Genetic research on nicotine dependence has utilized multiple assessments that are in weak agreement.

We conducted a genome-wide association study (GWAS) of nicotine dependence defined using the Diagnostic and Statistical Manual of Mental Disorders (DSM-NicDep) in 61,861 individuals (47,884 of European ancestry [EUR], 10,231 of African ancestry, and 3,746 of East Asian ancestry) and compared the results to other nicotine-related phenotypes.

We replicated the well-known association at the CHRNA5 locus (lead single-nucleotide polymorphism [SNP]: rs147144681, p = 1.27E−11 in EUR; lead SNP = rs2036527, p = 6.49e−13 in cross-ancestry analysis). DSM-NicDep showed strong positive genetic correlations with cannabis use disorder, opioid use disorder, problematic alcohol use, lung cancer, material deprivation, and several psychiatric disorders, and negative correlations with respiratory function and educational attainment. A polygenic score of DSM-NicDep predicted DSM-5 tobacco use disorder criterion count and all 11 individual diagnostic criteria in the independent National Epidemiologic Survey on Alcohol and Related Conditions-III sample. In genomic structural equation models, DSM-NicDep loaded more strongly on a previously identified factor of general addiction liability than a “problematic tobacco use” factor (a combination of cigarettes per day and nicotine dependence defined by the Fagerström Test for Nicotine Dependence). Finally, DSM-NicDep showed a strong genetic correlation with a GWAS of tobacco use disorder as defined in electronic health records (EHRs).

Our results suggest that combining the wide availability of diagnostic EHR data with nuanced criterion-level analyses of DSM tobacco use disorder may produce new insights into the genetics of this disorder.

The aim of this study was to evaluate the vestibular system in substance addicts.

A total of 34 substance addicts were included in the study. A demographic data form, the Dizziness Handicap Inventory, the Addiction Profile Index Screening – Short Form, the Video Head Impulse Test, videonystagmography, and cervical and ocular vestibular evoked myogenic potentials tests were administered in all participants.

A statistically significant difference was found between the study group and the control group (p < 0.05) in terms of gaze, saccade, pursuit and optokinetic results in the videonystagmography test; lateral, anterior and posterior semicircular canal gain values in the Video Head Impulse Test; P1 latency, P1–N1 interlatency, P1–N1 amplitude and asymmetry values in the cervical vestibular evoked myogenic potentials test; and N1–P1 interlatency, N1–P1 amplitude and asymmetry values in the ocular vestibular evoked myogenic potentials test (p < 0.05).

As a result of our study, it was observed that the vestibular system was affected in substance addicts.

To date, the NIH Helping to End Addiction Long-term (HEAL) Initiative has funded over 1,000 projects that aim to identify new therapeutic targets for pain and substance use disorder (SUD), develop nonpharmacological strategies for pain management, and improve overdose and addiction treatment across settings. This study conducted a portfolio analysis of HEAL’s research to assess opportunities to advance translation and implementation.

HEAL projects (FY 2018–2022) were classified into early (T0–T1) and later (T2–T4) translational stages. Eleven coders used a 54-item data collection tool based on the Consolidated Framework for Implementation Research (CFIR) to extract project characteristics (e.g., population, research setting) relevant to translation and implementation. Descriptive statistics and visualization techniques were employed to analyze and map aggregate characteristics onto CFIR’s domains (e.g., outer setting).

HEAL’s portfolio comprised 923 projects (33.7% T0–T1; 67.3% T2–T4), ranging from basic science (27.1%) and preclinical research (21.4%) to clinical (36.8%), implementation (27.1%), and dissemination research (13.1%). Most projects primarily addressed either addiction (46.3%) or pain (37.4%). Implementation-related gaps included the underrepresentation of certain populations (e.g., sexual/gender minorities: 0.5%). T0–T1 projects occurred primarily in laboratory settings (35.1%), while T2–T4 projects were concentrated in healthcare settings (e.g., hospitals: 21.6%) with limited transferability to other contexts (e.g., community: 12.9%).

Opportunities to advance translational and implementation efforts include fostering interdisciplinary collaboration, prioritizing underserved populations, engaging with community leaders and policy stakeholders, and targeting evidence-based practices in nonclinical settings. Ongoing analyses can guide strategic investments to maximize HEAL’s impact on substance use and pain crises.

Impulsivity is a multidimensional trait associated with substance use disorders (SUDs), but the relationship between distinct impulsivity facets and stages of substance use involvement remains unclear.

We used genomic structural equation modeling and genome-wide association studies (N = 79,729–903,147) to examine the latent genetic architecture of nine impulsivity traits and seven substance use (SU) and SUD traits.

We found that the SU and SUD factors were strongly genetically inter-correlated (rG=0.77) but their associations with impulsivity facets differed. Lack of premeditation, negative and positive urgency were equally positively genetically correlated with both the SU (rG=.0.30–0.50) and SUD (rG=0.38–0.46) factors; sensation seeking was more strongly genetically correlated with the SU factor (rG=0.27 versus rG=0.10); delay discounting was more strongly genetically correlated with the SUD factor (rG=0.31 versus rG=0.21); and lack of perseverance was only weakly genetically correlated with the SU factor (rG=0.10). After controlling for the genetic correlation between SU/SUD, we found that lack of premeditation was independently genetically associated with both the SU (β=0.42) and SUD factors (β=0.21); sensation seeking and positive urgency were independently genetically associated with the SU factor (β=0.48, β=0.33, respectively); and negative urgency and delay discounting were independently genetically associated with the SUD factor (β=0.33, β=0.36, respectively).

Our findings show that specific impulsivity facets confer risk for distinct stages of substance use involvement, with potential implications for SUDs prevention and treatment.

Combining different pharmaceuticals may be beneficial when treating disorders with complex neurobiology, including alcohol use disorder (AUD). The gut-brain peptides amylin and GLP-1 may be of potential interest as they individually reduce alcohol intake in rodents. While the combination of amylin receptor (AMYR) and glucagon-like peptide-1 receptor (GLP-1R) agonists have been found to decrease feeding and body weight in obese male rats synergistically, their combined impact on alcohol intake is unknown.

Therefore, the effect of the combination of an AMYR (salmon calcitonin (sCT)) and a GLP-1R (dulaglutide) agonist on alcohol intake in rats of both sexes was explored in two separate alcohol-drinking experiments. The first alcohol-drinking experiment evaluated the potential of adding sCT to an ongoing dulaglutide treatment, whereas the second alcohol-drinking experiment examined the effect when adding sCT and dulaglutide simultaneously.

When adding sCT to an ongoing dulaglutide treatment, a reduction in alcohol intake was observed in both male and female rats. However, when combining sCT and dulaglutide simultaneously, an initial reduction in alcohol intake was observed in rats of both sexes, whereas tolerance towards treatment was observed. In both alcohol-drinking experiments, this treatment combination consistently decreased food consumption and body weight in males and females. While the treatment combination did not affect inflammatory mediators, the gene expression of AMYR or GLP-1R, it changed fat tissue morphology.

Further investigation needs to be done on the combination of AMYR and GLP-1R agonists to assess their combined effects on alcohol intake.

Theoretical and empirical contributions have identified insula as key in addiction. However, anatomical modifications of the insula in addictive states, and their variations across substance use disorders (SUDs), remain to be specifically explored. We therefore explored the specificities and commonalities of insula gray matter (GM) alterations in severe alcohol use disorder (sAUD) and severe cocaine use disorder (sCUD).

We explored insula GM volume through a refined parcellation in 12 subregions (six bilateral): anterior inferior cortex (AIC), anterior short gyrus, middle short gyrus, posterior short gyrus, anterior long gyrus (ALG), and posterior long gyrus (PLG). Using a linear mixed model analysis, we explored the insula volume profiles of 50 patients with sAUD, 61 patients with sCUD, and 36 healthy controls (HCs).

In both sAUD and sCUD, we showed overall insular lower volume with a right-sided lateralization effect, and a major volume deficit in bilateral ALG. Moreover, differences emerged across groups, with higher left AIC and PLG volume deficits in sCUD compared to sAUD and HC.

We offered the first joint exploration of GM insular volumes in two SUD through refined parcellation, thus unveiling the similarities and dissimilarities in volume deficit profiles. Our results bring evidence complementing prior ones suggesting the core role of the right and posterior insula in craving and interoception, two crucial processes in addiction. Left AIC and PLG group differences also show that, while insula is a region of interest in SUD, sCUD and sAUD generate distinct insular profiles, which might parallel clinical differences across SUD.