The citizens of four US states-Alaska, Colorado, Oregon, and Washington-have voted to legalise the sale of cannabis to adults for recreational purposes, and more states look likely to follow. ...Experience with alcohol and tobacco suggests that a for-profit legal cannabis industry will increase use by making cannabis more socially acceptable to use, making it more readily available at a cheaper price, and increasing the number of users and frequency of their use. We argue that it is too early to see the full effects of legalised cannabis policies on use and harm because several factors could delay the full commercialisation of a legal cannabis industry. These factors include restrictions on various licensed producers and sellers, and legal conflicts between Federal and State laws that might provide a brake on the speed and scale of commercialisation in states that have legalised cannabis. Any increases in cannabis use and harm could be minimised if governments introduced public health policies that limited the promotional activities of a legal cannabis industry, restricted cannabis availability to adults, and maintained cannabis prices at a substantial fraction of the black market price. So far, no states have chosen to implement these policies.
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.
The number of people entering specialist drug treatment for cannabis problems has increased considerably in recent years. The reasons for this are unclear, but rising cannabis potency could be a ...contributing factor.
Cannabis potency data were obtained from an ongoing monitoring programme in the Netherlands. We analysed concentrations of δ-9-tetrahydrocannabinol (THC) from the most popular variety of domestic herbal cannabis sold in each retail outlet (2000-2015). Mixed effects linear regression models examined time-dependent associations between THC and first-time cannabis admissions to specialist drug treatment. Candidate time lags were 0-10 years, based on normative European drug treatment data.
THC increased from a mean (95% CI) of 8.62 (7.97-9.27) to 20.38 (19.09-21.67) from 2000 to 2004 and then decreased to 15.31 (14.24-16.38) in 2015. First-time cannabis admissions (per 100 000 inhabitants) rose from 7.08 to 26.36 from 2000 to 2010, and then decreased to 19.82 in 2015. THC was positively associated with treatment entry at lags of 0-9 years, with the strongest association at 5 years, b = 0.370 (0.317-0.424), p < 0.0001. After adjusting for age, sex and non-cannabis drug treatment admissions, these positive associations were attenuated but remained statistically significant at lags of 5-7 years and were again strongest at 5 years, b = 0.082 (0.052-0.111), p < 0.0001.
In this 16-year observational study, we found positive time-dependent associations between changes in cannabis potency and first-time cannabis admissions to drug treatment. These associations are biologically plausible, but their strength after adjustment suggests that other factors are also important.
Substance use in young people (aged 10-24 years) might disrupt key periods of transition that occur as the adolescent brain undergoes cognitive and emotional development, and key psychosocial ...transitions are made. Adolescence is the peak time for initiation of substance use, with tobacco and alcohol usually preceding the use of illicit drugs. Substantial variation is noted between countries in the levels, types, and sequences of substance use in young people, indicating that a young person's use of substances depends on their social context, drug availability, and their personal characteristics. The Global Burden of Disease (GBD) 2013 study suggests that the burden attributable to substance use increases substantially in adolescence and young adulthood. In young men aged 20-24 years, alcohol and illicit substance use are responsible for 14% of total health burden. Alcohol causes most health burden in eastern Europe, and illicit drug burden is higher in the USA, Canada, Australia, New Zealand, and western Europe. Large gaps exist in epidemiological data about the extent of drug use worldwide and much of what we know about the natural history of substance use comes from cohort studies in high-income countries undertaken decades ago, which hinders effective global policy responses. In view of the global epidemiological transitions from diseases of poverty to non-communicable diseases, the burden of disease and health risks among adolescents and young adults is likely to change substantially, in ways that will no doubt see substance use playing an increasingly large part.
Aims
To review three key and controversial comorbidities of cannabis use—other illicit drug use, psychosis and depression, as well as suicide, from a genetically informed perspective.
Design
...Selective review.
Results
Genetic factors play a critical role in the association between cannabis use, particularly early‐onset use and use of other illicit drugs, psychosis and depression, as well as suicide, albeit via differing mechanisms. For other illicit drugs, while there is strong evidence for shared genetic influences, residual association that is attributable to causal or person‐specific environmental factors cannot be ruled out. For depression, common genetic influences are solely responsible for the association with cannabis use but for suicidal attempt, evidence for person‐specific factors persists. Finally, even though rates of cannabis use are inordinately high in those with psychotic disorders, there is no evidence of shared genetic etiologies underlying this comorbidity. Instead, there is limited evidence that adolescent cannabis use might moderate the extent to which diathesis influences psychosis.
Conclusions
Overlapping genetic influences underlie the association between early‐onset cannabis use and other illicit drug use as well as depression and suicide. For psychosis, mechanisms other than shared genetic influences might be at play.
ABSTRACT
Aims To determine the prevalence of past 12‐month DSM‐5 alcohol use disorders (AUDs), to quantify and characterize individuals who remain stably unaffected or affected and those who ...‘switch’ diagnostically between DSM‐IV and DSM‐5 classifications.
Design Data from the nationally representative wave 2 of the National Epidemiological Survey of Alcohol and Related Conditions (NESARC) collected in 2004–05.
Setting General population survey.
Participants All surveyed participants (n = 34 653, aged 21 years and older) and 29 993 individuals reporting life‐time alcohol use across both waves of NESARC.
Measurements DSM‐IV and DSM‐5 criteria were coded using proposed guidelines.
Findings The prevalence of DSM‐5 AUDs was 10.8% with the corresponding prevalence of DSM‐IV abuse/dependence being 9.7%, implying a modest 11.3% increase. Those who switched diagnostically from affected to unaffected (19.6% of DSM‐IV affected) were most likely to have endorsed hazardous use, due particularly to drinking and driving, while those who transitioned from unaffected to affected (3.3% of DSM‐IV unaffected) were primarily DSM‐IV diagnostic orphans reporting larger/longer and quit/cut‐back. Dropping the legal criterion did not affect the prevalence significantly, while the addition of craving also had a relatively modest impact on prevalence.
Conclusion The proposed DSM‐5 revisions eliminate successfully individuals diagnosed previously with DSM‐IV alcohol abuse due primarily to hazardous use alone and incorporate diagnostic orphans into the diagnostic realm. Definitions of craving and importantly, hazardous use require considerable attention as it is likely that they will contribute to variations in reports of increased prevalence of alcohol use disorders between DSM‐IV to DSM‐5.
The Diagnostic and Statistical Manual of Mental Disorders (DSM; 5th ed.) reassignment of gambling disorder as an addictive disorder alongside the substance-related addictive disorders encourages ...research into their shared etiologies. The aims of this study were to examine: (a) the associations of Big Five personality dimensions with alcohol, nicotine, cannabis, and gambling disorders, (b) the comorbidity between these disorders, (c) the extent to which common personality underpinnings explain comorbidity, (d) whether results differed for men and women, and (e) the magnitude of personality differences corresponding to the 4 disorders. Participants were 3,785 twins and siblings (1,365 men, 2,420 women; Mage = 32 years, range = 21-46 years) from the Australian Twin Registry who completed psychiatric interviews and Big Five personality inventories. The personality profile of high neuroticism, low agreeableness, and low conscientiousness was associated with all 4 addictive disorders. All but 1 of the pairwise associations between the disorders were significant. After accounting for Big Five traits, the associations were attenuated to varying degrees but remained significant. The results were generally similar for men and women. The results suggest that the Big Five traits of neuroticism, agreeableness, and conscientiousness are associated with the general propensity to develop an addictive disorder and may in part explain their co-occurrence; however, they may be more broadly associated with the propensity for any psychiatric disorder. The effect sizes of the personality associations suggest that the diagnosis of gambling disorder as operationalized by the DSM may be more severe than the other addictive disorders. Calibration of the diagnosis of gambling disorder to the other addictive disorders may be warranted.
ABSTRACT
Aim Twin studies have shown that cannabis use disorders (abuse/dependence) are highly heritable. This review aims to: (i) review existing linkage studies of cannabis use disorders and (ii) ...review gene association studies, to identify potential candidate genes, including those that have been tested for composite substance use disorders and (iii) to highlight challenges in the genomic study of cannabis use disorders.
Methods Peer‐reviewed linkage and candidate gene association studies are reviewed.
Results Four linkage studies are reviewed: results from these have homed in on regions on chromosomes 1, 3, 4, 9, 14, 17 and 18, which harbor candidates of predicted biological relevance, such as monoglyceride lipase (MGLL) on chromosome 3, but also novel genes, including ELTD1epidermal growth factor (EGF), latrophilin and seven transmembrane domain containing 1 on chromosome 1. Gene association studies are presented for (a) genes posited to have specific influences on cannabis use disorders: CNR1, CB2, FAAH, MGLL, TRPV1 and GPR55 and (b) genes from various neurotransmitter systems that are likely to exert a non‐specific influence on risk of cannabis use disorders, e.g. GABRA2, DRD2 and OPRM1.
Conclusions There are challenges associated with (i) understanding biological complexity underlying cannabis use disorders (including the need to study gene–gene and gene–environment interactions), (ii) using diagnostic versus quantitative phenotypes, (iii) delineating which stage of cannabis involvement (e.g. use versus misuse) genes influence and (iv) problems of sample ascertainment.
ABSTRACT
Aims The genetic etiology of cannabis use, abuse and dependence has elicited significant interest from genetic epidemiologists.
Methods Genetically informative studies, including family, ...twin and adoption studies that have examined the role of genetic and environmental influences on the various stages of cannabis involvement, and the genetic relationship between cannabis, licit drugs and other hard drugs, are reviewed.
Results Findings across a number of such studies have indicated that there is a genetic basis to each stage of cannabis involvement although a proportion of the genetic factors influencing individual stages may be specific to that stage. Multivariate analyses that explore the association between cannabis and licit (alcohol and tobacco) as well as hard drugs (e.g. cocaine, opioids), using multiple methodological strategies, suggest the role of common genetic and environmental influences influencing the liability to cannabis and other drug involvement.
Conclusions The substantial evidence for the heritability of cannabis use, abuse and dependence underscore the importance of linkage and association studies that aim to find genes of etiologic significance.
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