Cannabis cue-reactivity in cannabis use disorder: Diverging evidence in two distinct cannabis cultures.

BACKGROUND: Cannabis policies and attitudes play a role in the development and presentation of cannabis use disorder (CUD), but it is unclear how these factors are related to biomarkers of addiction. The current study examined cross-cultural differences in cannabis attitudes, cannabis cue-reactivity in the brain and its associations with cannabis use measures and cannabis attitudes. DESIGN: Cross-sectional fMRI study. SETTING: The Netherlands (NL) and Texas (TX), USA. PARTICIPANTS: 104 cannabis users with CUD (44% female; NL-CUD = 54, TX-CUD = 50) and 83 non-using controls (52% female; NL-CON = 50, TX-CON = 33). MEASUREMENTS: Self-reported positive (perceived benefits) and negative (perceived harms) cannabis attitudes and tactile cannabis cue-reactivity assessed using a 3T MRI scanner. FINDINGS: While the CUD group overall was more positive and less negative about cannabis and reported higher craving, the TX-CUD group reported significantly more positive and less negative attitudes and less craving than the NL-CUD group. Cannabis cue-reactivity was observed in the CUD group in clusters including the precuneus, lateral occipital cortex, frontal medial cortex, nucleus accumbens, and thalamus. In the TX-CUD group, a positive association was observed between symptom severity and cue-induced craving and cannabis cue-reactivity in precuneus and occipital cortex clusters, while a negative association was observed in the NL-CUD group. In these clusters, individuals with more positive attitudes exhibited a positive association between craving and cue-reactivity and those with less positive attitudes exhibited a negative association. No associations with quantity of use were observed. CONCLUSIONS: Cue-induced craving might be deferentially associated with cannabis cue-reactivity across distinct cannabis use environments.

Examining associations between brain morphology in late childhood and early alcohol or tobacco use initiation in adolescence: Findings from a large prospective cohort.

A prominent challenge in understanding neural consequences of substance use involves disentangling predispositional risk factors from resulting consequences of substance use. Existing literature has identified pre-existing brain variations as vulnerability markers for substance use throughout adolescence. As early initiation of use is an important predictor for later substance use problems, we examined whether pre-existing brain variations are associated with early initiation of use. In the Generation R Study, a prospective population-based cohort, brain morphology (gray matter volume, cortical thickness and surface area) was assessed at ages 10 and 14 using neuroimaging. In the second wave, participants reported on alcohol and tobacco use initiation. From a base study population (N = 3019), we examined the longitudinal (N = 2218) and cross-sectional (N = 1817) association between brain morphology of frontolimbic regions of interest known to be associated with substance use risk, and very early (age < 13) alcohol/tobacco use initiation. Additionally, longitudinal and cross-sectional associations were examined with a brain surface-based approach. Models were adjusted for age at neuroimaging, sex and relevant sociodemographic factors. No associations were found between brain morphology (ages 10 and 14) and early alcohol/tobacco use initiation (<13 years). Sex-specific analyses suggested a cross-sectional association between smaller brain volume and early initiated tobacco use in girls. Our findings are important for interpreting studies examining neural consequences of substance use in the general population. Future longitudinal studies are needed to specify whether these findings can be extended to initiation and continuation of alcohol/tobacco use in later stages of adolescence.

From everyday life to measurable problematic smartphone use: The development and validation of the Smartphone Use Problems Identification Questionnaire (SUPIQ).

Background and aims: Problematic smartphone use (PSU) has gained attention, but its definition remains debated. This study aimed to develop and validate a new scale measuring PSU-the Smartphone Use Problems Identification Questionnaire (SUPIQ). Methods: Using two separate samples, a university community sample (N = 292) and a general population sample (N = 397), we investigated: (1) the construct validity of the SUPIQ through exploratory and confirmatory factor analyses; (2) the convergent validity of the SUPIQ with correlation analyses and the visualized partial correlation network analyses; (3) the psychometric equivalence of the SUPIQ across two samples through multigroup confirmatory factor analyses; (4) the explanatory power of the SUPIQ over the Short Version of Smartphone Addiction Scale (SAS-SV) with hierarchical multiple regressions. Results: The results showed that the SUPIQ included 26 items and 7 factors (i.e., Craving, Coping, Habitual Use, Social Conflicts, Risky Use, Withdrawal, and Tolerance), with good construct and convergent validity. The configural measurement invariance across samples was established. The SUPIQ also explained more variances in mental health problems than the SAS-SV. Discussion and conclusions: The findings suggest that the SUPIQ shows promise as a tool for assessing PSU. Further research is needed to enhance and refine the SUPIQ as well as to investigate its clinical utility.

Cannabis Dependence is Associated with Reduced Hippocampal Subregion Volumes Independently of Sex: Findings from an ENIGMA Addiction Working Group Multi-Country Study.

Background: Males and females who consume cannabis can experience different mental health and cognitive problems. Neuroscientific theories of addiction postulate that dependence is underscored by neuroadaptations, but do not account for the contribution of distinct sexes. Further, there is little evidence for sex differences in the neurobiology of cannabis dependence as most neuroimaging studies have been conducted in largely male samples in which cannabis dependence, as opposed to use, is often not ascertained. Methods: We examined subregional hippocampus and amygdala volumetry in a sample of 206 people recruited from the ENIGMA Addiction Working Group. They included 59 people with cannabis dependence (17 females), 49 cannabis users without cannabis dependence (20 females), and 98 controls (33 females). Results: We found no group-by-sex effect on subregional volumetry. The left hippocampal cornu ammonis subfield 1 (CA1) volumes were lower in dependent cannabis users compared with non-dependent cannabis users (p<0.001, d=0.32) and with controls (p=0.022, d=0.18). Further, the left cornu ammonis subfield 3 (CA3) and left dentate gyrus volumes were lower in dependent versus non-dependent cannabis users but not versus controls (p=0.002, d=0.37, and p=0.002, d=0.31, respectively). All models controlled for age, intelligence quotient (IQ), alcohol and tobacco use, and intracranial volume. Amygdala volumetry was not affected by group or group-by-sex, but was smaller in females than males. Conclusions: Our findings suggest that the relationship between cannabis dependence and subregional volumetry was not moderated by sex. Specifically, dependent (rather than non-dependent) cannabis use may be associated with alterations in selected hippocampus subfields high in cannabinoid type 1 (CB1) receptors and implicated in addictive behavior. As these data are cross-sectional, it is plausible that differences predate cannabis dependence onset and contribute to the initiation of cannabis dependence. Longitudinal neuroimaging work is required to examine the time-course of the onset of subregional hippocampal alterations in cannabis dependence, and their progression as cannabis dependence exacerbates or recovers over time.

Associations between hair-derived cannabinoid levels, self-reported use, and cannabis-related problems.

RATIONALE: As cannabis potency and cannabis use are increasing in newly legalized markets, it is increasingly important to measure and examine the effects of cannabinoid exposure. OBJECTIVES: The current study aims to assess how hair-derived cannabinoid concentrations - offering insight into three-month cumulative exposure - are associated with common self-report measures of cannabis use and cannabis use-related problems. METHODS: 74 near-daily dependent cannabis users self-reported their quantity of cannabis use, cannabis use-related problems, and estimated cannabis potency. Hair samples were provided to quantify Δ9-THC, CBD, and CBN using LC-MS/MS and THC-consumption was verified by analyzing THC-COOH in hair using GC-MS/MS. RESULTS: Cannabinoids were detectable in 95.95% of the hair samples from individuals who tested positive on a urine screen for cannabis. Δ9-THC concentrations were positively associated with measures of self-reported potency (relative potency, potency category, and perceived 'high'), but Δ9-THC, CBD, CBN concentrations and THC/CBD ratio were not associated with self-reported quantity of use. Self-reported potency, but not hair-derived concentrations, were associated with withdrawal and craving. Self-reported quantity of cannabis use, but not cannabinoid concentrations, were associated with cannabis use-related problems. CONCLUSIONS: The use of hair-derived cannabinoid quantification is supported for detecting cannabis use in near-daily users, but the lack of associations between hair-derived cannabinoid concentrations and self-report measures of use does not support the use of hair analyses alone for quantification of cannabinoid exposure. Further research comparing hair-derived cannabinoid concentrations with other biological matrices (e.g. plasma) and self-report is necessary to further evaluate the validity of hair analyses for this purpose.

Attentional Biases and Their Association with Substance-Use-Related Problems and Addictive Behaviors: The Utility of a Gamified Value-Modulated Attentional Capture Task.

Background: Attentional biases towards reward stimuli have been implicated in substance use-related problems. The value-modulated attentional capture (VMAC) task assesses such reward-related biases. The VMAC task widely used in lab studies tends to be monotonous and susceptible to low effort. We therefore tested a gamified online version of the VMAC that aimed to increase participant engagement. Our goal was to examine how VMAC is associated with substance use-related problems and addictive behaviors, and whether this association is moderated by cognitive control. Methods: We recruited 285 participants from an online community, including heavy alcohol users. All participants completed a novel gamified version of the VMAC task, measures of substance use and addictive behaviors (addictive-like eating behavior, problematic smartphone use), the WebExec measure of problems with executive functions, and the Stroop Adaptive Deadline Task (SDL) as a measure of cognitive control. Results: The gamified VMAC task successfully identified value-modulated attentional capture effects towards high-reward stimuli. We found no significant associations between VMAC scores, problematic alcohol or cannabis use, addictive behaviors, or any moderation by a behavioral measure of cognitive control. Exploratory analyses revealed that self-reported cognitive problems were associated with more alcohol-, and cannabis-related problems, and addictive behaviors. Greater attentional capture (VMAC) was associated with more cannabis use-related problems among individuals with higher levels of self-reported cognitive problems. Conclusions: Our study is one of the first to demonstrate the utility of the gamified version of the VMAC task in capturing attentional reward biases. Self-reported problems with cognitive functions represent a key dimension associated with substance use-related problems and addictive behaviors.

Computational simulation of transcranial magnetic stimulation-induced electric fields in the dorsolateral prefrontal cortex of heavy cannabis using individuals.

We aimed to investigate the influence of demographic and clinical modulators on the strength of transcranial magnetic stimulation (TMS)-induced electric fields (EFs) in the left dorsolateral prefrontal cortex (lDLPFC) in heavy cannabis using individuals. Structural T1-weighted magnetic resonance imaging scans of 20 heavy cannabis using individuals and 22 non-cannabis users (the controls) in the age range of 18-25 were retrieved. Computational simulations of TMS-induced EFs in the lDLPFC were performed. No significant difference in the strength of TMS-induced EFs was observed between heavy cannabis using individuals and the controls. A negative correlation between the scalp-to-cortex distance demonstrated and the strength of the induced EFs. The severity of cannabis use related problems did not correlate with the induced EFs in the lDLPFC of heavy cannabis using individuals. However, the severity of alcohol use related problems was negatively correlated with the induced EF in the lDLPFC localized by the 5-cm method in the whole sample. Early adulthood seems related to an increase in the induced EFs in the lDLPFC. In conclusion, the dominant factor influencing TMS-induced EFs was the scalp-to-cortex distance. In early adulthood, the interaction between age and comorbid substance use may influence with the magnitude of TMS-induced EFs, thereby complicating the treatment effect of TMS in young people with substance use disorders.

Does nitrous oxide addiction exist? An evaluation of the evidence for the presence and prevalence of substance use disorder symptoms in recreational nitrous oxide users.

BACKGROUND: Prevalence of nitrous oxide (N2 O) use appears to be increasing in numerous countries worldwide, and excessive use has been associated with physical and mental problems. Because there currently is no consensus whether N2 O has addictive potential, we aimed to evaluate the evidence for the presence and prevalence of DSM-5 substance use disorder (SUD) symptoms in N2 O users. ANALYSIS: A literature search was conducted to assess the evidence for the presence of any of the 11 DSM-5 SUD symptoms in N2 O users and the prevalence experiencing those symptoms. A substantial part of the studied N2 O users use more than intended (i.e. 46% to 98%) and spend a substantial amount of time using N2 O. At least some of the studied N2 O users experience interpersonal problems (i.e. 13% to 80%) and use N2 O in risky situations, such as driving under the influence. Evidence for the other criteria is either insufficient or inconclusive. CONCLUSIONS: The literature base for the presence and prevalence of DSM-5 substance use disorder (SUD) symptoms in nitrous oxide (N2 O) users is limited and largely consists of qualitative studies and case studies, but it provides consistent evidence for the presence of at least four SUD criteria in heavy N2 O users. N2 O could well be addictive and should be treated as a potentially addictive substance until systematic assessments can provide evidence-based guidance to users, healthcare professionals and legislators.

Brain volumes in alcohol use disorder: Do females and males differ? A whole-brain magnetic resonance imaging mega-analysis.

Emerging evidence suggests distinct neurobiological correlates of alcohol use disorder (AUD) between sexes, which however remain largely unexplored. This work from ENIGMA Addiction Working Group aimed to characterize the sex differences in gray matter (GM) and white matter (WM) correlates of AUD using a whole-brain, voxel-based, multi-tissue mega-analytic approach, thereby extending our recent surface-based region of interest findings on a nearly matching sample using a complementary methodological approach. T1-weighted magnetic resonance imaging (MRI) data from 653 people with AUD and 326 controls was analyzed using voxel-based morphometry. The effects of group, sex, group-by-sex, and substance use severity in AUD on brain volumes were assessed using General Linear Models. Individuals with AUD relative to controls had lower GM volume in striatal, thalamic, cerebellar, and widespread cortical clusters. Group-by-sex effects were found in cerebellar GM and WM volumes, which were more affected by AUD in females than males. Smaller group-by-sex effects were also found in frontotemporal WM tracts, which were more affected in AUD females, and in temporo-occipital and midcingulate GM volumes, which were more affected in AUD males. AUD females but not males showed a negative association between monthly drinks and precentral GM volume. Our results suggest that AUD is associated with both shared and distinct widespread effects on GM and WM volumes in females and males. This evidence advances our previous region of interest knowledge, supporting the usefulness of adopting an exploratory perspective and the need to include sex as a relevant moderator variable in AUD.

Alcohol cue reactivity in the brain: Age-related differences in the role of social processes in addiction in male drinkers.

Social attunement (SA)-the tendency to harmonize behavior with the social environment-has been proposed to drive the escalation of alcohol use in adolescence, while reducing use in adulthood. Little is known about how heightened social sensitivity in adolescence may interact with neural alcohol cue reactivity-a marker of alcohol use disorder-and its relationship to alcohol use severity over time. The aims of this study were to test whether (1) adolescents and adults differ in social alcohol cue reactivity in the nucleus accumbens, anterior cingulate cortex, and right medial prefrontal cortex (mPFC), and (2) age moderates the relationship between social alcohol cue reactivity and social attunement, measures of drinking at baseline, and changes in drinking over time. A sample of male adolescents (16-18 years) and adults (29-35 years) completed an fMRI social alcohol cue-exposure task at baseline and an online follow-up two to three years later. No main effects of age or drinking measures were observed in social alcohol cue reactivity. However, age significantly moderated associations of social alcohol cue reactivity in the mPFC and additional regions from exploratory whole-brain analyses with SA, with a positive association in adolescents and negative association in adults. Significant age interactions emerged only for SA in predicting drinking over time. Adolescents with higher SA scores escalated drinking, while adults with higher SA scores reduced drinking. These findings warrant further research on SA as a risk and protective factor and suggest that social processes influence cue reactivity differentially in male adolescents and adults.

A cross-cultural fMRI investigation of cannabis approach bias in individuals with cannabis use disorder.

Introduction: As cannabis policies and attitudes become more permissive, it is crucial to examine how the legal and social environment influence neurocognitive mechanisms underlying cannabis use disorder (CUD). The current study aimed to assess whether cannabis approach bias, one of the mechanisms proposed to underlie CUD, differed between environments with distinct recreational cannabis policies (Amsterdam, The Netherlands (NL) and Dallas, Texas, United States of America (TX)) and whether individual differences in cannabis attitudes affect those differences. Methods: Individuals with CUD (NL-CUD: 64; TX-CUD: 48) and closely matched non-using controls (NL-CON: 50; TX-CON: 36) completed a cannabis approach avoidance task (CAAT) in a 3T MRI. The cannabis culture questionnaire was used to measure cannabis attitudes from three perspectives: personal, family/friends, and state/country attitudes. Results: Individuals with CUD demonstrated a significant behavioral cannabis-specific approach bias. Individuals with CUD exhibited higher cannabis approach bias-related activity in clusters including the paracingulate gyrus, anterior cingulate cortex, and frontal medial cortex compared to controls, which was no longer significant after controlling for gender. Site-related differences emerged in the association between cannabis use quantity and cannabis approach bias activity in the putamen, amygdala, hippocampus, and insula, with a positive association in the TX-CUD group and a negative association in the NL-CUD group. This was not explained by site differences in cannabis attitudes. Conclusions: Pinpointing the underlying mechanisms of site-related differences-including, but not limited to, differences in method of administration, cannabis potency, or patterns of substance co-use-is a key challenge for future research.

Development and Validation of the Dutch Social Attunement Questionnaire (SAQ).

The social plasticity hypothesis proposes that social attunement, i.e., the adaptation to and harmonization with one's environment, plays a crucial role in the risk for developing alcohol use disorders (AUDs) during adolescence, whereas in adulthood it paradoxically may make individuals more sensitive to the social pull to reduce drinking. This study aimed to develop a valid measure of social attunement: the social attunement questionnaire (SAQ). A total of 26-items were developed and the questionnaire was completed by 576 Dutch mid to late adolescents and adults over three rounds of online data collection. Using exploratory factor analysis in part of the sample (N = 373), the final questionnaire was reduced to two subscales with a total of 11 items. This structure was confirmed using confirmatory factor analysis in the second part of the sample (N = 203). Results showed that the SAQ has acceptable internal consistency, good measurement invariance to gender, and subscales assessing both cognitive as well as behavioural components of social attunement. In line with expectations on alcohol use settings, SAQ scores were not associated directly with alcohol use, but they were predictive of alcohol use when taking into account the interaction between perceived peer drinking and age. The SAQ appears suitable for the assessment of social attunement in (young) adult men and women, particularly assessing the role of social attunement in alcohol use settings. Further research is needed to confirm the utility of the SAQ in older adults and a broader variety of social settings.

Working memory-related brain activity in cannabis use disorder: The role of cross-cultural differences in cannabis attitudes.

Cannabis legislation and attitudes towards use are changing. Given that evidence from cultural neuroscience research suggests that culture influences the neurobiological mechanisms underlying behaviour, it is of great importance to understand how cannabis legislation and attitudes might affect the brain processes underlying cannabis use disorder. Brain activity of 100 dependent cannabis users and 84 controls was recorded during an N-back working memory (WM) task in participants from the Netherlands (NL; users = 60, controls = 52) and Texas, USA (TX; users = 40, controls = 32). Participants completed a cannabis culture questionnaire as a measure of perceived benefits (positive) and perceived harms (negative) of cannabis from their personal, friends-family's and country-state's perspectives. Amount of cannabis use (grams/week), DSM-5 CUD symptoms and cannabis use-related problems were assessed. Cannabis users self-reported more positive and less negative (personal and friends-family) cannabis attitudes than controls, with this effect being significantly larger in the TX cannabis users. No site difference in country-state attitudes was observed. TX cannabis users, compared with NL cannabis users, and those cannabis users perceiving more positive country-state attitudes showed a more positive association between grams/week and WM-related activity in the superior parietal lobe. NL cannabis users, compared with TX cannabis users, and those cannabis users with less positive personal attitudes showed a more positive association between grams/week and WM-load-related activity in the temporal pole. Both site and cultural attitudes moderated the association of quantity of cannabis use with WM- and WM-load-related activity. Importantly, differences in legislation did not align with perceived cannabis attitudes and appear to be differentially associated with cannabis use-related brain activity.

Cannabis Use Disorder Symptoms in Weekly Cannabis Users: A Network Comparison Between Daily Cigarette Users and Nondaily Cigarette Users.

Background: Concurrent use (co-use) of cannabis and tobacco is common and associated with worse clinical outcomes compared with cannabis use only. The mechanisms and interactions of cannabis use disorder (CUD) symptoms underlying co-use remain poorly understood. Methods: We examined differences in the symptom presence and symptom network configurations between weekly cannabis users who use tobacco daily (co-users, n=789) or non- or nondaily (nondaily co-users, n=428). Results: First, we identified a range of symptoms (craving, failed reduce or quit attempts, neglected responsibilities, and negative social effects) that are most central to the highly interconnected CUD symptom network. Risky cannabis use was mostly associated with negative social and health effects, and independent of other CUD symptoms. Craving symptoms act as a bridge between different CUD and withdrawal symptoms. Among co-users, (1) craving is more strongly associated with negative psychosocial effects, (2) feelings of depression and negative health effects are more central to the network, and (3) the negative health effects are more strongly associated with failed attempts to reduce or quit attempts compared with nondaily co-users. Discussion: Our results go beyond existing findings focused on the mere increase in CUD symptom presence, and speak to the potential synergistic effects of co-use on dependence and withdrawal symptoms. We outline clinical implications with respect to targeting specific CUD symptoms in co-users, and point to future research to disentangle tobacco and cannabis craving symptoms.

The impact of age on olfactory alcohol cue-reactivity: A functional magnetic resonance imaging study in adolescent and adult male drinkers.

BACKGROUND: Adolescence is marked not only by rapid surges in the prevalence of alcohol use disorders (AUDs) but also by remarkable recovery rates, as most adolescent-onset AUDs naturally resolve over time. Little is known about the differential vulnerability of adolescents and adults. Therefore, this study aimed to unravel the moderating role of age by comparing neural alcohol cue-reactivity, an important AUD biomarker, between low-to-high beer-drinking adolescent (n = 50, 16 to 18 years), and adult (n = 51, 30 to 35 years) males matched on drinking severity. METHODS: Associations between beer odor-induced brain activity and AUD diagnosis, severity of alcohol use-related problems, recent alcohol use, binge-drinking frequency, and task-induced craving were investigated across and between age groups in regions of interest thought to be central in alcohol cue-reactivity: the medial prefrontal cortex, anterior cingulate cortex, and striatal subregions (nucleus accumbens and caudate putamen). These analyses were complemented by exploratory whole-brain analyses. RESULTS: Pre-task beer craving increased pre-to-post task in adolescents only. Individual differences in alcohol use, binge drinking, and craving did not relate to beer odor-induced activity. Although region-of-interest analyses did not reach significance, whole-brain analyses showed that adolescents with AUD, compared with adolescents without AUD and adults with AUD, had higher beer odor-induced activity in a large mesocorticolimbic cluster encompassing the right caudate, nucleus accumbens, orbitofrontal cortex, and the olfactory sulcus. Activity in the right caudate and putamen was positively associated with the severity of alcohol use-related problems in adolescents but negatively associated in adults. CONCLUSION: These findings suggest a differential role of alcohol cue-reactivity in adolescents compared with adults with AUD and highlight the need for further studies investigating the role of age in the fundamental processes underlying the development of and recovery from of AUD.

Direct Effects of Cannabis Intoxication on Motivations for Softer and Harder Drug Use: An Experimental Approach to the Gateway Hypothesis.

Aims: This study experimentally tested whether there is a gateway-type effect of cannabis administration on tobacco and cocaine motivation and whether motivational responses predicted use 6 months later. Methods: A 2 (condition: active cannabis vs. placebo joint)×3 (substance stimulus type: tobacco, cannabis, and cocaine) factor within-subjects design for both implicit and explicit motivation. Both experimental sessions were conducted in a cannabis dispensary ("coffeeshop") in Amsterdam and were separated by ∼1 week, followed by a 6-month online follow-up. Eighty-five participants between 18 and 27 years of age (57% male), who used cannabis, tobacco, and cocaine <15 times per month, participated in session 1 (session 2: N=79 and follow-up: N=81). Counterbalanced over sessions, participants smoked an active and a placebo joint following a paced puffing procedure. Before and after smoking, craving and avoidance (explicit motivation) were assessed using visual analog scales, and after smoking, the stimulus response compatibility test was completed to assess approach biases (implicit motivation). Self-reported intoxication and similarity to their usual smoking experience were assessed at the end of both sessions. Self-reported frequency/quantity and dependence symptoms for tobacco, cannabis, and cocaine were assessed at all time points. A linear mixed model approach was used to assess the effects of condition, substance stimulus type, and their interactions on explicit and implicit motivation. Results: In the active condition, participants reported higher levels of intoxication and an experience more similar to their usual smoking experience than in the placebo condition. There was no significant effect of condition, substance type, or their interaction on approach bias. Participants exhibited increased cannabis craving during the placebo condition only and increased explicit cannabis avoidance during the active condition only. Explicit tobacco avoidance decreased during both conditions. Baseline measures did not predict use at 6-month follow-up. Conclusions: In light users, cannabis intoxication did not affect implicit and explicit tobacco or cocaine motivations. Tobacco avoidance decreased regardless of condition, indicating that the cannabis cue-rich setting-rather than tetrahydrocannabinol itself-may momentarily increase the likelihood to smoke tobacco. However, motivation at baseline did not predict use 6 months later, deeming any gateway-like function unlikely.

Age-dependent effects of tobacco smoke and nicotine on cognition and the brain: A systematic review of the human and animal literature comparing adolescents and adults.

Cigarette smoking is often initiated during adolescence and an earlier age of onset is associated with worse health outcomes later in life. Paradoxically, the transition towards adulthood also marks the potential for recovery, as the majority of adolescents are able to quit smoking when adulthood emerges. This systematic review aimed to evaluate the evidence from both human and animal studies for the differential impact of adolescent versus adult repeated and long-term tobacco and nicotine exposure on cognitive and brain outcomes. The limited human studies and more extensive yet heterogeneous animal studies, provide preliminary evidence of heightened fear learning, anxiety-related behaviour, reward processing, nicotinic acetylcholinergic receptors expression, dopamine expression and serotonin functioning after adolescent compared to adult exposure. Effects of nicotine or tobacco use on impulsivity were comparable across age groups. These findings provide novel insights into the mechanisms underlying adolescents' vulnerability to tobacco and nicotine. Future research is needed to translate animal to human findings, with a focus on directly linking a broader spectrum of brain and behavioural outcomes.

Gender differences in cannabis use disorder symptoms: A network analysis.

BACKGROUND: While cannabis use in women is increasing worldwide, research into gender differences in cannabis use disorder (CUD) symptomology is lacking. In response to limited effectiveness of addiction treatment, research focus has been shifting from clinical diagnoses towards interactions between symptoms, as patterns of symptoms and their interactions could be crucial in understanding etiological mechanisms in addiction. The aim of this study was to evaluate the CUD symptom network and assess whether there are gender differences therein. METHODS: A total of 1257 Dutch individuals reporting weekly cannabis use, including 745 men and 512 women, completed online questionnaires assessing DSM-5 CUD symptoms and additional items on plans to quit or reduce use, cigarette use, and the presence of psychological diagnoses. Gender differences were assessed for all variables and an Ising model estimation method was used to estimate CUD symptom networks in men and women using network comparison tests to assess differences. RESULTS: There were gender differences in the prevalence of 6 of the 11 symptoms, but symptom networks did not differ between men and women. Cigarette use appeared to only be connected to the network through withdrawal, indicating a potential role of cigarette smoking in enhancing cannabis withdrawal symptoms. Furthermore, there were gender differences in the network associations of mood and anxiety disorders with CUD symptoms. CONCLUSION: The association between smoking and withdrawal as well as gender differences in the role of comorbidities in the CUD network highlight the value of using network models to understand CUD and how symptom interactions might affect treatment.