance) have not been investigated and may offer a novel avenue for understanding DA tone. Positron emission tomography (PET) data with [11C]raclopride in 22 social drinking controls and 17 AUD participants were used to generate group‐level striatal covariance (partial Pearson correlation) networks, which were compared edgewise as well as on global network metrics and community structure. An exploratory analysis examined the impact of tobacco cigarette use status. Striatal covariance was validated in an independent publicly available [18F]fallypride PET sample of healthy volunteers. Striatal covariance of control participants from both data sets showed a clear bipartition of the network into two distinct communities, one in the anterior and another in the posterior striatum. This organization was disrupted in the AUD participants' network, which showed significantly lower network metrics compared with the control participants' network. Stratification by cigarette use suggests differential consequences on group covariance networks. This work demonstrates that network neuroscience can quantify group differences in striatal DA and that its interregional interactions offer new insight into the consequences of AUD.

Reece, Albert Stuart; Hulse, Gary Kenneth

doi: 10.1111/adb.70003pmid: 39538372

Whilst mitochondrial inhibition and micronuclear fragmentation are well established features of the cannabis literature mitochondrial stress and dysfunction has recently been shown to be a powerful and direct driver of micronucleus formation and chromosomal breakage by multiple mechanisms. In turn genotoxic damage can be expected to be expressed as increased rates of cancer, congenital anomalies and aging; pathologies which are increasingly observed in modern continent‐wide studies. Whilst cannabinoid genotoxicity has long been essentially overlooked it may in fact be all around us through the rapid induction of aging of eggs, sperm, zygotes, foetus and adult organisms with many lines of evidence demonstrating transgenerational impacts. Indeed this multigenerational dimension of cannabinoid genotoxicity reframes the discussion of cannabis legalization within the absolute imperative to protect the genomic and epigenomic integrity of multiple generations to come.

Zhang, Bin; Yang, Chen; Zheng, Yuxiao; Li, Xinliang; Wang, Xingguo; Yuehui, Li

doi: 10.1111/adb.70005pmid: 39526639

Nan Bao detox capsule (NBDC), derived from ancient Chinese opioid detox protocols, shows promising therapeutic potential in substance abuse disorders, particularly for attenuating methamphetamine (MA) addiction. This study aimed to identify active ingredients, evaluate therapeutic efficacy in an MA addiction rat model and delineate pharmacodynamic mechanisms using metabolomics. In vitro phytochemical profiling characterized 258 drug‐related compounds, with 87 prototype entities mainly identified in rat plasma. NBDC significantly attenuated METH‐induced behavioural anomalies and modulated neurotransmitter levels, notably increasing brain DA and serotonin (5‐HT) content with concomitant upregulation of D1 dopamine receptor (DRD1) and 5‐HT1A receptor (5‐HT1AR) expression, ameliorating hippocampal pathology. Metabolomic analysis identified histamine receptor as a potential target and revealed the involvement of NBDC in metabolic pathways associated with cocaine addiction, amphetamine abuse and Parkinson's disease. Conclusively, NBDC presents a promising therapeutic agent for mitigating MA addiction through a synergistic interplay of multiple constituents, pharmacological targets and metabolic pathways.

Pan, Xiaoyu; Guo, Anqi; Guan, Kaiyu; Chen, Congcong; Xu, Shengnan; Tang, Yali; Li, Xi; Huang, Zhengwei

doi: 10.1111/adb.13445pmid: 39585236

Ethanol can directly or indirectly lead to cognitive and mental disorders. The long‐term intake of alcohol can directly affect the distribution of gut microbiota. Lactobacillus rhamnosus GG (LGG) is a natural bacterium isolated from healthy human intestines that has the function of preventing cytokine‐induced cell apoptosis and protecting cell barriers. However, the regulatory effect of LGG on cognitive and mental disorders caused by chronic ethanol exposure (CEE) is still unclear. In this study, we established a CEE mouse model through free alcohol consumption and added LGG or antibiotics in the later stages of the model. Sequencing analysis of the 16S rRNA gene showed that CEE resulted in a decrease in the abundance and diversity of mouse gut microbial communities accompanied by alterations in the relative abundance of multiple enterobacterial genera. The use of LGG and antibiotics alleviated the depression‐like behaviour and cognitive impairment of CEE‐induced mice, reduced expression of inflammatory factors such as interleukin (IL)‐6, IL‐1β and tumour necrosis factor (TNF)‐α in the ileum, serum and brain and increased the expression of synaptophysin (SYN), postsynaptic density protein‐95 (PSD‐95) and brain‐derived neurotrophic factor (BDNF) in the hippocampus. Together, LGG can alleviate depression‐like behaviour caused by CEE in mice while also improving cognitive and memory functions through reducing peripheral and nervous system inflammation factors and balancing gut microbiota.

doi: 10.1111/adb.13299pmid: N/A

Paschali, Magdalini; Zhao, Qingyu; Sassoon, Stephanie A.; Pfefferbaum, Adolf; Sullivan, Edith V.; Pohl, Kilian M.

doi: 10.1111/adb.70007pmid: 39532141

Grip strength is considered one of the simplest and reliable indices of general health. Although motor ability and strength are commonly affected in people with alcohol use disorder (AUD), factors predictive of grip strength decline in AUD have not been investigated. Here, we employed a data‐driven analysis predicting grip strength from measurements in 53 controls and 110 AUD participants, 53 of whom were comorbid with HIV infection. Controls and AUD were matched on sex, age, and body mass index. Measurements included commonly available metrics of brain structure, neuropsychological functioning, behavioural status, haematological and health status, and demographics. Based on 5‐fold stratified cross‐validation, a machine learning approach predicted grip strength separately for each cohort. The strongest (top 10%) predictors of grip were then tested against grip strength with correlational analysis. Leading grip strength predictors for both cohorts were cerebellar volume and mean corpuscular haemoglobin concentration. Predictors specific to controls were Backwards Digit Span, precentral gyrus volume, diastolic blood pressure, and mean platelet volume, which together significantly predicted grip strength (R2 = 0.255, p = 0.001). Unique predictors for AUD were comorbidity for HIV infection, social functioning, insular volume, and platelet count, which together significantly predicted grip strength (R2 = 0.162, p = 0.002). These cohort‐specific predictors were doubly dissociated. Salient predictors of grip strength differed by diagnosis with only modest overlap. The constellation of cohort‐specific predictive measurements of compromised grip strength provides insight into brain, behavioural, and physiological factors that may signal subtly affected yet treatable processes of physical decline and frailty.

Winterlind, Emma L.; Malone, Samantha G.; Setzer, Michael R.; Murphy, Mikela A.; Saunders, David; Gray, Joshua C.

doi: 10.1111/adb.70001pmid: 39556483

N‐acetylcysteine (NAC) may serve as a novel pharmacotherapy for substance use and substance craving in individuals with substance use disorders (SUDs), possibly through its potential to regulate glutamate. Though prior meta‐analyses generally support NAC's efficacy in reducing symptoms of craving, individual trials have found mixed results. The aims of this updated meta‐analysis were to (1) examine the efficacy of NAC in treating symptoms of craving in individuals with SUD and (2) explore subgroup differences, risk of bias and publication bias across trials. Database searches of PubMed, Cochrane Library and ClinicalTrials.gov were conducted in June and July of 2023 to identify relevant randomized control trials (RCTs). The meta‐analysis consisted of 9 trials which analysed data from a total of 623 participants. The most targeted substance in the clinical trials was alcohol (3/9; 33.3%), followed by tobacco (2/9; 22.2%) and multiple substances (2/9; 22.2%). Meta‐analysis, subgroup analyses and leave‐one‐out analyses were conducted to examine the treatment effect on craving symptoms and adverse events (AEs). Risk of bias assessments, Egger's tests and funnel plot tests were conducted to examine the risk of bias and publication bias. NAC did not significantly outperform placebo in reducing symptoms of craving in the meta‐analysis (SMD = 0.189, 95% CI = −0.015–0.393). Heterogeneity was very high in the meta‐analysis (99.26%), indicating that findings may have been influenced by clinical or methodological differences in the study protocols. Additionally, results indicate that there may be publication bias present. Overall, our findings are contrary to those of prior meta‐analyses, suggesting a limited impact of NAC on substance craving. However, the high heterogeneity and presence of publication bias identified warrants cautious interpretation of the meta‐analytic outcomes.

Liu, Yunpeng; Lu, Minghui; Yin, Huazhan; Yang, Chun; Wu, Dehua

doi: 10.1111/adb.70004pmid: 39542435

Acute alcohol consumption has been found to cause duration perception distortions, but the directions of these distortions are not consistent. The mechanisms underlying this effect are also unclear. The present study seeks to elucidate the effect of acute alcohol consumption on duration perception and the mechanisms involved. Forty‐one participants in the placebo group and 40 in the alcohol group completed time bisection tasks, attentional network tests, digit span backward tests and arousal reports to evaluate their duration perception, attentional network, working memory capacity and arousal. The results showed that the alcohol group overestimated duration compared to the placebo group. The alcohol group also showed increased arousal, impaired executive control of attention and reduced working memory capacity. Arousal mediated the effect of acute alcohol consumption on duration perception, whilst working memory capacity masked this effect. The findings are discussed based on the Scalar Timing Model and the Cognitive Resource Allocation Model.

Mithaiwala, Mustafa N.; Phillips, Nikki S.; Nguyen, Dylan H.; Beehler, Melanie S.; Ballard, Harrison S.; Vincent, Andrea S.; Lovallo, William R.; Kochunov, Peter; Hong, L. Elliot; O'Connor, Jason C.; Cole, Steve; Acheson, Ashley

doi: 10.1111/adb.70000pmid: 39558659

Individuals with a family history of alcohol or other substance use disorders (FH+) are at increased risk for developing alcohol and other substance use disorders (AUD/SUD) compared to individuals with no such family histories (FH−). FH+ young adults have blunted stress reactivity, lower cognitive performance and altered frontal white matter microstructure compared to FH− controls. We hypothesized that family history of AUD/SUD disrupts neuroendocrine regulation of the immune system in FH+ individuals, resulting in altered blood immune cell composition, inflammation and neurocognitive alterations that, ultimately, increases risk for AUD/SUD and associated psychopathology. We examined white blood cell (WBC) parameters derived from complete blood counts in FH+ (n = 37) and FH− (n = 77) young adults without AUD/SUD to test if immune system dysregulation is present in FH+ individuals. The total WBC count, number of neutrophils and number of monocytes and associated systemic inflammatory response index (SIRI) were significantly increased in the FH+ group. Further, WBC, neutrophil, monocyte counts and SIRI values were all positively correlated with FH density (number of biological parents and grandparents with AUD/SUD). These novel data are the first to identify an association between family history of AUD/SUD and increased circulating leukocytes, which is likely indicative of immune dysregulation in FH+ young adults prior to onset of AUD/SUD. Additional studies are warranted to characterize the functional relevance of the observed immune cell composition in FH+ individuals, but the notion that inexpensive and widely available blood tests may help identify addiction risk could be transformative.