Research News Roundup: October 16, 2025

Journal: Neuropsychopharmacology, 2025, doi: 10.1038/s41386-025-02255-4

Authors: Uri Bright, Sarah Beck, Marco Galimberti, Priya Gupta, Yu Chen, Cecilia Dao, … Joel Gelernter

Abstract:

Cannabis is one of the most commonly used drugs in the world, and use is trending alarmingly higher. We aimed to examine the genetic basis of cannabis lifetime use (CanLU) and its genetic relationships with a variety of psychiatric- and physical health-related phenotypes. We conducted a multi-ancestral genome-wide association study (GWAS) of CanLU using data from All of Us in five genetic populations. We meta-analyzed the results of EUR participants with previously published CanLU data (total effective sample size: 258,823), and conducted a set of post-GWAS analyses, including genetic correlation analysis using LDSC, local genetic correlation analysis with LAVA, Mendelian randomization (MR) to assess causality, and phenomewide association analysis. We found 11 independent variants significantly associated with CanLU, most prominently CADM2*rs7609594 (p = 7.4 × 10−20). CanLU was genetically correlated with traits related to openness to experience and risk taking, including substance use and sexual behaviors. MR demonstrated that most of these traits had a bidirectional causal relationship with CanLU, and six were locally genetically correlated with CanLU in a region that maps to CADM2. Genetic correlations sometimes differed from those previously observed for cannabis use disorder. Our results highlight the distinct genetic architecture of CanLU, and support the genetic, and biological, differentiation between CanLU and cannabis use disorder. Genetic correlations between CanLU and other risk taking- and substance use-related traits indicate a broad mutual genetic mechanism underlying these traits, and suggest involvement of CADM2. These findings provide potential targets for future prevention and intervention strategies for substance use and risk-taking behaviors.

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Journal: Drug and Alcohol Dependence, 2025, doi: 10.1016/j.drugalcdep .2025.112862

Authors: G. X. H. Liu, M. Tayebi, B. Bristow, J. Wang, Y. Lin, G. Newburn, P. Condron, … M. Scadeng

Abstract:

Methamphetamine (METH) is an addictive psychostimulant that is associated with significant physical and psychological harm. Magnetic resonance imaging (MRI) is a non-invasive imaging modality used to identify structural and functional brain changes. We conducted a systematic review to identify and appraise the existing literature on brain MRI differences associated with METH exposure. A comprehensive literature search was conducted on PubMed, Web of Science, and Scopus. Any study that evaluated the brain in people who used or had been exposed to METH using MRI were included. Data were collected on study design, participant demographics, METH use parameters, MRI acquisition details, and key findings. One hundred and eighty-one studies with 11997 participants were included in our review. Nearly all were conducted in adults/adolescents (164/181, 91 %), and most studies were cross-sectional (142/181, 78 %). Task-based functional MRI was the most common modality used (62/181, 34 %), followed by structural MRI (47/181, 26 %). Quality appraisal scores ranged from 40 – 100 % (mean 90 %). Overall, METH is associated with numerous differences in brain structure and function, including lower grey matter volume and thickness in frontal and limbic regions and lower fractional anisotropy in various white matter structures, with differences in socio-emotional functioning, decision-making and learning processes, and cognitive performance. Targeted multi-modal MRI sequences may be useful in further clarifying the brain differences associated with METH use and evaluating the use of potential therapeutic agents.

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Journal: Addictive Behaviors, 2025, doi: 10.1016/j.addbeh.2025.108501

Authors: Arwynn A. McKinty, Laura E. Hatz, Weichen Liu, Gianna Andrade, Neal Doran, & Kelly E. Courtney

Abstract:

Anxiety as a broad construct has been linked to nicotine craving, frequency of use, and relapse rates. However, there is limited research on the relationship between state anxiety and nicotine craving. This study explored the association between state anxiety and pre-cue versus post-cue craving among adults who use nicotine and tobacco products (NTPs) at different frequencies. Participants with either non-daily (n = 34) or daily (n = 80) NTP use completed a laboratory assessment including a virtual reality (VR) NTP cue-exposure paradigm and self-report assessments of state anxiety and nicotine craving. NTP use group membership was a significant predictor of pre-cue and post-cue craving, with daily NTP users exhibiting greater pre-cue (p = 0.001) and post-cue (p < 0.001) craving than non-daily users. State anxiety was positively associated with pre-cue craving (p = 0.03) but not post-cue craving. Notably, non-daily users showed a significant negative relationship between state anxiety and post-cue craving (p = 0.01). The results of this study suggest that NTP use (especially daily use), and state anxiety are more strongly associated with pre-cue craving, as opposed to post-cue-induced craving. This study provides insight into how the relationship between state anxiety and nicotine craving varies pre and post cue-exposure, which may inform treatment and intervention efforts targeting transient affective states to prevent or reduce nicotine craving.

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Journal: Brain Sciences, 2025, doi: 10.3390/brainsci15101056

Authors: Sabrina Correa da Costa, Nicholas L. Bormann, Tyler Oesterle, Michele T. McGinnis, Ming-Fen Ho, Sara A. Vettleson-Trutza, Teresa Rummans, & Mark S. Gold

Abstract:

Background: Substance use disorders (SUDs) are highly prevalent, affecting over 48.5 million Americans. Available treatments for SUD remain insufficient, and many patients do not respond to existing interventions despite adequate adherence to treatments. While novel therapies for SUD are urgently needed, the use of psychedelic drugs for the treatment of SUDs has shown promise.

Objectives: This overview of systematic reviews summarizes existing evidence on hallucinogens—serotonergic psychedelics and ketamine—for the treatment of SUD. Methods: A comprehensive search of the literature was conducted to identify relevant evidence for using serotonergic and non-serotonergic psychedelics for the treatment of SUDs. After initial screening (n = 468 studies), 62 studies were retrieved and assessed for eligibility, and a total of 16 systematic reviews were included.

Conclusions: Although preliminary, evidence suggests that the use of serotonergic and non-serotonergic psychedelics for the treatment of SUD may provide advantages over traditional therapeutics, and these compounds may eventually become part of the next generation of treatments for SUD under specific circumstances. Research with these drugs has faced significant challenges, though, and caution when interpreting results is warranted, given high risk of bias and several other methodological limitations from the studies to date. Furthermore, risks associated with these drugs are not negligible. For now, the use of psychedelic drugs for the treatment of SUDs remains experimental, and existing evidence is insufficient to support its use in clinical practice.

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