Overlap of heritable influences between Cannabis Use Disorder, frequency of use and opportunity to use cannabis: Trivariate twin modelling and implications for genetic design

Background: The genetic component of Cannabis Use Disorder may overlap with influences acting more generally on early stages of cannabis use. This paper aims to determine the extent to which genetic influences on the development of cannabis abuse/dependence are correlated with those acting on the opportunity to use cannabis and frequency of use. Methods: A cross-sectional study of 3303 Australian twins, measuring age of onset of cannabis use opportunity, lifetime frequency of cannabis use, and lifetime DSM-IV cannabis abuse/dependence. A trivariate Cholesky decomposition estimated additive genetic (A), shared environment (C) and unique environment (E) contributions to the opportunity to use cannabis, the frequency of cannabis use, cannabis abuse/dependence, and the extent of overlap between genetic and environmental factors associated with each phenotype. Results: Variance components estimates were A = 0.64 [95% confidence interval (CI) 0.58–0.70] and E = 0.36 (95% CI 0.29–0.42) for age of opportunity to use cannabis, A = 0.74 (95% CI 0.66–0.80) and E = 0.26 (95% CI 0.20–0.34) for cannabis use frequency, and A = 0.78 (95% CI 0.65–0.88) and E = 0.22 (95% CI 0.12–0.35) for cannabis abuse/dependence. Opportunity shares 45% of genetic influences with the frequency of use, and only 17% of additive genetic influences are unique to abuse/dependence from those acting on opportunity and frequency. Conclusions: There are significant genetic contributions to lifetime cannabis abuse/dependence, but a large proportion of this overlaps with influences acting on opportunity and frequency of use. Individuals without drug use opportunity are uninformative, and studies of drug use disorders must incorporate individual exposure to accurately identify aetiology

Characterising heterogeneity in the use of different cannabis products:Latent class analysis with 55 000 people who use cannabis and associations with severity of cannabis dependence

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 &amp; herbal (30.3% of the sample); sinsemilla, herbal &amp; hashish (20.4%); herbal (18.4%); hashish &amp; herbal (18.8%); all types (5.7%); edibles &amp; herbal (4.6%) and concentrates &amp; 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.ConclusionsThe identification of these distinct classes underscores heterogeneity among cannabis use behaviours and provides novel insight into their different associations with addiction and mental health.</p

An Australian twin study of cannabis and other illicit drug use and misuse, and other psychopathology

Cannabis is the most widely used illicit drug throughout the developed world and there is consistent evidence of heritable influences on multiple stages of cannabis involvement including initiation of use and abuse/dependence. In this paper, we describe the methodology and preliminary results of a large-scale interview study of 3,824 young adult twins (born 1972–1979) and their siblings. Cannabis use was common with 75.2% of males and 64.7% of females reporting some lifetime use of cannabis while 24.5% of males and 11.8% of females reported meeting criteria for DSM-IV cannabis abuse or dependence. Rates of other drug use disorders and common psychiatric conditions were highly correlated with extent of cannabis involvement and there was consistent evidence of heritable influences across a range of cannabis phenotypes including early (≤15 years) opportunity to use (h(2) = 72%), early (≤16 years) onset use (h(2) = 80%), using cannabis 11+ times lifetime (h(2) = 76%), and DSM abuse/dependence (h(2) = 72%). Early age of onset of cannabis use was strongly associated with increased rates of subsequent use of other illicit drugs and with illicit drug abuse/dependence; further analyses indicating that some component of this association may have been mediated by increasing exposure to and opportunity to use other illicit drugs

The short-term consequences of early onset cannabis use

The associations between early onset (prior to 15 years of age) cannabis use and rates of mental health or adjustment problems during the period from 15 to 16 years of age were studied in a New Zealand birth cohort. Early onset cannabis users were at increased risks of later substance use behaviors, conduct/oppositional disorders, juvenile offending, severe truancy, school dropout, anxiety, depression, and suicidal ideation. Early cannabis users had odds of these outcomes ranging from 2.7 to 30.8 times higher than the odds for those who did not use cannabis prior to age 15. Most of the elevated risks of early onset users were explained by the fact that they were a high- risk group of adolescents characterized by family disadvantages, early adjustment problems, and high affiliations with substance-using or delinquent peers. Nonetheless, even after adjustment for a wide range of confounding factors, early onset users had increased risks of later cannabis use. It is concluded that while most of the elevated risks of early onset users were explained by social, family, and individual characteristics of this group, early onset users were at increased risks of later cannabis use

A latent class analysis of cannabis use products in a general population sample of adolescents and their association with paranoia, hallucinations, cognitive disorganisation and grandiosity

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.</p