Treatment Seeking Nitrous Oxide Users in Addiction Care: A Comparison with Cocaine Users on Clinical and Treatment Characteristics.

INTRODUCTION: Over the past decade, frequent use of large quantities of nitrous oxide (N2O) has become more common in the Netherlands. Although N2O poses several negative health consequences for a subgroup of problematic N2O users, there is a lack of knowledge on what characterizes these intensive users. This study therefore aims to provide the demographic and substance use characteristics and experiences during treatment of treatment seeking problematic N2O users and to compare this with a matched group of treatment-seeking problematic cocaine users. METHODS: A retrospective chart review was performed of patients who were referred for treatment of problematic N2O use at a large Dutch addiction care facility from January 2020 to September 2022, extracting demographics, pattern of use and follow-up data. Additionally, a subgroup of N2O users was propensity-score matched (1:1) with a subgroup of treatment seeking problematic cocaine users, both groups excluding users with substance use disorders or frequent use of substances other than N2O and cocaine, respectively. RESULTS: 128 patients with a N2O use disorder were included in the total sample and a subgroup of 77 N2O-only users was propensity-score matched on age and sex to 77 cocaine-only users. N2O users were typically young (mean age 26.2 years), male (66.4%), unmarried (82.9%), with a low education level (59.0%) and born in the Netherlands (88.2%), with parents born in Morocco (45.3%). N2O was used intermittently (median 10 days/month, IQR 4.0-17.5 days) and often in very large quantities (median 5 kg [ca. 750 balloons] per average using day, IQR 2-10 kg). Compared to the patients with a cocaine use disorder, matched N2O users were lower educated, more often from Moroccan descent, and less likely to be alcohol or polysubstance users. Despite receiving similar treatments, N2O users were twice as likely to discontinue treatment before completion compared to cocaine users (63 vs. 35%, p = 0.004). CONCLUSION: Treatment-seeking problematic N2O users are demographically different from treatment-seeking problematic cocaine users and are much more likely to dropout from psychological treatment. Further research is needed into the needs and other factors of problematic N2O users that relate to poor treatment adherence in problematic N2O users.

Sodium Oxybate for Alcohol Dependence: A Network Meta-Regression Analysis Considering Population Severity at Baseline and Treatment Duration.

AIMS: The estimated effect of sodium oxybate (SMO) in the treatment of alcohol dependence is heterogeneous. Population severity and treatment duration have been identified as potential effect modifiers. Population severity distinguishes heavy drinking patients with <14 days of abstinence before treatment initiation (high-severity population) from other patients (mild-severity population). Treatment duration reflects the planned treatment duration. This study aimed to systematically investigate the effect of these potential effect moderators on SMO efficacy in alcohol-dependent patients. METHODS: Network meta-regression allows for testing potential effect modifiers. It was selected to investigate the effect of the above factors on SMO efficacy defined as continuous abstinence (abstinence rate) and the percentage of days abstinent (PDA). Randomized controlled trials for alcohol dependence with at least one SMO group conducted in high-severity and mild-severity populations were assigned to a high-severity and mild-severity group of studies, respectively. RESULTS: Eight studies (1082 patients) were retained: four in the high-severity group and four in the mild-severity group. The high-severity group was associated with larger SMO effect sizes than the mild-severity group: abstinence rate risk ratio (RR) 3.16, P = 0.004; PDA +26.9%, P < 0.001. For PDA, longer treatment duration was associated with larger SMO effect size: +11.3% per extra month, P < 0.001. In the high-severity group, SMO showed benefit: abstinence rate RR 2.91, P = 0.03; PDA +16.9%, P < 0.001. In the mild-severity group, SMO showed benefit only in PDA for longer treatment duration: +23.9%, P < 0.001. CONCLUSIONS: In the retained studies with alcohol-dependent patients, high-severity population and longer treatment duration were associated with larger SMO effect sizes.

Legal Approaches to New Psychoactive Substances: First Empirical Findings.

BACKGROUND: Generic drug legislation, i.e., simultaneously banning groups of drugs, has been introduced worldwide to counteract the trade and use of emerging "new psychoactive substances" (NPSs) more effectively. SUMMARY: The potential and de facto positive and negative effects of generic drug legislation have been described using an analysis based on documented evaluations of the experiences in the UK and Germany, supplemented with data from other publicly available sources. In particular, the effects of generic drug legislation on availability, use, sales, and overall health harms of NPS, and switches from NPS to traditional (classical) drugs are addressed. The results show that the introduction of generic drug legislation in the UK and Germany has enabled stricter regulation of NPS but has also led to some major harms within the domain of public health. Depending on the population considered, the rate of NPS use remained stable, slightly declined, or increased following the banning of NPS. Once banned, NPSs were more often purchased on the black market, often together with other (more harmful) drugs. Moreover, NPS-related harms did not reduce following the ban, and in some cases even increased. Finally, when harmful NPS, like potent synthetic opioids and cannabinoids, become substantially used and endanger public health, legislators already have the legal means to ban the problem drug, thus overruling the need for a generic ban. KEY MESSAGES: Generic drug legislation may facilitate drug law enforcement, but it is not (very) effective in counteracting NPS use and it may increase NPS-related public health problems. It is concluded that, overall, the advantages of generic drug legislation are overshadowed by its serious disadvantages.

Anabolic Androgenic Steroid Use Patterns and Steroid Use Disorders in a Sample of Male Gym Visitors.

INTRODUCTION: The use of anabolic androgenic steroids (AAS) and other image- and performance-enhancing drugs is a growing public health concern. AAS use is associated with various physical and mental harms, including cardiovascular risks, cognitive deficiencies, and dependence. The aim of this study was to determine whether patterns of AAS use and other variables are associated with the presence of an AAS use disorder (AASUD). METHODS: An online survey was completed by 103 male AAS consumers visiting gyms. The association of different patterns of AAS consumption (cycling vs. continuous forms of AAS use), psychoactive substance use, mental health disorders, and sociodemographic variables with moderate-severe AASUD (fifth edition of the Diagnostic and Statistical Manual of Mental Disorders ≥4 criteria) was investigated. The associations between duration of AAS use and the AAS dose with moderate-severe AASUD were investigated using logistic regression analysis with moderate-severe AASUD as the dependent variable. RESULTS: Moderate-severe AASUD was present in 25 (24.3%) of the participants. AAS consumers meeting criteria for moderate-severe AASUD, compared to those that did not, in the last 12 months reported a longer duration of AAS use (in weeks), a higher average AAS dose (mg/week), and a greater number of AAS side effects. Duration of AAS use and the AAS dose were the only independent predictors, with an increase of 3.4% in the probability of moderate-severe AASUD with every week increase of the duration of AAS use in the last year (p < 0.05) and an increase in moderate-severe AASUD of 0.1% with every 10 mg increase in the average AAS dose per week (p < 0.05), respectively. CONCLUSION: Our findings show that moderate-severe AASUD is relatively frequent among male AAS consumers and is positively associated with the duration and average dose of AAS use in the last 12 months.

The clinical course of comorbid substance use disorder and attention deficit/hyperactivity disorder: protocol and clinical characteristics of the INCAS study.

BACKGROUND: Substance use disorders (SUD) often co-occur with attention deficit hyperactivity disorder (ADHD). Although the short-term effects of some specific interventions have been investigated in randomized clinical trials, little is known about the long-term clinical course of treatment-seeking SUD patients with comorbid ADHD. AIMS: This paper presents the protocol and baseline clinical characteristics of the International Naturalistic Cohort Study of ADHD and SUD (INCAS) designed and conducted by the International Collaboration on ADHD and Substance Abuse (ICASA) foundation. The overall aim of INCAS is to investigate the treatment modalities provided to treatment-seeking SUD patients with comorbid ADHD, and to describe the clinical course and identify predictors for treatment outcomes. This ongoing study employs a multicentre observational prospective cohort design. Treatment-seeking adult SUD patients with comorbid ADHD are recruited, at 12 study sites in nine different countries. During the follow-up period of nine months, data is collected through patient files, interviews, and self-rating scales, targeting a broad range of cognitive and clinical symptom domains, at baseline, four weeks, three months and nine months. RESULTS: A clinically representative sample of 578 patients (137 females, 441 males) was enrolled during the recruitment period (June 2017-May 2021). At baseline, the sample had a mean age (SD) of 36.7 years (11.0); 47.5% were inpatients and 52.5% outpatients; The most prevalent SUDs were with alcohol 54.2%, stimulants 43.6%, cannabis 33.1%, and opioids 14.5%. Patients reported previous treatments for SUD in 71.1% and for ADHD in 56.9%. Other comorbid mental disorders were present in 61.4% of the sample: major depression 31.5%, post-traumatic stress disorder 12.1%, borderline personality disorder 10.2%. CONCLUSIONS: The first baseline results of this international cohort study speak to its feasibility. Data show that many SUD patients with comorbid ADHD had never received treatment for their ADHD prior to enrolment in the study. Future reports on this study will identify the course and potential predictors for successful pharmaceutical and psychological treatment outcomes. TRIAL REGISTRATION: ISRCTN15998989 20/12/2019.

Smoking As an Outcome Moderator In the Treatment of Alcohol Use Disorders.

AIMS: To clarify whether smoking interferes with successful treatment of alcohol use disorder (AUD). METHODS: The current systematic review investigates the potential moderating effect of smoking on behavioural and pharmacological treatment of AUD. In addition, this review summarizes the results of randomized controlled trials investigating the effect of smoking cessation treatments in subjects with AUD on drinking outcomes. RESULTS: Overall, the results show that 16 out of the 31 pharmacological and psychotherapeutic alcohol treatment studies showed that being a non-smoker or decreased tobacco consumption during AUD treatment is associated with beneficial drinking outcomes, including reduced drinking, later relapse and prolonged alcohol abstinence. As such, smoking predicts poorer drinking outcomes in alcohol treatments. In the stop-smoking studies in patients with AUD, reduced smoking had virtually no effect on drinking behaviours. The inverse association between smoking and drinking outcome observed here indicates that non-smokers may be more successful to attain alcohol abstinence than smokers do. However, this association does not imply per se that smoking triggers alcohol consumption, since it can also mean that alcohol consumption promotes smoking. CONCLUSIONS: It is concluded that (continued) tobacco smoking may have a negative moderating effect on the treatment outcome of AUD treatments. To optimize treatment outcome of AUD one may consider informing and counselling patients with AUD about the risks of smoking for treatment outcomes and offering support for smoking cessation.

The Added Value of Pharmacotherapy to Cognitive Behavior Therapy And Vice Versa in the Treatment of Alcohol Use Disorders: A Systematic Review.

AIM: To explore whether combined interventions i.e. psychotherapeutic plus psychosocial interventions are more effective than monotherapies in the treatment of alcohol use disorders. METHODS: Systematic review of the results of randomized controlled trials that compared combined therapies with monotherapies (either pharmacotherapy or psychotherapy). RESULTS: The search resulted in 28 eligible studies. Data from these RCTs showed that 10 out of 19 RCTs (53%) demonstrated an added value of combined therapy (psychotherapy + pharmacotherapy) compared to psychotherapy only, whereas only three out of nine RCTs (33%) comparing combined therapy with pharmacotherapy showed a possible added value for combined therapy. CONCLUSIONS: Pharmacotherapy is effective to treat AUD with or without psychotherapy and that psychotherapy can best be offered in combination with pharmacotherapy.

Identification of Latent Alcohol Use Groups and Transitions over Time Using a 9-Year Follow-Up Study in the Adult General Population.

INTRODUCTION: Studies investigating latent alcohol use groups and transitions of these groups over time are scarce, while such knowledge could facilitate efficient use of screening and preventive interventions for groups with a high risk of problematic alcohol use. Therefore, the present study examines the characteristics, transitions, and long-term stability of adult alcohol use groups and explores some of the possible predictors of the transitions. METHODS: Data were used from the baseline, 3-, 6-, and 9-year follow-up waves of the Netherlands Mental Health Survey and Incidence Study-2 (NEMESIS-2), a representative study of Dutch adults aged 18-64 at baseline (N = 6,646; number of data points: 20,574). Alcohol consumption, alcohol use disorder (AUD), and mental disorders were assessed with the Composite International Diagnostic Interview 3.0. Latent Markov Modelling was used to identify latent groups based on high average alcohol consumption (HAAC) and AUD and to determine transition patterns of people between groups over time (stayers vs. movers). RESULTS: The best fitting model resulted in four latent groups: one nonproblematic group (91%): no HAAC, no AUD; and three problematic alcohol use groups (9%): HAAC, no AUD (5%); no HAAC, often AUD (3%); and HAAC and AUD (1%). HAAC, no AUD was associated with a high mean age (55 years) and low educational level (41%), and no HAAC, often AUD with high proportions of males (78%) and people with high educational level (46%). Eighty-seven percent of all respondents - mostly people with no HAAC, no AUD - stayed in their original group during the whole 9-year period. Among movers, people in a problematic alcohol use group (HAAC and/or AUD) mostly transitioned to another problematic alcohol use group and not to the nonproblematic alcohol use group (no HAAC, no AUD). Explorative analyses suggested that lack of physical activity possibly plays a role in transitions both from and to problematic alcohol use groups over time. CONCLUSION: The detection of three problematic alcohol use groups - with transitions mostly between the different problematic alcohol use groups and not to the group without alcohol problems - points to the need to explicitly address both alcohol consumption and alcohol-related problems (AUD criteria) in screening measures and interventions in order not to miss and to adequately treat all problematic alcohol users. Moreover, explorative findings suggest that prevention measures should also include physical activity.

Monitoring Opioids in Europe: The Need for Shared Definitions and Measuring Drivers of Opioid Use and Related Harms.

The past 20 years, the USA is facing a serious opioid crisis initiated by an increase in prescription opioid use. Europe has also seen an increase in prescription opioid use, but the extent of related harm is still largely unknown. Given the impact of the US opioid epidemic, it is important to closely monitor signs of emerging opioid-related problems to guarantee early warnings and timely actions. Shared and meaningful definitions for opioid use and related harms, and relevant information about specific drivers for opioid use and related problems are needed for an adequate policy response. In this commentary, we discuss these definitions, the need to know more about the specific drivers for increased opioid use, its related harm, and proposals for strategies to move forward. Policy recommendations include making a distinction between licit and illicit opioids when monitoring and reporting on opioid-related harm, and using oral morphine equivalents to quantify prescription opioid use in a clinically relevant and comparable manner. A major topic of further research is exploring unique and universal drivers of prescription opioid (mis)use across Europe, in particular the role of opioid diversion.

Slamsex in The Netherlands among men who have sex with men (MSM): use patterns, motives, and adverse effects.

BACKGROUND: This paper describes an online survey of men who have sex with men (MSM) and use drugs before or during sex ('chemsex') via injection ('slamming' or 'practising slamsex'). Approximately 15-30% of the MSM population in The Netherlands have practiced chemsex at some point, and 0.5-3.1% of them ever had 'slamsex'. This study investigates which substances are used in The Netherlands during slamsex, the motives for slamming and the health risks involved. METHOD: In total, 175 MSM from The Netherlands, who had used substances before or during sex via injection completed an ad hoc online questionnaire designed for this study. RESULTS: Mean age of respondents was 47.8years. During chemsex, almost every substance was used; the most common substances that were injected (slammed) were 3-methylmethcathinone (3-MMC), methamphetamine, ketamine, 4-methylethcathinone (4-MEC) and mephedrone (4-MMC). Reasons for slamming were mainly to experience a more intense rush and longer sex. Virtually none of the respondents used a condom during slamsex, but needles were almost never shared or used only once. Slammers reported health problems associated with injecting drugs (skin problems, collapsed veins and infections). Of most concern were the psychological symptoms reported by about three-quarters of respondents (e.g. insomnia, sadness, depressed mood, anxiety, suicidal tendencies). About half of respondents reported some degree of loss of control or concerns about their slamming behaviour. CONCLUSION: Results show that slamsex is associated with consciously chosen sexual risk behaviours and risk-avoidance slam behaviours. This study may contribute to the reinforcement of accessible, non-judgmental and well informed prevention and harm reduction activities to support MSM practising slamsex.

Mechanisms Involved in the Neurotoxicity and Abuse Liability of Nitrous Oxide: A Narrative Review.

The recreational use of nitrous oxide (N2O) has increased over the years. At the same time, more N2O intoxications are presented to hospitals. The incidental use of N2O is relatively harmless, but heavy, frequent and chronic use comes with considerable health risks. Most importantly, N2O can inactivate the co-factor cobalamin, which, in turn, leads to paresthesia's, partial paralysis and generalized demyelinating polyneuropathy. In some patients, these disorders are irreversible. Several metabolic cascades have been identified by which N2O can cause harmful effects. Because these effects mostly occur after prolonged use, it raises the question of whether N2O has addictive properties, explaining its prolonged and frequent use at high dose. Several lines of evidence for N2O's dependence liability can be found in the literature, but the underlying mechanism of action remains controversial. N2O interacts with the opioid system, but N2O also acts as an N-methyl-D-aspartate (NMDA) receptor antagonist, by which it can cause dopamine disinhibition. In this narrative review, we provide a detailed description of animal and human evidence for N2O-induced abuse/dependence and for N2O-induced neurotoxicity.

Enhancing help-seeking behaviour among men who have sex with men at risk for sexually transmitted infections: the syn.bas.in randomised controlled trial.

OBJECTIVES: Men who have sex with men (MSM) are at increased risk for STIs and mental disorders. Syndemic theory holds that psychosocial issues co-occur and interact, and thus increase sexual risk behaviour. Psychosocial issue identification, referral and management might reduce risk behaviour. METHODS: In the syndemic-based intervention study, an open-label randomised controlled trial, MSM were enrolled at the STI outpatient clinic of the Public Health Service of Amsterdam. We screened participants using validated questionnaires on the following problem domains: alcohol and substance use, sexual compulsivity, anxiety, depression, attention deficit hyperactivity disorder, alexithymia, intimate partner violence and childhood sexual abuse. Individuals were randomly assigned (1:1) to receive either tailored, face-to-face feedback and help-seeking advice on mental health screening, or no feedback and no help-seeking advice. Participants were followed trimonthly for a year. The primary outcomes were self-reported and confirmed help-seeking behaviour. RESULTS: We included 155 MSM: 76 in the intervention group and 79 in the control group. At inclusion, 128 participants (83.1%) scored positive in at least one problem domain. We found no significant differences in self-reported or confirmed help-seeking behaviour between the intervention and the control group: 41% vs 29% (p=0.14) and 28% vs 22% (p=0.44), respectively. There were also no differences in STI incidence and condomless anal sex acts between the two groups. CONCLUSION: Screening showed high prevalence of problems related to mental health and substance use, while tailored feedback, advice and referral did not significantly increase help-seeking behaviour. Other interventions are needed to tackle the high burden of mental disorders among MSM. TRIAL REGISTRATION NUMBER: NCT02859935.

Smoking and the risk for bipolar disorder: evidence from a bidirectional Mendelian randomisation study.

BACKGROUND: There is increasing evidence that smoking is a risk factor for severe mental illness, including bipolar disorder. Conversely, patients with bipolar disorder might smoke more (often) as a result of the psychiatric disorder. AIMS: We conducted a bidirectional Mendelian randomisation (MR) study to investigate the direction and evidence for a causal nature of the relationship between smoking and bipolar disorder. METHOD: We used publicly available summary statistics from genome-wide association studies on bipolar disorder, smoking initiation, smoking heaviness, smoking cessation and lifetime smoking (i.e. a compound measure of heaviness, duration and cessation). We applied analytical methods with different, orthogonal assumptions to triangulate results, including inverse-variance weighted (IVW), MR-Egger, MR-Egger SIMEX, weighted-median, weighted-mode and Steiger-filtered analyses. RESULTS: Across different methods of MR, consistent evidence was found for a positive effect of smoking on the odds of bipolar disorder (smoking initiation ORIVW = 1.46, 95% CI 1.28-1.66, P = 1.44 × 10-8, lifetime smoking ORIVW = 1.72, 95% CI 1.29-2.28, P = 1.8 × 10-4). The MR analyses of the effect of liability to bipolar disorder on smoking provided no clear evidence of a strong causal effect (smoking heaviness betaIVW = 0.028, 95% CI 0.003-0.053, P = 2.9 × 10-2). CONCLUSIONS: These findings suggest that smoking initiation and lifetime smoking are likely to be a causal risk factor for developing bipolar disorder. We found some evidence that liability to bipolar disorder increased smoking heaviness. Given that smoking is a modifiable risk factor, these findings further support investment into smoking prevention and treatment in order to reduce mental health problems in future generations.

Baseline severity and the prediction of placebo response in clinical trials for alcohol dependence: A meta-regression analysis to develop an enrichment strategy.

BACKGROUND: There is considerable unexplained variability in alcohol abstinence rates (AR) in the placebo groups of randomized controlled trials (RCTs) for alcohol dependence (AD). This is of particular interest because placebo responses correlate negatively with treatment effect size. Recent evidence suggests that the placebo response is lower in very heavy drinkers who show no "spontaneous improvement" prior to treatment initiation (high-severity population) than in a mild-severity population and in studies with longer treatment duration. We systematically investigated the relationship between population severity, treatment duration, and the placebo response in AR to inform a strategy aimed at reducing the placebo response and thereby increasing assay sensitivity in RCTs for AD. METHODS: We conducted a systematic literature review on placebo-controlled RCTs for AD.We assigned retained RCTs to high- or mild-severity groups of studies based on baseline drinking risk levels and abstinence duration before treatment initiation. We tested the effects of population severity and treatment duration on the placebo response in AR using meta-regression analysis. RESULTS: Among the 19 retained RCTs (comprising 1996 placebo-treated patients), 11 trials were high-severity and 8 were mild-severity RCTs. The between-study variability in AR was lower in the high-severity than in the mild-severity studies (interquartile range: 7.4% vs. 20.9%). The AR in placebo groups was dependent on population severity (p = 0.004) and treatment duration (p = 0.017) and was lower in the high-severity studies (16.8% at 3 months) than the mild-severity studies (36.7% at 3 months). CONCLUSIONS: Pharmacological RCTs for AD should select high-severity patients to decrease the magnitude and variability in the placebo effect and and improve the efficiency of drug development efforts for AD.

Is Europe Facing an Emerging Opioid Crisis Comparable to the U.S.?

ABSTRACT: In the U.S., an opioid overdose crisis has emerged, attributable to over-prescription of opioid analgesics, driven by aggressive marketing by pharmaceutical companies, followed by surging heroin overdose deaths, and more recently, by the high mortality rates predominately because of illicitly manufactured fentanyl and analogs of fentanyl. In Europe, the use of prescription opioids for pain management has also increased in the last 2 decades, although it is debatable as to whether this could lead to a similar opioid overdose crisis. To address this issue, recent trends in opioid prescription rates, prevalence rates of fatal and nonfatal incidents, and addiction care treatment were used as proxies of opioid-related harm. The current overview, comparing opioid use and its negative consequences in Germany, France, the U.K., and the Netherlands, using the same indicators as in the U.S., demonstrates that there is no evidence of a current or emerging opioid crisis in these European countries. Scotland, however, is an alarming exception, with high rates of opioid-related harms. Considering that the use of prescription opioids has been declining rather than increasing in Europe, an opioid crisis is not anticipated there yet. Authorities should, however, remain vigilant.

Explaining the Differences in Opioid Overdose Deaths between Scotland and England/Wales: Implications for European Opioid Policies.

BACKGROUNDS: Between 2009 and 2018, the number of opioid-related deaths (ORDs) in Scotland showed a dramatic increase, whereas in England and Wales, a much lower increase in ORD was seen. This regional difference is remarkable, and the situation in Scotland is worrisome. Therefore, it is important to identify the drivers of ORD in Scotland. METHODS: A systematic literature review according to PRISMA guidelines was conducted to identify peer-reviewed studies about key drivers for the observed differences in ORDs between Scotland and England/Wales. In addition, non-peer-reviewed reports on nationwide statistical data were retrieved via Google and Google Scholar and analysed to quantify differences in ORD drivers between Scotland and England/Wales. RESULTS: The systematic review identified some important drivers of ORD, but none of these studies provided direct or indirect comparisons of ORD drivers in Scotland and England/Wales. However, the reports with nationwide statistical data showed important differences in ORD drivers between Scotland and England/Wales, including a higher prevalence of people using opioids in a problematic way (PUOP), more polydrug use in people using drugs in a problematic way (PUDP), a higher age of PUDP, and lower treatment coverage and efficacy of PUDP in Scotland compared to England/Wales, but no regional differences in injecting drug use, incarceration/prison release without treatment, and social deprivation in PUDP. CONCLUSION: It is concluded that the opioid crisis in Scotland is best explained by a combination of drivers, consisting of a higher population involvement in (problematic) opioid use (notably methadone), relatively more polydrug use (notably benzodiazepines and gabapentinoids), a steeper ageing of the PUOP population in the past 2 decades, and lower treatment coverage and efficacy in Scotland compared to England/Wales. The findings have important consequences for strategies to handle the opioid crisis in Scotland.

Potential influence of socioeconomic status on genetic correlations between alcohol consumption measures and mental health.

BACKGROUND: Frequency and quantity of alcohol consumption are metrics commonly used to measure alcohol consumption behaviors. Epidemiological studies indicate that these alcohol consumption measures are differentially associated with (mental) health outcomes and socioeconomic status (SES). The current study aims to elucidate to what extent genetic risk factors are shared between frequency and quantity of alcohol consumption, and how these alcohol consumption measures are genetically associated with four broad phenotypic categories: (i) SES; (ii) substance use disorders; (iii) other psychiatric disorders; and (iv) psychological/personality traits. METHODS: Genome-Wide Association analyses were conducted to test genetic associations with alcohol consumption frequency (N = 438 308) and alcohol consumption quantity (N = 307 098 regular alcohol drinkers) within UK Biobank. For the other phenotypes, we used genome-wide association studies summary statistics. Genetic correlations (rg) between the alcohol measures and other phenotypes were estimated using LD score regression. RESULTS: We found a substantial genetic correlation between the frequency and quantity of alcohol consumption (rg = 0.52). Nevertheless, both measures consistently showed opposite genetic correlations with SES traits, and many substance use, psychiatric, and psychological/personality traits. High alcohol consumption frequency was genetically associated with high SES and low risk of substance use disorders and other psychiatric disorders, whereas the opposite applies for high alcohol consumption quantity. CONCLUSIONS: Although the frequency and quantity of alcohol consumption show substantial genetic overlap, they consistently show opposite patterns of genetic associations with SES-related phenotypes. Future studies should carefully consider the potential influence of SES on the shared genetic etiology between alcohol and adverse (mental) health outcomes.

A Comparison of Excessive Drinking, Binge Drinking and Alcohol Dependence in Ethnic Minority Groups in the Netherlands: The HELIUS Study.

BACKGROUND: The Dutch multi-ethnic Healthy Life in an Urban Setting study recently showed that alcohol consumption was lower in ethnic minority groups than those of Dutch origin, but that binge drinking in drinkers of Turkish and Moroccan origin was relatively high. The aim of the current study is to examine factors that may contribute to the differences in drinking patterns and how they relate to the relationship between drinking patterns and alcohol dependence (AD) across ethnic groups. METHODS: The rate of last year alcohol use, alcohol use patterns and AD was assessed in 4,635 Dutch, 4,317 Moroccan, 4,036 Turkish, 2,459 Ghanaian, 4,426 African Surinamese and 3,357 South-Asian Surinamese participants (both men and women) born in Amsterdam, the Netherlands. RESULTS: Compared to the Dutch, the prevalence of (regular) drinking is substantially lower in all ethnic minority groups and regular drinkers among most ethnic minority groups have a lower adjusted risk to develop binge drinking and AD than the Dutch. For the prevalence of regular drinking, the ethnic differences are bigger than for the prevalence of current drinking. However, regular drinkers of Moroccan origin have a risk similar to the Dutch to develop binge drinking and AD; a finding that could not be explained by group differences in age, sex, religiosity, perceived discrimination, depression or guilt feelings about drinking. DISCUSSION: The prevalence data show that current drinking is lower and that regular drinking is much lower in ethnic minorities and - with the exception of those of Moroccan origin - ethnic minority regular drinkers also have a significant lower risk to develop binge drinking or AD than regular drinkers of Dutch origin. This implies that the magnitude of problematic alcohol use is substantially smaller in ethnic minorities than in the ethnic Dutch population of Amsterdam. Unfortunately, no explanation was found for the special risk situation of regular drinkers of Moroccan origin.

Differential Diagnosis in Patients with Substance Use Disorder and/or Attention-Deficit/Hyperactivity Disorder Using Continuous Performance Test.

BACKGROUND: Although substance use disorders (SUD) and attention-deficit/hyperactivity disorder (ADHD) show significant symptomatic overlap, ADHD is often overlooked in SUD patients. OBJECTIVE: The aim of the present study was to characterize aspects of attention and inhibition (as assessed by a continuous performance test [CPT]) in SUD patients with and without a comorbid diagnosis of ADHD and in healthy controls, expecting the most severe deficits in patients with a combined diagnosis. METHODS: The MOXO-CPT version, which incorporates visual and auditory environmental distractors, was administered to 486 adults, including healthy controls (n = 172), ADHD (n = 56), SUD (n = 150), and combined SUD and ADHD (n = 108). RESULTS: CPT performance of healthy controls was better than that of individuals in each of the 3 clinical groups. The only exception was that the healthy control group did not differ from the ADHD group on the Timing index. The 3 clinical groups differed from each other in 2 indices: (a) patients with ADHD (with or without SUD) showed increased hyperactivity compared to patients with SUD only and (b) patients with ADHD showed more responses on correct timing as compared with the SUD groups (with or without ADHD). CONCLUSION: The CPT is sensitive to ADHD-related deficits, such as disinhibition, poor timing, and inattention, and is able to consistently differentiate healthy controls from patients with ADHD, SUD, or both. Our results are in line with previous research associating both ADHD and SUD with multiple disruptions across a broad set of cognitive domains such as planning, working memory, decision-making, inhibition control, and attention. The lack of consistent differences in cognitive performance between the 3 diagnostic groups might be attributed to various methodological aspects (e.g., heterogeneity in severity, type, and duration of substances use). Our results support the view that motor activity should be considered a significant marker of ADHD.

The International Collaboration on ADHD and Substance Abuse (ICASA): Mission, Results, and Future Activities.

BACKGROUND: The International Collaboration on ADHD and Substance Abuse (ICASA) is a network of 28 centers from 16 countries initiated to investigate the link between attention deficit-hyperactivity disorder (ADHD) and substance use disorder (SUD). In this article, we present the mission, the results of finished studies, and the current and future research projects of ICASA. METHODS: During the past 10 years, 3 cross-sectional studies were conducted: two International ADHD in Substance use disorders Prevalence (IASP-1 and IASP-2) studies, directed at the screening, diagnosis, and the prevalence of adult ADHD in treatment-seeking patients with SUD, and the Continuous performance test for ADHD in SUD Patients (CASP) study, testing a novel continuous performance test in SUD patients with and without adult ADHD. Recently, the prospective International Naturalistic Cohort Study of ADHD and Substance Use Disorders (INCAS) was initiated, directed at treatment provision and treatment outcome in SUD patients with adult ADHD. RESULTS: The IASP studies have shown that approximately 1 in 6 adult treatment-seeking SUD patients also have ADHD. In addition, those SUD patients with adult ADHD compared to SUD patients without ADHD report more childhood trauma exposure, slower infant development, greater problems controlling their temperament, and lower educational attainment. Comorbid patients also reported more risk-taking behavior, and a higher rate of other psychiatric disorders compared to SUD patients without ADHD. Screening, diagnosis, and treatment of this patient group are possible even before abstinence has been achieved. The results of the CASP study are reported separately in this special issue. CONCLUSIONS: The ICASA research to date has demonstrated a high prevalence of comorbid ADHD and SUD, associated with elevated rates of additional comorbidities and risk factors for adverse outcomes. More research is needed to find the best way to treat these patients, which is the main topic of the ongoing INCAS study.