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.

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.

The role of sex in the association between cannabis use and working memory-related brain activity.

Although cannabis use patterns differ between men and women, studies on sex differences on the effects of cannabis on the brain and cognitive control are largely lacking. Working memory (WM) is a component of cognitive control believed to be involved in the development and maintenance of addiction. In this study, we evaluated the association between cannabis use and WM (load) related brain activity in a large sample, enabling us to assess sex effects in this association. The brain activity of 104 frequent cannabis users (63% men) and 85 controls (53% men) was recorded during an N-back WM task. Behavioral results showed a significant interaction between WM load and group for both accuracy and reaction time, with cannabis users showing a relatively larger decrease in performance with increasing WM load. Cannabis users compared to controls showed a relatively smaller reduction in WM (load) related activity in the precuneus and posterior cingulate cortex at higher WM load. This WM (load) related activity was not associated with performance nor cannabis use and related problems. An exploratory analysis showed higher WM-related activity in the superior frontal gyrus in men compared to women. While cannabis users showed higher WM (load) related activity in central nodes of the default mode network, this was not directly attributable to group specific worsening of performance under higher cognitive load. Further research is necessary to assess whether observed group differences increase with higher cognitive load, how group differences relate to measures of cannabis use, and how sex affects these group differences.

Unraveling the role of cigarette use in neural cannabis cue reactivity in heavy cannabis users.

Cue reactivity is an important biomarker of cannabis use disorder (CUD). Despite high rates of cigarette and cannabis co-use, its role in cannabis cue reactivity remains unclear. Using a visual functional magnetic resonance imaging cue reactivity paradigm, we investigated interactive effects of cannabis and cigarette use on cannabis cue relative to cigarette and neutral cue reactivity in a priori regions of interest-the amygdala, striatum, anterior cingulate cortex (ACC), ventral tegmental area (VTA), and orbitofrontal cortex-and a whole-brain analysis. In our sample of cannabis users and controls closely matched on cigarette use, significant interactions between cannabis and cigarette use status emerged in the amygdala, striatum, ACC, frontal pole, and inferior frontal gyrus. Cannabis-only users showed heightened cue reactivity in the amygdala compared with nonusing controls. Co-users did not show heightened cue reactivity compared with cigarette smoking controls, although cue-induced VTA activity was positively correlated with grams per week of cannabis. Cigarette smoking controls showed unexpectedly heightened cue reactivity compared to co-users and nonsmoking controls. These findings and the high prevalence of cannabis and cigarette co-use underscore the importance of considering cigarette smoking status when investigating the role of cue reactivity in heavy cannabis use.

Age-related differences in the impact of cannabis use on the brain and cognition: a systematic review.

The impact of cannabis on the adolescent compared to adult brain is of interest to researchers and society alike. From a theoretical perspective, adolescence represents a period of both risk and resilience to the harms of cannabis use and cannabis use disorders. The aim of this systematic review is to provide a critical examination of the moderating role of age on the relationship between cannabis use and cognition. To this end, we reviewed human and animal studies that formally tested whether age, adolescent or adult, changes the relationship between cannabis exposure and cognitive outcomes. While the results of this review do not offer a conclusive answer on the role of age, the novel review question, along with the inclusion of both human and animal work, has allowed for the formation of new hypotheses to be addressed in future work. First, general executive functioning seems to be more impaired in adolescent frequent cannabis users compared to adult frequent cannabis users. Second, age-effects may be most prominent among very heavy and dependent users. Third, craving and inhibitory control may not decrease as much post-intoxication in adolescents compared to adults. Lastly, adolescents' vulnerability to reduced learning following cannabis use may not persist after sustained abstinence. If these hypotheses prove correct, it could lead to important developments in policy and prevention efforts.

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.

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.

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.

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.

The who and how of attentional bias in cannabis users: associations with use severity, craving and interference control.

AIMS: Cognitive and motivational processes are thought to underlie cannabis use disorder (CUD), but research assessing how cognitive processes [e.g. interference control (IC)] interact with implicit [e.g. attentional bias (AB)] and explicit motivation (i.e. craving) is lacking. We assessed the presence of AB in cannabis users with varying use severity and tested models of moderation, mediation and moderated mediation to assess how AB, craving and IC interact in their association with measures of cannabis use. DESIGN: A cross-sectional study design was used. SETTING AND PARTICIPANTS: Eight studies performed by our laboratory in the Netherlands including never-sporadic, occasional (≤ 1/month) and regular cannabis users (≥ 2/week), and individuals in treatment for CUD were combined (n = 560; 71% male). MEASUREMENTS: Studies included a classic Stroop task (IC), a cannabis Stroop task (AB) and measures of session-induced and average session craving. Both heaviness of cannabis use (grams/week) and severity of use related problems were included. FINDINGS: Only those in treatment for CUD showed an AB to cannabis (P = 0.019) and group differences were only observed when comparing CUD with never-sporadic users (P = 0.007). In occasional and regular users, IC was negatively associated with heaviness (ß = 0.015, P < 0.001), but not severity of use. Average session craving (exploratory), but not session-induced craving (confirmatory), mediated this association between AB and heaviness (ß = 0.050, P = 0.011) as well as severity of use (ß = 0.083, P = 0.009); higher AB was associated with heavier use and more severe problems through increased craving. CONCLUSIONS: Attentional bias only appears to be present in cannabis users with the most severe problems and craving appears to mediate the association between attentional bias and both heaviness and severity of use in occasional and regular users. The association of interference control with heaviness but not severity of use may point to subacute intoxication effects of cannabis use on interference control.

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.

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.

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.

Associations between cannabis use, cannabis use disorder, and mood disorders: longitudinal, genetic, and neurocognitive evidence.

RATIONALE: Cannabis use among people with mood disorders increased in recent years. While comorbidity between cannabis use, cannabis use disorder (CUD), and mood disorders is high, the underlying mechanisms remain unclear. OBJECTIVES: We aimed to evaluate (1) the epidemiological evidence for an association between cannabis use, CUD, and mood disorders; (2) prospective longitudinal, genetic, and neurocognitive evidence of underlying mechanisms; and (3) prognosis and treatment options for individuals with CUD and mood disorders. METHODS: Narrative review of existing literature is identified through PubMed searches, reviews, and meta-analyses. Evidence was reviewed separately for depression, bipolar disorder, and suicide. RESULTS: Current evidence is limited and mixed but suggestive of a bidirectional relationship between cannabis use, CUD, and the onset of depression. The evidence more consistently points to cannabis use preceding onset of bipolar disorder. Shared neurocognitive mechanisms and underlying genetic and environmental risk factors appear to explain part of the association. However, cannabis use itself may also influence the development of mood disorders, while others may initiate cannabis use to self-medicate symptoms. Comorbid cannabis use and CUD are associated with worse prognosis for depression and bipolar disorder including increased suicidal behaviors. Evidence for targeted treatments is limited. CONCLUSIONS: The current evidence base is limited by the lack of well-controlled prospective longitudinal studies and clinical studies including comorbid individuals. Future studies in humans examining the causal pathways and potential mechanisms of the association between cannabis use, CUD, and mood disorder comorbidity are crucial for optimizing harm reduction and treatment strategies.

Context dependent differences in working memory related brain activity in heavy cannabis users.

RATIONALE: Compromised cognitive control in cannabis use-tempting situations is thought to play a key role in the development of cannabis use disorders. However, little is known about how exposure to cannabis cues and contexts may influence cognitive control and the underlying neural mechanisms in cannabis users. OBJECTIVES: Working memory (WM) is an attention reliant executive function central to cognitive control. In this study, we investigated how distracting cannabis words affected WM load-dependent performance and related brain activity in near-daily cannabis users (N = 36) relative to controls (N = 33). METHODS: Brain activity was recorded during a novel N-back flanker WM task with neutral and cannabis flankers added as task-irrelevant distractors. RESULTS: On a behavioural level, WM performance did not differ between groups, and the presence of cannabis flankers did not affect performance. However, in cannabis users compared to controls, the presence of cannabis flankers reduced WM load-related activity in multiple regions, including the insula, thalamus, superior parietal lobe and supramarginal gyrus. CONCLUSIONS: The group specificity of these effects suggest that cannabis users might differ from controls in the way they process cannabis-related cues and that cannabis cue exposure could interfere with other cognitive processes under cognitively demanding circumstances. Future studies should focus on the role of context in cognitive control-related processes like WM and attention to further elucidate potential cognitive impairments in heavy cannabis users and how these relate to loss of control over drug seeking itself.

Age-related differences in the effect of chronic alcohol on cognition and the brain: a systematic review.

Adolescence is an important developmental period associated with increased risk for excessive alcohol use, but also high rates of recovery from alcohol use-related problems, suggesting potential resilience to long-term effects compared to adults. The aim of this systematic review is to evaluate the current evidence for a moderating role of age on the impact of chronic alcohol exposure on the brain and cognition. We searched Medline, PsycInfo, and Cochrane Library databases up to February 3, 2021. All human and animal studies that directly tested whether the relationship between chronic alcohol exposure and neurocognitive outcomes differs between adolescents and adults were included. Study characteristics and results of age-related analyses were extracted into reference tables and results were separately narratively synthesized for each cognitive and brain-related outcome. The evidence strength for age-related differences varies across outcomes. Human evidence is largely missing, but animal research provides limited but consistent evidence of heightened adolescent sensitivity to chronic alcohol's effects on several outcomes, including conditioned aversion, dopaminergic transmission in reward-related regions, neurodegeneration, and neurogenesis. At the same time, there is limited evidence for adolescent resilience to chronic alcohol-induced impairments in the domain of cognitive flexibility, warranting future studies investigating the potential mechanisms underlying adolescent risk and resilience to the effects of alcohol. The available evidence from mostly animal studies indicates adolescents are both more vulnerable and potentially more resilient to chronic alcohol effects on specific brain and cognitive outcomes. More human research directly comparing adolescents and adults is needed despite the methodological constraints. Parallel translational animal models can aid in the causal interpretation of observed effects. To improve their translational value, future animal studies should aim to use voluntary self-administration paradigms and incorporate individual differences and environmental context to better model human drinking behavior.

For better or for worse? A pre-post exploration of the impact of the COVID-19 lockdown on cannabis users.

BACKGROUND AND AIMS: Lockdown measures aimed at limiting the number of infections and deaths from the coronavirus disease 2019 (COVID-19) have introduced substantial psychosocial stressors in everyday life. We aimed to investigate the influence of the Dutch lockdown on cannabis use and cannabis use disorder (CUD) and investigate relations with change in mental wellbeing and experienced psychosocial stressors during the lockdown. DESIGN: Explorative longitudinal baseline-, pre- and during lockdown survey study. SETTING: The Netherlands, on-line between January 2019 and May 2020. PARTICIPANTS: Community sample of 120 monthly to daily cannabis users and reference group of 63 non-using controls. MEASUREMENTS: Change in cannabis use and CUD symptom severity from baseline to pre- to post-lockdown. Change in cannabis use motives, mental health, quality of social relationships and job status from pre- to post-lockdown. FINDINGS: In cannabis users, lockdown related to increased cannabis use [B = 1.96, 95% confidence interval (CI) = 0.26-3.66, P = 0.024], but not CUD symptom severity. Cannabis users experienced 30% job loss and increased loneliness [P < 0.001, Bayes factor (BF)10 > 100], while contact with partners (P = 0.005, BF10 = 8.21) and families improved (P < 0.001, BF10  = 19.73), with no differences between cannabis users and control. Generally, mental health problems (all Ps > 0.277, all BF10  < 0.139) did not change, but individual differences were significant and severity of cannabis use pre-lockdown, COVID-19-related worries, change in anxiety, expansion motives, social motives and family contact all uniquely related to variance in change in cannabis use or CUD. CONCLUSIONS: While cannabis use among daily cannabis users in the Netherlands increased at the group level during the period of COVID-19 lockdown, the effect of the first months of lockdown on cannabis use disorder severity and mental wellbeing varied significantly among individual daily cannabis users.

The short-term and long-term effects of cannabis on cognition: recent advances in the field.

The aim of this review is to discuss the most recent evidence for the short-term and long-term effects of cannabis on cognition. The evidence that cannabis intoxication is associated with short-term impairment across several basal cognitive domains, including learning and (episodic) memory, attentional control, and motor inhibition is increasing. However, evidence regarding the effects of long-term heavy cannabis use on cognition remains equivocal. Cannabis research suffers from difficulties in measuring cannabis exposure history, poor control over potential subacute effects, and heterogeneity in cognitive measures and sample composition. Multidisciplinary collaborations and investment in studies that help overcome these difficulties should be prioritized.

Heavy cannabis use, dependence and the brain: a clinical perspective.

AIMS: To summarize and evaluate our knowledge of the relationship between heavy cannabis use, cannabis use disorder (CUD) and the brain. METHODS: Narrative review of relevant literature identified through existing systematic reviews, meta-analyses and a PubMed search. Epidemiology, clinical representations, potential causal mechanisms, assessments, treatment and prognosis are discussed. RESULTS: Although causality is unclear, heavy and dependent cannabis use is consistently associated with a high prevalence of comorbid psychiatric disorders and learning and memory impairments that seem to recover after a period of abstinence. Evidence regarding other cognitive domains and neurological consequences, including cerebrovascular events, is limited and inconsistent. Abstinence after treatment is only achieved in a minority of cases; treatment targeted at reduction in use appears have some success. Potential moderators of the impact of CUD on the brain include age of onset, heaviness of use, CUD severity, the ratio of ∆9-tetrahydrocannabinol to cannabidiol and severity of comorbid disorders. CONCLUSIONS: Current evidence of long-term effects of daily cannabis use and cannabis use disorder on brain-related outcomes is suggestive rather than conclusive, but use is associated with psychiatric morbidity and with cognitive impairments that recover after a period of abstinence.