However, adjusting for covariates in models 2 and 3progressively attenuated the beta estimate and increased the width of the confidence intervals to include null and positive values. All other categories of self-reported cannabis use produced wide confidence intervals that include null values. Fibrinogen. In bivariate analysis, self-reported cannabis use within the past 30 days was associated with lower levels of fibrinogen compared to nonuse with confidence intervals around the beta point estimates excluding null and positive value. Like IL-6, adjusting covariates in models 2 and 3 attenuated the point estimates and widened the confidence intervals to include the null value. Full model estimates with covariate results are included in the Supplementary Material Table S3.In this analysis of nationally representative data from Wave 1 of the PATH study, there was a pattern of lower levels of biomarkers of systemic inflammation, particularly hs-CRP among respondents self-reporting recent cannabis use compared to never use, although the wide confidence intervals around the point estimates indicated findings were not statistically significant. Furthermore, statistical tests to determine whether the association between self-reported cannabis use and biomarkers of systemic inflammation differed by sex were also not statistically significant. The findings from our study are based on a multivariable analysis that adjusted for important confounding variables, including respondent’s BMI and use of antiinflammatory medications. The potential therapeutic effects of cannabis have been proposed to be mediated via its anti-inflammatory properties . Findings from preclinical and animal studies converge to suggest that the active constituents in the cannabis plant – particularly THC and CBD induce anti-inflammatory properties . Our study found that more recent cannabis use is associated with lower levels of biomarkers of systemic inflammation is consistent with anti-inflammatory hypothesis and with findings from prior research. Data from the National Health and Nutrition Examination Survey showed lower serum CRP levels in active cannabis users compared to never users, but only when CRP levels were below the median . Also, self-reported cannabis use was not statistically associated with lower levels of CRP in a recent analysis using data from the Adolescent to Adult Health study, after adjusting for sociodemographic characteristics, tobacco exposure, BMI and anti-inflammatory medication use .
In a recent longitudinal analysis of participants in the CARDIA cohort study, self-reported recent cannabis use was not statistically associated with lower levels of CRP, IL-6 and fibrinogen among the CARDIA sample.In sum,trimming tray most epidemiologic studies investigating the association between self-reported cannabis use and biomarkers of inflammation have found negative associations that were non-significant with the exception of a few that reported statistically significant negative associations . The reason for the disparate findings may be related to differences in the study sample that focused on primarily African Americans and in the set of con-founders included in the multi-variable models . Our study adjusted for important con-founders such as anti-inflammatory medication use and BMI, which these prior studies did not address in their analysis . Indeed, our study found statistically significant associations between recent cannabis use and lower levels of hs-CRP, IL-6 and fibrinogen in limited models , which was no longer statistically significant in the fully adjusted model 3, underscoring the importance of fully adjusting for important con-founders when investigating the relationships between cannabis use and inflammation. Our study extends findings from the extant literature by utilizing a large nationally representative data to analyze the association between self-reported cannabis use and three biomarkers of systemic inflammation. Although our results suggest lower levels of biomarkers of systemic inflammation in respondents self-reporting cannabis use in the past 30 days , the estimates produced had wide confidence intervals. The wide confidence intervals observed in our study might be a source of measurement error related to the imprecise measurement of cannabis. Our study relied on self-report of cannabis use, which is prone to inaccuracies. specifically, respondents may not accurately recall the last time they used cannabis, making it possible that some respondents who reported that they used cannabis within the past year, but more than 30 days ago, might have used in the past 30 days. Also, the cannabis use measurement in this analysis did not collect data on the amount and or concentrations of the different active compounds in marijuana. This is particularly relevant as emerging evidence suggest that the two primary active constituents in cannabis – tetrahydrocannabinol and cannabidiol – may have opposing immunomodulatory effects . Therefore, to move the field forward, better measurement of cannabis use, that includes the amount, THC and CBD content and mode of consumption would help us ascertain the dose-response relationship between cannabis, inflammatory markers, and symptomatology and whether findings differ by THC/CBD concentrations and mode of consumption. Our study also analyzed hs-CRP data which is a more stable and sensitive molecule than the standard CRP test. The hs-CRP assay can detect trace amounts of CRP than the standard CRP test. Although statistically non-significant, our analysis showed that the differences between recent cannabis use and other categories of cannabis use were more prominent for hs-CRP than other sensitive biomarkers of systemic inflammation. This suggests that more sensitive biomarkers of systemic inflammation should be employed in future research.
Our analysis was based on only three biomarkers of systemic inflammation; with the blood specimen to measure these biomarkers collected on a separate visit from the visit cannabis data was collected. Future studies should include a broad panel of biomarkers, particularly anti-inflammatory molecules in order to increase our understanding of the immunomodulatory effects of cannabis use. We note that mean levels of all biomarkers of systemic inflammation were higher among respondent self-reporting cannabis use within the past year, but not in the past 30-days . It is possible that this group includes respondents who recently ceased cannabis use due to illness that can drive inflammation response. The cross-sectional design of our analysis precluded the assessment of directional relationships. Specifically, a cross-sectional finding indicates a correlational association, precluding a directional or causal relationship between cannabis use and biomarkers of systemic inflammation. Therefore, future research using longitudinal and experimental designs that follow subjects across multiple time points are needed to broaden our understanding of the cannabis and inflammation relationship, specifically whether reductions in inflammatory markers mediate the association between cannabis use and reduced self-reported chronic disease symptomatology or differences in incident or recurring inflammatory-related disease .Cannabis is the most commonly used illicit drug globally, with some 250 million estimated active users. Policy approaches for cannabis have been shifting gradually around the world recently. While criminal prohibition has been the main control framework for decades, Canada, Uruguay, and 11 US states have recently legalized non-medical cannabis use and supply, with reference to public health and safety objectives. New Zealand, alongside other jurisdictions, is actively considering a similar policy reform towards legalization of non-medical cannabis use and supply that will be decided in a public referendum in late 2020. Public opinion polls suggest an about split for and against a legalization framework as presented in the draft ‘Cannabis Legalization and Control Bill’. This proposal is very similar to Canada’s laws in: legal use age of 20 years; no public use; commercial production and retail of diverse cannabis products; and home-growing of cannabis allowed.
New Zealand, along with North America and Australia, is part of a group of ‘high-use’ countries in which 8%–15% of the population report cannabis use, the majority of whom have tried cannabis in their teens. While survey evidence is not wholly consistent, cannabis use has increased among young adults in the general population in New Zealand but declined among adolescents. Cannabis use remains concentrated among youth/young adults , with about one in three reporting recent use but its prevalence of is lower than that of alcohol and tobacco. These include: acute cognitive,psychomotor control and memory impairment ; moderately increased driving impairment increasing risks of injury/death; cannabis use disorder/dependence ; weak to moderate associations with chronic mental health problems, primarily schizophrenia and depression ; chronic bronchitis or other pulmonary problems among those who smoke cannabis ; select adverse reproductive/maternal health outcomes among women using cannabis during pregnancy; and possibly cardio-vascular problems among users of high-potency cannabinoid products. With notable exceptions , there are few, if any directly attributable deaths from cannabis. The lion’s share of the cannabis-related burden of disease is attributable to cannabis-related impairment, and consequential injuries or deaths, and cannabis use disorder . The cannabis-related disease burden is substantially lower than that for alcohol, tobacco or psychostimulants. The main adverse social consequences of cannabis use can include compromised educational attainment, and adverse consequences of arrests and convictions e.g. restrictions on travel and professional disadvantage. Arrests commonly involve young and socio-economically marginalized males as a result of selective enforcement practices with related social injustices. Among youth and young adults, adverse health and social outcomes primarily occur among sub-groups of vulnerable users characterized by select, shared risks characteristics. This fact has major implications for the foci of targeted prevention of cannabis-related harms from a public health point of view, namely the need to give priority to protecting young people from the adverse effects of their youthful cannabis use on their life chances and courses. Among its essential prospective benefits, cannabis legalization allows authorities to regulate cannabis products, distribution and use. It furthermore makes it easier to directly facilitate interventions aimed at users, and specifically to systematically provide risk reduction advise to users. Targeted or secondary prevention measures to reduce risky or harmful cannabis use have traditionally been limited, and general prevention efforts have mostly focused on reducing availability and advising against cannabis use. This, in part, because risk reduction advice has been seen as implicitly ‘endorsing’ cannabis use as an illegal activity. Recent reviews suggest some evidence for a limited impact of individual targeted risk-reduction interventions, for example, in the form of ‘brief interventions’, for cannabis use. A tailor-made population-level targeted prevention tool for cannabis use, the ‘Lower-Risk Cannabis Use Guidelines ’, was developed, originally in 2011 and updated in 2017, in anticipation of cannabis legalization in 2018 in Canada. The LRCUG embody health-focused education and ‘behavioral choice’ models that focus on risk factors for adverse harm outcomes from cannabis use, identifified by reviews of relevant scientific evidence, trim tray pollen that users can modify if they wish to reduce risk of harm with ongoing use. The LRCUG comprise a total of 10 recommendation clusters advising users on how to reduce cannabis use-related risks developed from the consensus of an international group of addiction and health scientists. Important for general uptake and dissemination, the LRCUG have been endorsed by ten leading Canadian organizations [e.g., the Canadian Medical Association [CMA], the Canadian Public Health Association [CPHA], the Canadian Society of Addiction Medicine [CSAM], among others with health, substance use and addiction focus or mandate.
They were also included in education and prevention strategies devised by different levels of governments as part of the implementation of cannabis legalization in Canada. To practically facilitate wide dissemination and uptake, a suite of customized ‘knowledge translation’ products was developed for different target audiences and distributed jointly with key stakeholders. The LRCUG, or similar frameworks, have been adapted for use in Latin America and other jurisdictions. Based on the proposed parameters of possible legalization policy in New Zealand, and available assessments of the impact of legalization on cannabis use and harm outcomes to date in other jurisdictions, it is possible that some of these harm indicators, at least in the short-term, may increase. Given this, the LRCUG provide a ready-made, evidence-informed population health tool with the potential to reduce the risks of adverse effects among the sizeable population of cannabis users in New Zealand. Moreover, the New Zealand government’s draft legalization bill stipulates mandatory ‘harm minimization messaging’ to be provided to users at cannabis retail interfaces, for which the LRCUG provide a ready and fitting foundation or template. While the scientific evidence informing the LRCUG is evolving and will require future updating, the LRCUG’s concept and approach resemble other, established health behavior guidelines, for example targeting nutritional, cardio-vascular, sexual health promotion or related risk reduction, and – the closely topic-related – low-risk drinking guidelines in place in many English-speaking and other countries.