Recreational cannabis legalization has had limited effects on a wide range of adult psychiatric and psychosocial outcomes.

BACKGROUND: The causal impacts of recreational cannabis legalization are not well understood due to the number of potential confounds. We sought to quantify possible causal effects of recreational cannabis legalization on substance use, substance use disorder, and psychosocial functioning, and whether vulnerable individuals are more susceptible to the effects of cannabis legalization than others. METHODS: We used a longitudinal, co-twin control design in 4043 twins (N = 240 pairs discordant on residence), first assessed in adolescence and now age 24-49, currently residing in states with different cannabis policies (40% resided in a recreationally legal state). We tested the effect of legalization on outcomes of interest and whether legalization interacts with established vulnerability factors (age, sex, or externalizing psychopathology). RESULTS: In the co-twin control design accounting for earlier cannabis frequency and alcohol use disorder (AUD) symptoms respectively, the twin living in a recreational state used cannabis on average more often (ßw = 0.11, p = 1.3 × 10-3), and had fewer AUD symptoms (ßw = -0.11, p = 6.7 × 10-3) than their co-twin living in an non-recreational state. Cannabis legalization was associated with no other adverse outcome in the co-twin design, including cannabis use disorder. No risk factor significantly interacted with legalization status to predict any outcome. CONCLUSIONS: Recreational legalization was associated with increased cannabis use and decreased AUD symptoms but was not associated with other maladaptations. These effects were maintained within twin pairs discordant for residence. Moreover, vulnerabilities to cannabis use were not exacerbated by the legal cannabis environment. Future research may investigate causal links between cannabis consumption and outcomes.

Evaluating substance use outcomes of recreational cannabis legalization using a unique co-twin control design.

Background: As more states pass recreational cannabis legalization (RCL), we must understand how RCL affects substance use.Objectives: The current study aims to examine the effect of RCL on lifetime and past-year use of cannabis, alcohol, tobacco, and other drugs, frequency of cannabis, alcohol, and tobacco use, co-use of cannabis with alcohol and tobacco, and consequences from cannabis and alcohol use.Methods: We used a unique, co-twin control design of twin pairs who were discordant for living in a state with RCL between 2018 and 2021. The sample consisted of 3,830 adult twins (41% male), including 232 twin pairs discordant for RCL. Problems from alcohol and cannabis use were assessed via the Brief Marijuana Consequences Questionnaire and the Brief Young Adult Alcohol Consequences Questionnaire.Results: Results indicated that the twin living in an RCL state was more likely to endorse past-year cannabis use (OR = 1.56, p = .009), greater number of cannabis use days in the past 6 months (ß = 0.47, p = .019), but not more negative consequences from cannabis use (ß = 0.21, p = .456) compared to their co-twin in a non-RCL state. There were no differences within-twin pairs in frequency of alcohol use (ß=-0.05, p = .601), but the RCL twin reported fewer negative consequences from alcohol use (ß=-0.29, p = .016) compared to their co-twin in a non-RCL state. We did not observe any other differences within-twin pairs on other outcomes.Conclusion: These results suggest that living in an RCL state is associated with greater cannabis frequency but not more negative consequences from cannabis use than living in a non-RCL state.

Addendum to "Evaluating substance use outcomes of recreational cannabis legalization using a unique co-twin control design".

An earlier version of this article was published in error. Our prior publication was missing reference to a prior study on this topic. Our prior research has not found an association between recreational cannabis legalization (RCL) and negative psychosocial and psychiatric outcomes. We reported significant associations between RCL with greater cannabis frequency and fewer alcohol use disorder symptoms. The current study expands on our previous research by using a cross-sectional design and different measures of problems from cannabis and alcohol use and including additional substance use variables. The current study found similar results to our previous research.

Leveraging genome-wide data to investigate differences between opioid use vs. opioid dependence in 41,176 individuals from the Psychiatric Genomics Consortium.

To provide insights into the biology of opioid dependence (OD) and opioid use (i.e., exposure, OE), we completed a genome-wide analysis comparing 4503 OD cases, 4173 opioid-exposed controls, and 32,500 opioid-unexposed controls, including participants of European and African descent (EUR and AFR, respectively). Among the variants identified, rs9291211 was associated with OE (exposed vs. unexposed controls; EUR z = -5.39, p = 7.2 × 10-8). This variant regulates the transcriptomic profiles of SLC30A9 and BEND4 in multiple brain tissues and was previously associated with depression, alcohol consumption, and neuroticism. A phenome-wide scan of rs9291211 in the UK Biobank (N > 360,000) found association of this variant with propensity to use dietary supplements (p = 1.68 × 10-8). With respect to the same OE phenotype in the gene-based analysis, we identified SDCCAG8 (EUR + AFR z = 4.69, p = 10-6), which was previously associated with educational attainment, risk-taking behaviors, and schizophrenia. In addition, rs201123820 showed a genome-wide significant difference between OD cases and unexposed controls (AFR z = 5.55, p = 2.9 × 10-8) and a significant association with musculoskeletal disorders in the UK Biobank (p = 4.88 × 10-7). A polygenic risk score (PRS) based on a GWAS of risk-tolerance (n = 466,571) was positively associated with OD (OD vs. unexposed controls, p = 8.1 × 10-5; OD cases vs. exposed controls, p = 0.054) and OE (exposed vs. unexposed controls, p = 3.6 × 10-5). A PRS based on a GWAS of neuroticism (n = 390,278) was positively associated with OD (OD vs. unexposed controls, p = 3.2 × 10-5; OD vs. exposed controls, p = 0.002) but not with OE (p = 0.67). Our analyses highlight the difference between dependence and exposure and the importance of considering the definition of controls in studies of addiction.

The Void in Clinician Counseling of Cannabis Use.

As more states legalize cannabis for medical use, people increasingly use cannabis to treat medical conditions. Well-documented harms of cannabis use include increased risk of fatal auto accidents, neurocognitive deficits, and increased risk of addiction. Observational data supports the use of cannabis for pain, nausea and vomiting related to chemotherapy, and multiple sclerosis spasticity symptoms. Given potential harms versus benefits of cannabis use, how should physicians counsel patients regarding their cannabis use? This paper briefly reviews the evidence supporting medical cannabis use for pain. We consider cannabis use as a harm reduction strategy for pain management. We encourage routine, longitudinal assessments of cannabis use among patients. We discuss the commercialization of cannabis for financial gain, contributing to potent and addictive cannabis. We highlight the concerning phenomena of cannabis dispensary workers as proxy clinicians. Finally, we present three strategies to reduce public harms associated with potent cannabis use including required testing and reporting of tetrahydrocannabinol/cannabidiol concentrations, rigorous study of high-potency cannabis available for purchase in dispensaries across the USA, and large-scale efforts to measure cannabis consumption in medical records so prospective, longitudinal studies can be conducted to correlate consumption measures with medical and psychiatric outcomes.

Opioid and non-opioid utilization at home following gastrointestinal procedures: a prospective cohort study.

BACKGROUND: Overprescribing of opioid medications for patients to be used at home after surgery is common. We sought to ascertain important patient and procedural characteristics that are associated with low versus high rates of self-reported utilization of opioids at home, 1-4 weeks after discharge following gastrointestinal surgery. METHODS: We developed a survey consisting of questions from NIH PROMIS tools for pain intensity/interference and queries on postoperative analgesic use. Adult patients completed the survey weekly during the first month after discharge. Using regression procedures we determined the patient and procedure characteristics that predicted high post-discharge opioid use operationalized as 75 mg oral morphine equivalents/50 mg oxycodone reported taken. RESULTS: The survey response rate was 86% (201/233). High opioid use was reported by 52.7% of patients (106/201). Median reported intake of opioid pain pills was 7 for week #1 and 0 for weeks #2-4. Combinations of acetaminophen and non-steroidal and anti-inflammatory drugs were used by 8.9%-12.5% of patients after discharge. Following adjustment for significant variables of the univariate analysis, last 24-h in-hospital opioid intake remained as a significant co-variate for post-discharge opioid intake. CONCLUSIONS: After gastrointestinal surgery, the equivalent of each oxycodone 5 mg tablet taken in the last 24 h before discharge increases the likelihood of taking the equivalent of > 10 oxycodone 5 mg tablets by 5%. Non-opioid analgesia was utilized in less than half of the cases. Maximizing non-opioid analgesic therapy and basing opioid prescriptions on 24-h pre-discharge opioid intake may improve the quality of post-discharge pain management.

Cannabis Oil Use by Adolescents and Young Adults With Inflammatory Bowel Disease.

OBJECTIVES: The aim of the study was to describe use of oral or sublingual cannabis oil (CO) by adolescent and young adult patients with inflammatory bowel disease (IBD). METHODS: A descriptive study of IBD patients 13 to 23 years of age seen between January 2015 through December 2017 at Children's Hospital Colorado. Information obtained included chart abstraction, electronic and interview self-report, and serum cannabinoid levels. We compared CO users and cannabis non-users for clinical characteristics and perceptions of risk. Users of CO provided information on routes, patterns, motivations, and perceived benefits and problems with use. RESULTS: The 15 users and 67 non-users were similar for clinical characteristics and pain and appetite scores. 9 of 15 (60%) CO users had used in the past 30 days, an average of 22 ±â€Š9 times; and 4 used daily. A variety of strengths and CBD:THC ratios were reported. Most common perceived effect of use was on sleep quality, nausea, and increase in appetite. Of the 15 users, 6 used only CO and no additional forms of cannabis. Of these 6 CO only users, 5 reported a medical reason for use, most commonly to relieve pain. CONCLUSIONS: Adolescent and young adults with IBD used oral CO and many used other cannabis products as well. Users perceived some medical benefit. Care teams should strive for open communication about use until further information on safety and efficacy becomes available.

Marijuana Use by Adolescents and Young Adults with Inflammatory Bowel Disease.

OBJECTIVE: To evaluate marijuana use by adolescents and young adults with inflammatory bowel disease (IBD). STUDY DESIGN: This descriptive cross-sectional study of patients seen between December 2015 through June 2017 at Children's Hospital Colorado for IBD enrolled patients 13-23 years of age, independent of marijuana use status. Information obtained consisted of chart review, electronic and interview self-report, and serum cannabinoid levels. Marijuana ever-users were compared with never-users for clinical characteristics and perceptions of risk with use; users provided information on routes, patterns, motivations, and perceived benefits and problems with use. RESULTS: Of 99 participants, ever-use was endorsed by 32% (32 of 99) and daily or almost daily use by 9% (9 of 99). Older age was the only characteristic related to endorsing marijuana use. Twenty-nine ever-users completed all questionnaires. After adjusting for age, users were 10.7 times more likely to perceive low risk of harm with regular use (P < .001). At least 1 medical reason for use was endorsed by 57% (17 of 30), most commonly for relief of physical pain (53%, 16 of 30) (2 did not complete all questionnaires). Problems from use were identified by 37% (11 of 30), most commonly craving/strong urge to use. Most common route of use was smoking (83%) followed by edibles (50%), dabbing (40%), and vaping (30%). CONCLUSIONS: Marijuana use by adolescents and young adults with IBD is common and perceived as beneficial. Guidelines for screening, testing, and counseling of marijuana use should be developed for patients with IBD.

Impulsivity Dimensions and Risky Sex Behaviors in an At-Risk Young Adult Sample.

Impulsivity is a personality-based risk factor that has been well studied in relation to risky sexual behavior. Recent conceptualizations of impulsivity have proposed multidimensional facets comprised of premeditation, perseverance, sensation seeking, negative urgency, and positive urgency (UPPS-P model). Prior studies have found that these facets are associated with risky sexual behavior in adolescent and college student samples, but no prior studies have evaluated them in clinical samples. The current study examined how impulsivity-related traits related to two different risky sexual behaviors in a clinical sample of at-risk young adults who had both conduct disorder and substance use disorder symptoms as adolescents (n = 529). Lack of premeditation was also tested as a moderator of the relationship between facets of impulsivity and both risky sex outcomes. Results demonstrated that sensation seeking, negative urgency, and positive urgency were correlated with risky sex behaviors. Additionally, multiple regression analyses indicated that sensation seeking was uniquely associated with the number of sexual partners in the past 5 years, whereas positive urgency was uniquely associated with unprotected sex while under the influence. Finally, a significant interaction between lack of premeditation and negative urgency suggests that at-risk young adults with both high negative urgency and lack of premeditation were the likeliest to have the most sexual partners in the past 5 years. This study adds to the current understanding of the relationship between reward- and affect-driven facets of impulsivity and risky sexual behaviors and may lend utility to the development of interventions for at-risk populations.

Positive expectancies mediate the association between sensation seeking and marijuana outcomes in at-risk young adults: A test of the acquired preparedness model.

BACKGROUND AND OBJECTIVES: The acquired preparedness model (APM) integrates personality trait research and psychosocial learning, which are theorized to ultimately increase risk for problematic substance use outcomes. METHODS: The present study uses the APM to examine the potential mediational role of positive and negative expectancies on the relationship between impulsivity and two marijuana outcomes (ie, frequency of use and marijuana use disorder [MUD] symptom count) among an at-risk sample of young adults with history of antisocial behavior and substance use in adolescence and their siblings (n = 312). RESULTS: Results suggest a significant indirect effect of sensation seeking on recent marijuana use through positive marijuana expectancies. There also was a significant indirect effect of sensation seeking on past-year MUD symptoms through positive expectancies. No significant indirect effects through negative expectancies were found for either outcome. DISCUSSION AND CONCLUSIONS: Our findings are consistent with the APM and suggest that higher sensation seeking is related to increased positive beliefs about marijuana outcomes, which is related to higher marijuana use and more MUD symptoms. SCIENTIFIC SIGNIFICANCE: These findings suggest that positive expectancies are an important risk factor for marijuana use and misuse, particularly for at-risk individuals with elevated rates of sensation seeking. Positive marijuana expectancies may be important to address in interventions for at-risk individuals. (Am J Addict 2018;XX:1-6).

Unique and interactive effects of impulsivity facets on reckless driving and driving under the influence in a high-risk young adult sample.

Risky driving behaviors are disproportionately high among young adults and impulsivity is a robust risk factor. Recent conceptualizations have proposed multidimensional facets of impulsivity comprised of negative urgency, premeditation, perseverance, sensation seeking, and positive urgency (UPPS-P model). Prior studies have found these facets are associated with risky driving behaviors in college student samples, but no prior studies have examined these facets in clinical samples. This study examined the unique and interactive effects of UPPS-P impulsivity facets on past-year risky driving behaviors in a sample of high-risk young adults (ages 18-30 years) with a history of substance use and antisocial behavior and their siblings (n=1,100). Multilevel Poisson regressions indicated that sensation seeking and negative urgency were uniquely and positively associated with both frequency of past-year reckless driving and driving under the influence. Moreover, lack of premeditation was uniquely and positively associated with reckless driving, whereas lack of perseverance was uniquely and positively associated with driving under the influence. Furthermore, lack of premeditation moderated and strengthened the positive association between sensation seeking and driving under the influence. These study findings suggest that assessing multiple facets of trait impulsivity could facilitate targeted prevention efforts among young adults with a history of externalizing psychopathology.

Evidence for Association Between Low Frequency Variants in CHRNA6/CHRNB3 and Antisocial Drug Dependence.

Common SNPs in nicotinic acetylcholine receptor genes (CHRN genes) have been associated with drug behaviors and personality traits, but the influence of rare genetic variants is not well characterized. The goal of this project was to identify novel rare variants in CHRN genes in the Center for Antisocial Drug Dependence (CADD) and Genetics of Antisocial Drug Dependence (GADD) samples and to determine if low frequency variants are associated with antisocial drug dependence. Two samples of 114 and 200 individuals were selected using a case/control design including the tails of the phenotypic distribution of antisocial drug dependence. The capture, sequencing, and analysis of all variants in 16 CHRN genes (CHRNA1-7, 9, 10, CHRNB1-4, CHRND, CHRNG, CHRNE) were performed independently for each subject in each sample. Sequencing reads were aligned to the human reference sequence using BWA prior to variant calling with the Genome Analysis ToolKit (GATK). Low frequency variants (minor allele frequency < 0.05) were analyzed using SKAT-O and C-alpha to examine the distribution of rare variants among cases and controls. In our larger sample, the region containing the CHRNA6/CHRNB3 gene cluster was significantly associated with disease status using both SKAT-O and C-alpha (unadjusted p values <0.05). More low frequency variants in the CHRNA6/CHRNB3 gene region were observed in cases compared to controls. These data support a role for genetic variants in CHRN genes and antisocial drug behaviors.

Adolescent Male Conduct-Disordered Patients in Substance Use Disorder Treatment: Examining the "Limited Prosocial Emotions" Specifier.

To our knowledge, this is the first study to examine the DSM-5-defined conduct disorder (CD) with limited prosocial emotions (LPE) among adolescents in substance use disorder (SUD) treatment, despite the high rates of CD in this population. We tested previously published methods of LPE categorization in a sample of male conduct-disordered patients in SUD treatment (n=196). CD with LPE patients did not demonstrate a distinct pattern in terms of demographics or co-morbidity regardless of the categorization method utilized. In conclusion, LPE, as operationalized here, does not identify a distinct subgroup of patients based on psychiatric comorbidity, SUD diagnoses, or demographics.

Genome-Wide Association Study of Behavioral Disinhibition in a Selected Adolescent Sample.

Behavioral disinhibition (BD) is a quantitative measure designed to capture the heritable variation encompassing risky and impulsive behaviors. As a result, BD represents an ideal target for discovering genetic loci that predispose individuals to a wide range of antisocial behaviors and substance misuse that together represent a large cost to society as a whole. Published genome-wide association studies (GWAS) have examined specific phenotypes that fall under the umbrella of BD (e.g. alcohol dependence, conduct disorder); however no GWAS has specifically examined the overall BD construct. We conducted a GWAS of BD using a sample of 1,901 adolescents over-selected for characteristics that define high BD, such as substance and antisocial behavior problems, finding no individual locus that surpassed genome-wide significance. Although no single SNP was significantly associated with BD, restricted maximum likelihood analysis estimated that 49.3 % of the variance in BD within the Caucasian sub-sample was accounted for by the genotyped SNPs (p = 0.06). Gene-based tests identified seven genes associated with BD (p ≤ 2.0 × 10(-6)). Although the current study was unable to identify specific SNPs or pathways with replicable effects on BD, the substantial sample variance that could be explained by all genotyped SNPs suggests that larger studies could successfully identify common variants associated with BD.

Distinct loci in the CHRNA5/CHRNA3/CHRNB4 gene cluster are associated with onset of regular smoking.

Neuronal nicotinic acetylcholine receptor (nAChR) genes (CHRNA5/CHRNA3/CHRNB4) have been reproducibly associated with nicotine dependence, smoking behaviors, and lung cancer risk. Of the few reports that have focused on early smoking behaviors, association results have been mixed. This meta-analysis examines early smoking phenotypes and SNPs in the gene cluster to determine: (1) whether the most robust association signal in this region (rs16969968) for other smoking behaviors is also associated with early behaviors, and/or (2) if additional statistically independent signals are important in early smoking. We focused on two phenotypes: age of tobacco initiation (AOI) and age of first regular tobacco use (AOS). This study included 56,034 subjects (41 groups) spanning nine countries and evaluated five SNPs including rs1948, rs16969968, rs578776, rs588765, and rs684513. Each dataset was analyzed using a centrally generated script. Meta-analyses were conducted from summary statistics. AOS yielded significant associations with SNPs rs578776 (beta = 0.02, P = 0.004), rs1948 (beta = 0.023, P = 0.018), and rs684513 (beta = 0.032, P = 0.017), indicating protective effects. There were no significant associations for the AOI phenotype. Importantly, rs16969968, the most replicated signal in this region for nicotine dependence, cigarettes per day, and cotinine levels, was not associated with AOI (P = 0.59) or AOS (P = 0.92). These results provide important insight into the complexity of smoking behavior phenotypes, and suggest that association signals in the CHRNA5/A3/B4 gene cluster affecting early smoking behaviors may be different from those affecting the mature nicotine dependence phenotype.

Examination of genetic variation in GABRA2 with conduct disorder and alcohol abuse and dependence in a longitudinal study.

Previous studies have shown associations between single nucleotide polymorphisms (SNPs) in gamma aminobutyric acid receptor alpha 2 (GABRA2) and adolescent conduct disorder (CD) and alcohol dependence in adulthood, but not adolescent alcohol dependence. The present study was intended as a replication and extension of this work, focusing on adolescent CD, adolescent alcohol abuse and dependence (AAD), and adult AAD. Family based association tests were run using Hispanics and non-Hispanic European American subjects from two independent longitudinal samples. Although the analysis provided nominal support for an association with rs9291283 and AAD in adulthood and CD in adolescence, the current study failed to replicate previous associations between two well replicated GABRA2 SNPs and CD and alcohol dependence. Overall, these results emphasize the utility of including an independent replication sample in the study design, so that the results from an individual sample can be weighted in the context of its reproducibility.

Limited psychological and social effects of lifetime cannabis use frequency: Evidence from a 30-year community study of 4,078 twins.

BACKGROUND: Cannabis use is associated with outcomes like income, legal problems, and psychopathology. This finding rests largely on correlational research designs, which rely at best on statistical controls for confounding. Here, we control for unmeasured confounders using a longitudinal study of twins. METHOD: In a sample of 4,078 American adult twins first assessed decades ago, we used cotwin control mixed effects models to evaluate the effect of lifetime average frequency of cannabis consumption measured on substance use, psychiatric, and psychosocial outcomes. RESULTS: On average, participants had a lifetime cannabis frequency of about one to two times per month, across adolescence and adulthood. As expected, in individual-level analyses, cannabis use was significantly associated with almost all outcomes in the expected directions. However, when comparing each twin to their cotwin, which inherently controls for shared genes and environments, we observed within-pair differences consistent with possible causality in three of the 22 assessed outcomes: cannabis use disorder symptoms (ßW-Pooled = .15, SE = .02, p = 1.7 × 10-22), frequency of tobacco use (ßW-Pooled = .06, SE = .01, p = 1.2 × 10-5), and illicit drug involvement (ßW-Pooled = .06, SE = .02, p = 1.2 × 10-4). Covariate specification curve analyses indicated that within-pair effects on tobacco and illicit drug use, but not cannabis use disorder, attenuated substantially when covarying for lifetime alcohol and tobacco use. CONCLUSIONS: The cotwin control results suggest that more frequent cannabis use causes small increases in cannabis use disorder symptoms, approximately 1.3 symptoms when going from a once-a-year use to daily use. For other outcomes, our results are more consistent with familial confounding, at least in this community population of twins. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Prevalence and predictors of injection drug use and risky sexual behaviors among adolescents in substance treatment.

BACKGROUND AND OBJECTIVES: The longitudinal risk for human immunodeficiency virus (HIV) infection following adolescent substance treatment is not known. Therefore, it is not known if adolescent substance treatment should include HIV prevention interventions. To address this important research gap, this study evaluates the longitudinal prevalence and predictors of injection drug use (IDU) and sex risk behaviors among adolescents in substance treatment. METHODS: Participants were 260 adolescents (13-18 years) in substance treatment and 201 community control adolescents (11-19 years). Participants were assessed at baseline and follow-up (mean time between assessments = 6.9 years for the clinical sample and 5.6 years for the community control sample). Outcomes included self-report lifetime history of IDU, number of lifetime sex partners and frequency of unprotected sexual intercourse. RESULTS: At baseline, 7.5% of the clinical sample, compared to 1.0% of the community control sample had a lifetime history of IDU (χ12=10.53, p = .001). At follow-up, 17.4% of the clinical sample compared to 0% of the community control sample had a lifetime history of IDU (χ12=26.61, p = .0005). The number of baseline substance use disorders and onset age of marijuana use significantly predicted the presence of lifetime IDU at follow-up, after adjusting for baseline age, race, and sex. The clinical sample reported more lifetime sex partners and more frequent unprotected sex than the community control sample at baseline and follow-up. CONCLUSIONS: Many adolescents in substance treatment develop IDU and report persistent risky sex. Effective risk reduction interventions for adolescents in substance treatment are needed that address both IDU and risky sex.

Subjective effects as predictors of substance use disorders in a clinical sample: A longitudinal study.

BACKGROUND: The literature on the association between subjective effects (SEs; i.e., how an individual perceives their physiological and psychological reactions to a drug) and substance use disorders (SUDs) is largely limited to community samples. The present study addressed the following aims in a clinical sample: whether SEs predict general versus substance-specific SUD in adolescence and adulthood after controlling for conduct disorder symptoms (CDsymp); whether SEs predict SUDs across drug classes; whether SEs predict change in SUD from adolescence to adulthood; and whether there are racial/ethnic differences in associations. METHODS: Longitudinal analyses were conducted using data from a sample of 744 clinical probands recruited from residential and outpatient SUD treatment facilities in CO during adolescence (Mage = 16.26) and re-assessed twice in adulthood (Mages = 22.56 and 28.96), approximately seven and twelve years after first assessment. SEs and CDsymp were assessed in adolescence. SUD severity was assessed at adolescence and twice during adulthood. RESULTS: SEs assessed in adolescence robustly predicted general SUD for legal and illegal substances in adolescence and adulthood, whereas CDsymp predicted SUD primarily in adolescence. Higher positive and negative SEs in adolescence were associated with greater SUD severity after controlling for CDsymp, with similar magnitudes. Results indicated cross-substance effects of SEs on SUD. We found no evidence for racial/ethnic differences in associations. CONCLUSIONS: We investigated the progression of SUD in a high-risk sample with greater odds of sustained SUD. In contrast to CDsymp, both positive and negative SEs consistently predicted general SUD across substances in adolescence and adulthood.

Impacts of recreational cannabis legalization on cannabis use: a longitudinal discordant twin study.

AIMS: To estimate the effect of recreational legalization on cannabis use frequency and sources of variance across legal environments. DESIGN: Longitudinal discordant twin and gene-environment interaction models in twins recruited from birth records and assessed prospectively. SETTING: The United States, including states with different recreational cannabis policies before and after 2014, when recreational cannabis was first legalized. PARTICIPANTS: Two longitudinal, prospectively assessed samples of American twins aged 24-47 (n = 1425 in legal states, n = 1996 in illegal states), including 111 monozygotic pairs discordant for residence. MEASUREMENTS: Current cannabis use frequency (measured continuously and ordinally) was the primary outcome, and the predictor was recreational status of cannabis (legal/illegal) in the participant's state of residence at the time of assessment. Covariates include age, sex and cannabis use frequency prior to 2014. FINDINGS: Accounting for pre-2014 use, residents of legal states used cannabis more frequently than residents of illegal states (b = 0.21, P = 8.08 × 10-5 ). Comparing 111 pairs of monozygotic twins discordant for residence confirmed the effect (b = 0.18, P = 0.014). There was inconclusive evidence for genetic influences on cannabis use frequency that were specific to the legal environment [χ2  = 2.9 × 10-9 , degrees of freedom (d.f.) = 1, P > 0.999]. Existing genetic influences were moderated by the legal environment, as the genetic correlation between marijuana use before and after legalization was lower in states that legalized (rgenetic  = 0.24) compared with states that did not (rgenetic  = 0.78, Pdifference  = 0.016). CONCLUSIONS: In the United States, there appears to be a ~ 20% average increase in cannabis use frequency attributable to recreational legalization, consistent across increasingly rigorous designs. In addition, the heritability of cannabis use frequency appears to be moderated by legalization.