Neurofilament light chain (NfL) and glial fibrillary acidic protein (GFAP) are biomarkers for neuroaxonal damage and astroglial injury, respectively. The present study aimed to quantify NfL and GFAP as well as investigate their association with psychiatric symptoms in a sample of recreational cannabis users. Blood samples from 331 individuals with regular recreational cannabis use were collected. Serum NfL (sNfL) and GFAP (sGFAP) levels were quantified in duplicate by an ultrasensitive single-molecule array (Simoa) technology. Reference populations were used to calculate age-, BMI-, and (for GFAP) sex-adjusted Z scores. Participants completed validated psychometric instruments assessing symptoms of cannabis use disorder, alcohol use disorder, psychosis, depression, and anxiety. Mean GFAP levels were significantly lower than those in the reference population (t(330) = −6.718, p < 0.001), whereas NfL levels did not differ (t(330) = 1.3, p = 0.19). Participants with hazardous cannabis use and those screening positive for psychotic symptoms showed higher NfL levels. Psychotic symptoms were additionally associated with lower GFAP levels. NfL correlated positively with total Cannabis Use Disorder Identification Test–Revised (CUDIT-R) scores (ρ(329) = 0.12, p = 0.03) and specifically with the items “memory/concentration problems” (ρ(329) = 0.11, p = 0.04) and “time spent buying/using/recovering” (ρ(329) = 0.13, p = 0.02). In multiple regression analysis, psychotic and cannabis use disorder symptoms independently predicted higher NfL levels. No variables predicted GFAP levels. There was no association between self-reported cannabis use amount or frequency in the past 30 days and GFAP or NfL. The results provide preliminary evidence of cannabis-related neuroaxonal alterations, warranting longitudinal studies to clarify the temporal relationship between these biomarkers and cannabis use.

Substance use disorders (SUD) are chronic conditions with devastating effects on brain health, functioning, and survival. In this study, we compared brain morphometry of 2,782 individuals with SUD to 1,951 controls and assessed the topographic overlap of these differences with brain connectivity and receptor architecture. Across SUD, we identified a morphometric signature involving frontal, parietal, temporal and limbic systems that overlapped with cortical hub regions and harbored cortical and subcortical disease epicenters. Findings were highly consistent across six substances and numerous robustness and generalizability analyses. Transdiagnostic comparisons showed high spatial overlap of SUD epicenters with those of schizophrenia and bipolar disorder, suggesting shared network-constrained cortical differences. Finally, multivariate mapping revealed that SUD brain differences aligned with two neurotransmitter axes contrasting cannabinoid-opioid and dopaminergic systems. These findings indicate that addiction-related brain differences are shaped by connectome and neurotransmitter architecture, positioning brain network and neurochemical organization as key principles of SUD-related brain alterations.

Although associations between cannabis use and mental health have been widely examined, temporal relationships between cannabis use patterns and psychopathological symptoms in regulated settings remain underexplored. We investigated longitudinal associations between cannabis use patterns (frequency, quantity, and problematic use) and psychopathological symptoms (depression, anxiety, and psychosis) over one year of pharmacy-based regulated cannabis access in Switzerland among 378 adult regular cannabis users. Assessments were conducted at baseline, 6 months, and 12 months using validated instruments (PHQ-9, GAD-7, adapted ERIraos) and standardized measures of cannabis use (use days in the past 30 days, quantity per use day, CUDIT-R). Cross-lagged linear mixed-effects models and Bonferroni correction for multiple testing were applied. Problematic cannabis use (CUDIT-R) prospectively predicted higher depressive symptom load (β = 0.113, p < 0.001) and higher anxiety symptom load (β = 0.066, p = 0.015). Anxiety symptoms were associated with subsequent increased cannabis use frequency (β = 1.055, p = 0.047). No longitudinal associations were observed for psychosis symptoms. These findings suggest that problematic cannabis use, rather than frequency or quantity alone, may be particularly relevant for depressive and anxiety symptom trajectories in regulated cannabis access settings and should be considered in clinical assessment and public health discussions surrounding cannabis regulation.

Die Bedeutung, Diagnostik und Therapie von subsyndromalen Angstzuständen (SSA) war Thema eines Expertengremiums. Dabei wurde auch deutlich, dass die Hausärzte meist die ersten Ansprechpartner für die Betroffenen sind und deren Einbindung und Befähigung zur Erstversorgung der Patienten daher eine wichtige Rolle im Management der SSA spielt. Nachfolgend soll dem Hausarzt eine praktische Anleitung für den Umgang mit SSA-Patienten an die Hand gegeben werden. The significance, diagnosis and treatment of subsyndromal anxiety disorders was the topic of an expert panel. It also became clear that GPs are usually the first point of contact for those affected and that their involvement and ability to provide primary care for patients therefore plays an important role in the management of subsyndromal anxiety (SSA). The following is intended to provide GPs with practical instructions for dealing with SSA patients. PEER REVIEWED ARTICLE **Peer reviewers:** Prof. Dr. Rainer Rupprecht, Universität Regensburg, Lehrstuhl für Psychiatrie und Psychotherapie, Universitätsstrasse 84, 93053 Regensburg, Deutschland Ein anonymer Peer-Reviewer Artikel erhalten am 22. April 2025; artikel akzeptiert am 22. Juni 2025, artikel veröffentlicht am 30. Juni 2025.

AIMS:We measured the effects of public health-oriented cannabis access compared with the illegal market on cannabis use and related mental health outcomes in adult cannabis users. DESIGN:This was a two-arm, parallel group, open-label, randomized controlled trial. Follow-up outcome measurement took place after 6 months. SETTING:The study was conducted in Basel-Stadt, Switzerland. PARTICIPANTS:A total of 378 adult (aged ≥18 years) cannabis users were enrolled and randomized between August 2022 and March 2023, although only 374 users who completed baseline measures could be included. INTERVENTION AND COMPARATOR:Participants were randomly assigned to the intervention group with public health-oriented recreational cannabis access in pharmacies (regulated cannabis products, safer use information, voluntary counseling, no advertisement; 189/188) or the illegal market control group (continued illicit cannabis sourcing; 189/186). MEASUREMENTS:The primary outcome was self-reported severity of cannabis misuse after 6 months, as measured by the Cannabis Use Disorders Identification Test - Revised (range 0-32). Secondary outcomes involved depressive, anxiety, and psychotic symptoms, cannabis consumption amount, alcohol, and drug use. FINDINGS:Ten participants were not followed (2.7%). Primary analysis included those with complete data (182 vs. 182). There was some evidence of a difference in cannabis misuse between the legal cannabis intervention group (mean [M] = 10.1) and the illegal market control group (M = 10.9; β = -0.69, 95% confidence interval [CI] = -1.4 to 0.0, P = 0.052). These results were supported by an intention-to-treat multiple imputation analysis (n = 374). Additional sub-group analysis by whether the participant used other drugs or not suggested that any reduction in cannabis misuse was confined to those in the legal cannabis intervention group who used other drugs (PInteraction < 0.001). We found no statistically significant changes in any of the secondary outcomes. CONCLUSIONS:Public health-oriented recreational cannabis access may decrease cannabis use and cannabis-related harms, especially among those using other drugs.

IntroductionIndividuals with exercise addiction (EA) report being unable to stop exercising despite its negative psychological, physical, or social impact. Due to a lack of evidence, EA has so far not been officially recognized as a behavioral addiction. Only one study exists, that investigated mental disorders in individuals with EA by utilizing the Structured Clinical Interview for DSM-5 Disorders (SCID-5). The present study followed up on this sample, providing the first longitudinal data on EA.MethodsAll participants of the baseline study were invited to complete validated psychometric instruments assessing symptoms of depression, attention deficit hyperactivity disorder, trauma, and EA. Furthermore, an exhaustive diagnostic assessment with the SCID-5-CV, the SCID-5-PD (following a SAPAS screening), and a self-designed clinical interview to assess EA criteria were conducted.ResultsThe response rate was 59.4% (n=19) and the mean duration of follow-up was 634.5 (SD=155.8) days. Number of fulfilled EA criteria in the sample remained largely stable over time with no change in seven (36.8%), a reduction in nine (47.4%), and an increase in three (15.8%). Eighteen out of 19 participants fulfilled the criteria for at least one mental disorder. The most prevalent disorders were major depressive disorder (lifetime prevalence 73.7%; n=14) and obsessive-compulsive personality disorder (52.6%; n=10).DiscussionThis data suggests that EA is a temporary stable and distinct disorder with affected individuals suffering from severe psychological distress. Further studies are necessary to investigate potential cause-effect relationships between co-occurring mental disorders and EA.

The Self and Interpersonal Functioning Scale (SIFS) is a 24-item self-report questionnaire assessing personality functioning according to the alternative DSM-5 model for personality disorders. We evaluated the German SIFS version in a total sample of 886 participants from Germany and Switzerland. Its factor structure was investigated with confirmatory factor analysis comparing bifactor models with two specific factors (self- and interpersonal functioning) and four specific factors (identity, self-direction, empathy, and intimacy). The SIFS sum and domain scores were tested for reliability and convergent validity with self-report questionnaires and interviews for personality functioning, -organization, -traits, -disorder categories, and well-being. None of the bifactor models yielded good model fit, even after excluding two items with low factor loadings and including a method factor for reverse-keyed items. Based on a shortened 22-item SIFS version, models suggested that the g-factor explained 52.9-59.6% of the common variance and that the SIFS sum score measured the g-factor with a reliability of .68-.81. Even though the SIFS sum score showed large test-retest reliability and correlated strongly with well-established self-report questionnaires and interviews, the lack of structural validity appears to be a serious disadvantage of the SIFS compared to existing self-reports questionnaires of personality functioning.

BackgroundTo date, there are no official diagnostic criteria for the frequently reported phenomenon of exercise addiction. Therefore, the aim of the present study was to investigate how mental disorders, specifically depression and attention-deficit hyperactivity disorder (ADHD), are related to exercise addiction (EA).MethodsA total of 173 participants aged between 18 and 70 years, who reported exercising more than 10 h a week and continued to exercise despite injury or illness, answered questionnaires including the Exercise Dependence Scale, the Beck Depression Inventory, and the Homburger ADHD scale for adults. Multiple linear regression analyses were performed adjusting for relevant confounders (age, gender) and stepwise regression was used to identify which of the two mental disorders is the more influential predictor of EA.ResultsPearson correlation analysis showed that depressive symptoms [r (171) = 0.422, p < 0.00] and ADHD symptoms [r (171) = 0.308, p < 0.001] were positively correlated with EA symptoms. The relation between depressive symptoms and EA remained after adjusting for confounders in the regression model (B = 20.531; t(170) = 5.950; 95% CI [13.719, 27.343]; p < 0.001). Similarly, the positive link between ADHD symptoms and EA persisted after controlling for confounders (B = 15.507; t(170) = 3.771; 95% CI [7.389, 23.625]; p < 0.001). Additionally, a stepwise regression model identified that depressive symptoms are a stronger predictor for EA than ADHD symptoms.ConclusionDepressive symptoms seem to be a stronger predictor for EA compared to ADHD symptoms in frequent exercisers. Although individuals with ADHD May exercise extensively, they might be less at risk for EA than individuals with depression. These results contribute to the complex characterization of the psychiatric profile of individuals with exercise addiction, and underline the need for further research elucidating the interplay between mental disorders and EA.

Objective: Patients suffering from psychological disorders report decreased quality of life and low mood. The relationship of these symptoms to daily upsetting events or environments, and in the context of active coping mechanisms is poorly understood. The present study thus investigates the association between mood, psychological flexibility, upsetting events, and environment in the daily life of outpatients.Method: We investigated 80 outpatients at the beginning of treatment, using event sampling methodology (ESM). Patients' mood, occurrence of upsetting events, current environment, and psychological flexibility were sampled six times per day during a one-week intensive longitudinal examination. Data were analyzed using linear mixed models (LMMs).Results: Participants reported worse mood the more upsetting events they experienced. Further, participants reported better mood when in private environments (e.g., with friends), and worse mood when at the hospital, compared to being at home. Higher levels of psychological flexibility, however, were associated with better mood, irrespective of the occurrence of upsetting events or current environment.Conclusion: Results suggest that mood is positively associated with psychological flexibility, not despite, but especially during the dynamic and context-specific challenges of daily life. Psychological flexibility may thus potentially act as a buffer against distress-provoking situations as patients go about their daily lives.Trial registration: ISRCTN.org identifier: ISRCTN11209732.

Abstract Background Cannabinoids have been of increasing interest mainly due to their putative efficacy in a wide array of psychiatric, psychosomatic, and neurological conditions. Aims This systematic review aims to synthesize results from randomized placebo-controlled trials regarding the efficacy and the dosage of cannabinoids as therapeutics in psychiatric disorders in children, adolescents, and young adults. Methods All publications up to June 30th, 2024, were included from PubMed and Embase. Eligibility criteria in accordance with the PRISMA-guidelines was applied. RCTs providing pre- and post-treatment parameters on cannabinoid therapies for mental disorders in comparison to controls in an age range from 0 to 25 years were included. Effect sizes were calculated as Hedges’ g for primary outcomes, and a multilevel random-effects meta-analysis was conducted to account for dependent outcomes from same study populations. Results We identified 7603 records, of which 8 independent clinical trials (reported in 9 publications) met the pre-established eligibility criteria, comprising 474 unique participants (245 treatment, 229 control). Analysis of 13 primary outcomes (of 7 clinical trials) revealed a modest positive overall effect for symptom improvement or normalization of brain physiology (Hedges’ g = 0.308, 95% CI: 0.167, 0.448). Autism spectrum disorder studies showed the most consistent evidence (g = 0.264, 95% CI: 0.107, 0.421), while other conditions showed wider confidence intervals. Age-stratified analysis showed that adult populations (mean age 23.3 years, n = 5 outcomes) demonstrated higher effect sizes (g = 0.463, SD = 0.402) compared to pediatric populations (mean age 11.8 years, n = 8 outcomes; g = 0.318, SD = 0.212). Whole plant preparations (g = 0.328, 95% CI: 0.083, 0.573) and pharmaceutical cannabinoids (g = 0.292, 95% CI: 0.069, 0.515) showed comparable effects. CBD dosages ranged from 17.5 mg to 600 mg per day, with no significant correlation between dosage and effect size (ρ = -0.014, p = 0.963). Mild to moderate side effects were reported, but no serious adverse events. Risk of bias assessment ranged from low (n = 3) to high (n = 5). Conclusion While meta-analysis of effect sizes for primary outcomes revealed modest positive effects, particularly for autism spectrum disorders, the current evidence remains insufficient to broadly recommend cannabinoids for treating mental disorders in youth populations. Larger, controlled studies with standardized outcomes are needed to establish definitive clinical recommendations.

BackgroundAs the most commonly used illicit substance, cannabis is gaining global acceptance through increasing legalization efforts. This shift intensifies the need for research to guide policymakers and healthcare providers in harm reduction and treatment strategies. Nonetheless, the relationship between psychopathological symptoms and cannabis use remains inadequately understood.MethodsA sample of regular cannabis consumers completed self-reported assessments for depression (Patient Health Questionnaire-9), anxiety (General Anxiety Disorder-7), Attention-Deficit/Hyperactivity Disorder (ADHD; Adult ADHD Self-Report Scale V1.1), and psychosis (Early Recognition Inventory based on IRAOS) as well as previous black-market cannabis use patterns. Cannabis Use Disorder Identification Test Revised (CUDIT-R) was used to identify cannabis use disorder (CUD). To understand psychopathological symptom load related to cannabis consumption as well as cannabis use motives, multiple regression models were performed to identify psychopathological variables predicting cannabis use frequency and quantity. Linear regression and correlation analyses were conducted, adjusting for relevant covariates (age, gender, education, alcohol, other substance use).ResultsThree-hundred-sixty regular cannabis users interested in a study on regulated cannabis access in Basel, Switzerland were examined. In bivariate analysis, cannabis use frequency correlated with depressive (r(358) = 0.16, p = 0.003) and anxiety symptom load (r(358) = 0.11, p = 0.034). Cannabis quantity correlated with depressive (r(358) = 0.15, p = 0.005), ADHD (r(358) = 0.14, p = 0.008), and psychosis symptom load (r(358) = 0.16, p = 0.002). However, in the adjusted regression models only depressive and ADHD symptom loads were significantly associated with cannabis use frequency (p = 0.006 and p = 0.034, respectively) and quantity (p = 0.037 and p = 0.019, respectively). No significant correlations between cannabis consumption and anxiety or psychosis remained after adjustment.ConclusionADHD and depressive symptoms correlate with increased cannabis use in a cohort of regular users, suggesting potential self-medication in nonclinical populations. With the rising availability of cannabis worldwide, these results highlight the necessity for longitudinal studies to disentangle the complex dynamics between cannabis consumption and mental health symptoms.

BACKGROUND:Suicide remains a significant public health concern worldwide. Ecological studies reported decreased suicide rates with higher levels of trace lithium levels in drinking water, leading to suggestions of adding lithium to drinking water as a preventative anti-suicide strategy. However, the evidence remains inconclusive, and thus more data are needed. METHODS:This pre-registered study analyzed the association between lithium concentrations in drinking water and suicide rates across 1043 municipalities in Switzerland between 1981 and 2021. We used bivariate correlation analysis, ordinary regression models, and spatial regression models, while accounting for potential confounding variables. RESULTS:There were no significant associations between lithium levels in drinking water and suicide rates, as determined by correlation analysis (r = -0.03, 95 % CI -0.09-0.03, p = 0.33), and by multivariable ordinary and spatial regression models. LIMITATIONS:The correlation between levels of lithium in tap water and the serum of individuals is unknown and ecological studies are inherently limited to establish a causal association. CONCLUSIONS:The null finding in our study adds to the ongoing debate on the effectiveness of trace lithium in drinking water as a public health intervention for suicide prevention, indicating that calls for lithium supplementation are still premature. These findings highlight the need for further research with transparent and replicable methodologies to clarify the potential role of lithium in suicide prevention.

Background Exercise dependence (ED) is characterised by behavioural and psychological symptoms that resemble those of substance use disorders. However, it remains inconclusive whether ED is accompanied by similar brain alterations as seen in substance use disorders. Therefore, we investigated brain alterations in individuals with ED and inactive control participants. Methods In this cross-sectional neuroimaging investigation, 29 individuals with ED as assessed with the Exercise Dependence Scale (EDS) and 28 inactive control participants (max one hour exercising per week) underwent structural and functional resting-state magnetic resonance imaging (MRI). Group differences were explored using voxel-based morphometry and functional connectivity analyses. Analyses were restricted to the striatum, amygdala, and inferior frontal gyrus (IFG). Exploratory analyses tested whether relationships between brain structure and function were differently related to EDS subscales among groups. Results No structural differences were found between the two groups. However, right IFG and bilateral putamen volumes were differently related to the EDS subscales “time” and “tolerance”, respectively, between the two groups. Resting-state functional connectivity was increased from right IFG to right superior parietal lobule in individuals with ED compared to inactive control participants. Furthermore, functional connectivity of the angular gyrus to the left IFG and bilateral caudate showed divergent relationships to the EDS subscale “tolerance” among groups. Discussion The findings suggest that ED may be accompanied by alterations in cognition-related brain structures, but also functional changes that may drive compulsive habitual behaviour. Further prospective studies are needed to disentangle beneficial and detrimental brain effects of ED.

Background: Clinical data are usually analyzed with the assumption that knowledge gathered from group averages applies to the individual. Doing so potentially obscures patients with meaningfully different trajectories of therapeutic change. Needed are “idionomic” methods that first examine idiographic patterns before nomothetic generalizations are made. The objective of this paper is to test whether such an idionomic method leads to different clinical conclusions.Methods: 51 patients completed weekly process measures and symptom severity over a period of eight weeks. Change trajectories were analyzed using a nomothetic approach and an idiographic approach with bottom-up clustering of similar individuals. The outcome was patients’ well-being at post-treatment.Results: Individuals differed in the extent that underlying processes were linked to symptoms. Average trend lines did not represent the intraindividual changes well. The idionomic approach readily identified subgroups of patients that differentially predicted distal outcomes (well-being).Conclusions: Relying exclusively on average results may lead to an oversight of intraindividual pathways. Characterizing data first using idiographic approaches led to more refined conclusions, which is clinically useful, scientifically rigorous, and may help advance individualized psychotherapy approaches.