Successor representation has been proposed as a reinforcement-learning strategy that may support nuanced forms of habitual behavior, making it a candidate mechanism for mental health conditions involving habitual control, including addiction. However, the study notes that existing paradigms used to assess habits in humans cannot detect the use of SR. Many such paradigms are also conducted in contexts unrelated to the disorder under investigation, which may help explain inconsistent evidence for a proposed shift from goal-directed to habitual behavior in addiction. Behavioral results supported the involvement of a reduced, random-policy SR-like strategy in both risk groups, but high-risk drinkers did not differ from low-risk drinkers in their overall use of that strategy.

The reported group-related finding concerned performance in the alcohol-related context: both groups appeared to rely less on the reduced SR-like strategy and more on model-free control. The results therefore do not support the interpretation that high-risk drinkers categorically favor a more rigid strategy across every component of the task. The authors interpret the pattern as evidence that an adaptive, resource-efficient decision-making strategy may be selectively downregulated in substance-related settings.

The study highlights the possible importance of contextual modulation and of distinguishing nuanced decision strategies when examining habitual and goal-directed behavior in addiction. As a comparison between high- and low-risk drinking groups, however, the analysis does not show that individual participants shifted from goal-directed to habitual behavior over time. It also does not establish that model-free control causes high-risk drinking, and the supplied findings report neither clinical outcomes nor treatment effects.

Subject of Research: Computational decision strategies associated with high-risk drinking in alcohol-related contexts

Article Title: The successor representation in high-risk drinking and alcohol-related contexts

Article References: Musial, M. P. M., Hall-McMaster, S., Shimomura, K., Kato, A., Bode, E. L., Grundmann, C. C., Ebrahimi, C., Morita, K., Gershman, S. J., Endrass, T., & Schlagenhauf, F. (2026). The successor representation in high-risk drinking and alcohol-related contexts. PLOS Computational Biology, 22(10), e1014873. https://doi.org/10.1371/journal.pcbi.1014873

Image Credits: AI Generated

DOI: 10.1371/journal.pcbi.1014873

Keywords: successor representation, high-risk drinking, alcohol-related contexts, model-free control, reinforcement learning, habitual behavior, goal-directed behavior, decision-making, context dependence, addiction, successor, representation

Researchers surveyed students in Years 3 through 6, including interns in Year 6, with a content-validated 29-item questionnaire. It assessed knowledge of addictive drugs, opioid-related clinical knowledge, legal awareness and students’ perceptions of curriculum coverage. Adequate knowledge was defined before analysis as a composite score of at least 9 out of 12, or 75%.

Multiple linear regression was used to identify predictors of knowledge. As a single-centre, cross-sectional study, the survey did not track learning over time or test whether a particular educational intervention improved students’ competence. Median composite scores rose across the later stages of the degree: 3 out of 12 for Year 3 students, 4 for Year 4, 4.5 for Year 5 and 5 among interns in Year 6.

The respective interquartile ranges were 2–6, 2–6, 3–6.5 and 3–7. Differences among Years 3 through 5 were minimal, while scores were higher in the intern year. Even then, the intern-year median remained below the predefined 9-point threshold.

The survey therefore shows a measured association between academic stage and knowledge scores, but it does not identify what produced the differences. The opioid-specific questions exposed gaps in recognizing an urgent overdose sign and identifying first-line treatment. Correctly identifying naloxone as the first-line treatment for opioid overdose was achieved by 56.1% of students, while 44.2% recognized slow or shallow breathing as the primary overdose sign.

These percentages describe responses to a questionnaire rather than clinical behaviour during an emergency. They indicate that substantial proportions of respondents did not answer these two knowledge items correctly. Students’ perceptions of the curriculum added detail to the low questionnaire scores.

The area most frequently reported as missing was the pharmacist’s role in addiction recovery, selected by 40.6% of respondents, followed by legal aspects of Saudi drug regulations at 37.7%. Pharmacological management of substance-use disorders was reported as missing by 33.9%, and 40.0% described patient-counselling skills as inadequately covered. Overall, students reported deficiencies in addiction recovery, patient counselling, pharmacological management and Saudi drug regulations.

The authors said the observed gaps broadly resembled deficits reported internationally, but the supplied findings do not provide direct international comparisons from this survey. The sample was confined to students at a single Saudi university, and its cross-sectional design could not determine whether academic-stage differences reflected coursework, clinical experience or other factors associated with progression through the program. The results also cannot determine whether comparable patterns occur in other institutions, regions or professional programs.

The authors therefore called for confirmation through multi-institution and international studies. Convergence between the questionnaire results and students’ assessments of missing content gives the study a specific curricular dimension. At the same time, students reported several of these topics as absent or inadequately covered.

The study did not test a revised curriculum or evaluate an educational intervention, so it cannot establish whether any specific change would improve learning or clinical competence. Instead, the findings support the authors’ call for integrating addiction-related competencies longitudinally into the Doctor of Pharmacy curriculum at King Abdulaziz University and comparable programs. The present study does not demonstrate clinical benefits, changes in prescribing behaviour or effects on patient outcomes.

Its defensible conclusion is narrower: among 310 students at one Saudi institution, measured addiction and opioid knowledge was limited, and students reported gaps in several related areas of the curriculum.

Subject of Research: Cross-sectional assessment of addiction and opioid knowledge among Saudi pharmacy students

Article Title: Addiction and opioid knowledge gaps among pharmacy students at King Abdulaziz University, Saudi Arabia: a cross-sectional study with implications for global curriculum review

Article References: Baamer, R. (2026). Addiction and opioid knowledge gaps among pharmacy students at King Abdulaziz University, Saudi Arabia: a cross-sectional study with implications for global curriculum review. BMC Medical Education. https://doi.org/10.1186/s12909-026-10668-y

Image Credits: AI Generated

DOI: 10.1186/s12909-026-10668-y

Keywords: pharmacy education, addiction knowledge, opioid overdose, naloxone, King Abdulaziz University, Saudi Arabia, curriculum gaps, student competency, cross-sectional survey, Addiction, opioid, knowledge

The convergence is occurring against a widening public-health backdrop. The review reports that an estimated 2.4 million people aged 12 or older in the United States reported past-year methamphetamine use in 2024, while self-reported concurrent methamphetamine and fentanyl use nearly doubled between 2011 and 2017. Fentanyl positivity among methamphetamine-positive urine samples rose from 0.9% to 7.9% between 2013 and 2018. Because methamphetamine is sometimes intentionally mixed with fentanyl, people who believe they are using only a stimulant may be exposed to a potent opioid without knowing it, increasing the danger of overdose and other adverse outcomes.

Methamphetamine and fentanyl act through distinct but overlapping systems. The stimulant is highly lipophilic, enters the brain rapidly and has a substantially longer half-life than cocaine—about 12 hours in the cited pharmacological literature. It acts at trace amine-associated receptor 1 and disrupts vesicular monoamine transporter 2, producing marked increases in extracellular dopamine, noradrenaline and serotonin. These changes in mesocorticolimbic circuitry support reinforcement, cue learning and incentive salience. Repeated exposure can also sensitize behavioral responses, meaning that a fixed dose produces progressively stronger locomotor effects, and can alter brain systems associated with reward seeking and anxiety-like states.

Fentanyl, meanwhile, is a highly lipid-soluble opioid that binds with high efficacy to μ-opioid receptors. These Gi/o-coupled receptors reduce neuronal excitability and neurotransmitter release when activated. In the ventral tegmental area, where dopamine neurons project toward the nucleus accumbens and other reward-related regions, μ-opioid receptor activation on inhibitory GABAergic neurons can disinhibit dopamine cells. Acute fentanyl exposure therefore increases dopaminergic activity in circuits that participate in reward. Its high potency, rapid onset and relatively long half-life—three to seven hours—help explain why it can support both powerful reinforcement and substantial dependence.

Rodent studies show that both drugs readily become highly reinforcing. Methamphetamine-taking animals escalate their intake over repeated sessions, develop persistent preference for drug-paired environments and reinstate drug seeking after exposure to drug cues, stressors or a priming injection. Chronic exposure also produces withdrawal-related reductions in motivation for natural rewards and increases in anxiety-like behavior. Fentanyl produces a similar broad addiction profile: rodents rapidly acquire conditioned preference for fentanyl-paired locations, self-administer escalating amounts and reinstate seeking after extinction. Withdrawal from either drug can include stress, agitation, anxiety-like symptoms, anhedonia and reduced motivation, potentially supporting continued use through negative reinforcement as well as positive reinforcement.

The direct evidence for combined exposure points to a behavioral interaction rather than merely the sum of two separate drug effects. In one conditioned place-preference experiment in adult male rats, doses of methamphetamine and fentanyl that were ineffective when given separately successfully produced preference and reinstatement when administered together. In concurrent-access studies, rats adjusted their responses according to the relative reinforcing value of methamphetamine and fentanyl, showing that the drugs could function as substitutes under some conditions. Another study found that rats did not reduce their inter-infusion interval as fentanyl doses increased during combined self-administration to the same degree seen with fentanyl alone, resulting in greater overall intake. These findings indicate changes in reinforcement, but their magnitude depends on dose and experimental schedule.

Combined exposure may also join the motivational pathways associated with the two drugs. Rats trained to self-administer methamphetamine and fentanyl through concurrent access later showed cross-reinstatement after extinction: fentanyl-associated cues or fentanyl priming injections restored methamphetamine seeking, while methamphetamine-associated cues or priming injections restored fentanyl seeking. The result suggests that repeated co-exposure can create overlapping associations, allowing one substance or its cues to trigger pursuit of the other. The experiment was conducted in rats, and the finding cannot by itself establish how the same processes operate in human relapse.

Neurochemical findings are similarly intriguing but not yet conclusive. Methamphetamine-fentanyl self-administration produced significant reductions in dopamine release and reuptake in the nucleus accumbens, with a more pronounced hypodopaminergic state in males exposed to the combination than in animals receiving methamphetamine alone. Measurements were made roughly 22 hours after the final self-administration session, outside the acute drug effects, suggesting compensatory adaptations after repeated exposure rather than the immediate neurochemical response to intoxication. The contrast with evidence that acute μ-opioid receptor activation increases dopamine is not necessarily contradictory: intoxication and withdrawal-like states may involve different phases of mesolimbic signaling. A state that feels highly rewarding during exposure may therefore be followed by diminished responsiveness to ordinary rewards.

μ-opioid receptors are the leading candidate mechanism because they sit at the intersection of the two drugs’ reward circuitry. Blocking these receptors with naltrexone attenuates methamphetamine-induced conditioned place preference, behavioral sensitization and cue-induced craving in animal studies, while genetic deletion reduces methamphetamine sensitization in mice. Human studies likewise found that naltrexone reduced cue-induced craving and subjective hedonic responses to methamphetamine. Opioid antagonism also reduces methamphetamine-related drug seeking in some rodent paradigms. However, these experiments did not directly test fentanyl-methamphetamine combinations. Studies with morphine or heroin offer additional support for stimulant-opioid interactions, but their pharmacology differs from fentanyl, and sequential exposure cannot establish the consequences of simultaneous use.

Human reports add another dimension but remain limited by variable doses, routes and timing. People who use psychostimulants with opioids often describe the combination as balancing two drugs: the stimulant may counter opioid-related sedation, while the opioid may reduce stimulant-associated anxiety or restlessness. Such accounts suggest that both enhanced pleasure and relief from aversive states can motivate co-use. Clinical studies also associate stimulant-opioid use with more anxiety, depression, impulsivity, anhedonia and psychotic symptoms than stimulant use alone, but those findings do not prove that withdrawal from the combination is more severe than withdrawal from either constituent drug. Direct evidence on withdrawal after repeated methamphetamine-fentanyl exposure is particularly sparse.

The review’s central conclusion is therefore both promising and restrained: existing evidence supports a synergistic addiction potential for concurrent methamphetamine and fentanyl use, but the specific mechanism and full behavioral consequences remain under-examined. The most important research gaps are systematic dose-response comparisons, experiments separating simultaneous from sequential exposure, direct characterization of spontaneous and precipitated withdrawal, and studies that manipulate μ-opioid signaling during combined exposure. Measuring neural activity alongside dopamine release would also help distinguish changes in ventral tegmental circuit function from downstream alterations in the nucleus accumbens. Until those studies fill the gaps, the evidence supports concern about the combination, not a complete causal map of how it alters the human brain or whether every dose and pattern of use produces the same effect.

Subject of Research: Behavioral and neurobiological consequences of concurrent methamphetamine and fentanyl use

Article Title: Separate and concurrent use of methamphetamine and fentanyl: behavioral and neurobiological consequences

Article References: Madden, J. T., Clark, B. J., Hamilton, D. A., & Pentkowski, N. S. (2026). Separate and concurrent use of methamphetamine and fentanyl: behavioral and neurobiological consequences. Frontiers in Behavioral Neuroscience, 20, Article 1966221. https://doi.org/10.3389/fnbeh.2026.1966221

Image Credits: AI Generated

DOI: 10.3389/fnbeh.2026.1966221

Keywords: methamphetamine, fentanyl, polydrug use, addiction, dopamine signaling, μ-opioid receptors, conditioned reward, drug seeking, rodent studies, withdrawal, Separate, concurrent

The study, led by Akgün Yeşiltepe of Munzur University and Canan Demir Barutcu of Burdur Mehmet Akif Ersoy University, surveyed 296 undergraduate nursing students during the 2022–2023 academic year. Participants completed a sociodemographic information form along with two validated instruments: the Smartphone Addiction Scale and the Nomophobia Questionnaire. The researchers then applied a battery of statistical techniques, including Pearson correlation, multiple linear regression, confirmatory factor analysis, and structural equation modeling, to untangle the relationships between problematic phone use and the fear of being disconnected.

The headline result is striking. Smartphone addiction was positively and moderately correlated with nomophobia, with a correlation coefficient of r = 0.544 and a p-value below 0.001, meaning the association is extremely unlikely to be a statistical fluke. In plain terms, students who scored higher on measures of compulsive smartphone use also reported markedly greater anxiety at the prospect of losing phone access. The multiple linear regression model was statistically significant and explained 47.0% of the variance in nomophobia scores, an unusually high figure for behavioral research, where models often account for far less.

Within that regression model, higher smartphone addiction scores significantly predicted higher nomophobia levels, with an unstandardized coefficient of B = 1.109, a standardized coefficient of β = 0.493, and p < 0.001. This means that even after accounting for other variables, smartphone addiction remained the dominant predictor of nomophobia in the sample. But the model also revealed a supporting cast of significant predictors that the researchers say deserve attention in their own right.

Age emerged as a significant predictor, with B = 2.107, β = 0.138, and p < 0.05, suggesting that older students in the sample reported higher nomophobia. Monthly income also played a role, with B = 0.002, β = 0.211, and p < 0.001, indicating that students with higher monthly income tended to report greater nomophobia, possibly because greater financial means facilitate more extensive smartphone and data use. Daily sleep duration was another significant factor, with B = 1.850, β = 0.094, and p < 0.05, hinting at a relationship between sleep patterns and phone-related anxiety that the authors say warrants further study.

Social media usage characteristics also mattered. The researchers found that use of specific platforms, namely Facebook, Instagram, and Twitter, were significant predictors of nomophobia among the students. This suggests that it is not merely the device itself but the social ecosystems it hosts that feed the fear of disconnection. For nursing students, who often rely on digital communication for coordination with peers and clinical staff, the stakes of staying connected may be particularly high.

To test the robustness of their findings, the researchers turned to structural equation modeling, a technique that allows researchers to test theoretical models rather than just correlations between individual variables. The SEM results further supported the relationship, indicating that smartphone addiction positively and significantly predicted nomophobia with β = 0.62 and p < 0.001, and explained 38% of its variance with R² = 0.38. Confirmatory factor analysis was used to verify that the measurement instruments performed as intended in this specific population, adding methodological weight to the conclusions.

The authors frame nomophobia not as an isolated quirk but as a potential signal of technology-related psychological vulnerability. Nursing students may be particularly susceptible due to a combination of academic demands, frequent smartphone use, and heavy reliance on digital communication. The concern is not trivial: nomophobia has been linked in prior research to anxiety, sleep disturbance, and reduced academic performance, and nursing students face the added pressure of preparing for a profession where attention and emotional regulation are literally matters of patient safety.

The practical implications are significant for nursing education settings. The authors suggest that early identification of problematic smartphone use, combined with educational interventions addressing healthy smartphone habits, may help reduce nomophobia and support students’ well-being. Such interventions could include digital literacy training, awareness campaigns about the signs of compulsive phone use, and structured guidance on balancing screen time with clinical and academic responsibilities. Because the study is cross-sectional, it cannot prove causation; it is possible that nomophobia drives compulsive use just as much as the reverse, or that both stem from a common underlying vulnerability such as anxiety proneness.

The study was approved by the Mehmet Akif Ersoy University non-interventional clinical research ethics committee, and all participants gave informed consent electronically before completing the online questionnaire. The authors declare no competing interests and received no external funding. As smartphones continue to weave themselves into every corner of professional and personal life, the researchers argue that understanding the line between healthy connectivity and harmful dependence is becoming a core competency for the next generation of healthcare workers, not just a personal habit to be managed quietly.

Understanding why these findings matter requires a closer look at what nomophobia actually measures. The term, a shorthand for “no-mobile-phone phobia,” describes the situational anxiety that arises when a person cannot access their phone, whether because the battery has died, the device has been forgotten, or network coverage is unavailable. Researchers typically assess it across several dimensions, including fear of losing communication, losing connectedness, being unable to access information, and giving up convenience or the ability to check in with others. In the present study, the Nomophobia Questionnaire captured these dimensions, and the confirmatory factor analysis step was important precisely because it verified that the questionnaire’s underlying structure held together in this particular Turkish nursing student sample, rather than simply assuming that instruments validated elsewhere would behave identically here.

The distinction between smartphone addiction and nomophobia, while related, is worth drawing out. Smartphone addiction, as measured by the Smartphone Addiction Scale, generally reflects patterns of compulsive use: preoccupation with the device, tolerance effects, withdrawal-like feelings, and interference with daily functioning. Nomophobia, by contrast, is more specifically an anticipatory or situational anxiety about disconnection. The moderate correlation of r = 0.544 observed here suggests substantial overlap between the two constructs but not identity, meaning that a student can score high on compulsive use without necessarily experiencing severe separation anxiety, and vice versa. This partial independence is one reason the regression approach was informative: it allowed the researchers to isolate how much of nomophobia is uniquely attributable to addictive use patterns once demographic and behavioral factors were held constant.

The demographic predictors deserve careful interpretation. The positive association between age and nomophobia, for instance, runs counter to a common assumption that younger students, having grown up entirely within the smartphone era, would be the most attached to their devices. One plausible reading is that older nursing students face accumulating responsibilities, including clinical placements, family obligations, and financial pressures, that make constant availability feel more consequential. Similarly, the income finding, in which higher monthly income predicted greater nomophobia, may reflect the fact that students with more disposable income can afford premium data plans, newer devices, and continuous connectivity, making disconnection both more likely to be noticed and more disruptive when it occurs.

The sleep duration finding is particularly intriguing given the broader literature. Prior research has repeatedly documented bidirectional relationships between problematic smartphone use and sleep: late-night scrolling delays sleep onset, blue light exposure suppresses melatonin, and sleep deprivation in turn weakens the self-regulation capacities that normally restrain compulsive checking. The present study’s finding that daily sleep duration significantly predicted nomophobia, with a positive coefficient suggesting that longer sleepers reported somewhat higher nomophobia in this sample, complicates the simple narrative that phone use merely erodes sleep. It may instead reflect students using extended sleep as recovery from the fatigue of constant connectivity, or it may signal that the relationship between rest and phone-related anxiety is more nuanced than commonly assumed. The authors themselves flag this as an area warranting further study, and the cross-sectional design means no causal direction can be established.

The platform-specific findings also merit attention. That Facebook, Instagram, and Twitter use each emerged as significant predictors suggests that the architecture of social platforms, with their notification systems, algorithmic feeds, and social validation loops, may cultivate the very attachment patterns that underlie nomophobia. For nursing students, whose professional socialization increasingly occurs through digital channels, including group chats for clinical scheduling, online learning platforms, and professional networking, the boundary between necessary and problematic use becomes genuinely difficult to draw. A student cannot simply disconnect without risking professional consequences, which may amplify the anxiety associated with unavailability.

Methodologically, the use of structural equation modeling alongside multiple regression strengthens the study’s contribution. Whereas regression treats predictors as independent contributors to an outcome, SEM allows researchers to specify and test a theoretical structure, in this case one in which smartphone addiction functions as a latent driver of nomophobia. The convergence of the two approaches, with the regression model explaining 47.0% of variance and the SEM model explaining 38%, provides internal consistency, though the difference between the figures reflects the different variables and constraints each model incorporates. The very high proportion of variance explained in the regression model is notable for behavioral research, where models explaining 20 to 30 percent of variance are common, and suggests that the measured variables capture much of what drives nomophobia in this population.

Several limitations frame how these results should be generalized. The sample consisted of 296 nursing students at Turkish universities, and cultural context, nursing curricula structure, and institutional norms around phone use during clinical placements may differ substantially elsewhere. The cross-sectional design precludes causal inference, and self-report instruments are vulnerable to response biases, including social desirability and inaccurate self-assessment of usage. Longitudinal follow-up would help clarify whether smartphone addiction precedes nomophobia, follows from it, or whether both emerge from shared vulnerabilities such as trait anxiety or low emotional regulation. Nonetheless, the consistency of the findings across analytical methods, combined with the careful psychometric validation, makes this study a useful reference point for educators designing interventions. Screening for problematic smartphone use during nursing education, the authors suggest, could identify students at risk before phone-related anxiety interferes with clinical performance or well-being, an approach that aligns with growing interest in behavioral health support within health professional training programs.

Subject of Research: Smartphone addiction, social media use, and nomophobia among Turkish nursing students: a cross-sectional study

Article Title: Smartphone addiction, social media use, and nomophobia among Turkish nursing students: a cross-sectional study

Article References: Yeşiltepe, A., & Demir Barutcu, C. (2026). Smartphone addiction, social media use, and nomophobia among Turkish nursing students: a cross-sectional study. BMC Nursing. https://doi.org/10.1186/s12912-026-05265-9

Image Credits: AI Generated

DOI: 10.1186/s12912-026-05265-9

Keywords: Smartphone, addiction, social, media, nomophobia, Turkish, nursing, students, cross-sectional, scientific research

The technological core of this shift lies in the ability to measure behavior and neural activity with unprecedented temporal, chemical, and spatial resolution. Genetically encoded biosensors can now report the release of neuropeptides such as opioids in living tissue, a capability highlighted in a 2024 Nature Neuroscience study that the editorial cites as emblematic of the new toolkit. Fiber photometry systems, paired with open-source analysis software such as the Python library Pyfiber, allow researchers to integrate operant behavior with real-time fluorescence signals, linking moment-to-moment neural dynamics to the choices animals make. Optogenetic approaches have matured to the point where researchers can mimic aspects of drug action in defined circuits, dissecting the dopamine-dependent core of addiction with cell-type specificity. Automated behavioral tracking and computational analyses complete the picture, replacing coarse endpoints such as total drug consumed with rich, continuous streams of data that capture how brain activity and behavior shape one another over time.

That temporal dimension matters because, as the editors emphasize, addiction is not a static state. It is a dynamic sequence of processes, including drug use, seeking, withdrawal, craving, and relapse, each shaped by internal states and external cues and expressed in environments full of competing rewards. Conventional experimental designs, which typically sample behavior at isolated time points, can miss exactly the transitions that matter most clinically: the moment a cue triggers craving, the slow emergence of social withdrawal during abstinence, or the drift from controlled use to compulsive consumption. Continuous monitoring and increasingly sophisticated behavioral models offer a way to capture those processes. Within the Research Topic, Mathis and colleagues introduce a novel, automated, and unbiased approach to characterizing the emergence of social deficits during morphine abstinence in mice. By providing long-term longitudinal and quantitative assessment of social behavior, the work reveals dimensions of withdrawal that conventional assays simply do not register, illustrating how better phenotyping can expose previously invisible features of the addicted state.

Human studies in the collection follow the same logic of dynamic, quantified measurement. Yilmazer and colleagues investigate whether new neurophysiological biomarkers can track gambling disorder, focusing specifically on theta cordance, an electroencephalographic measure. Their approach exemplifies how analytical methods such as Granger Causality, which tests whether activity in one brain region predictively influences activity in another, can be leveraged to move diagnosis beyond self-report and toward objective, physiology-based indicators. The editors suggest that such biomarkers could eventually improve diagnosis and guide the implementation of treatment, a prospect that resonates far beyond gambling. If neural signatures can index the severity and trajectory of a behavioral addiction, the same logic may apply across the spectrum of substance use disorders, where clinicians currently lack reliable tools for predicting who will relapse and when.

Yet the editors are careful to temper enthusiasm with a caution: methodological innovation and basic discovery alone will not revolutionize clinical practice. More detailed behavioral phenotyping does not automatically yield mechanistic understanding, and identifying patterns of neural circuit activity that correlate with addictive states does not reveal the core cognitive disruptions that seed maladaptive behavior. The central challenge, they argue, is determining which measurements meaningfully explain the emergence and persistence of maladaptive behaviors, and translating that understanding into new diagnostic and prognostic tools. Correlation is not explanation, and a flood of high-resolution data is only as valuable as the questions it is used to answer. This framing sets the intellectual agenda for the rest of the collection, which repeatedly asks not just what the brain is doing during addiction, but which of those measurements actually matter.

Several contributions point toward a redefinition of addiction itself, shifting from substance-centered categories to shared mechanisms. Insalaco and colleagues examined longitudinal changes in physiological and mental-health functioning among individuals receiving treatment for substance use disorders, underscoring the importance of tracking addiction-related outcomes over time. Their findings offer insight into the dynamics of substance use disorder as a clinical condition and could be used to tailor therapeutic interventions at different points in its trajectory, rather than applying the same strategy regardless of stage. Allache and colleagues go further, proposing craving as a potential transdiagnostic marker for both substance and behavioral addictions. The implication is provocative: instead of defining addiction by the substance or behavior involved, clinicians and researchers might orient diagnosis around core mechanisms shared across different forms of pathological behavior, unifying disorders that the current diagnostic framework keeps separate.

The reach of addiction biology may extend even beyond the brain. Tyrode and colleagues suggest that gut microbiota signatures could be predictive of both cocaine use and binge eating disorder, a viewpoint that pushes addiction research into peripheral biological systems and reinforces the idea that seemingly distinct disorders may share biological fingerprints. The gut-brain axis has become one of the most active frontiers in neuroscience, and its appearance in addiction research signals how far the field has traveled from a purely dopaminergic account of reward. Alongside this, a review by O’Connor revisits the controversial concept of food addiction in the context of GLP-1-based obesity pharmacotherapy, the class of drugs that has transformed treatment of metabolic disease. By examining the overlap between neural pathways regulating feeding and those implicated in substance use, the review illustrates both the value and the limitations of identifying shared reward mechanisms across disorders. Crucially, it also demonstrates how societal motives must be considered in the evolution of the addiction concept, a reminder that scientific categories are shaped as much by culture as by data.

What emerges from the collection as a whole is a convergence, despite contributions spanning animal and human research, experimental and clinical investigations, and multiple subtypes of addiction-like behavior, on a single message: understanding addiction requires studying the dynamic interactions between biological mechanisms, behavior, and context. The editors highlight three complementary shifts now reshaping the field, moving from static measures to dynamic trajectories, from isolated brain circuits to interacting biological systems, and from substance-centered definitions to mechanistically informed models of maladaptive behavior. They also stress nuance: food and drugs engage overlapping motivational systems, but feeding is embedded within metabolic regulation and physiological homeostasis, so problematic eating necessarily manifests with both overlapping and unique underpinnings relative to psychoactive drugs. Not every reward-based behavior leads to addiction, and true progress will require acknowledging the complex interplay of environmental, cognitive, neurochemical, and genetic predispositions that seed addiction in certain individuals rather than in others.

The editorial closes with a formulation that may define the next decade of the field. The future of addiction research, the authors write, will not be defined solely by the ability to measure more molecules, record more neurons, or quantify more behavioral dimensions; progress will depend on using those technologies to ask better questions and to improve analysis and interpretation. Rethinking addiction, they suggest, does not necessarily mean expanding its definition. It may instead mean refining it: identifying when, why, and for whom a behavior becomes persistent, maladaptive, and difficult to control. That conceptual refinement, supported by increasingly sophisticated technologies and integrative approaches spanning brain, body, and environment, may ultimately provide a stronger foundation for more precise diagnosis, prevention, and treatment, turning a period of methodological exuberance into a period of genuine clinical advance.

Subject of Research: Technological and conceptual advances in addiction neuroscience and the re-evaluation of substance use disorders

Article Title: Editorial: Rethinking addiction: technological advances, mechanistic insights, and the re-evaluation of substance use disorders

Article References: Darcq, E., Howe, W. M., Nicolas, C., & Mathis, V. P. (2026). Editorial: Rethinking addiction: technological advances, mechanistic insights, and the re-evaluation of substance use disorders. Frontiers in Behavioral Neuroscience, 20, Article 2009605. https://doi.org/10.3389/fnbeh.2026.2009605

Image Credits: AI Generated

DOI: 10.3389/fnbeh.2026.2009605

Keywords: addiction, substance use disorders, behavioral neuroscience, biosensors, craving, gambling disorder, gut microbiota, food addiction, GLP-1, neural circuits, biomarkers, relapse

The research, published in the International Journal of Mental Health and Addiction, tracked 1,205 Chinese college students across three waves of assessment, spaced six months apart, from November 2024 to December 2025. At each wave, participants completed online questionnaires measuring their problematic use of short-form video (PUSV), depressive symptoms, and anxiety symptoms, alongside demographic variables. The team, led by Guangyu Sun of South China Normal University, then applied sophisticated statistical techniques—growth mixture modeling and parallel-process latent class growth analysis—to identify distinct trajectories of symptom change over time, rather than treating all students as a homogeneous group.

The results revealed a striking pattern. For depressive symptoms alone, three independent trajectories emerged: a low-decreasing group whose symptoms started low and improved, a moderate-increasing group whose symptoms worsened from a moderate starting point, and a high-increasing group whose symptoms began high and climbed further. Anxiety symptoms followed the same three-profile structure. Crucially, the researchers found that students with higher baseline levels of problematic short-form video use were significantly more likely to belong to the moderate-increasing and high-increasing trajectory groups for both types of symptoms.

What makes this study particularly compelling is its parallel-process analysis, which examined how depressive and anxiety symptoms co-developed within the same individuals over time. When the researchers modeled joint trajectories—tracking the simultaneous evolution of both symptom types—three profiles again emerged: low-decreasing, moderate-increasing, and high-increasing. Once again, higher baseline PUSV predicted membership in the worsening groups. This suggests that problematic short-form video use isn’t just linked to one type of internalizing symptom; it appears to differentiate students whose depression and anxiety co-escalate together from those whose symptoms remain stable or improve.

The findings extend a growing body of evidence on the mental health impacts of short-form video platforms. Previous research has shown that viewing personalized video clips recommended by TikTok activates the default mode network and ventral tegmental area—brain regions associated with self-referential thought and reward processing. Other studies have documented an imbalance between goal-directed and habitual systems in problematic short-form video users, suggesting that the behavior becomes increasingly automatic and less under deliberate control. A 2025 systematic review and meta-analysis in the Journal of Medical Internet Research further confirmed associations between short-form video use and poorer mental health outcomes.

Several theoretical frameworks help explain these dynamics. The Interaction of Person-Affect-Cognition-Execution (I-PACE) model proposes that specific internet-use disorders develop through interactions among individual vulnerabilities, emotional states, cognitive processes, and executive control. The compensatory internet use model, meanwhile, suggests that people turn to online behaviors to escape negative emotions—a pattern that could create a vicious cycle in which short-form video use temporarily relieves distress but ultimately deepens it. The new study’s longitudinal design strengthens the case that problematic use may actively contribute to symptom escalation rather than simply reflecting it.

The co-development of depression and anxiety is itself well documented. Comorbidity research spanning two decades has shown that these conditions frequently occur together, particularly in young people, and time-varying dynamics studies have demonstrated how co-occurring depressed mood and anxiety influence each other over time. By identifying joint trajectories, the new research captures this co-escalation in a way that single-symptom analyses cannot, revealing that the same behavioral risk factor—problematic short-form video use—may push students toward worsening profiles across both symptom domains simultaneously.

The practical implications are significant. The authors suggest that early screening for problematic short-form video use could help identify college students at risk for developing or worsening internalizing symptoms before they escalate. Interventions targeting PUSV—whether through self-control training, cognitive bias modification, or behavioral alternatives such as physical exercise—might then prevent or alleviate depressive and anxiety symptoms. Previous intervention research has shown promise: a cluster randomized controlled trial demonstrated that short video-based mental health interventions could reduce depressive symptoms in students, while a table tennis intervention study found that physical activity reduced short video addiction through chained effects on cognitive bias and self-control.

Limitations remain. The study relied on self-report questionnaires, which may be subject to reporting biases, and the sample consisted exclusively of Chinese college students, raising questions about generalizability to other populations and cultural contexts. The three-wave design, while stronger than cross-sectional studies, still cannot definitively establish causation. Nevertheless, the consistency of the findings across independent and joint trajectory analyses, and the prospective prediction from baseline PUSV to later symptom trajectories, provides compelling evidence that how students engage with short-form video matters for their mental health futures.

As short-form video applications continue their global proliferation, the study offers a timely warning: the mental health consequences of these platforms may not be immediately visible but can unfold gradually over months. For the millions of young people worldwide who use these apps daily, the message is clear—problematic engagement with the endless scroll may be quietly shaping not just how they feel today, but how their symptoms will develop over the year ahead. Early recognition and intervention, the researchers argue, may be key to breaking that trajectory before it takes hold.

Subject of Research: A one-year longitudinal study shows problematic short-form video use predicts worsening depression and anxiety trajectories among Chinese college students.

Article Title: Problematic Use of Short-form Video Predicts Independent and Joint Trajectories of Depressive and Anxiety Symptoms: A Three-wave Longitudinal Study on Chinese College Students

Article References: Sun, G., Wang, D., & Zhang, W. (2026). Problematic Use of Short-form Video Predicts Independent and Joint Trajectories of Depressive and Anxiety Symptoms: A Three-wave Longitudinal Study on Chinese College Students. International Journal of Mental Health and Addiction. https://doi.org/10.1007/s11469-026-01749-6

Image Credits: AI Generated

DOI: 10.1007/s11469-026-01749-6

Keywords: short-form video, depression, anxiety, college students, longitudinal study, mental health, TikTok, addiction, Problematic, Short-form, Video, Predicts

The review, registered prospectively on PROSPERO and funded by the Health Research Board, followed PRISMA 2020 guidelines and searched PubMed, PsycINFO, Web of Science, CINAHL, Embase and Scopus from inception to June 2025. To be eligible, studies had to include participants aged 12 to 30, contain a comparison group of non-users or infrequent users, defined as use on no more than one to two of the past 30 days, and report at least one validated self-report measure of emotion regulation. The team prespecified three instruments: the Emotion Regulation Questionnaire, which captures cognitive reappraisal and expressive suppression; the Difficulties in Emotion Regulation Scale, known as DERS, which probes six domains including nonacceptance, goals, strategies, clarity, impulsivity and awareness; and the Cognitive Emotion Regulation Questionnaire, which covers nine adaptive and maladaptive strategies from acceptance to catastrophizing. Risk of bias was assessed with the ROBINS-E tool, and findings were synthesised narratively.

The scarcity of qualifying evidence is itself a headline. Despite cannabis being used by an estimated 23 million Europeans aged 16 to 64 in the past year, and despite around one in five users developing cannabis use disorder, only four cross-sectional studies worldwide had examined the relationship with validated emotion regulation questionnaires in this age range. Three samples were drawn from university settings and one from an online survey. Cannabis exposure was defined in several distinct ways, including the SCID-5 structured clinical interview for DSM-5, the Marijuana Problem Scale, the Cannabis Use Disorders Identification Test, and simple frequency of use. Three of the four studies were rated at high or very high risk of bias, mainly because they relied on self-reported cannabis exposure and adjusted only limitedly for confounding variables such as psychiatric comorbidity and polysubstance use.

The most statistically powerful of the included studies came from Spain. Sara Weidberg and colleagues at the University of Oviedo examined 2,762 undergraduates with a mean age of 19.5 years, comparing 318 past-month cannabis users against 2,444 infrequent users or abstainers. Users showed higher global dysregulation scores on the DERS, but the significant associations were confined entirely to women. Within the female group, differences clustered in non-acceptance of emotional responses, impulse control difficulties, reduced goal-directed behaviour and lower emotional clarity. Mediation analyses indicated that DERS scores statistically mediated the association between past-month cannabis use and emotional distress in women, with no comparable effects appearing in men. Given the enormous sample, the absence of associations in men is unlikely to reflect low statistical power and instead suggests that cannabis use and reported regulation difficulties align more strongly among women in this cohort, though the cross-sectional design prevents any conclusion about temporal direction.

The remaining studies added texture to that pattern. Mohsen Akbari and colleagues in Iran studied 144 university students divided into cannabis use disorder, problematic internet use and non-affected comparison groups, using the SCID-5 to diagnose cannabis use disorder. Cannabis users reported significantly lower cognitive reappraisal scores on the ERQ than both comparison groups, and while expressive suppression also differed across groups, the reappraisal differences appeared larger and more decisive. This emphasis on reappraisal matters theoretically, because reappraisal is widely regarded as a protective strategy associated with resilience and better mental health outcomes, whereas habitual suppression and rumination are linked to greater symptom severity in depression and anxiety. In the United States, Julia Cavalli and Adriana Cservenka assessed 852 adults with a mean age of 26.9 years and found that higher DERS scores moderated the association between recent stress and cannabis-related problems, with emotion regulation difficulties amplifying the consequences of cannabis use most strongly at higher levels of stress.

The fourth study, by Benjamin Stone in the United States, illustrates how fragile the evidence base remains. Stone examined 198 undergraduates with a mean age of 19.2 years, but only 43 participants had available cannabis-use data for the review’s analyses. Descriptive patterns suggested that students with stronger positive substance-use expectancies and heavier cannabis involvement tended to show higher DERS scores, but none of these trends reached statistical significance, and neither total DERS scores nor any of the six subscales differed significantly between users and controls. The review team re-analysed Stone’s openly available data from the Open Science Framework to obtain comparable summary statistics, a methodological nicety that shows the lengths to which the synthesis went to align reporting across studies with heterogeneous aims and definitions.

What emerges from the cross-study synthesis is a pattern of specific regulatory deficits rather than a generalised inability to manage emotions. The domains most consistently implicated were impulse control, non-acceptance of emotions, goal-directed behaviour and emotional clarity, with reduced cognitive reappraisal also reported on the ERQ. The magnitude of associations appears modest throughout, suggesting small-to-moderate relationships. This specificity fits with broader cognitive-affective models in which emotion regulation depends on core executive functions such as working memory, inhibitory control and cognitive flexibility, processes that frequent cannabis users are known to show subtle deficits in. A major meta-analysis of youth cannabis users reported small deficits in executive functioning, learning and memory that largely dissipated with abstinence, though it did not extend to emotion regulation specifically. Neuroimaging studies outside this review also report altered activation in prefrontal and anterior cingulate regions among regular users, strengthening the theoretical plausibility that regulation difficulties may stem from disruptions in control systems involved in both cognition and affect.

The review’s authors are careful to stress that these findings should be interpreted as strictly associations. It remains unclear whether emotion regulation differences precede cannabis involvement, arise from it, or reflect underlying characteristics common to both. None of the included studies examined emotion regulation in the context of polysubstance use, despite cannabis frequently co-occurring with alcohol, nicotine and stimulants in this age group. No studies reported or controlled for psychiatric comorbidity, even though depression, anxiety and attention-deficit disorders are independently associated with emotion dysregulation. No studies incorporated neurocognitive, behavioural or imaging investigations alongside the prespecified questionnaires. The reliance on cross-sectional self-report designs, variation in how cannabis exposure was defined, the absence of potency or cumulative-use data, and a dependence on university-based convenience samples further restrict generalisability. As sex differences were identified within a single large-scale study, it also remains unclear whether the female-specific pattern reflects sample-specific variation or a more generalised phenomenon requiring extensive investigation.

Even within these constraints, the association between cannabis use and specific regulation difficulties was replicated in all four studies, and the authors argue it carries potential clinical and developmental relevance. The findings are consistent with the idea that cannabis may function as a maladaptive strategy to manage distress or suppress unwanted emotions, and they point toward interventions that enhance regulatory flexibility, such as reappraisal training, mindfulness-based relapse prevention and structured emotion regulation skills programmes, as candidates for reducing reliance on cannabis during adolescence and early adulthood. The developmental focus on ages 12 to 30 captures a critical window in which both emotion regulation and substance-use behaviours are still forming, making the findings particularly relevant to prevention and early intervention. Future longitudinal and experimental studies are needed to clarify causal directions, delineate recovery trajectories following abstinence and identify moderators such as age of onset and psychiatric comorbidity. For now, the message is preliminary but pointed: cannabis use in youth appears linked not to a wholesale breakdown of emotional control, but to specific cracks in the regulatory system, and those cracks may be exactly where prevention efforts should aim.

Subject of Research: A systematic review finds that cannabis use in adolescents and young adults is associated with specific emotion regulation difficulties, particularly impulse control, goal-directed behaviour and non-acceptance of emotions, with evidence limited to four cross-sectional studies.

Article Title: Emotion regulation and cannabis use in young people: a systematic review

Article References: Fleury, R., Riaz, S., O’Higgins, F., Anih, A. N., Dooley, N., Staines, L., Healy, C., Gillan, D., Smyth, B., & Cannon, M. (2026). Emotion regulation and cannabis use in young people: a systematic review. Frontiers in Adolescent Medicine, 4, Article 1766637. https://doi.org/10.3389/fradm.2026.1766637

Image Credits: AI Generated

DOI: 10.3389/fradm.2026.1766637

Keywords: cannabis, emotion regulation, adolescence, systematic review, mental health, impulse control, young adults, addiction, Emotion, regulation, young, people

The scale of the problem is particularly stark in the United States, where alcohol use disorders alone afflict 29 million individuals and cause more than 140,000 deaths annually. Layered on top of this is the opioid crisis, which claims more than 100,000 lives every year. The COVID-19 pandemic made matters worse. Lockdowns and isolation drove excessive alcohol drinking, drug addiction, opioid overdose and death, and the emergence of so-called Long Hauler symptoms and neuroCOVID disorders has exacerbated substance use disorders as the disease transitions to endemic status. Onaivi argues that bridging the treatment gap and discovering new, more effective medications are urgent priorities that demand fresh research strategies and targets.

One of the most technically intriguing preclinical studies in the Special Issue came from North and colleagues, who examined how alcohol interacts with pregnenolone, a hormone supplement popular among people seeking cognitive and anti-aging benefits. Using male and female C57BL/6J mice, the team investigated the consequences for cerebral arteries in a scenario where humans take pregnenolone supplements while binge drinking. The results showed that pregnenolone at low concentrations synergized with alcohol to constrict the middle cerebral artery, a critical vessel supplying the brain. Remarkably, this synergism disappeared when both substances were studied at higher doses, suggesting a dose-dependent complexity in how the two compounds converge on the same vascular pathway.

Additional in vitro electrophysiological data and measurements of cerebral artery diameter provided evidence that pregnenolone and alcohol act on a common molecular route to evoke artery constriction. Specifically, both compounds inhibit large-conductance calcium- and voltage-gated potassium channels, known as BK channels, by disrupting the allosteric coupling that normally links calcium binding to channel gating. Because pregnenolone regulates several physiological processes, the study highlights that combining the supplement with alcohol may meaningfully impair brain artery function. This is particularly relevant given that alcohol use disorders occur in populations aged 65 and older, who may already be at risk for cerebrovascular ischemic conditions, making the supplement-alcohol interaction a genuine clinical concern rather than a laboratory curiosity.

A second preclinical study, by Roberts and colleagues, shifted attention to the CB2 cannabinoid receptor, a receptor increasingly recognized for its role in inflammation rather than the psychoactive effects typically associated with cannabinoid signaling. The team used conditional knockout mice with selective deletion of CB2 receptors from dopamine neurons and, in a separate group, from microglia, the resident immune cells of the brain. Motor function tests in activity monitors, wheel-running activity, rotarod performance and alcohol preference tests were used to evaluate behavioral alterations induced by alcohol, while ELISA assays measured levels of pro-inflammatory cytokines including tumor necrosis factor-alpha, interleukin-6, interleukin-1alpha and interleukin-1beta in the hippocampus.

The data revealed that cell-type specific deletion of CB2 receptors from dopamine neurons and microglia differentially altered behavioral and alcohol preference outcomes, and that this deletion enhanced alcohol-induced inflammation. Pharmacological intervention with the non-specific cannabinoid agonist WIN55212-2 reduced alcohol preference in both the conditional knockout and wild-type mice. These findings suggest that CB2 receptors modulate behavioral and immune perturbations caused by alcohol and may be exploited as a potential therapeutic target in alcohol use disorders, offering a route to treatment that avoids the psychoactive baggage of CB1 receptor targeting.

Turning to mechanisms that shape addiction across the lifespan, Crews and colleagues reviewed epigenetic regulation of microglia and neurons by proinflammatory signaling following adolescent intermittent ethanol exposure and in human alcohol use disorder. Their review centers on high mobility group box 1, or HMGB1, a cytokine-like molecule associated with brain proinflammatory signals in alcohol-induced changes. Adolescent intermittent ethanol exposure alters neuroimmune gene expression in neurons, microglia and astrocytes, increasing adult drinking and preference, anxiety and reward seeking. HMGB1 activates multiple proinflammatory receptors, including Toll-like receptors, which mediate proinflammatory gene induction. Epigenetic mechanisms of adolescent ethanol exposure have now emerged as drivers of alcohol-induced pathology in both rodents and post-mortem human alcohol use disorder hippocampus, linking adolescent drinking to lifelong signaling associated with pathological behavior and hyperkatifeia, the amplified negative emotional state that fuels addiction.

Two further reviews also focused on adolescent alcohol use. Hauser and colleagues examined how adolescent alcohol and nicotine exposure alters the adult response to alcohol, drawing on basic and clinical human research as well as preclinical rodent models, including alcohol-preferring rat lines. Their review summarized evidence that voluntary alcohol consumption and nicotine exposure during adolescence can promote alcohol consumption during adulthood, and identified mechanisms involving dopamine and cholinergic systems as potential pharmacological targets. Compounds such as varenicline, cholinesterase inhibitors, bupropion, lobeline and cytisine may reverse or prevent some of the deleterious adult changes following adolescent exposure. Getachew and colleagues, meanwhile, explored the growing importance of the bidirectional gut-brain axis, focusing on how adolescent alcohol use reshapes the gut microbiota. Dysbiosis, gut microbiome-microglia interactions and Toll-like receptor signaling suggest that crosstalk between the gut and brain may influence fetal alcohol spectrum disorder and adult alcohol use disorder, positioning the gut microbiome, nutrients and GPCR signaling as emerging therapeutic targets.

Rounding out the Special Issue, Vigorito and Chang reviewed alcohol use and the pain system, examining how nociception, nociceptive pain sensation and pain perception contribute to alcohol use, misuse and dependence. Their review covered the effects of alcohol at all levels of the pain system, from neuroimmune interactions and molecular aspects of nociception to spinal, supraspinal and affective-emotional circuits, along with maladaptive homeostasis and allostasis that drive the progression of alcohol use disorders. Taken together, the two research articles and four review articles in the Special Issue provide preclinical data and comprehensive discussion of multiple mechanisms associated with the effects of drugs and alcohol, while highlighting the treatment gaps that persist for substance use disorders.

Looking forward, Onaivi points to generative Artificial Intelligence systems as promising tools to improve individual health outcomes by streamlining diagnosis and treatment with clinical applications. While generative AI holds potential in the field of substance use disorders, caution is required as the functionalities of AI continue to evolve, as do the challenges of substance use disorders themselves. AI systems beyond ChatGPT, combined with advanced sensing and large quantitative approaches, may offer useful opportunities to identify more urgent and effective treatment medications for substance use disorders. As the research presented at the IDARS conference and captured in this Special Issue demonstrates, the path to better addiction treatment will likely require converging insights from vascular biology, neuroimmunology, epigenetics, the gut microbiome and computational science, each contributing pieces to a puzzle that has resisted simple solutions for decades.

Subject of Research: Neuroscience

Article Title: Editorial: 8th biennial international drug and alcohol research society conference 2022

Article References: Onaivi, E. S. (2025). Editorial: 8th biennial international drug and alcohol research society conference 2022. Advances in Drug and Alcohol Research, 4, Article 13706. https://doi.org/10.3389/adar.2024.13706

Image Credits: AI Generated

DOI: 10.3389/adar.2024.13706

Keywords: addiction, alcohol use disorder, substance use disorder, CB2 cannabinoid receptors, gut microbiome, epigenetics, neuroimmune signaling, pregnenolone, BK channels, artificial intelligence, Editorial, biennial

Locomotor sensitization is a cornerstone paradigm in addiction neuroscience. When an animal receives repeated doses of a psychostimulant such as nicotine, its spontaneous movement in response to the drug does not stay constant; instead, the locomotor response grows progressively stronger with each exposure. This escalation is thought to mirror long-lasting neuroadaptations in the mesolimbic dopamine system, the same circuitry that mediates craving and drug seeking in humans. Because sensitization can persist for weeks after the last dose, researchers use it as a measurable proxy for the latent brain changes that make relapse so likely. A drug that suppresses the expression of sensitization is therefore considered a candidate for reducing the neural drive behind addiction.

Agomelatine occupies a distinctive pharmacological niche. Unlike classical antidepressants that primarily target monoamine reuptake, agomelatine is a melatonergic agent: it activates MT1 and MT2 melatonin receptors while blocking serotonin 5-HT2B and 5-HT2C receptors. This dual profile underlies its antidepressant and sleep-regulating effects and has made it attractive for disorders in which circadian disruption and mood pathology overlap. Importantly for the present study, the same laboratory had previously shown that agomelatine decreases the reinforcing and neurochemical effects of cocaine in Wistar rats, raising the question of whether its anti-addiction properties extend to nicotine, a drug with a very different primary mechanism acting through nicotinic acetylcholine receptors.

To find out, the researchers turned to the nicotine locomotor sensitization paradigm, one of the most widely used behavioral screens in preclinical addiction research. In this model, rats are given repeated nicotine administrations across several days while their horizontal movement is recorded in activity monitors. The design allowed the team to separate two distinct questions: whether agomelatine changes the acute locomotor activation produced by nicotine itself, and whether it interferes with the expression of sensitization, the amplified response that emerges after repeated dosing. The distinction matters clinically, because the expression phase is thought to reflect the established neuroadaptations that persist into withdrawal and craving.

The results were clear on both fronts. When agomelatine was administered at a dose of 10 milligrams per kilogram intraperitoneally during the expression phase and during nicotine withdrawal, it attenuated the expression of locomotor sensitization induced by multiple doses of nicotine. In practical terms, rats that had been sensitized by repeated nicotine no longer showed the exaggerated locomotor response once they received agomelatine. The drug also shortened the duration of the locomotor effects and reduced overall locomotor activity after binge nicotine administration, meaning that both the intensity and the time course of nicotine’s behavioral impact were blunted.

These findings fit into a broader mechanistic picture. Nicotine’s sensitizing effects depend heavily on dopamine release in the nucleus accumbens and on glutamatergic and serotonergic modulation of ventral tegmental area neurons. By antagonizing 5-HT2C receptors, agomelatine indirectly enhances dopaminergic and noradrenergic tone in frontal regions, while its melatonergic activity may normalize circadian signaling that is disrupted in addiction. The authors note that the drug’s prior success against cocaine-induced sensitization and reinforcement, combined with the present nicotine data, suggests a convergent action on shared final pathways of psychostimulant sensitization rather than on nicotine’s specific receptor target.

The clinical context gives the result its urgency. Smoking remains the leading preventable cause of death worldwide, and current cessation pharmacotherapies, including nicotine replacement, varenicline, and bupropion, leave a substantial fraction of smokers unable to quit permanently. Because agomelatine is already approved for depression in many countries, has a known safety profile, and addresses the mood and sleep disturbances that often accompany nicotine withdrawal, a repurposing strategy is attractive. If sensitization in rodents reflects the human phenomena of craving and relapse, a drug that suppresses sensitization expression could theoretically reduce the pull of cigarette cues during abstinence.

The authors are careful, however, about the limits of the present evidence. Their conclusions state that the results support the need for further preclinical studies before proposing agomelatine for clinical trials in smoking cessation. The study was conducted exclusively in male rats, so sex differences, which are well documented in nicotine reinforcement, remain unexplored. The dose was delivered intraperitoneally, a route that does not translate directly to human oral dosing, and the behavioral endpoint was locomotion rather than drug self-administration or relapse-like behavior, which are closer analogues of human addiction.

Methodological rigor in the study was supported by ethical approval from the Institutional Animal Care and Bioethics Committee under protocols CICUAL/0003/2022 and CEI/C/IC22177015/2022, conducted in compliance with the NIH Guide for the Care and Use of Laboratory Animals. The work was funded by grants INP-2000-2040 and CI-IC092020.2, and the authors declared no competing interests. The article was received in April 2026, accepted in October 2026, and published on 13 October 2026 as an open-access contribution to BMC Pharmacology and Toxicology, making the full dataset available to the research community without paywall.

For the field of addiction pharmacotherapy, the study is a proof of concept rather than a prescription. It demonstrates that a melatonergic antidepressant with serotonergic antagonist properties can reach into the neural machinery of nicotine sensitization, a finding that invites follow-up work with self-administration models, female subjects, and withdrawal-related measures such as anhedonia and anxiety. If those experiments confirm and extend the present results, agomelatine could join a small group of repurposed psychiatric drugs being tested not for their original indication but for their ability to weaken the grip that nicotine exerts on the addicted brain.

Subject of Research: Effects of the melatonergic antidepressant agomelatine on nicotine-induced locomotor sensitization in male rats

Article Title: Agomelatine attenuates the expression of nicotine-induced locomotor sensitization in male rats

Article References: Barbosa-Méndez, S., & Salazar-Juárez, A. (2026). Agomelatine attenuates the expression of nicotine-induced locomotor sensitization in male rats. BMC Pharmacology and Toxicology. https://doi.org/10.1186/s40360-026-01260-7

Image Credits: AI Generated

DOI: 10.1186/s40360-026-01260-7

Keywords: agomelatine, nicotine, locomotor sensitization, addiction, melatonin receptors, serotonin receptors, smoking cessation, psychostimulant, preclinical study, rats, neuropharmacology, antidepressant

The first cluster of studies zeroes in on the close relationship between emotional distress and problematic digital media use. Zhou and Feng demonstrated that loneliness partially mediated the association between social anxiety and smartphone addiction in Chinese college students, hinting that socially anxious young adults may reach for their phones, in part, to cope with interpersonal disconnection. Zhu and colleagues, studying a similar population, found that negative emotions and problematic phone use went hand in hand with poorer life satisfaction and mental health. Tian and colleagues extended the picture with adolescent athletes, showing that resilience was associated with lower mobile phone addiction, an effect explained by reduced anxiety and depressive symptoms. Taken together, these findings converge on a clinically important message: problematic smartphone use is not simply a matter of excessive exposure to technology, but is often embedded in broader difficulties with affective regulation, distress tolerance, and adaptive coping.

A second group of articles emphasizes that addiction-related behaviors take shape within relational and environmental contexts that can either buffer or amplify risk. In a two-wave longitudinal study with children, Wei and Xu found that a more positive school climate predicted lower internet gaming addiction one year later, with deviant peer affiliation acting as a mediator and sensation seeking as a moderator. The results underscore the importance of school environments as potential risk or protective factors during development, a point with obvious implications for prevention programs aimed at children before gaming habits harden into compulsive patterns.

Family dynamics emerged as another powerful contextual force. Xu and colleagues reported that excessive parental psychological control was associated with greater psychological distress in Chinese university students with smartphone addiction. Intriguingly, it was inhibitory emotion regulation, rather than cognitive reappraisal, that helped explain this relationship, suggesting that maladaptive family environments may raise addiction risk not only directly but also by eroding the very self-regulatory capacities that would normally protect against compulsive behavior. Li and colleagues broadened the scope further by examining cosmetic surgery addiction in Chinese adults, finding that adverse childhood experiences, defined as a range of traumatic events before age 18, were linked to greater symptom severity, with insecure attachment and self-alienation serving as mediating factors. Although this form of addiction differs from digital or substance-related addictions, it points to the same long-term role of early adversity, disrupted attachment, and impaired self-related processes in driving compulsive, reward-seeking behavior.

The neurobiological heart of the collection comes from three complementary studies probing how reward circuitry and executive networks miscommunicate. Zhang and colleagues used resting-state functional MRI and dynamic causal modeling to compare brain connectivity in adults with tobacco use disorder against non-smokers. They found altered effective connectivity between the default mode network, an internally oriented circuit active during self-referential thought, and the central executive network, which governs working memory and cognitive control. Specifically, connectivity from the right dorsolateral prefrontal cortex and the medial prefrontal cortex was increased, and this pattern predicted heightened motivation for smoking. If confirmed in larger samples, the authors argue, these findings would support the view that addiction involves altered interactions between internally oriented and executive-control circuits, and they raise the possibility that network-level markers could eventually aid early assessment or risk stratification in clinical settings.

Sensation seeking, a trait long associated with adolescent risk-taking, received its own neural spotlight. Qianlan and colleagues examined sensation seeking, reward sensitivity, and risk adjustment in young adults facing uncertain conditions, measuring behavior alongside electroencephalographic responses. High sensation seekers adjusted more poorly to varying levels of risk and showed weaker neural responses to reward. The findings link reward-related personality traits to reduced flexibility in decision-making under uncertainty, a combination that could help explain why some young people persist in risky choices even as evidence of mounting losses accumulates. The editors note that these promising results deserve expansion with advanced neuroimaging and cognitive modeling techniques that can dissect the precise computational failures involved.

Genetics added a third layer to the mechanistic story. Emond and colleagues genotyped two dopaminergic polymorphisms, ANKK1 rs1800497, better known as Taq1A, and COMT rs4680, along with one nicotinic polymorphism, CHRNA4 rs1044396, in American children aged nine to twelve. All three variants had previously been linked to internet and video gaming addiction. The results showed that the Taq1A polymorphism, which is associated with reduced dopamine sensitivity, was related to higher problematic media use scores in these pre-adolescent children. Although replication in larger samples is needed, the study illustrates how genetic differences in reward sensitivity may quietly shape addiction vulnerability well before the transition to adolescence, potentially setting the stage for later compulsive behaviors.

Together, the mechanistic studies strongly support the core premise of the Research Topic: addiction risk in youth is best understood through the dynamic interplay of genetic predisposition, reward sensitivity, emotion regulation systems, and executive functions. Heightened reward seeking, reduced adaptability to risk, altered large-scale brain connectivity, and possible dopaminergic genetic vulnerability all describe pathways through which impulsive or compulsive behaviors may outpace still-maturing control systems. Crucially, the editors stress that these vulnerabilities are not purely biological. They are shaped by mental health status, family relationships, school context, and adverse early experiences, meaning that any account of youth addiction limited to brain or genes alone would be incomplete.

The translational value of the collection is reinforced by studies on assessment and intervention. Diaz-Guerra and colleagues validated the Executive Functions Scale for University Students, known as UEF-1, in a large sample of Cuban university students. The scale focuses on academic skills and self-regulation in Spanish-speaking populations, and the results supported its seven-factor structure, covering domains such as self-regulation, behavioral monitoring, decision-making, and emotion regulation. This contribution matters psychometrically and conceptually, because culturally appropriate tools are essential for identifying executive-function profiles relevant to addiction risk in diverse populations. Meanwhile, Haenjohn and colleagues piloted the Integrative Cognitive Neuropsychological Program for Inhibitory Control, or ICNIC, in Thai adults with substance use problems. The program combined psychoeducation, behavioral control skills, and computerized tasks aimed at improving inhibition and reducing impulsivity. Participants reported greater self-efficacy in behavioral control, although accuracy rates on visual and auditory Substance Stop Signal Tasks measuring motor inhibition to drug cues did not improve. Even with this mixed pattern, the editors suggest that gains in perceived control may emerge before measurable changes in specific inhibitory processes, meaning multifaceted approaches to cognitive control hold promise for treatment.

Finally, two contributions situate addiction within a broader developmental framework. Using a very large national sample of South Korean adolescents, Jeong and colleagues showed that earlier alcohol use and smoking predicted a later increase in addiction risk, and that smartphone overdependence interacted with substance-related behaviors. Behavioral addictions and substance-related risk behaviors, in other words, may reinforce each other over development rather than unfold in isolation. Complementing this empirical work, Lozano Wun and Luciana reviewed developmental models of addiction and argued for a dual-systems perspective in which an imbalance between reward-related systems and executive control during specific phases of adolescence, interacting with individual differences, heightens vulnerability to reward-seeking behaviors. Both developmental timing and individual differences matter: addiction risk is not static across adolescence, and future prevention efforts may need to be tailored to specific developmental windows. The editors conclude that the collection points toward operational targets for prevention and intervention, including strengthening inhibitory control and emotion regulation, promoting resilience, addressing early adverse experiences, and improving family and school environments, while future longitudinal, multimodal, and cross-cultural research will be essential to clarify causal mechanisms and translate these findings into developmentally sensitive interventions.

Subject of Research: Developmental and neurobiological mechanisms of addiction vulnerability in adolescents and young adults

Article Title: Editorial: Executive functions, reward systems, and addiction in adolescents and young adults

Article References: Passarotti, A. M., & Lee, M. (2026). Editorial: Executive functions, reward systems, and addiction in adolescents and young adults. Frontiers in Adolescent Medicine, 4, Article 1835532. https://doi.org/10.3389/fradm.2026.1835532

Image Credits: AI Generated

DOI: 10.3389/fradm.2026.1835532

Keywords: addiction, adolescence, executive functions, reward systems, smartphone addiction, tobacco use disorder, sensation seeking, default mode network, dopamine genetics, emotion regulation, developmental psychology, public health