Converging evidence of changes in the prevalence of drug use disorders (occasionally large changes) and in the types, patterns, and route of administration (eg, injecting vs non-injecting) of drug ...use have been provided by a number of recent trends in patterns of drug use, including a recent increase in prescription opioid misuse in the USA and changing patterns of tobacco and alcohol use in low-income and middle-income countries.
During puberty, when young people are completing their education, transitioning into employment, and forming longer-term intimate relationships, a shift in emotional regulation and an increase in ...risky behaviour, including substance use, is seen. This Series paper considers the potential effects of alcohol, tobacco, and illicit drug use during this period on: social, psychological, and health outcomes in adolescence and young adulthood; role transitions, and later health and social outcomes of regular substance use initiated in adolescence; and the offspring of young people who use substances. We sourced consistent support for causal relations between substance use and outcomes and evidence of biological plausibility from different but complementary research designs. Many adverse health and social outcomes have been associated with different types of substance use. The major challenge lies in deciding which are causal. Furthermore, qualitatively different harms are associated with different substances, differences in life stage when these harms occur, and the quality of evidence for different substances and health outcomes varies substantially. The preponderance of evidence comes from a few high-income countries, thus whether the same social and health outcomes would occur in other countries and cultures is unclear. Nonetheless, the number of harms that are causally related to substance use in young people warrant high-quality research design interventions to prevent or ameliorate these harms.
Issues. To conduct a comprehensive search of the peer‐reviewed literature to assess risk of cannabis‐related mortality. Approach. Systematic peer‐reviewed literature searches were conducted in ...Medline, EMBASE and PsycINFO to identify data on mortality associated with cannabis use. Search strings for cannabis and mortality were used. Searches were limited to human subjects and the publication timeframe of January 1990 to January 2008. Reference lists of review articles and of specific studies deemed important by colleagues were searched to identify additional studies. A list of the selected articles was emailed to experts in the field asking for comment on completeness. Key Findings. There is insufficient evidence, particularly because of the low number of studies, to assess whether the all‐cause mortality rate is elevated among cannabis users in the general population. Case–control studies suggest that some adverse health outcomes may be elevated among heavy cannabis users, namely, fatal motor vehicle accidents, and possibly respiratory and brain cancers. The evidence is as yet unclear as to whether regular cannabis use increases the risk of suicide. Conclusions. There is a need for long‐term cohort studies that follow cannabis using individuals into old age, when the likelihood of any detrimental effects of cannabis use are more likely to emerge among those who persist in using cannabis into middle age and older. Case–control studies of cannabis use and various causes of mortality are also needed.Calabria B, Degenhardt L, Hall W, Lynskey M. Does cannabis use increase the risk of death? Systematic review of epidemiological evidence on adverse effects of cannabis use. Drug Alcohol Rev 2010
ABSTRACT
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; Mage = 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 (a2 = 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.
Prior neuroimaging studies have suggested that alterations in brain structure may be a consequence of cannabis use. Siblings discordant for cannabis use offer an opportunity to use cross-sectional ...data to disentangle such causal hypotheses from shared effects of genetics and familial environment on brain structure and cannabis use.
To determine whether cannabis use is associated with differences in brain structure in a large sample of twins/siblings and to examine sibling pairs discordant for cannabis use to separate potential causal and predispositional factors linking lifetime cannabis exposure to volumetric alterations.
Cross-sectional diagnostic interview, behavioral, and neuroimaging data were collected from community sampling and established family registries from August 2012 to September 2014. This study included data from 483 participants (22-35 years old) enrolled in the ongoing Human Connectome Project, with 262 participants reporting cannabis exposure (ie, ever used cannabis in their lifetime).
Cannabis exposure was measured with the Semi-Structured Assessment for the Genetics of Alcoholism. Whole-brain, hippocampus, amygdala, ventral striatum, and orbitofrontal cortex volumes were related to lifetime cannabis use (ever used, age at onset, and frequency of use) using linear regressions. Genetic (ρg) and environmental (ρe) correlations between cannabis use and brain volumes were estimated. Linear mixed models were used to examine volume differences in sex-matched concordant unexposed (n = 71 pairs), exposed (n = 81 pairs), or exposure discordant (n = 89 pairs) sibling pairs.
Among 483 study participants, cannabis exposure was related to smaller left amygdala (approximately 2.3%; P = .007) and right ventral striatum (approximately 3.5%; P < .005) volumes. These volumetric differences were within the range of normal variation. The association between left amygdala volume and cannabis use was largely owing to shared genetic factors (ρg = -0.43; P = .004), while the origin of the association with right ventral striatum volumes was unclear. Importantly, brain volumes did not differ between sex-matched siblings discordant for use (fixed effect = -7.43; t = -0.93, P = .35). Both the exposed and unexposed siblings in pairs discordant for cannabis exposure showed reduced amygdala volumes relative to members of concordant unexposed pairs (fixed effect = 12.56; t = 2.97; P = .003).
In this study, differences in amygdala volume in cannabis users were attributable to common predispositional factors, genetic or environmental in origin, with little support for causal influences. Causal influences, in isolation or in conjunction with predispositional factors, may exist for other brain regions (eg, ventral striatum) or at more severe levels of cannabis involvement and deserve further study.
Despite well-known adverse health effects of maternal smoking during pregnancy (MSP), it is still unclear if MSP varies geographically and if neighborhood socioeconomic deprivation (SED) plays an ...important role in MSP. This study aims to investigate small-area geographic variation in MSP and examine the association of SED with MSP.
The Missouri Adolescent Female Twin Study (MOAFTS) is a cohort study of female like-sex twins born in Missouri to Missouri-resident parents during 1975-1985. Biological mothers completed a baseline interview in 1995-1998 and reported MSP with the twins. Residential address of the mother at birth was geocoded. We developed a census tract-level SED index using a common factor approach based on 21 area-level socioeconomic variables from the 1980 Census data. Multilevel logistic regressions estimated geographic heterogeneity (random effect) in MSP and the odds ratios (ORs, fixed effects) of neighborhood SED associated with MSP.
Of 1658 MOAFTS mothers, 35.2% reported any MSP and 21.9% reported MSP beyond the first trimester. Neighborhood SED was associated with any MSP (the highest vs. the lowest quartile: OR = 1.90, 95% confidence interval CI = 1.40-2.57, Ptrend<0.001) and MSP beyond the first trimester (OR = 1.98, 95% CI = 1.38-2.85, Ptrend = 0.002) in unadjusted analyses. After adjusting for individual covariates (demographics, socioeconomic conditions, alcohol use, and parents' cohabitation), neighborhood SED was not associated with MSP, but geographic variation still persisted in MSP (variance = 0.41, P = 0.003) and in MSP beyond the first trimester (variance = 0.82, P<0.001).
Neighborhood SED was associated with MSP in unadjusted analyses but this association could be explained by individual socioeconomic conditions. Nonetheless, significant geographic variation in MSP persisted and was not accounted for by differences in neighborhood SED. To develop effective interventions to reduce MSP, further studies are necessary to explore underlying reasons for its geographic variation.
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.
Previous research indicates that cannabis use is associated with psychotic-like experiences (PLEs). However, it is unclear whether this association results from predispositional (ie, shared genetic) ...factors or individual-specific factors (eg, causal processes, such as cannabis use leading to PLEs).
To estimate genetic and environmental correlations between cannabis use and PLEs, and to examine PLEs in twin and nontwin sibling pairs discordant for exposure to cannabis use to disentangle predispositional from individual-specific effects.
In this cross-sectional analysis, diagnostic interviews and self-reported data were collected from 2 separate population-based samples of twin and nontwin sibling pairs. Data from the Human Connectome Project were collected between August 10, 2012, and September 29, 2015, and data from the Australian Twin Registry Cohort 3 (ATR3) were collected between August 1, 2005, and August 31, 2010. Data were analyzed between August 17, 2017, and July 6, 2018. The study included data from 1188 Human Connectome Project participants and 3486 ATR3 participants, totaling 4674 participants.
Three cannabis-involvement variables were examined: frequent use (ie, ≥100 times), a DSM-IV lifetime cannabis use disorder diagnosis, and current cannabis use. Genetic and environmental correlations between cannabis involvement and PLEs were estimated. Generalized linear mixed models examined PLE differences in twin and nontwin sibling pairs discordant for cannabis use.
Among the 4674 participants, the mean (SD) age was 30.5 (3.2) years, and 2923 (62.5%) were female. Data on race/ethnicity were not included as a covariate owing to lack of variability within the ATR3 sample; among the 1188 participants in the Human Connectome Project, 875 (73.7%) were white. Psychotic-like experiences were associated with frequent cannabis use (β = 0.11; 95% CI, 0.08-0.14), cannabis use disorder (β = 0.13; 95% CI, 0.09-0.16), and current cannabis use (β = 0.07; 95% CI, 0.04-0.10) even after adjustment for covariates. Correlated genetic factors explained between 69.2% and 84.1% of this observed association. Within discordant pairs of twins/siblings (Npairs, 308-324), Psychotic-like experiences were more common in cannabis-exposed individuals compared with their relative who used cannabis to a lesser degree (β ≥ .23, P < .05; eg, frequent and infrequent cannabis-using relatives significantly differed, z = -5.41; P < .001).
Despite the strong contribution of shared genetic factors, frequent and problem cannabis use also appears to be associated with PLEs via person-specific pathways. This study's findings suggest that policy discussions surrounding legalization should consider the influence of escalations in cannabis use on traitlike indices of vulnerability, such as PLEs, which could contribute to pervasive psychological and interpersonal burden.
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.
Subjective effects of initial opioid misuse were assessed in two samples of opioid misusers that included low‐level users who never met criteria for opioid use disorder (OUD) and heavier users with OUD. In both samples, OUD+ individuals reported greater euphoria, activation, pruritus, and internalizing symptoms (replication sample data are displayed).
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.
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