Daily associations with cannabis use and sleep quality in anxious cannabis users.

INTRODUCTION: Cannabis is increasingly used to self-treat anxiety and related sleep problems, without clear evidence of either supporting or refuting its anxiolytic or sleep aid effects. In addition, different forms of cannabis and primary cannabinoids ∆9-tetrahydrocannabinol (THC) and cannabidiol (CBD) have differing pharmacological effects. METHODS: Thirty days of daily data on sleep quality and cannabis use were collected in individuals who use cannabis for mild-to-moderate anxiety (n = 347; 36% male, 64% female; mean age = 33 years). Participants self-reported both the form (flower or edible) and the ratio of THC to CBD in the cannabis used during the observation period. RESULTS: Individuals who reported cannabis use on a particular day also reported better sleep quality the following night. Moderation analyses showed that better perceived sleep after cannabis use days was stronger for respondents with higher baseline affective symptoms. Further, respondents who used cannabis edibles with high CBD concentration reported the highest perceived quality of sleep. CONCLUSIONS: Among individuals with affective symptoms, naturalistic use of cannabis was associated with better sleep quality, particularly for those using edible and CBD dominant products.

Acute objective and subjective intoxication effects of legal-market high potency THC-dominant versus CBD-dominant cannabis concentrates.

As the market for cannabis concentrate products grows, the lack of research regarding the effects of concentrated THC and CBD becomes more glaring. The present study analyzes cannabinoid blood levels and subjective outcomes of physical sensation and affective state after ad libitum use of legal-market concentrate products. Recreational cannabis users were randomly assigned to THC- or CBD-dominant concentrate products, completing a baseline session, and an experimental mobile laboratory session consisting of timepoints before, immediately after, and one-hour after concentrate use. THC-dominant concentrates induced higher intoxication, and higher ratings of drug effect and drug liking than the CBD-dominant concentrate. Both products induced immediate feelings of elation, diminishing over the subsequent hour. Subjective outcomes in the CBD-dominant group revealed immediate decreases in tension and anxiety relative to pre-use, while the THC-dominant group only saw significant decreases in anxiety after one hour. Paranoia spiked immediately post-use in THC-dominant concentrate users, returning to baseline within an hour. Overall, the CBD-dominant concentrate invoked positive mood effects, lower intoxication and an absence of undesirable effects experienced with the THC-dominant concentrate, potentially mitigating negative effects when combined. Results support the need for further investigation into harm-reduction potential of concentrated CBD when used alone and with THC.

The transformation of a gold standard in-person substance use assessment to a web-based, REDCap integrated data capture tool.

The adoption of computer systems for gathering, managing, and analyzing health data is resulting in the replacement of pen-and-paper methods for collecting data and managing health records by computerized methods. One classic "pen-and-paper" assessment in health and substance use research is the Timeline Follow-Back (TLFB), the gold standard in self-reported substance use developed in 1996 by Sobell et al. to assess alcohol consumption patterns and later other substances such as marijuana or tobacco over discreet timeframes [1-7]. The TLFB has been modified by some research groups for use as a web-based assessment [8-10], but not without significant limitations. As such, this paper describes the team-oriented, interdisciplinary process by which a new online TLFB (O-TLFB) was conceptualized, the technical details of development towards a dynamic data capture tool fully integrated with REDCap via application programming interface (API), and the potential for this optimized O-TLFB to be leveraged broadly across the domains of substance use, health, and behavioral research.

Genome-wide single nucleotide polymorphism heritability of nicotine dependence as a multidimensional phenotype.

BACKGROUND: Heritability estimates from twin studies of the multi-faceted phenotype of nicotine dependence (ND) range from moderate to high (31-60%), but vary substantially based on the specific ND-related construct examined. The current study estimated the aggregate role of common genetic variants on key ND constructs. METHOD: Genomic-relationship-matrix restricted maximum likelihood (GREML) was used to decompose phenotypic variance across multiple ND indices using 796 125 polymorphisms from 2346 unrelated 'lifetime ever smokers' of European ancestry. Measures included DSM-IV ND and Fagerström Test for Nicotine Dependence (FTND) summary measures and constituent constructs (e.g. withdrawal severity, tolerance, heaviness of smoking and time spent smoking). Exploratory and confirmatory factor models were used to describe the covariance structure across ND measures; resulting factor(s) were the subject(s) of GREML analyses. RESULTS: Factor models indicated highly correlated DSM-IV and FTND factors for ND (0.545, 95% confidence interval 0.50-0.60) that could be represented as a higher-order factor (NIC DEP). Additive genetic influence on NIC DEP was 33% (s.e. = 0.14, p = 0.009). Post-hoc analyses indicated moderate genetic effects on the DSM-IV (34%, s.e. = 0.14, p = 0.008) and FTND (26%, s.e. = 0.14, p = 0.032) factors, both of which were influenced by the same genetic effects (r G-SNP = 1.00, s.e. = 0.09, p < 0.00001). CONCLUSIONS: Overall, common single nucleotide polymorphisms accounted for a large proportion of the genetic influences on ND-related phenotypes that have been observed in twin studies. Genetic contributions across distinct ND scales were largely influenced by shared genetic factors.

An initial investigation of associations between dopamine-linked genetic variation and smoking motives in African Americans.

Nicotine dependence (ND) is a heterogeneous phenotype with complex genetic influences that may vary across ethnicities. The use of intermediate phenotypes may clarify genetic influences and reveal specific etiological pathways. Prior work in European Americans has found that the four Primary Dependence Motives (PDM) subscales (Automaticity, Craving, Loss of Control, and Tolerance) of the Wisconsin Inventory of Smoking Motives represent core features of nicotine dependence and are promising intermediate phenotypes for understanding genetic pathways to ND. However, no studies have examined PDM as an intermediate phenotype in African American smokers, an ethnic population that displays unique patterns of smoking and genetic variation. In the current study, 268 African American daily smokers completed a phenotypic assessment and provided a sample of DNA. Associations among haplotypes in the NCAM1-TTC12-ANKK1-DRD2 gene cluster, a dopamine-related gene region associated with ND, PDM intermediate phenotypes, and ND were examined. Dopamine-related genetic variation in the DBH and COMT genes was also considered on an exploratory basis. Mediational analysis was used to test the indirect pathway from genetic variation to smoking motives to nicotine dependence. NCAM1-TTC12-ANKK1-DRD2 region variation was significantly associated with the Automaticity subscale and, further, Automaticity significantly mediated associations among NCAM1-TTC12-ANKK1-DRD2 cluster variants and ND. DBH was also significantly associated with Automaticity, Craving, and Tolerance; Automaticity and Tolerance also served as mediators of the DBH-ND relationship. These results suggest that PDM, Automaticity in particular, may be a viable intermediate phenotype for understanding dopamine-related genetic influences on ND in African American smokers. Findings support a model in which putatively dopaminergic variants exert influence on ND through an effect on patterns of automatic routinized smoking.

NCAM1-TTC12-ANKK1-DRD2 variants and smoking motives as intermediate phenotypes for nicotine dependence.

RATIONALE: Nicotine dependence (ND) is a heterogeneous phenotype with complex genetic influences. The use of intermediate ND phenotypes may clarify genetic influences and reveal specific etiological pathways. Prior work has found that the four Primary Dependence Motives (PDM) subscales (Automaticity, Craving, Loss of Control, and Tolerance) of the Wisconsin Inventory of Smoking Motives (WISDM) represent heavy, pervasive smoking, which is a core feature of nicotine dependence, making these motives strong candidates as intermediate phenotypes. OBJECTIVE: This study examines the WISDM PDM as a novel intermediate phenotype of nicotine dependence. METHODS: The study used data from 734 European Americans who smoked at least 5 cigs/day [M = 16.2 (SD = 9.5) cigs/day], completed a phenotypic assessment, and provided a sample of DNA. Based on prior evidence of the role of genetic variation in the NCAM1-TTC12-ANKK1-DRD2 region on chromosome 11q23 in smoking behavior, associations among 12 region loci with nicotine dependence and PDM phenotypes were examined using haplotype and individual loci approaches. In addition, mediational analysis tested the indirect pathway from genetic variation to smoking motives to nicotine dependence. RESULTS: NCAM1-TTC12-ANKK1-DRD2 region loci and haplotypes were significantly associated with the motive of Automaticity and, further, Automaticity significantly mediated associations among NCAM1-TTC12-ANKK1-DRD2 cluster variants and nicotine dependence. CONCLUSIONS: These results suggest that motives related to automaticity are a viable intermediate phenotype for understanding genetic contributions to nicotine dependence. Further, NCAM1-TTC12-ANKK1-DRD2 variants may increase the likelihood that a person will become dependent via a highly automatic smoking ritual that can be elicited with little awareness.

DSM-IV defined conduct disorder and oppositional defiant disorder: an investigation of shared liability in female twins.

BACKGROUND: DSM-IV specifies a hierarchal diagnostic structure such that an oppositional defiant disorder (ODD) diagnosis is applied only if criteria are not met for conduct disorder (CD). Genetic studies of ODD and CD support a combination of shared genetic and environmental influences but largely ignore the imposed diagnostic structure. METHOD: We examined whether ODD and CD share an underlying etiology while accounting for DSM-IV diagnostic specifications. Data from 1446 female twin pairs, aged 11-19 years, were fitted to two-stage models adhering to the DSM-IV diagnostic hierarchy. RESULTS: The models suggested that DSM-IV ODD-CD covariation is attributed largely to shared genetic influences. CONCLUSIONS: This is the first study, to our knowledge, to examine genetic and environmental overlap among these disorders while maintaining a DSM-IV hierarchical structure. The findings reflect primarily shared genetic influences and specific (i.e. uncorrelated) shared/familial environmental effects on these DSM-IV-defined behaviors. These results have implications for how best to define CD and ODD for future genetically informed analyses.

Childhood and current ADHD symptom dimensions are associated with more severe cannabis outcomes in college students.

BACKGROUND: Numerous studies have shown that attention deficit/hyperactivity disorder (ADHD) is associated higher risk of cannabis use disorders (CUD). However, these studies are limited in that most did not: (a) differentiate the role of hyperactivity-impulsivity (HI) and inattention (IN); (b) control for associated psychopathology; and (c) consider more fine-grained CUD-related measures. Our aim was to clarify the unique and interactive contributions of inattention and hyperactivity symptoms to age of cannabis initiation and DSM-IV cannabis dependence, craving, and severity of problems related to cannabis use while statistically controlling for symptoms of comorbid psychopathology in a non-clinical sample of young adults. METHODS: Cannabis variables, current use of cigarettes and alcohol, current and childhood ADHD, and comorbid internalizing and externalizing psychopathology were assessed in 376 male and female undergraduates. RESULTS: Results indicate that current and childhood IN were independently associated with more severe cannabis use, craving, and problem use-related outcomes in young adulthood (p's<.01) and that childhood HI symptoms were associated with earlier initiation of cannabis (p<.01). Further, current IN symptoms moderated the relationships between level of use and more severe outcomes (p's<.01), such that higher IN strengthened positive associations among use and problem cannabis use. Associations with ADHD symptom dimensions and current use of alcohol and cigarettes were also present. CONCLUSIONS: Thus, current and childhood inattention symptoms as well as childhood hyperactive-impulsive symptoms emerged as significant factors in cannabis-related outcomes in young adults, even after statistically controlling for important confounding variables.