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BACKGROUND: Major depressive disorder (MDD) and alcohol use disorders (AUDs) are among the most prevalent psychiatric disorders and are frequently co-morbid. However, some component of this co-morbidity may be artifactual and arise from the influence of current mental state on self-reports of AUD.MethodThis study examined whether past-year MDD is associated with differential criterion functioning (DCF) in reports of AUD symptomatology in male and female participants in the National Epidemiological Survey on Alcohol and Related Conditions (NEASRC). RESULTS: Reports of past-year AUD symptomatology were adequately summarized by a single-factor model in which each of the 11 abuse and dependence criteria had high factor loadings (0.71-0.93) and did not vary between men and women after allowing for threshold differences. Co-morbid MDD was associated with higher AUD mean scores. There was some evidence for DCF with past-year MDD being associated with a lower endorsement of use in hazardous situations among men whereas women with MDD were more likely to endorse both social/interpersonal problems and emotional/physical problems. CONCLUSIONS: Several items assessing AUD display DCF in the presence of MDD. While these findings highlight the need to consider the possibility that mental state can influence reporting of psychiatric symptoms and potentially inflate estimates of co-morbidity, they suggest that only a negligible component of the co-morbidity between MDD and AUDs can be attributed to over-reporting of alcohol symptomatology conditional on current MDD. [ABSTRACT FROM AUTHOR]

ABSTRACT BACKGROUND: We investigated the genetic and environmental contributions to covariation between smoking age-at-onset, cigarette consumption and smoking persistence.MethodMultivariate biometrical modelling methods were applied to questionnaire data from Australian twins and their siblings (14 472 individuals from 6247 families). The contributions of genetic and environmental factors to covariation between the three traits were estimated, allowing for sex differences in both trait prevalence and the magnitude of genetic and environmental effects. RESULTS: All traits were moderately heritable in males and females (estimates between 0.40 and 0.62), but there were sex differences in the extent to which additive genetic influences were shared across traits. Twin-specific environmental factors accounted for a substantial proportion of the variance in smoking age-at-onset in females (0.19) and males (0.12), but had little influence (<0.08) on other traits. Unique environmental factors were estimated to have a moderate influence on smoking age-at-onset (0.17 for females, 0.19 for males), but a stronger influence on other traits (between 0.39 and 0.49). CONCLUSIONS: These results provide some insight into observed sex differences in smoking behaviour, and suggest that searching for pleiotropic genes may prove fruitful. However, further work on phenotypic definitions of smoking behaviour, particularly persistence, is warranted. [ABSTRACT FROM AUTHOR]

ABSTRACT BACKGROUND: DSM-IV criteria for illicit drug abuse and dependence are largely based on criteria developed for alcohol use disorders and there is a lack of research evidence on the psychometric properties of these symptoms when applied to illicit drugs.MethodThis study utilizes data on abuse/dependence criteria for cannabis, cocaine, stimulants, sedatives, tranquilizers, opiates, hallucinogens and inhalants from the National Epidemiological Survey on Alcohol and Related Conditions (NESARC, n=43 093). Analyses included factor analysis to explore the dimensionality of illicit drug abuse and dependence criteria, calculation of item difficulty and discrimination within an item response framework and a descriptive analysis of 'diagnostic orphans': individuals meeting criteria for 1-2 dependence symptoms but not abuse. Rates of psychiatric disorders were compared across groups. RESULTS: Results favor a uni-dimensional construct for abuse/dependence on each of the eight drug classes. Factor loadings, item difficulty and discrimination were remarkably consistent across drug categories. For each drug category, between 29% and 51% of all individuals meeting criteria for at least one symptom did not receive a formal diagnosis of either abuse or dependence and were therefore classified as 'orphans'. Mean rates of disorder in these individuals suggested that illicit drug use disorders may be more adequately described along a spectrum of severity. CONCLUSIONS: While there were remarkable similarities across categories of illicit drugs, consideration of item difficulty suggested that some alterations to DSM regarding the relevant severity of specific abuse and dependence criteria may be warranted. [ABSTRACT FROM AUTHOR]

BACKGROUND: This paper explores the magnitude of - and extent of overlap between - additive genetic, shared environmental and non-shared environmental influences on lifetime stimulant use and on stimulant abuse/dependence symptoms; the associations between stimulant use and cannabis use and the extent to which these associations can be attributed to common or correlated genetic and environmental influences. METHODS: Self-report data on lifetime stimulant use, abuse/dependence symptoms and corresponding measures of cannabis involvement were collected from a sample of 6265 male and female Australian twins born 1964-1971. RESULTS: Approximately one in five study participants reported lifetime stimulant use while 5% reported experiencing at least one symptom of abuse/dependence. Multivariate genetic model fitting indicated moderate genetic influences on stimulant use (40%) and symptoms (65%) while there was no evidence of sex differences in the magnitude of these influences. Despite some overlap in genetic influences on these measures, approximately 60% of the genetic variance in symptoms was specific to this phenotype. There were also strong genetic and shared environmental correlations between the factors associated with stimulant use and those associated with cannabis use. CONCLUSIONS: There were moderate genetic influences on stimulant use and stimulant abuse/dependence with moderate overlap between the genetic factors associated with these outcomes. Additionally, there were strong associations between measures of lifetime stimulant use and analogous measures of cannabis use which, importantly, could be largely attributed to shared familial risk factors predisposing to both stimulant and cannabis use. [ABSTRACT FROM AUTHOR]

Background. This study examined the relationships between self-reported childhood sexual abuse (CSA) and drug-related outcomes in an Australian twin panel.Method. A semi-structured psychiatric interview was conducted in 1996-2000 by telephone with young adult Australian twins (mean age 29.9 years). Data reported here are from 6050 twins who responded to both CSA and drug-related items.Results. A history of CSA was associated with significant risk for subsequently occurring regular smoking and use of each illicit drug class. Further CSA-associated risk was found among regular users, for nicotine and alcohol dependence, and among illicit drug users, for abuse/dependence of most drug classes. In same-sex discordant pairs, significant risk for regular smoking and illicit drug use was found in twins with a history of CSA compared to their non-abused co-twins. Similar analyses for abuse/dependence found significant risk for opioids, any illicit drug, and any non-cannabis illicit drug. CSA was associated with significantly earlier drug use. Despite the association of CSA with risk for early-onset cannabis use and regular smoking, risks for illicit drug outcomes associated with CSA and with either form of early-onset use combine in near-additive fashion.Conclusions. CSA is associated with risk for subsequently occurring regular smoking and illicit drug use and abuse/dependence. Risks for drug use are mildly attenuated with control for familial contributions; similar risks for abuse/dependence remain significant for opioids and for illicit drugs combined across classes. Although we found evidence of earlier onset drug use with CSA, risks associated with CSA and with early-onset use combine in a largely additive manner. [ABSTRACT FROM AUTHOR]

Objective: A majority of individuals that meet criteria for alcohol abuse based on the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV), do so by endorsing the hazardous use criterion. We used a large, nationally representative data set to investigate whether alcohol abuse due to hazardous use is distinct from abuse attributable to other abuse criteria and whether abuse due to hazardous use is a less severe form of alcohol abuse.Method: Two waves of data, collected 3 years apart, from 34,653 individuals who participated in the National Epidemiological Survey on Alcohol and Related Conditions were used. Logistic regression was used to compare those with alcohol abuse due to hazardous use and those with alcohol abuse due to other criteria across several sociodemographic and psychiatric correlates at Wave 1 and across alcohol-related outcomes at the 3-year follow-up. Those with a lifetime history of alcohol dependence at Wave 1 were excluded.Results: Abuse due to hazardous use was more commonly noted in older individuals, those not living below the poverty line, and those without nicotine dependence and was more likely to be noted in White participants. Abuse due to hazardous use was also associated with lower rates of problematic drinking, alcohol dependence, and help seeking at 3-year follow-up.Conclusions: Individuals endorsing hazardous use are at greater risk than those endorsing no abuse criteria, but abuse due to hazardous use may represent a less severe form of alcohol-use disorders. This is troubling, because current DSM conceptualizations allow for endorsement of hazardous use to denote alcohol-use disorders. Future classifications may wish to consider a higher threshold for alcohol-use disorders, particularly when hazardous use is endorsed. [ABSTRACT FROM AUTHOR]

The μ-opioid receptor is the primary site of action of most opioids. The 118A>G (rs1799971) polymorphism in exon 1 of the μ-opioid receptor gene (OPRM1) leads to an Asn40Asp amino acid change that affects a putative N-glycosylation site. It has been widely investigated for association with alcohol and drug dependence and pain sensitivity, with mixed results. The aim of the current study was to examine whether this polymorphism was associated with heroin dependence in a large Bulgarian cohort of 1842 active users and 1451 population controls. SNP genotyping was done using Real-Time PCR TaqMan technology. Association analyses were conducted, separately for Roma and non-Roma participants. Our results suggest that there is no direct effect of 118A>G genotype on the risk for heroin dependence among active heroin users. [ABSTRACT FROM AUTHOR]

Objective: To document the prevalence and correlates of suicidal ideation (SI) among individuals seeking cannabis-based medicinal products (CBMPs); to test whether SI declines or intensifies after three months of CBMP treatment and to document 12-month trajectories of depression in those reporting SI and other patients., Method: Observational data were available for 3781 patients at entry to treatment, 2112 at three months and 777 for 12 months. Self-reported depressed mood and SI were assessed using items from the PHQ-9. Additional data included sociodemographic characteristics and self-reported well-being., Results: 25% of the sample reported SI at treatment entry and those with SI had higher levels of depressed mood (mean = 17.4 vs. 11.3; F (1,3533) = 716.5, p < .001) and disturbed sleep (mean = 13.8 vs. 12.2, F (1,3533) = 125.9, p < .001), poorer general health (mean = 43.6 vs. 52.2, F (1,3533) = 118.3, p < .001) and lower quality of life (mean = 0.44 vs. 0.56 ( F (1,3533) = 118.3, p < .001). The prevalence of SI reduced from 23.6% to 17.6% ( z  = 6.5, p < .001) at 3 months. Twelve-month follow-up indicated a substantial reduction in depressed mood with this reduction being more pronounced in those reporting SI (mean (baseline) = 17.7 vs. mean (12 months) = 10.3) than in other patients (mean (baseline) = 11.1 vs. mean (12 months) = 7.0)., Conclusions: SI is common among individuals seeking CBMPs to treat a range of chronic conditions and is associated with higher levels of depressed mood and poorer quality of life. Treatment with CBMPs reduced the prevalence and intensity of suicidal ideation.

Background: Previous research has suggested that the use of cannabis-based medicinal products is increasing most rapidly among older aged individuals (65+ years). Despite this, little is known about the characteristics of older people using cannabis-based medicinal products and their effectiveness., Objectives: We aimed to document the characteristics, outcomes and prescribing patterns of individuals aged 65+ years receiving prescribed cannabis compared to younger individuals receiving prescribed cannabis., Methods: Data from T21, an observational study of patients seeking treatment with medicinal cannabinoids, including self-report ratings of quality of life (assessed via the EQ-5D-5L), general health (assessed via the visual analogue scale of the EQ-5D-5L), mood (assessed via the Patient Health Questionnaire-9) and sleep (assessed using four items derived from the Pittsburgh Sleep Quality Index) were available at treatment entry [n = 4228; 198 (4.7%) 65+ years] and at a 3-month follow-up [n = 2455; 98 (4.2%) = 65+ years]., Results: Relative to younger individuals, those aged over 64 years were more likely to be female (52.5% vs 47.0%; p < 0.001), more likely to report pain as their primary condition (76.3% vs 45.6%; p < 0.001) and less likely to report current daily use (20.2% vs 60.3%, p < 0.001). They received fewer cannabis-based medicinal products (mean = 1.4 vs 2.1; F (1,2199) = 32.3, p < 0.001) and were more likely to receive a prescription for a cannabidiol dominant oil (17.5% vs 5.7%; p < 0.001) and less likely to receive a prescription for delta-9-tetrahydrocannabinol dominant flower (32.5% vs 75.2%; p < 0.001). There were significant improvements across all measures of well-being (p < 0.001), but the extent of improvements in sleep were more marked in younger individuals (p < 0.001)., Conclusions: There are important differences between individuals aged 65+ years and younger individuals receiving cannabis-based medicinal products. Older aged individuals experience considerable improvement in health and well-being when prescribed cannabis-based medicinal products., (© 2024. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Background: Cannabis-based medicinal products (CBMPs) are increasingly being used to treat post-traumatic stress disorder (PTSD), despite limited evidence of their efficacy. PTSD is often comorbid with major depression, and little is known about whether comorbid depression alters the effectiveness of CBMPs., Aims: To document the prevalence of depression among individuals seeking CBMPs to treat PTSD and to examine whether the effectiveness of CBMPs varies by depression status., Method: Data were available for 238 people with PTSD seeking CBMP treatment (5.9% of the treatment-seeking sample) and 3-month follow-up data were available for 116 of these. Self-reported PTSD symptoms were assessed at treatment entry and at 3-month follow-up using the PTSD Checklist - Civilian Version (PCL-C). The probable presence of comorbid depression at treatment entry was assessed using the nine-item Patient Health Questionnaire (PHQ-9). Additional data included sociodemographic characteristics and self-reported quality of life., Results: In total, 77% met screening criteria for depression, which was associated with higher levels of PTSD symptomatology (mean 67.8 v. 48.4, F (1,236) = 118.5, P < 0.001) and poorer general health, quality of life and sleep. PTSD symptomatology reduced substantially 3 months after commencing treatment (mean 58.0 v. 47.0, F (1,112) = 14.5, P < 0.001), with a significant interaction ( F (1,112) = 6.2, P < 0.05) indicating greater improvement in those with depression (mean difference 15.3) than in those without (mean difference 7)., Conclusions: Depression is common among individuals seeking CBMPs to treat PTSD and is associated with greater symptom severity and poorer quality of life. Effectiveness of CBMPs for treating PTSD does not appear to be impaired in people with comorbid depression.

Background and Aims: Previous studies have demonstrated associations between substance use and reduced educational attainment; however, many were unable to account for potential confounding factors like genetics and the rearing environment. In the few studies that controlled for these factors, the substances assessed were limited to alcohol, cannabis, and tobacco. To address these limitations, we examined the relationship between adolescent use of seven kinds of substances, the number of additional substances used, and high school noncompletion within a large sample of Australian twins., Design: A series of two-level generalized mixed effects logistic regressions were conducted to examine associations between adolescent substance use and high school noncompletion., Setting: Australia., Participants: A total of 9579 adult Australian twins from two cohorts of the Australian Twin Registry., Measurements: Assessments of high school completion, childhood major depression, conduct disorder symptoms, substance use initiation, demographics, and parental educational attainment using the Australian version of the Semi-Structured Assessment for the Genetics of Alcoholism., Findings: There were unique within-twin-pair effects of use of sedatives (odds ratio [OR] = 22.39 [95% confidence interval (CI) = 1.18-423.48]) and inhalants/solvents (OR = 10.46 [95% CI = 1.30-84.16]) on high school noncompletion. The number of substances used in adolescence was strongly associated with high school noncompletion across all discordant twin models (ORs from 1.50-2.32, Ps < 0.03)., Conclusions: In Australia, adolescent substance use appears to be associated with early school dropout, with the effects of any given substance largely because of the confounding factors of parental education, childhood conduct disorder symptoms, and use of other substances. Sedatives and inhalants/solvents have effects on high school noncompletion that cannot be explained by polysubstance use or familial factors., (© 2022 Society for the Study of Addiction.)

Randomised controlled trials (RCTs) have long been considered the gold standard of medical evidence. In relation to cannabis based medicinal products (CBMPs), this focus on RCTs has led to very restrictive guidelines in the UK, which are limiting patient access. There is general agreement that RCT evidence in relation to CBPMs is insufficient at present. As well as commercial reasons, a major problem is that RCTs do not lend themselves well to the study of whole plant medicines. One solution to this challenge is the use of real world evidence (RWE) with patient reported outcomes (PROs) to widen the evidence base. Such data increasingly highlights the positive impact medical cannabis can have on patients' lives. This paper outlines the value of this approach which involves the study of interventions and patients longitudinally under medical care. In relation to CBMPs, RWE has a broad range of advantages. These include the study of larger groups of patients, the use of a broader range and ratio of components of CBMPs, and the inclusion of more and rarer medical conditions. Importantly, and in contrast to RCTs, patients with significant comorbidities-and from a wider demographic profile-can also be studied, so providing higher ecological validity and increasing patient numbers, whilst offering significant cost savings. We conclude by outlining 12 key recommendations of the value of RWE in relation to medical cannabis. We hope that this paper will help policymakers and prescribers understand the importance of RWE in relation to medical cannabis and help them develop approaches to overcome the current situation which is detrimental to patients., Competing Interests: Author DN was Chair of the charity Drug Science. Author ML was Chief Research Officer of Drug Science. Author AS was Head of Research of Drug Science and scientific advisor to the Primary Care Cannabis Network, and an executive member of the Cannabis Industry Council, both unpaid roles. Author AA-F was study co-ordinator of Project Twenty21. Author RZ was Researcher at Drug Science. Author LP was expert member of the Drug Science Medical Cannabis Working Group. Drug Science receives an unrestricted educational grant from a consortium of medical cannabis companies to further its mission, that is the pursuit of an unbiased and scientific assessment of drugs regardless of their regulatory class. All Drug Science committee members, including the Chair, are unpaid by Drug Science for their effort and commitment to this organization. None of the authors would benefit from the wider prescription of medical cannabis in any form., (Copyright © 2022 Schlag, Zafar, Lynskey, Athanasiou-Fragkouli, Phillips and Nutt.)

Background: Drug classes are grouped based on their chemical and pharmacological properties, but prescription and illicit drugs differ in other important ways. Potential differences in genetic and environmental influences on the (mis)use of prescription and illicit drugs that are subsumed under the same class should be examined. Opioid and stimulant classes contain prescription and illicit forms differentially associated with salient risk factors (common route of administration, legality), making them useful comparators for addressing this etiological issue., Methods: A total of 2410 individual Australian twins [M age = 31.77 (s.d. = 2.48); 67% women] were interviewed about prescription misuse and illicit use of opioids and stimulants. Univariate and bivariate biometric models partitioned variances and covariances into additive genetic, shared environmental, and unique environmental influences across drug types., Results: Variation in the propensity to misuse prescription opioids was attributable to genes (41%) and unique environment (59%). Illicit opioid use was attributable to shared (71%) and unique (29%) environment. Prescription stimulant misuse was attributable to genes (79%) and unique environment (21%). Illicit stimulant use was attributable to genes (48%), shared environment (29%), and unique environment (23%). There was evidence for genetic influence common to both stimulant types, but limited evidence for genetic influence common to both opioid types. Bivariate correlations suggested that prescription opioid use may be more genetically similar to prescription stimulant use than to illicit opioid use., Conclusions: Prescription opioid misuse may share little genetic influence with illicit opioid use. Future research may consider avoiding unitary drug classifications, particularly when examining genetic influences.

Gambling disorder is associated with suicidal behaviors, but it is not clear whether the association is due to common etiologic factors or to gambling disorder being causally related to suicidality. This question was examined from epidemiologic, longitudinal, and discordant twin study perspectives. The results suggested that the causes of the association with disordered gambling differed for suicidal ideation, plan, and attempt, and differed for men and women. The association of suicidal thoughts with disordered gambling was non-causally explained by common genetic influences among women (but not men). Conversely, there was evidence consistent with a potentially causal influence of disordered gambling on suicide attempt among men (but not women), which might have been related to gambling-related financial problems. The use of monetary data to identify individuals experiencing financial harms associated with their gambling may represent a more practicable target for screening, intervention, and prevention and may reduce gambling-related financial crises, thereby warding off a potential gambling-related suicide attempt., Competing Interests: Declarations of Interest: None.

Background: Substance use and psychiatric illness, particularly psychotic disorders, contribute to violence in emergency healthcare settings. However, there is limited research regarding the relationship between specific substances, psychotic symptoms and violent behaviour in such settings. We investigated the interaction between recent cannabinoid and stimulant use, and acute psychotic symptoms, in relation to violent behaviour in a British emergency healthcare setting., Methods: We used electronic medical records from detentions of 1089 individuals under Section 136 of the UK Mental Health Act (1983 amended 2007), an emergency police power used to detain people for 24-36 h for psychiatric assessment. The relationship between recent cannabinoids and/or stimulant use, psychotic symptoms, and violent behaviour, was estimated using logistic regression., Findings: There was evidence of recent alcohol or drug use in 64.5% of detentions. Violent incidents occurred in 12.6% of detentions. Psychotic symptoms increased the odds of violence by 4.0 [95% confidence intervals (CI) 2.2-7.4; p < 0.0001]. Cannabinoid use combined with psychotic symptoms increased the odds of violence further [odds ratios (OR) 7.1, 95% CI 3.7-13.6; p < 0.0001]. Recent use of cannabinoids with stimulants but without psychotic symptoms was also associated with increased odds of violence (OR 3.3, 95% CI 1.4-7.9; p < 0.0001)., Interpretation: In the emergency setting, patients who have recently used cannabinoids and exhibit psychotic symptoms are at higher risk of violent behaviour. Those who have used both stimulants and cannabinoids without psychotic symptoms may also be at increased risk. De-escalation protocols in emergency healthcare settings should account explicitly for substance use.

Synthetic cannabinoid receptor agonists (SCRAs) may be used as an alternative to natural cannabis; however, they may carry a greater risk of problematic use and withdrawal. This study aimed to characterise the withdrawal symptom profile of SCRAs and compare their profile of effect with high-potency herbal cannabis. Global Drug Survey data (2015 and 2016) were used to access a clinically relevant sample of people reporting use of SCRAs >10 times in the past 12-months, a previous SCRA quit attempt, and lifetime use of high-potency herbal cannabis. Participants completed an 11-item SCRA withdrawal symptom checklist and compared SCRAs and high-potency herbal cannabis on their onset and duration of effects, speed of the development of tolerance, severity of withdrawal, and difficulty with dose titration. Participants (n = 284) reported experiencing a mean of 4.4 (95% CI: 4.1, 4.8) withdrawal symptoms after not using SCRAs for >1 day; most frequently reported were sleep issues (59.2%), irritability (55.6%), and low mood (54.2%). Withdrawal symptoms were significantly associated with frequency (>51 vs. 11-50 times per year: IRR = 1.43, 95% CI: 1.16, 1.77, p = 0.005) and quantity (grams per session: IRR = 1.13, 95% CI: 1.05, 1.22, p = 0.001) of SCRA use. Compared to high-potency herbal cannabis, SCRAs were rated as having a faster onset and shorter duration of effects, faster development of tolerance, and more severe withdrawal (p's < 0.001). In conclusion, SCRA withdrawal symptoms are more likely to occur after greater SCRA exposure. The effects of SCRA indicate a more severe withdrawal syndrome and a greater risk of problematic use than natural cannabis., (© 2021. The Author(s).)

Attempts to identify opioid users with increased risk of escalating to opioid use disorder (OUD) have had limited success. Retrospectively assessed subjective effects of initial opioid misuse were compared in a pilot sample of opioid misusers (nonmedical use ≤60 times lifetime) who had never met criteria for OUD (N = 14) and heroin-addicted individuals in treatment for OUD (N = 15). Relative to opioid misusers without a lifetime OUD diagnosis, individuals with OUD reported greater euphoria and other positive emotions, activation, pruritus, and internalizing symptoms. Consistent with these findings, proxy Addiction Research Center Inventory (ARCI) Amphetamine Group, and Morphine Benzedrine Group scale mean item scores were significantly higher in those with OUD. Replication was attempted in opioid misusers with (N = 25) and without OUD (N = 25) who were assessed as part of an ongoing genetic study. We observed similar significant between-group differences in individual subjective effect items and ARCI scale mean item scores in the replication sample. We, thus confirm findings from prior reports that retrospectively assessed subjective responses to initial opioid exposure differ significantly between opioid users who do, and do not, progress to OUD. Our report extends these findings in comparisons limited to opioid misusers. Additional research will be necessary to examine prospectively whether the assessment of subjective effects after initial use has predictive utility in the identification of individuals more likely to progress to OUD., (© 2020 Wiley Periodicals, Inc.)

Background: Despite an overall decline in tobacco use in the United States, secular trends of smoking and nicotine dependence with co-occurring substance use are not well characterized., Methods: We examined self-reported tobacco and other substance use in 22,245 participants age 21-59 in the United States from six waves of the National Health and Nutrition Examination Survey (NHANES). Using Joinpoint regression, we assessed secular trends of smoking and nicotine dependence as a function of co-occurring use of alcohol, prescription opioids, marijuana/hashish, cocaine/heroin/methamphetamine, or other injection drug use. Multivariable logistic regressions were fitted to identify the potential risk factors., Results: During 2005-2016, the prevalence of current smoking decreased (without co-occurring substance use: 17.0 %-12.7 %; with co-occurring use of one substance: 35.3 % to 24.6 %; with co-occurring use of two or more substances: 53.8 %-42.2 %), and moderate-to-severe nicotine dependence decreased as well (8.0 %-4.2 %, 16.0 %-8.8 %, and 23.9 %-15.7 %, respectively). Smoking and nicotine dependence were more likely in those with co-occurring use of one substance (current smoking: odds ratio [OR] = 2.22, 95 % confidence interval [CI] = 2.01-2.45); nicotine dependence: OR = 1.88, 95 % CI = 1.63-2.17) and in those with co-occurring use of two or more substances (current smoking: OR = 5.25, 95 % CI = 4.63-5.95; nicotine dependence: OR = 3.24, 95 % CI = 2.72-3.87)., Conclusions: Co-occurring substance use was associated with smaller reductions in tobacco use, over time, and with increased odds of nicotine dependence. This suggests that co-occurring substance users should be regarded as a tobacco-related disparity group and prioritized for tobacco control interventions., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Diagnostic categories do not completely reflect the heterogeneous expression of psychosis. Using data from the EU-GEI study, we evaluated the impact of schizophrenia polygenic risk score (SZ-PRS) and patterns of cannabis use on the transdiagnostic expression of psychosis. We analysed first-episode psychosis patients (FEP) and controls, generating transdiagnostic dimensions of psychotic symptoms and experiences using item response bi-factor modelling. Linear regression was used to test the associations between these dimensions and SZ-PRS, as well as the combined effect of SZ-PRS and cannabis use on the dimensions of positive psychotic symptoms and experiences. We found associations between SZ-PRS and (1) both negative (B = 0.18; 95%CI 0.03-0.33) and positive (B = 0.19; 95%CI 0.03-0.35) symptom dimensions in 617 FEP patients, regardless of their categorical diagnosis; and (2) all the psychotic experience dimensions in 979 controls. We did not observe associations between SZ-PRS and the general and affective dimensions in FEP. Daily and current cannabis use were associated with the positive dimensions in FEP (B = 0.31; 95%CI 0.11-0.52) and in controls (B = 0.26; 95%CI 0.06-0.46), over and above SZ-PRS. We provide evidence that genetic liability to schizophrenia and cannabis use map onto transdiagnostic symptom dimensions, supporting the validity and utility of the dimensional representation of psychosis. In our sample, genetic liability to schizophrenia correlated with more severe psychosis presentation, and cannabis use conferred risk to positive symptomatology beyond the genetic risk. Our findings support the hypothesis that psychotic experiences in the general population have similar genetic substrates as clinical disorders., (© 2021. The Author(s).)

Background: Daily use of high-potency cannabis has been reported to carry a high risk for developing a psychotic disorder. However, the evidence is mixed on whether any pattern of cannabis use is associated with a particular symptomatology in first-episode psychosis (FEP) patients., Method: We analysed data from 901 FEP patients and 1235 controls recruited across six countries, as part of the European Network of National Schizophrenia Networks Studying Gene-Environment Interactions (EU-GEI) study. We used item response modelling to estimate two bifactor models, which included general and specific dimensions of psychotic symptoms in patients and psychotic experiences in controls. The associations between these dimensions and cannabis use were evaluated using linear mixed-effects models analyses., Results: In patients, there was a linear relationship between the positive symptom dimension and the extent of lifetime exposure to cannabis, with daily users of high-potency cannabis having the highest score ( B = 0.35; 95% CI 0.14-0.56). Moreover, negative symptoms were more common among patients who never used cannabis compared with those with any pattern of use ( B = -0.22; 95% CI -0.37 to -0.07). In controls, psychotic experiences were associated with current use of cannabis but not with the extent of lifetime use. Neither patients nor controls presented differences in depressive dimension related to cannabis use., Conclusions: Our findings provide the first large-scale evidence that FEP patients with a history of daily use of high-potency cannabis present with more positive and less negative symptoms, compared with those who never used cannabis or used low-potency types.

Adolescents have access to a wide range of cannabis products with patterns of use becoming increasingly diverse. This study aimed to identify subgroups of adolescents in the general population who use similar types of cannabis and their association with psychotic experiences. Data on cannabis use were obtained from 467 adolescents aged between 16 and 17 years. Latent class analysis (LCA) identified groups of adolescents based on the type of cannabis used in the past 12 months. Univariate analysis explored differences in socio-demographics, substance use and mental health symptoms between groups. Multivariate analysis examined associations between class membership and psychotic experiences controlling for frequency and amount of cannabis. Finally, we explored the association between motives for cannabis and class membership using multi-nominal logistic regression. LCA identified 3 classes of adolescents: (i) herbal only (47.9%); (ii) skunk only (20.8%) and (3) mixed use (31.3%). Relative to non-users, skunk only use was associated with a 2-fold increase in paranoia (OR = 2.45, 95% CI = 1.29-4.63), along with, sleep disturbance and anxiety. Monthly cannabis use and consuming 2 or more joints on one occasion was associated with a 2-fold increase in hallucinations (OR = 2.2; 95% CI = 1.0-4.8 and OR = 1.9; 95% CI = 1.2-3.2), but did not reach the Bonferroni corrected p-value. Expansion and conformity motives differentiated the mixed cannabis class from the herbal only class. The findings suggest that different subgroups of cannabis users exist in adolescence as defined by the type of cannabis consumed and are differentially related to psychotic experiences and motives for use., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Background: The emergence of legal cannabis industries poses a new public health challenge. Health information labels are part of the public health strategy for tobacco and alcohol, but there is limited research on cannabis-related messaging. This study explored perceptions of cannabis health information labels among people who used cannabis in the last 12 months residing in the U.S. and Canada., Methods: The Global Drug Survey (GDS) is a large anonymous cross-sectional web-survey. In GDS2019, respondents were presented with six labels with cannabis-related health information (dependence; driving stoned; harms of smoking; harms to developing brain; lack of motivation; effects on memory), and asked if information was new, believed, would it change behavior, and about acceptability of having health labels on legal products. This paper includes 1,275 respondents from Canada and 2,224 from U.S. states where cannabis was legal at the time of the survey, and 5,230 from other U.S. states., Results: Few respondents said that the information was new (6.6-24.6%). Most said the information was believable (63.5-72.0%) other than for the dependence message (28.1% new, 56.8% believed), which was perceived to be the least likely to change behavior (10.2%). Driving stoned was the message perceived to be the most likely to change behavior (58.5%). Respondents living in Canada were less likely to say information was new and rated most messages more believable than those in the U.S. Respondents from legal U.S. states were less likely to say information was new compared to other states. Respondents who used cannabis daily rated acceptability of labels lower (27.8%) than those using 1-48 days (40.6%)., Conclusions: Novel, believable information may be more effective at changing behavior. Regular consumers may be less susceptible to messages. Information focusing on safer use strategies and benefits of reducing use may be more acceptable and should be assessed in future research., Competing Interests: Declarations of interest ARM is the founder and director of the Global Drug Survey. The other authors have no conflicts of interest to declare. Global Drug Survey receives no funding from the alcohol, tobacco or cannabis industries., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Background and Aims: Cannabis products with high delta-9-tetrahydrocannabinol (THC) concentrations carry an increased risk of addiction and mental health disorders, while it has been suggested that cannabidiol (CBD) may moderate the effects of THC. This study aimed to systematically review and meta-analyse changes in THC and CBD concentrations in cannabis over time (PROSPERO registration: CRD42019130055)., Design: Embase, MEDLINE® and Epub Ahead of Print, In-Process and Other Non-Indexed Citations and Daily, Global Health, PsycINFO and Scopus were searched from inception to 27/03/2019 for observational studies reporting changes in mean THC and/or CBD concentration in cannabis over at least three annual time points. Searches and extraction were conducted by two independent reviewers. Random effects meta-regression models estimated annual changes in THC and CBD for each product within each study; these estimates were pooled across studies in random effects models., Results: We identified 12 eligible studies from the USA, UK, Netherlands, France, Denmark, Italy and New Zealand. For all herbal cannabis, THC concentrations increased by 0.29% each year (95% CI: 0.11, 0.47), P < 0.001 based on 66 747 cannabis samples from eight studies, 1970-2017. For cannabis resin, THC concentrations increased by 0.57% each year (95% CI: 0.10, 1.03), P = 0.017 based on 17 371 samples from eight studies, 1975-2017. There was no evidence for changes in CBD in herbal cannabis [-0.01% (95% CI: -0.02, 0.01), P = 0.280; 49 434 samples from five studies, 1995-2017] or cannabis resin [0.03% (95% CI: -0.11, 0.18), P = 0.651; 11 382 samples from six studies, 1992-2017]. Risk of bias was low apart from non-random sampling in most studies. There was evidence of moderate to substantial heterogeneity., Conclusions: Concentrations of delta-9-tetrahydrocannabinol (THC) in international cannabis markets increased from 1970 to 2017 while cannabidiol (CBD) remained stable. Increases in THC were greater in cannabis resin than herbal cannabis. Rising THC in herbal cannabis was attributable to an increased market share of high-THC sinsemilla relative to low-THC traditional herbal cannabis., (© 2020 The Authors. Addiction published by John Wiley & Sons Ltd on behalf of Society for the Study of Addiction.)

Aims: To identify drug use typologies based on substances used and persistence of use over two time points, use a genetically informed design to explore twin concordance of and genetic influence on the use typologies and compare patterns of declined/discontinued ("desistant") and persistent drug use on drug use correlates., Design: Latent class analysis was applied to data from a cross-sectional self-report survey on current and past drug use. Use characteristics, use disorder, and psychiatric problems were compared across classes., Setting: Computer-assisted telephone interview in respondents' homes., Participants: A total of 3785 individual twins and siblings (1365 men, 2420 women; M age  = 32) from the Australian Twin Registry Cohort III., Measurements: A comprehensive interview assessed prior to past year and past year use of cannabis, stimulants, cocaine/crack, hallucinogens, opioids, sedatives, inhalants, dissociatives, and solvents; age of first use; opportunity to use; peer drug use; attention deficit/hyperactivity, conduct, antisocial personality, depressive, and substance use disorders; and suicidality., Findings: A five-class solution emerged: no/low use (50%), desistant cannabis use (23%), desistant party drug use (18%), persistent prescription drug misuse (4%), and persistent polydrug use (5%). Twin concordances were higher among monozygotic (k = 0.30-0.35) than dizygotic pairs (same-sex k = 0.19-0.20; opposite sex k = 0.07), and biometric modeling suggested that the persistent polydrug use class, in particular, was highly heritable (a 2  = 0.94). Conduct disorder (OR = 2.40), antisocial personality disorder (OR = 3.27), and suicidal ideation (OR = 1.98) increased persistent polydrug use risk; depression (OR = 2.38) and lifetime suicide attempt (OR = 2.31) increased persistent prescription misuse risk. Relative to persistent prescription drug misuse, persistent polydrug use was associated with higher rates of cannabis and stimulant use disorder (OR = 6.14-28.01), younger first substance use (OR = 0.82-0.83), more drug use opportunity (OR = 10.66-66.06), and more drug-using peers (OR = 4.66-9.20)., Conclusions: Unique patterns of declined/discontinued ("desistant") and persistent drug use are differentially heritable and differentially associated with risk factors, psychiatric symptoms, and substance use disorder outcomes., (© 2020 Society for the Study of Addiction.)

Background: Previous research has reported increased risk for psychosis among individuals who use cannabis during adolescence. We conducted a systematic review and meta-analysis to investigate the interaction between adolescent cannabis use and other factors in moderating risk for psychosis later in life. Method: We searched four electronic databases in June 2020 for articles that assessed adolescent cannabis use, had psychosis as an outcome and analyzed for the association between adolescent cannabis use and psychosis. Analysis was done using random-effects meta-analysis and narrative synthesis. Results : A total of 63 studies were included in the narrative review and 18 studies were included in the meta-analysis. Adolescent cannabis use was found to increase risk for psychosis (RR = 1.71 (95%CI, 1.47-2.00, p  < 0.00001) and predict earlier onset of psychosis. The following factors moderate the relationship between cannabis use and the risk of psychosis: age of onset of cannabis use, frequent cannabis use, exposure to childhood trauma, concurrent use of other substances and genetic factors. Conclusion: Adolescent cannabis use is associated with an increased risk for psychosis later in life. In addition, there are factors that moderate this relationship; therefore there is a need for research to assess the interaction between these factors, adolescent cannabis use and psychosis risk.

Eating disorders and substance use disorders frequently co-occur. Twin studies reveal shared genetic variance between liabilities to eating disorders and substance use, with the strongest associations between symptoms of bulimia nervosa and problem alcohol use (genetic correlation [r g ], twin-based = 0.23-0.53). We estimated the genetic correlation between eating disorder and substance use and disorder phenotypes using data from genome-wide association studies (GWAS). Four eating disorder phenotypes (anorexia nervosa [AN], AN with binge eating, AN without binge eating, and a bulimia nervosa factor score), and eight substance-use-related phenotypes (drinks per week, alcohol use disorder [AUD], smoking initiation, current smoking, cigarettes per day, nicotine dependence, cannabis initiation, and cannabis use disorder) from eight studies were included. Significant genetic correlations were adjusted for variants associated with major depressive disorder and schizophrenia. Total study sample sizes per phenotype ranged from ~2400 to ~537 000 individuals. We used linkage disequilibrium score regression to calculate single nucleotide polymorphism-based genetic correlations between eating disorder- and substance-use-related phenotypes. Significant positive genetic associations emerged between AUD and AN (r g = 0.18; false discovery rate q = 0.0006), cannabis initiation and AN (r g = 0.23; q < 0.0001), and cannabis initiation and AN with binge eating (r g = 0.27; q = 0.0016). Conversely, significant negative genetic correlations were observed between three nondiagnostic smoking phenotypes (smoking initiation, current smoking, and cigarettes per day) and AN without binge eating (r gs = -0.19 to -0.23; qs < 0.04). The genetic correlation between AUD and AN was no longer significant after co-varying for major depressive disorder loci. The patterns of association between eating disorder- and substance-use-related phenotypes highlights the potentially complex and substance-specific relationships among these behaviors., (© 2020 Society for the Study of Addiction.)

Background: As new cannabis products and administration methods proliferate, patterns of use are becoming increasingly heterogeneous. However, few studies have explored different profiles of cannabis use and their association with problematic use., Methods: Latent class analysis (LCA) was used to identify subgroups of past-year cannabis users endorsing distinct patterns of use from a large international sample (n = 55 240). Past-12-months use of six different cannabis types (sinsemilla, herbal, hashish, concentrates, kief, edibles) were used as latent class indicators. Participants also reported the frequency and amount of cannabis used, whether they had ever received a mental health disorder diagnosis and their cannabis dependence severity via the Severity of Dependence Scale (SDS)., Results: LCA identified seven distinct classes of cannabis use, characterised by high probabilities of using: sinsemilla & herbal (30.3% of the sample); sinsemilla, herbal & hashish (20.4%); herbal (18.4%); hashish & herbal (18.8%); all types (5.7%); edibles & herbal (4.6%) and concentrates & sinsemilla (1.7%). Relative to the herbal class, classes characterised by sinsemilla and/or hashish use had increased dependence severity. By contrast, the classes characterised by concentrates use did not show strong associations with cannabis dependence but reported greater rates of ever receiving a mental health disorder diagnosis., Conclusions: The identification of these distinct classes underscores heterogeneity among cannabis use behaviours and provides novel insight into their different associations with addiction and mental health.

Marriage and parenthood are associated with alcohol use and use disorder (AUD), although they are confounded such that many studies struggle to identify their unique and/or causal effects. The present study utilized a genetically informed discordant twin design that strengthens the putative causal role of marital and parental status in the presentation of AUD symptoms by using each individual's cotwin as their own control while simultaneously modeling both predictors among men and women. Participants were 980 complete same-sex twin pairs from the Australian Twin Registry ( M age = 31.70 [ SD = 2.48]; 71% women). Marital status, parental status, and past year AUD symptoms were assessed via semistructured interview. Three random-intercept generalized linear mixed models were fit in men and women including (a) marital status only, (b) parental status only, and (c) both marital and parental status; demographics, past year pregnancy, age of first drink, age of regular drinking, personality traits, and antisociality were included as covariates. Models tested for quasi-causal and familial effects. The sole-predictor marital status model (Model 1) provided the best fit among men, while the simultaneous-predictor marital and parental status model (Model 3) provided the best fit among women. Sole-predictor models showed familial effects of both predictors among men and quasi-causal and familial effects of both predictors among women; the simultaneous-predictor model revealed familial effects of marital status only among men and quasi-causal effects of parental status only among women. The present study elucidates important sex differences in the presentation of AUD among midlife adults in the context of notable developmental milestones. (PsycInfo Database Record (c) 2020 APA, all rights reserved).

Age of first drink (AFD) has repeatedly been found to be associated with alcohol use disorder (AUD); however, some studies suggest this is a noncausal effect that may be due to childhood risk factors or familial influences. In contrast to indicators of any early alcohol use, such as AFD, indicators of a pattern of repeated drinking may be more likely to be causally associated with later problematic alcohol use. The current study examined AFD and age of onset of regular drinking (ARD; defined as drinking at least once a month for 6 or more months) as quasicausal predictors of lifetime AUD symptoms. Participants were 3,005 adult Australian twins who reported having been regular drinkers in their lifetime. Semistructured interviews were conducted to assess AFD, ARD, AUD, externalizing symptomatology, and other substance use. Personality traits were assessed via questionnaire. Unadjusted and adjusted multilevel discordant twin models were conducted using data from 1,041 complete twin pairs; adjusted models included socioeconomic status, personality, conduct disorder, and early initiation of regular smoking and marijuana use as covariates. Results from fully adjusted models controlling for familial confounds provided evidence for a causal influence of ARD on AUD symptoms, whereby twins with an earlier age of regular drinking than their cotwin had more lifetime AUD symptoms. However, AFD did not significantly predict AUD symptoms after adjusting for confounds. These results suggest that early regular drinking may serve as a causal risk factor for future problems, while early initiation of any alcohol use may indicate genetic liability. (PsycInfo Database Record (c) 2020 APA, all rights reserved).

Background: Many adult drinkers consume far beyond the binge threshold. This "high-intensity drinking" (HID), defined as 2 (HID-2) and 3 (HID-3) times the binge threshold, is of public health interest due to its role in acute alcohol-related harms. Research on HID has mostly been limited to college-aged young adults, focused on contextual factors, and neglected the potential role of genetic influences on the propensity to engage in HID., Methods: Structured diagnostic interviews assessing past-year alcohol involvement were conducted with 3,785 individuals (1,365 men, 2,420 women; M age  = 32, range = 21 to 46), including 3,314 twins and 471 nontwin siblings from the Australian Twin Registry. Multinomial logistic regression analyses were conducted to compare HID-2 and HID-3 to binge drinking on demographic correlates, drinking characteristics, and drinking-related consequences. Biometric modeling was conducted to estimate the role of genetic, common, and individual-specific environmental factors in HID propensity., Results: Among past-year drinkers, the prevalence of HID-2 and HID-3 was both 22%, with men disproportionally represented. The frequencies of drinking, intoxication, and binge drinking significantly increased across the heavier drinking categories, which also evidenced higher average consumption quantities and higher rates of alcohol-related consequences. The propensity to engage in HID was significantly heritable (A = 37% [95% CI: 28 to 46%]), with individual-specific environmental influences accounting for the remainder of the variance., Conclusions: This study convincingly demonstrates that HID is not restricted to college-aged young adults, but also can be highly prevalent among those of working age, and that the propensity to engage in HID is partially explained by genetic influences., (© 2020 by the Research Society on Alcoholism.)

Background: Cannabis use patterns vary considerably, with many users reporting simultaneous and non-simultaneous use (co-use) of other substances. Despite this, little research has examined the extent to which subtypes of cannabis users may be identified based on their simultaneous and co-use behaviors., Methods: The sample consisted of adult Australian twins and siblings who reported lifetime cannabis use (n = 2590). A latent class analysis was conducted to determine subtypes of cannabis users based on five indicators of substance co-use and simultaneous use. Adolescent correlates (age of substance initiation and conduct disorder) and adult correlates (substance use/disorder and depression) of class membership were assessed. Twin similarity for class membership was also examined., Results: Four subtypes of users were identified: 1) alcohol co-users, 2) simultaneous alcohol users, 3) simultaneous tobacco users, and 4) simultaneous alcohol, tobacco, and drug users. Compared to co-users of alcohol, simultaneous alcohol users were at increased risk for alcohol problems. Patterns of use that involved simultaneous tobacco and cannabis use (i.e., simultaneous tobacco users and simultaneous alcohol, tobacco, and drug users) were associated with the most problematic outcomes, including substance use and disorder. There was evidence for genetic influences (12-58%) on cannabis use patterns, with higher concordance for latent class membership among monozygotic compared to dizygotic twins (χ 2 (1) = 7.19, p = 0.007)., Conclusions: The current study identified four classes of cannabis users at varying degrees of risk. Results suggest that simultaneous tobacco and cannabis use may be especially associated with deleterious outcomes., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Background: Gambling disorder (GD), recognized in Diagnostic and Statistical Manual of Mental Disorders, Version 5 (DSM-5) as a behavioral addiction, is associated with a range of adverse outcomes. However, there has been little research on the genetic and environmental influences on the development of this disorder. This study reports results from the largest twin study of GD conducted to date., Methods: Replication and combined analyses were based on samples of 3292 (mean age 31.8, born 1972-79) and 4764 (mean age 37.7, born 1964-71) male, female, and unlike-sex twin pairs from the Australian Twin Registry. Univariate biometric twin models estimated the proportion of variation in the latent GD liability that could be attributed to genetic, shared environmental, and unique environmental factors, and whether these differed quantitatively or qualitatively for men and women., Results: In the replication study, when using a lower GD threshold, there was evidence for significant genetic (60%; 95% confidence interval (CI) 45-76%) and unique environmental (40%; 95% CI 24-56%), but not shared environmental contributions (0%; 95% CI 0-0%) to GD liability; this did not significantly differ from the original study. In the combined analysis, higher GD thresholds (such as one consistent with DSM-5 GD) and a multiple threshold definitions of GD yielded similar results. There was no evidence for quantitative or qualitative sex differences in the liability for GD., Conclusions: Twin studies of GD are few in number but they tell a remarkably similar story: substantial genetic and unique environmental influences, with no evidence for shared environmental contributions or sex differences in GD liability.

Aims: To quantify changes in (i) potency (concentration of Δ 9 -tetrahydrocannabinol; %THC), (ii) price (euros/g of cannabis) and (iii) value (mg THC/euro) of cannabis resin and herbal cannabis in Europe., Design: Repeated cross-sectional study., Setting and Participants: Data collected from 28 European Union (EU) member states, Norway and Turkey by the European Monitoring Centre for Drugs and Drug Addiction., Measurements: Outcome variables were potency, price and value for cannabis resin and herbal cannabis in Europe, 2006-16. Inflation was estimated using the Harmonised Indices of Consumer Prices. Mixed-effects linear regression models were used to estimate linear and quadratic time trends, with a random intercept and slope fitted to account for variation across countries., Findings: Resin potency increased from a mean [95% confidence interval (CI)] of 8.14% THC (6.89, 9.49) in 2006 to 17.22 (15.23, 19.25) in 2016. Resin price increased from 8.21 euros/g (7.54, 8.97) to 12.27 (10.62, 14.16). Resin increased in value, from 11.00 mg THC per euro (8.60, 13.62) to 16.39 (13.68, 19.05). Quadratic time trends for resin potency and value indicated minimal change from 2006 to 2011, followed by marked increases from 2011 to 2016. Herbal cannabis potency increased from 5.00% THC (3.91, 6.23) to 10.22 (9.01, 11.47). Herbal price increased from 7.36 euros/g (6.22, 8.53) to 12.22 (10.59, 14.03). The value of herbal cannabis did not change from 12.65 mg of THC per euro (10.18, 15.34) to 12.72 (10.73, 14.73). All price trends persisted after adjusting for inflation., Conclusions: European cannabis resin and herbal cannabis increased in potency and price from 2006 to 2016. Cannabis resin (but not herbal cannabis) increased in the quantity of Δ 9 -tetrahydrocannabinol per euro spent. Marked increases in resin potency and value from 2011 to 2016 are consistent with the emergence of new resin production techniques in European and neighbouring drug markets., (© 2018 The Authors. Addiction published by John Wiley & Sons Ltd on behalf of Society for the Study of Addiction.)

Background: Individuals differ in their sensitivity to alcohol's physiological effects, including blacking and passing out. Blackouts are periods of impaired memory formation when an individual engages in activities they later cannot recall, while passing out results in loss of consciousness., Methods: The sample consisted of 3,292 adult twins from the Australian Twin Registry. Univariate twin analyses were conducted to examine the contributions of genetic and environmental influences to blacking and passing out occurrence and susceptibility (accounting for frequency of intoxication). Evidence for shared etiology of susceptibility to blacking and passing out was examined using bivariate twin analyses., Results: Although blacking and passing out were strongly associated (odds ratio (OR) = 4.45, 95% confidence interval (CI): [3.85, 5.14]), the genetic epidemiology was quite different. Genetic (43%) and nonshared environmental (57%) influences contributed to liability for blackout occurrence. For passing out occurrence, there was evidence of sex differences. Among men, genetic (32%) and nonshared environmental (68%) influences contributed, whereas among women, there were shared (29%) and nonshared environmental (72%) influences. After accounting for frequency of intoxication, genetic influences on blackout susceptibility remained significant; in contrast, only nonshared environmental influences were significant for passing out susceptibility. There was evidence for overlapping genetic and nonshared environmental factors influencing susceptibility to blacking and passing out among men; among women, there were overlapping nonshared environmental influences., Conclusions: Blacking and passing out are 2 common sedative-like effects of heavy drinking, and people differ considerably in their susceptibility to these effects. This study suggests that differences in blackout susceptibility can be explained by genetic factors in both men and women, while differences in susceptibility to pass out after consuming alcohol may be attributable to environmental influences, particularly among women. These environmental factors may include changing social and cultural norms about alcohol use, drinking context, and the type(s) of alcohol consumed., (© 2019 by the Research Society on Alcoholism.)