How have cannabis use and related indicators changed since legalization of cannabis for non-medical purposes? Results of the Canadian Cannabis Survey 2018-2022.

BACKGROUND: Cannabis use for non-medical purposes was legalized and regulated in Canada through the Cannabis Act in October 2018. This paper examined trends in use of cannabis for non-medical purposes and related indicators from pre- to post-legalization in Canada (2018-2022). METHODS: Data from 5 years of the Canadian Cannabis Survey, an annual web-based survey administered to Canadians 16 years of age or older, were used in the analysis (n2018=12,952; n2019=11,922; n2020=10,821; n2021=10,733; n2022=10,048). Cannabis measures include questions about use, types of products, sources, risk perceptions and beliefs, and exposure to public education campaigns and health warnings. Adjusted logistic regression models tested differences in outcomes over time. RESULTS: Past 12-month cannabis consumption increased among Canadians from 22 % in 2018 to 27 % in 2022 (AOR=1.41;99 % CI:1.28-1.54). Similarly, daily/almost daily (DAD) consumption increased from 5 % in 2018 to 7 % in 2022 (AOR=1.36;99 % CI:1.16-1.59). Consumption of dried flower, hash/kief, and concentrates/extracts (e.g., wax, shatter, budder) decreased since 2018, whereas consumption of edibles, beverages and vape pens/cartridges increased (p < 0.001). Legal purchasing increased from 4 % in 2018 to 69 % in 2022, while accessing cannabis through social and illegal sources decreased over time (p < 0.001). CONCLUSION: More Canadians are reporting cannabis consumption since legalization and regulation of cannabis for non-medical purposes, continuing a pre-existing trend despite an increase in awareness of the risks of consuming cannabis. Trends in product use indicate a transition from dried flower and concentrates/extracts towards consumption of cannabis foods, drinks and vape pens/cartridges. The legal market is increasingly displacing the illicit cannabis market in Canada.

Co-Use, Simultaneous Use, and Mixing of Cannabis and Tobacco: A Cross-National Comparison of Canada and the US by Cannabis Administration Type.

INTRODUCTION: Increasing cannabis legalization raises concerns that the use of tobacco, frequently used with cannabis, will also increase. This study investigated the association between the legal status of cannabis in places of residence and the prevalence of cannabis and tobacco co-use, simultaneous use, and mixing by comparing the prevalence among adults in Canada (prior to cannabis legalization) vs. adults in US states that had legalized recreational cannabis vs. US states that had not as of September 2018. METHODS: Data were drawn from the 2018 International Cannabis Policy Study, conducted with respondents aged 16-65 in Canada and the US recruited from nonprobability consumer panels. Differences in the prevalence of co-use, simultaneous use, and mixing between tobacco and different cannabis products were examined using logistic regression models by legal status of place of residence among past-12-month cannabis consumers (N = 6744). RESULTS: Co-use and simultaneous use in the past 12 months were most common among respondents in US legal states. Among cannabis consumers, co-use and simultaneous use were less common in US legal states, while mixing was less frequent in US states with both legal and illegal cannabis compared to Canada. Use of edibles was associated with lower odds of all three outcomes, while smoking dried herb or hash was associated with higher odds. CONCLUSIONS: The proportion of cannabis consumers who used tobacco was lower in legal jurisdictions despite higher prevalence of cannabis use. Edible use was inversely associated with co-use, suggesting that edible use does not appear to be associated with increased tobacco use.

Self-reported Impact of the COVID-19 Pandemic on Cannabis Use in Canada and the United States.

The current study examined the self-reported impact of the COVID-19 pandemic on cannabis consumption and behaviors among past 12-month cannabis consumers in Canada and the U.S. across different cannabis laws. Cross-sectional survey data were collected in 2020 from respondents recruited through online commercial panels, aged 16-65, who consumed cannabis in the past 12 months (n = 13,689). Weighted multinomial logistic regression models examined differences between jurisdictions for five outcomes: 1) cannabis consumption; 2) use of product types; 3) use of sources to obtain cannabis; 4) legality of source used; and 5) access to cannabis. Approximately one third of cannabis consumers reported changes to their consumption during the pandemic. Edibles (23% - 31%) and dried flower (21% - 30%) were the two most common products that respondents reported they were "more likely" to use during the pandemic. Most consumers reported "no difference" to changes in sourcing cannabis. Compared to consumers in U.S. recreational states, consumers in U.S. medical (AOR = 1.27, 95% CI: 1.07, 1.50) and illegal states (AOR = 1.22, CI: 1.00,1.48) had higher odds of reporting it was "harder" to access cannabis, and consumers in Canada had lower odds (AOR = 0.73, CI: 0.63,0.84). Future research should examine whether these changes remain after public health restrictions due to the pandemic are removed.

Consumer perceptions of legal cannabis products in Canada, 2019-2021: a repeat cross-sectional study.

BACKGROUND: Consumer perceptions of legal cannabis products may drive willingness to purchase from the illegal or legal market; however, little is known on this topic. The current study examined perceptions of legal products among Canadian cannabis consumers over a 3-year period following federal legalization of non-medical cannabis in 2018. METHODS: Data were analyzed from Canadian respondents in the International Cannabis Policy Study, a repeat cross-sectional survey conducted in 2019-2021. Respondents were 15,311 past 12-month cannabis consumers of legal age to purchase cannabis. Weighted logistic regression models examined the association between perceptions of legal cannabis and province of residence, and frequency of cannabis use over time. RESULTS: In 2021, cannabis consumers perceived legal cannabis to be safer to buy (54.0%), more convenient to buy (47.8%), more expensive (47.2%), safer to use (46.8%) and higher quality (29.3%) than illegal cannabis. Except for safety of purchasing, consumers had more favourable perceptions of legal cannabis in 2021 than 2019 across all outcomes. For example, consumers had higher odds of perceiving legal cannabis as more convenient to buy in 2021 than 2019 (AOR = 3.09, 95%CI: 2.65,3.60). More frequent consumers had less favourable perceptions of legal cannabis than less frequent consumers. CONCLUSIONS: Three years since legalization, Canadian cannabis consumers generally had increasingly favourable perceptions of legal vs. illegal products - except for price - with variation across the provinces and frequency of cannabis use. To achieve public health objectives of legalization, federal and provincial governments must ensure that legal cannabis products are preferred to illegal, without appealing to non-consumers.

Epigenetic alterations induced by genotoxic occupational and environmental human chemical carcinogens: An update of a systematic literature review.

Epigenetic alterations, such as changes in DNA methylation, histones/chromatin structure, nucleosome positioning, and expression of non-coding RNAs, are recognized among key characteristics of carcinogens; they may occur independently or concomitantly with genotoxic effects. While data on genotoxicity are collected through standardized guideline tests, data collected on epigenetic effects is far less uniform. In 2016, we conducted a systematic review of published studies of genotoxic carcinogens that reported epigenetic endpoints to better understand the evidence for epigenetic alterations of human carcinogens, and the potential association with genotoxic endpoints. Since then, the number of studies of epigenetic effects of chemicals has nearly doubled. This review stands as an update on epigenetic alterations induced by occupational and environmental human carcinogens that were previously and recently classified as Group 1 by the International Agency for Research on Cancer. We found that the evidence of epigenetic effects remains uneven across agents. Studies of DNA methylation are most abundant, while reports concerning effects on non-coding RNA have increased over the past 5 years. By contrast, mechanistic toxicology studies of histone modifications and chromatin state alterations remain few. We found that most publications of epigenetic effects of carcinogens were studies in exposed humans or human cells. Studies in rodents represent the second most common species used for epigenetic studies in toxicology, in vivo exposures being the most predominant. Future studies should incorporate dose- and time-dependent study designs and also investigate the persistence of effects following cessation of exposure, considering the dynamic nature of most epigenetic alterations.

Meat-Reduced Dietary Practices and Efforts in 5 Countries: Analysis of Cross-Sectional Surveys in 2018 and 2019.

BACKGROUND: Diets that reduce reliance on animal-source foods are recommended in some contexts. OBJECTIVES: This study aimed to compare proportions of respondents who reported following meat-reduced dietary practices (i.e., vegetarian, vegan, or pescatarian diets) and/or making efforts to reduce animal-source foods, and to examine sociodemographic correlates across 5 countries. METHODS: Online surveys were conducted in November and December 2018 and 2019 with 41,607 adults from Australia (n = 7926), Canada (n = 8031), Mexico (n = 8110), the United Kingdom (n = 9129), and the United States (n = 8411) as part of the International Food Policy Study. Respondents were asked whether they would describe themselves as vegetarian, vegan, or pescatarian, and whether they had made efforts to consume less red meat, less of all meats, or less dairy in the past year. Logistic regressions examined differences in the likelihood of each behavior between countries and sociodemographic subgroups. RESULTS: Approximately 1 in 10 respondents reported following a vegetarian, vegan, or pescatarian diet, ranging from 8.6% (Canada) to 11.7% (UK). In the past 12 months, the proportions of respondents who reported efforts to consume less red meat ranged from 34.5% (Australia) to 44.4% (Mexico), less of all meats ranged from 27.9% (US) to 35.2% (Mexico), and to consume less dairy ranged from 20.6% (UK) to 41.3% (Mexico). Respondents were more likely to report efforts to consume less animal-source products in 2019 compared to 2018 in most countries. Sociodemographic patterns varied by country; in general, women, those with higher education levels, and those in minority ethnic groups were more likely to report following meat-reduced dietary practices or efforts to consume fewer animal-source products. CONCLUSIONS: Nearly half of respondents reported following a meat-reduced diet or efforts to reduce animal-source products, with differences between countries and population subgroups. Population-level approaches and policies that support meat reduction may further reduce consumption of animal-source products.

Reasons for Purchasing Cannabis From Illegal Sources in Legal Markets: Findings Among Cannabis Consumers in Canada and U.S. States, 2019-2020.

OBJECTIVE: Nonmedical cannabis is legal in Canada and several U.S. states. Displacing the illegal market is a primary goal of legalization; however, there are little data on factors that predict consumers' transition from the illegal to the legal market. The current study aimed to examine reasons for purchasing illegal cannabis and, thus, potential barriers to purchasing legal cannabis among consumers in Canada and U.S. states. METHOD: Data are from the 2019 and 2020 International Cannabis Policy Study, a repeat cross-sectional survey conducted among 16- to 65-year-olds. Reasons for purchasing illegally in the past 12 months were asked of male and female cannabis consumers in Canada and U.S. legal states (n = 11,659). Changes over time in reasons for illegal purchasing were tested. Analyses among Canadians also examined associations between reasons for illegal purchasing and objective data on cannabis prices and retail density. RESULTS: In both years, the most commonly reported barriers to legal purchasing were price (Canada: 35%-36%; United States: 27%) and inconvenience (Canada: 17%-20%; U.S.: 16%-18%). In 2020 versus 2019, several factors were less commonly reported as barriers in Canada, including inconvenience (17% vs. 20%, p = .011) and location of legal sources (11% vs. 18%, p < .001). Certain barriers increased in the United States, including slow delivery (5% vs. 8%, p = .002) and requiring a credit card (4% vs. 6%, p = .008). In Canada, consumers in provinces with more expensive legal cannabis were more likely to report price as a barrier, and those in provinces with fewer legal retail stores were more likely to report inconvenience as a barrier (p < .001). CONCLUSIONS: Higher prices and inconvenience of legal sources were common barriers to purchasing legal cannabis. Future research should examine how perceived barriers to legal purchasing change as legal markets mature.

Trends in the use of cannabis products in Canada and the USA, 2018 - 2020: Findings from the International Cannabis Policy Study.

BACKGROUND AND AIMS: There is little information on consumption patterns across the diverse range of cannabis product types. This paper examines trends in consumption patterns in Canada and the United States (US) between 2018-2020. DESIGN: Repeat cross-sectional surveys were conducted as part of the International Cannabis Policy Study online survey in 2018 (n=27,024), 2019 (n=45,426), and 2020 (n=45,180). SETTING: Respondents were recruited from commercial panels in Canada and US states that had and had not legalized non-medical cannabis (US 'legal' and 'illegal' states, respectively). PARTICIPANTS: Respondents were male and female participants aged 16-65 years. MEASUREMENTS: Data on frequency and consumption amounts were collected for nine types of cannabis products, including dried flower and processed products (e.g., oils and concentrates). Consumers were also asked about mixing cannabis with tobacco. Socio-demographic information was collected. FINDINGS: Dried flower was the most commonly used product, although use in the past 12 months declined between 2018 and 2020 in Canada (81% to 73%), US legal (78% to 72%) and illegal states (81% to 76%; p<0.05 for all). Prevalence of past 12-month use increased for virtually all other product forms, although prevalence of daily use remained stable across years. In 2020, edibles and vape oils were the most commonly used products after flower. Use of non-flower products was highest in US legal states, although similar trends were observed in all jurisdictions. Males were more likely to report using processed products, and vape oils were the most commonly processed product among 16-20-year-olds. Daily use of cannabis flower increased in US legal and illegal states, and average joint size increased across all jurisdictions over time. CONCLUSIONS: Dried flower remains the dominant product in Canada and the US; however, use of processed cannabis products has increased, with the largest increases observed in legal cannabis markets.

THC labeling on cannabis products: an experimental study of approaches for labeling THC servings on cannabis edibles.

BACKGROUND: Over-consumption is a common adverse outcome from cannabis edibles. States such as Colorado require each serving of cannabis edible to carry a THC symbol. This study aimed to test whether packaging edibles in separate servings and/or indicating the THC level per serving improves consumer understanding of serving size. METHODS: An 3 × 2 experimental task was conducted as part of the 2019 International Cannabis Policy Study online survey. Respondents from Canada and the US (n = 45,504) were randomly assigned to view an image of a chocolate cannabis edible. Packages displayed THC labels according to 1 of 6 experimental conditions: packaging (3 levels: whole multi-serving bar; individual chocolate squares; separately packaged squares) and THC stamp (2 levels: stamp on each square vs. no stamp). Logistic regression tested the effect of packaging and THC stamp on odds of correctly identifying a standard serving, among edible consumers and non-consumers separately. Edible consumers were also asked about their awareness of a standard THC serving. RESULTS: Only 14.6% of edible consumers reported knowing the standard serving of THC for cannabis edibles. In the experimental task, among non-consumers who saw stamped bars, the multi-serving bar (AOR = 1.16 (1.08, 1.24) p < 0.001) and individually packaged squares (AOR = 1.08 (1.01, 1.16), p = 0.031) elicited more correct responses than individual squares. There was no difference in packaging formats when stamps were absent (p > 0.05 for all). Among edible consumers, there was no effect of the packaging (p = 0.992) or stamp manipulation (p = 0.988). Among both edible consumers and non-consumers, respondents in US states with legal recreational cannabis performed better than Canadians (p < 0.001). CONCLUSIONS: Regulations that require THC information to be stamped or indicated on each serving of cannabis edible may facilitate understanding of how much to consume, especially among novice consumers.

Perceptions of the health risks of cannabis: estimates from national surveys in Canada and the United States, 2018-2019.

Few studies have compared knowledge of the specific health risks of cannabis across jurisdictions. This study aimed to examine perceptions of the health risks of cannabis in Canada and US states with and without legal non-medical cannabis. Cross-sectional data were collected from the 2018 and 2019 International Cannabis Policy Study online surveys. Respondents aged 16-65 (n = 72 459) were recruited from Nielsen panels using non-probability methods. Respondents completed questions on nine health effects of cannabis (including two 'false' control items). Socio-demographic data were collected. Regression models tested differences in outcomes between jurisdictions and by frequency of cannabis use, adjusting for socio-demographic factors. Across jurisdictions, agreement with statements on the health risks of cannabis was highest for questions on driving after cannabis use (66-80%), use during pregnancy/breastfeeding (61-71%) and addiction (51-62%) and lowest for risk of psychosis and schizophrenia (23-37%). Additionally, 12-18% and 6-7% of respondents agreed with the 'false' assertions that cannabis could cure/prevent cancer and cause diabetes, respectively. Health knowledge was highest among Canadian respondents, followed by US states that had legalized non-medical cannabis and lowest in states that had not legalized non-medical cannabis (P < 0.001). Overall, the findings demonstrate a substantial deficit in knowledge of the health risks of cannabis, particularly among frequent consumers.

Self-Reported Impacts of the COVID-19 Pandemic on Diet-Related Behaviors and Food Security in 5 Countries: Results from the International Food Policy Study 2020.

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic has impacted many aspects of daily life, including dietary intake; however, few studies have reported its impacts on dietary behaviors and food security across multiple countries. OBJECTIVES: We examined self-reported impacts of COVID-19 on food behaviors, food security, and overall diet healthfulness in 5 countries. METHODS: Adults aged 18-100 years (n = 20,554) in Australia, Canada, Mexico, the United Kingdom, and the United States completed an online survey in November and December 2020 as part of the International Food Policy Study, an annual, repeat cross-sectional survey. Survey measures assessed perceived impacts of the COVID-19 pandemic on eating food prepared away from home, having food delivered from a restaurant, and buying groceries online, as well as perceived food security and overall diet healthfulness. Regression models examined associations between each outcome and sociodemographic correlates. RESULTS: Across all countries, 62% of respondents reported eating less food prepared away from home due to the pandemic, while 11% reported eating more. Some participants reported having less food delivered from a restaurant (35%) and buying fewer groceries online (17%), while other respondents reported more of each (19% and 25%, respectively). An average of 39% reported impacts on their food security, and 27% reported healthful changes to their overall diet. The largest changes for all outcomes were observed in Mexico. Participants who were younger, ethnic minorities, or had lower income adequacy tended to be more likely to report food-related changes in either direction; however, these relationships were often less pronounced among respondents in Mexico. CONCLUSIONS: Respondents reported important changes in how they sourced their food during the pandemic, with trends suggesting shifts towards less food prepared away from home and more healthful diets overall. However, changes in diet and food behaviors occurred in both healthful and less healthful directions, suggesting that dietary responses to the pandemic were highly variable.

Awareness of and Participation in School Food Programs in Youth from Six Countries.

BACKGROUND: School-based meal programs can promote healthy dietary intake in youth. However, limited data exist regarding the impact of income-targeted school meal programs across countries, particularly among food-insecure youth. OBJECTIVES: We examined self-reported awareness of and participation in free school meal programs, and associations with dietary intake in youth from 6 countries with differing national school meal policies. METHODS: Data were collected through the 2019 International Food Policy Study Youth Survey, a cross-sectional survey of 10,565 youth aged 10-17 y from Australia, Canada, Chile, Mexico, the United Kingdom, and the United States. Regression models examined: 1) country differences in awareness of and participation in breakfast and lunch programs; and 2) associations between lunch program participation and intake of fruit and vegetables, and "less healthy" foods during the previous school lunch day. RESULTS: Awareness of and participation in free breakfast and lunch programs varied across countries. Approximately half of USA and Chilean students participated in school lunch programs-the countries with the most comprehensive national policies-compared with one-fifth of students in the United Kingdom, and ∼5% in Australia, Canada, and Mexico (P < 0.001 for all contrasts). In the United States and Chile, more than two-thirds of youth with the highest level of food insecurity participated in lunch programs, compared with 45% in the United Kingdom, 27% in Canada, and ≤20% in Australia and Mexico. In all countries, youth reporting school lunch program participation were more likely to report fruit and vegetable intake during their previous school lunch (P < 0.001), and higher intake of "less healthy" food in all countries except the United States and Chile. CONCLUSIONS: More comprehensive national policies were associated with greater participation in school meal programs, particularly among youth at greatest risk of food insecurity, as well as healthier dietary intake from school lunches.

Prevalence and factors associated with self-reported exposure to secondhand cannabis smoke in the United States and Canada in 2019.

Little is known about exposure to secondhand cannabis smoke (SHCS) among residents of detached single-family homes and multiunit housing (MUH). Using data from the 2019 International Cannabis Policy Study, the prevalence of (a) self-reported exposure to SHCS at home (n = 33,024) and (b) self-reported SHCS incursions into MUH (defined as SHCS from another unit/the outdoors, n = 15,634) was estimated in (1) Canada; (2) US states where non-medical cannabis use was legal, and (3) US states where it remained illegal. Factors associated with exposures and incursions were assessed using weighted logistic regression. Overall, 16.9% of residents in Canada, 20.6% in US legal states, and 15.5% in US illegal states reported exposure to SHCS in their homes at least once in the previous month. One quarter (25.7%) of Canadian MUH residents, 26.6% from US legal states, and 20.1% from US illegal states reported at least monthly incursions. Sociodemographic factors associated with incursions suggested MUH residents reporting incursions lived in qualitatively different MUH than those not reporting incursions. Irrespective of the legality of non-medical cannabis use, smoke-free policies in MUH should protect residents from involuntary exposure to all types of secondhand smoke.

Do Mandatory Health Warning Labels on Consumer Products Increase Recall of the Health Risks of Cannabis?

INTRODUCTION: Warning labels are an important source of health information. This study examined awareness of health warnings on cannabis packages over time in Canada-where large rotating messages are mandated-versus US states with legal adult-use cannabis, which have less comprehensive regulations. METHODS: Repeat cross-sectional data were collected from the International Cannabis Policy Study online surveys among past 12-month cannabis consumers in Canada and the US (n = 38,448). Free recall of warning messages was assessed in 2018-2020, followed by a prompted recognition task (2020 only). Adjusted logistic regression models tested differences in free recall and recognition of warnings between Canada and US states with and without legal adult-use cannabis ("legal" and "illegal" states, respectively). RESULTS: Free recall of ≥1 warning increased to a greater extent in Canada from 2018 (5%; pre-legalization) to 2019 (13%; post-legalization) compared to US "legal" (AOR = 1.93, p < 0.001) and "illegal" states (AOR = 1.80, p = 0.007), and from 2018 to 2020 (5% vs. 15%) compared to US "legal" states (AOR = 2.23, p = 0.027). In all jurisdictions, free recall of warnings was higher among more frequent consumers (p < 0.001) and those who purchased products from legal retail stores/websites (p < 0.001). With few exceptions, when a specific message was mandated (e.g., impaired driving), consumers were more likely to both freely recall and recognize that message (all p < 0.05). CONCLUSIONS: Cannabis legalization is associated with greater recall of health warning messages. Awareness of specific warning messages was higher in jurisdictions where the associated warning was mandated on packages, suggesting that warning labels may improve knowledge of cannabis-related health risks.Supplemental data for this article is available online at.

Knowledge of Tetrahydrocannabinol and Cannabidiol Levels Among Cannabis Consumers in the United States and Canada.

Objective: This study aimed to examine consumer knowledge of tetrahydrocannabinol (THC) and cannabidiol (CBD) levels for usual cannabis products. Methods: Data are from the International Cannabis Policy Study conducted online in August-September 2018. Respondents included 6471 past 12-month cannabis users, aged 16-65 years, recruited from the Nielsen Global Insights Consumer Panel using nonprobability methods. Respondents were recruited from Canada, which had not yet legalized nonmedical cannabis (n=2354), and US states that had (n=2160) and had not (n=1957) legalized nonmedical cannabis. Results: Participants reported descriptive THC:CBD ratios (e.g., high THC, low CBD) and numeric THC and CBD levels (mg or %) for products they usually use in each of nine product categories. Few consumers knew and were able to report the numeric THC or CBD levels of their usual cannabis products. For example, only 10% of dried herb consumers reported the THC level, approximately 30% of whom reported implausible values. A greater proportion of consumers reported a descriptive THC:CBD ratio of their usual product, ranging from 50.9% of edible users to 78.2% of orally ingested oil users. Consumers were substantially more likely to report products high in THC versus low in THC for all products except topicals and tinctures, whereas similar proportions reported using products high and low in CBD. Despite some evidence of greater knowledge in legal jurisdictions, knowledge was still low in states with legal cannabis markets. Conclusions: Consumer knowledge of THC and CBD levels was low, with only modest differences between consumers living in jurisdictions that had and had not legalized nonmedical cannabis. The findings cast doubt on the validity of self-reported cannabinoid levels.

Use and Perceptions of Cannabidiol Products in Canada and in the United States.

Objectives: This study aimed to characterize use and perceptions of cannabidiol (CBD) products. Materials and Methods: Participants aged 16-65 years in Canada (n=15,042) and the United States (n=30,288) completed measures on prevalence and patterns of CBD product use and perceptions of CBD oil as part of the 2019 International Cannabis Policy Study online survey. Results: Past 12-month CBD product use was significantly more prevalent among respondents in the United States (26.1%) than in Canada (16.2%). Consumers in the United States and Canada reported using a range of CBD products, including drops (46.3% vs. 47.3%, respectively), topicals (26.0% vs. 16.7%), edibles/foods (23.8% vs. 17.6%), vape oils (18.9% vs. 13.3%), capsules (13.3% vs. 16.7%), and dried flower (10.1% vs. 16.1%). CBD was most commonly reported for management of pain, anxiety, and depression. Over half of CBD consumers in both countries reported that CBD oil was beneficial for health. Conclusions: Use of CBD products is common in both the United States and Canada, primarily to manage self-reported health conditions for which there is little or no evidence of efficacy. Clearer public health messaging regarding the therapeutic effects of CBD is warranted.

Intra- and Inter-Species Variability in Urinary N7-(1-Hydroxy-3-buten-2-yl)guanine Adducts Following Inhalation Exposure to 1,3-Butadiene.

1,3-Butadiene is a known carcinogen primarily targeting lymphoid tissues, lung, and liver. Cytochrome P450 activates butadiene to epoxides which form covalent DNA adducts that are thought to be a key mechanistic event in cancer. Previous studies suggested that inter-species, -tissue, and -individual susceptibility to adverse health effects of butadiene exposure may be due to differences in metabolism and other mechanisms. In this study, we aimed to examine the extent of inter-individual and inter-species variability in the urinary N7-(1-hydroxy-3-buten-2-yl)guanine (EB-GII) DNA adduct, a well-known biomarker of exposure to butadiene. For a population variability study in mice, we used the collaborative cross model. Female and male mice from five strains were exposed to filtered air or butadiene (590 ppm, 6 h/day, 5 days/week for 2 weeks) by inhalation. Urine samples were collected, and the metabolic activation of butadiene by DNA-reactive species was quantified as urinary EB-GII adducts. We quantified the degree of EB-GII variation across mouse strains and sexes; then, we compared this variation with the data from rats (exposed to 62.5 or 200 ppm butadiene) and humans (0.004-2.2 ppm butadiene). We show that sex and strain are significant contributors to the variability in urinary EB-GII levels in mice. In addition, we find that the degree of variability in urinary EB-GII in collaborative cross mice, when expressed as an uncertainty factor for the inter-individual variability (UFH), is relatively modest (≤threefold) possibly due to metabolic saturation. By contrast, the variability in urinary EB-GII (adjusted for exposure) observed in humans, while larger than the default value of 10-fold, is largely consistent with UFH estimates for other chemicals based on human data for non-cancer endpoints. Overall, these data demonstrate that urinary EB-GII levels, particularly from human studies, may be useful for quantitative characterization of human variability in cancer risks to butadiene.

Quantitative NanoLC/NSI+-HRMS Method for 1,3-Butadiene Induced bis-N7-guanine DNA-DNA Cross-Links in Urine.

1,3-Butadiene (BD) is a common environmental and industrial chemical widely used in plastic and rubber manufacturing and also present in cigarette smoke and automobile exhaust. BD is classified as a known human carcinogen based on evidence of carcinogenicity in laboratory animals treated with BD by inhalation and epidemiological studies revealing an increased risk of leukemia and lymphohematopoietic cancers in workers occupationally exposed to BD. Upon exposure via inhalation, BD is bioactivated to several toxic epoxides including 3,4-epoxy-1-butene (EB), 3,4-epoxy-1,2-butanediol (EBD), and 1,2,3,4-diepoxybutane (DEB); these are conjugated with glutathione and excreted as 2-(N-acetyl-L-cystein-S-yl)-1-hydroxybut-3-ene/1-(N-acetyl-L-cystein-S-yl)-2-hydroxybut-3-ene (MHBMA), 4-(N-acetyl-L-cystein-S-yl)-1,2-dihydroxybutane (DHBMA), and 1,4-bis-(N-acetyl-L-cystein-S-yl)butane-2,3-diol (bis-BDMA). Exposure to DEB generates monoalkylated DNA adducts, DNA-DNA crosslinks, and DNA-protein crosslinks, which can cause base substitutions, genomic rearrangements, and large genomic deletions. In this study, we developed a quantitative nanoLC/NSI+-HRMS methodology for 1,4-bis-(gua-7-yl)-2,3-butanediol (bis-N7G-BD) adducts in urine (LOD: 0.1 fmol/mL urine, LOQ: 1.0 fmol/mL urine). This novel method was used to quantify bis-N7G-BD in urine of mice treated with 590 ± 150 ppm BD for 2 weeks (6 h/day, 5 days/week). Bis-N7G-BD was detected in urine of male and female BD-exposed mice (574.6 ± 206.0 and 571.1 ± 163.4 pg/mg of creatinine, respectively). In addition, major urinary metabolites of BD, bis-BDMA, MHBMA and DHBMA, were measured in the same samples. Urinary bis-N7G-BD adduct levels correlated with DEB-derived metabolite bis-BDMA (r = 0.80, Pearson correlation), but not with the EB-derived DNA adducts (EB-GII) or EB-derived metabolites MHBMA and DHBMA (r = 0.24, r = 0.14, r = 0.18, respectively, Pearson correlations). Urinary bis-N7G-BD could be employed as a novel non-invasive biomarker of exposure to BD and bioactivation to its most mutagenic metabolite, DEB. This method will be useful for future studies of 1,3-butadiene exposure and metabolism.

Influence of package colour, branding and health warnings on appeal and perceived harm of cannabis products among respondents in Canada and the US.

'Plain packaging' and health warnings can reduce appeal and increase risk perceptions of tobacco products. This study tested the effect of health warnings and restricted brand imagery on perceptions of cannabis products. Participants in Canada and the US (n = 45,378) were randomized to view packages of three cannabis brands in 2019. A 3 (health warning) x 4 (brand imagery) between-group factorial experimental design was used. Health warning conditions were: none, Canadian or US warning. The Canadian warning conditions had three messages counterbalanced across brands: pregnancy, adolescent risk, and impaired driving. The US warning mentioned the same broad risk categories. The four branding conditions ranged from packages displaying no brand imagery and uniform colours-'plain packaging'-to full brand imagery. Regression tested differences between conditions on product appeal, perceived harm, and free recall of warning messages. Overall, full branding and plain packaging were rated the most and least appealing, respectively (p < 0.001). Products were rated as significantly less harmful when they had a white background with no or limited branding versus a coloured background (p ≤ 0.01). Products with health warnings were rated significantly less appealing and more harmful than those with no warning (p < 0.001). Message recall was significantly higher for Canadian versus US health warnings, and for the US warning versus no warning (p < 0.001). Message recall was greater among those who saw plain versus fully branded packages for two of the three warning messages (p < 0.01). Prominent health warnings and restrictions on brand imagery may be warranted in jurisdictions considering non-medical cannabis legalization.

Noticing of cannabis health warning labels in Canada and the US. / Perception des étiquettes de mise en garde concernant la santé apposées sur les produits du cannabis au Canada et aux États-Unis.

INTRODUCTION: Product labelling and health warnings are important components of regulatory frameworks for consumer products such as tobacco, alcohol and food. However, evidence in the cannabis domain is limited. This study aimed to examine the reach of mandated health warnings on cannabis products using a natural experimental design. METHODS: Data are from the online International Cannabis Policy Study 2018 and 2019 surveys. Respondents were men and women aged 16 to 65 years in Canada and US states with illegal and legal nonmedical cannabis ("illegal" and "legal" states, respectively) (n = 72 549). Regression models tested differences in noticing health warnings on cannabis packages pre- and post-legalization in Canada, with comparisons to US states, adjusting for cannabis use, cannabis source and sociodemographics. RESULTS: Respondents in Canada showed a greater increase in noticing warnings (+8.9%) in 2019 (14.7%) versus 2018 (5.8%) than respondents in US "illegal" states (+2.8%) and "legal" states (+3.2%). In 2019, consumers residing in jurisdictions with legal recreational cannabis who purchased from legal retail sources were more likely to report noticing warnings than consumers who obtained cannabis from illegal/unstated sources (Canada: 40.4% vs. 15.3%; US "legal" states: 35.3% vs. 17.0%). Regular cannabis consumers were more likely to notice warnings than less frequent consumers. CONCLUSION: Mandating warning labels on cannabis products may increase exposure to messages communicating the health risks of cannabis, especially among frequent consumers and those who access the legal market.