In addition, about 15-30% of PWUC drive under the influence of cannabis, with roughly 20% of cannabis related traffic injuries being fatal Furthermore, it is estimated that only about 2% or less of PWUC experience a severe cannabis induced mental health problem. The population-based probabilities of PWUC experiencing many of the other identified cannabis-associated adverse health outcomes are even smaller. In addition, except for cannabis-related motor-vehicle-crash fatalities, cannabis use makes virtually no direct contribution to mortality. Recent national and global estimates have identified cannabis-impaired driving and related injuries/death – which may include non-using others – and CUD as leading contributors to the cannabis-related disease burden . While the estimated contribution of cannabis to disease burden is not insubstantial, it is far smaller than that for alcohol or tobacco. In many jurisdictions, longstanding laws prohibiting non-medical cannabis use under penalties have been liberalized in recent years. This has, partly, been because cannabis has limited adverse health consequences and partly because of the excess of personal and societal costs of criminal penalties for cannabis use . The most liberal policies have included the legalization and regulation of non-medical cannabis use and supply to adults in Uruguay , Canada , Mexico , and in a growing number of state jurisdictions in the United States , initially including Colorado and Washington .
These legalization regimes, however, feature rather heterogeneous regulatory frameworks . In addition, other jurisdictions have been contemplating legalization reforms. Commonly, the case for cannabis legalization is made to improve public health and safety outcomes . specifically, it is assumed that under legalization, the distribution of cannabis products will shift from criminal to legal markets allowing better regulation of cannabis products and targeted interventions to minimize adverse cannabis-related health and social outcomes from – now legal – use . While mostly US-dominated, evidence suggests that legalization has reduced some social harms.The evidence on public health impacts is mixed. Specifically, data have suggested select increases in the prevalence and intensity of use among adults , hospitalizations, and cannabis-related MVCs,drying racks mostly by comparison to non-legalized settings . The effects of legalization on CUD or treatment seeking has been mixed, while attitudes towards risks of cannabis use have softened in several sub-groups.The success of cannabis legalization as a policy experiment that benefits public health and safety outcomes therefore remains uncertain. However, these desired beneficial outcomes will require PWUC, especially the disproportionately large number of young users, to have guidance on how to reduce key risk-behaviours that contribute to adverse health outcomes and related disease burden . To that general end, international expert teams had previously tabled evidence-based ‘Lower-Risk Cannabis Use Guidelines’ including targeted recommendations for PWUC, with the principal aim of identifying use behaviour-related risk factors modifiable by the user-individual that will aid to reduce risks of adverse health outcomes from non-medical cannabis use . The LRCUG are based on concepts of health behavior change and similar guidance-oriented interventions implemented in other areas of population health.
They represent a targeted prevention tool to complement universal prevention and treatment measures on the intervention continuum . The LRCUG’ previous iterations were endorsed by leading government agencies and health/addiction stakeholder organizations in Canada and internationally to encourage their widespread utilization to reduce cannabis-related health harms among PWUC. They were communicated and distributed widely in different formats customised to different target audiences.The body of scientific evidence on cannabis use and its health outcomes has evolved substantially since the most recent version of the LRCUG. Given these developments, and the building momentum towards cannabis policy liberalization, we undertook a comprehensive review of new scientific evidence to inform an update and refinement of the LRCUG and their recommendations.Literature searches were conducted using the Embase, Medline, CINAHL, PsycInfo, the Cochrane Library, and Web of Science databases. Initial search strategies were developed for use in Embase and modified for other databases. Medical Subject Headings were used where applicable and combined with appropriate keywords for each risk factor topic. An example of the Embase search strategy used can be found in [Supplement 1]. Searches principally focussed on recent systematic or other comprehensive reviews, or other topically pertinent, high-quality studies. Subject areas where systematic review evidence was limited or absent were supplemented by reviewing individual studies identified through targeted or secondary searches, Google Scholar, and manual searches of reference lists. Given that this review was not conceptualized as a systematic review, in addition to the multiple risk factor topics involved, this paper does not present a routinised system for reporting systematic reviews specific inclusion and exclusion criteria were developed for each topical area, but general selection criteria applied to all topics.
In general, we included English language, peer-reviewed journal reviews and individual studies that contained data on behavior-based and -modifiable risk factors for adverse health outcomes associated with cannabis use. As this effort was principally approached as a review and update focusing on new evidence and insights following previously published LRCUG content, we only included literature published in 2016 or later that had not been included in the most recent iteration of the LRCUG. Given our primary focus on modifiable risks of adverse health outcomes among PWUC non-medically, we did not include in our scope studies whose main focus was on the medical benefits of cannabis, use of synthetic cannabinoids, social/legal harms, or risks-to-others.Its main psychotropic effects – as documented per seminal reviews – occur through the central nervous system’s endocannabinoid system , which undergoes major neurodevelopment during this transition period. This renders young, and especially adolescents’ neurological systems, vulnerable to adverse effects from exogenous cannabinoid exposure . Some evidence suggest that the neurobiological effects of cannabis use are similar in adult and adolescent PWUC. Extensive data, however, suggest that those initiating use by their mid-teens are at higher risk of transitioning to regular use and experiencing more persistent adverse outcomes than older PWUC, such as possible alterations in brain structure and functioning, although confounding conditions may contribute and causality is not consistently clear . Systematic and other reviews of human neuroimaging studies suggest that adolescent cannabis use is associated with structural brain alterations expressed in reduced volumes in the hippocampus and orbitofrontal cortex, thicker cerebral cortices, and decreased integrity of prefrontal and medial temporal brain regions .
Functional brain imaging studies among adolescent PWUC show alterations in frontal and parietal brain regions related to inhibition, reward, and memory.Despite these alterations, adolescents with cannabis use do not consistently show impaired performance in functional magnetic resonance imaging tasks, suggesting the possible employment of compensatory cognitive resources to offset performance decrements . In adult PWUC, evidence shows inconsistent associations between age-of-onset of use and brain functioning metrics . A systematic review detected a small overall reduction in cognitive functioning in youth-aged persons with frequent cannabis use but no variation with age or age-of-onset of use . A subsequent study involving persons aged 14-21 with frequent and occasional use found similar brain metrics among both adolescent and young adult cannabis using and non-using individuals , whereas other studies have have not identified long-term effects of adolescent cannabis use on neuropsychological or executive functions . Systematic and other reviews have found both more severe and persistent executive functioning impairment among adolescent compared with adult PWUC . Mental health outcomes of adolescent PWUC may also be affected by cannabis use. A systematic review found associations between adolescent cannabis use and the development of depression , suicidal ideation , and suicide attempts in young adulthood . A systematic review found adolescent PWUC at the highest risk of suicidal behaviours . Earlier age-of-initiation was associated with a higher risk for psychosis in all but one study and with increased symptoms of depression or anxiety by age 25 in a systematic review . A prospective longitudinal study found cannabis drying initiation before age 18 was associated with a higher risk for major depressive disorder , especially in individuals with higher-frequency compared with lower frequency early-onset use It is unclear, however, to which extent use and mental health disorders are causal, as they may be multi-directional and are likely to co-occur because the prevalence of mental health problems and cannabis use are both high in adolescence.
In an age-stratified placebo-controlled, double-blind cross-over trial involving exposure to equivalent doses of cannabis, adults showed greater impairment and intoxication, while adolescents showed impaired inhibitory processes and increased desire for cannabis use, suggesting differential age-based neuro-behavioral response profiles to use . Some evidence from prospective longitudinal studies suggests that adolescent PWUC have lower or declining IQs than non-using peers, but the possible role of confounders is unclear . Adolescent PWUC have shown lower educational attainment, more substance use/problems, and higher levels of antisocial behavior and other health problems in later adult life . In the US population, PWUC aged 15–19 years had a significantly higher risk of developing CUD than those aged 20 and older . In a study of cannabis-related driving skills among individuals with intensive recreational use, significant impairment was concentrated among those indicating early-onset use . Overall, it is unclear whether early-onset cannabis use has an independent effect on adverse outcomes from cannabis use, and the magnitude of any effects on brain functioning . Most adverse effects observed in individuals reporting early-onset use appear to involve frequent and/or high-potency cannabis use as relevant factors , and young people with poorer cognitive functioning are more likely to transition to frequent cannabis use patterns . While assessments of early-onset related impairments typically focus on nominal ages , neurological vulnerabilities can vary between youth of the same age. Therefore, it would be better to apply “adolescent pubertal markers” that more accurately index the stage of brain development . A systematic review failed to find evidence of the effects of cannabis use specifically on pubertal outcomes themselves .Many reviews on the adverse health effects of cannabis use have selectively focused on outcomes among those with intensive or chronic cannabis use only. Moreover, definitions of intensive use have varied, but it is commonly defined as ‘daily/near-daily’ use. On this basis, there is substantial evidence that frequent cannabis use, also when directly compared with less frequent use, represents and functions as a strong predictor of adverse health outcomes . A systematic review including multiple meta-analyses of the associations between cannabis use and brain volume found that frequent cannabis use was associated with significantly smaller volumes in the hippocampus , orbitofrontal cortex and lateral regions than in controls . While acute tetrahydrocannabinol exposure leads to acute increases in cerebral blood flow in multiple brain regions, chronic cannabis use results in an overall reduction in CBF, especially in the prefrontal cortex, in a dose-dependent manner . Other reviews have confirmed deficits are more common in persons with intensive cannabis use than controls in both brain structure and neurocognitive performance.
A systematic review and meta-analyses found a significant association between frequent, heavy cannabis use and deficits in cognitive functioning in adolescents and young adults Another systematic review of studies on cerebellar structure and functioning found that deficits in behavioral performance were associated with chronic cannabis use . Another comprehensive review identified strong associations between intensive cannabis use and short term impairments in cognition , with mixed evidence for long-term effects, and symptoms of depression, anxiety, and psychosis . Systematic reviews have found stronger associations between adverse outcomes and heavy/chronic rather than less intensive cannabis use for psychotic symptoms, suicide-related behaviors, depression,and dependence . Other systematic reviews and meta-analyses have confirmed a relationship between frequency of cannabis use and the risk of psychosis and dependence . In a US-based study, cannabis use frequency was associated with psychosis and depression symptoms among a youth cohort and with mental health symptoms in the general population at later ages A multi-country modelling study on first-episode psychosis found a linear relationship between symptom dimensions and cannabis exposure, with the highest scores observed in individuals with daily use of high-potency cannabis.In a retrospective cohort study of monozygotic twins, the twin who used cannabis more frequently was more likely to report a MDD or suicidal ideation.