Relationships between sales of legal medical cannabis and alcohol in Canada.

The extent to which legalizing cannabis use might lead to increased or decreased alcohol use has important implications for public health, economic growth, and government policy. This study analyzed Canada's monthly per capita sales of alcohol and legal medical cannabis using fixed effect panel data linear regressions. The data covered seven Canadian regions from January 2011 to September 2018, and controlled for changing levels of retail activity, alcohol prices, tertiary education, unemployment, and impaired driving penalties. The analysis estimated that each dollar of legal medical cannabis sold was associated with an average alcohol sales decrease of roughly $0.74 to $0.84. This suggests that medical cannabis was an economic substitute for alcohol in Canada, and that the country's 2017-2018 alcohol sales were roughly 1.8% lower than they would have been without legal medical cannabis. The results therefore indirectly imply that reduced alcohol consumption might have partly offset cannabis legalization's health and economic impacts.

Interrupted time series analysis of Canadian legal cannabis sales during the COVID-19 pandemic.

INTRODUCTION: There were repeated reports of increased cannabis sales, use and health impacts in Canada during the COVID-19 pandemic. However, it was unclear whether the increases were due to pandemic effects or industry expansion. METHODS: We performed interrupted time series regressions of monthly per capita legal cannabis sales from March 2019 to February 2021, first with national averages, then with provincial/territorial data after adjusting for store density. We considered two interruption alternatives: January 2020, when product variety increased; and March 2020, when pandemic restrictions began. RESULTS: The provincial/territorial regression with the January interruption explained R2  = 69.6% of within-jurisdiction variation: baseline monthly per capita sales growth averaged $0.21 (95% confidence interval [CI] 0.15, 0.26), sales immediately dropped in January by $1.02 (95% CI -1.67, -0.37), and monthly growth thereafter increased by $0.16 (95% CI 0.06, 0.25). With the March interruption, the regression instead explained 68.7% of variation: baseline sales growth averaged $0.14 (95% CI 0.06, 0.22), there was no immediate drop and growth thereafter increased by $0.22 per month (95% CI 0.08, 0.35). DISCUSSION AND CONCLUSIONS: Increasing cannabis sales during the pandemic was consistent with pre-existing trends and increasing store numbers. The extra increased growth was more aligned with January's new product arrivals than with March's pandemic measures, though the latter cannot be ruled out. We found little evidence of pandemic impacts on Canada's aggregate legal cannabis sales. We therefore caution against attributing increased population-level cannabis use or health impacts primarily to the pandemic.

Relationships between increases in Canadian cannabis stores, sales, and prevalence.

BACKGROUND: This study estimated the relationships between increases in legal cannabis stores, legal cannabis sales, and cannabis prevalence in Canadian provinces between 2018 and 2020. METHOD: Government data were used to calculate changes in licensed store numbers, retail sales dollars, and past-three-month users in 10 provinces across six time periods. The resulting N = 60 observations were standardized per million residents aged 15 and up, and then analyzed via linear regression. RESULTS: Store growth explained 46.3% of the variation in provincial sales growth; each added store was associated with added quarterly sales of $305 (95% CI: $208 to $402) thousand. By contrast, store growth explained only 7.7% of the variation in provincial user growth; each added store was associated with 696 (95% CI: 58-1334) added users. CONCLUSION: From 2018 to 2020, Canada's rapid cannabis retail expansion was strongly related to legal sales growth but only weakly related to prevalence growth. This implies prevalence growth during that period was related more to legalization's other aspects and/or to the continuation of already-existing trends.

Legal cannabis market shares during Canada's first year of recreational legalisation.

BACKGROUND: This study estimated legal products' share of Canada's total cannabis consumption during the first year of recreational legalisation, October 2018 to September 2019. METHODS: Government data was used to estimate monthly recreational sales in dollars per capita, grams per user, and percentage share of kilograms or litres consumed. As explanatory factors, the analysis considered provincial differences in retail pricing (percentage mark-ups) and store density (stores per million users), as well as national monthly production of dry cannabis (kilograms) and cannabis oil (litres) finished products. RESULTS: Legal recreational products' share of Canada's overall cannabis consumption began at 7.8% in October 2018 and grew to 23.7% by September 2019, with an average of 14.5% over the first 12 months. Sales growth was delayed by shortages of both dry cannabis products and licensed stores, but not cannabis oils. Across the 10 provinces, legal recreational shares in September 2019 varied from 13% to 70%; differences in store densities and retail prices partly explained the variation. Prince Edward Island's large 70% share seemed due to it having minimal product shortages, high store densities, and low prices. CONCLUSIONS: Legal recreational products captured market share to the extent they were available, accessible, and low-priced. Problems with those factors slowed the initial expansion of legal product sales but also suggested ways to gradually increase their market share.

Case-controlled comparison of video-assisted and conventional minimally invasive parathyroidectomy.

Video-assisted parathyroidectomy (VAP) is a new approach to parathyroid exploration for primary hyperparathyroidism (PH). We examined the VAP learning curve and hypothesized that compared with conventional minimally invasive parathyroidectomy (MIS), VAP has similar complication rates and the added benefit of a shorter hospital length of stay. Using a case-control study design, patients with PH with single-focus imaging results undergoing VAP or MIS were compared during a 5-year VAP implementation period. VAP was possible in 18 per cent of patients undergoing initial parathyroid exploration. In comparing 125 VAP cases with 95 MIS control subjects, patients undergoing MIS had higher mean preoperative levels of calcium (P = 0.007) and parathyroid hormone (P = 0.008), greater mean adenoma weight (P < 0.001), and increased long-term mortality (4% MIS vs 0% VAP, P = 0.03). Mean operative time, in-house analgesia use, and operative complications did not differ. The rate of conversion from VAP to MIS was 14 per cent. Patients undergoing VAP were less likely to require an overnight hospital stay (P = 0.01). VAP is a safe surgical option for selected patients with PH, offering improved cosmesis with operative times comparable to conventional MIS. VAP can be done with a low conversion rate even during implementation and allows the added benefit of shorter hospital stay.

Population doubling: a simple and more accurate estimation of cell growth suppression in the in vitro assay for chromosomal aberrations that reduces irrelevant positive results.

International guidelines for cytotoxicity limits for the in vitro chromosomal aberration assay require reductions in cell growth of greater than 50%. This sets no upper limit on toxicity and there is concern about the number of false or irrelevant results obtained in the aberration assay, i.e., positive results at toxic dose levels only, with no evidence for primary DNA damaging ability and with negative results in the other genotoxicity tests. We have previously proposed that no truly genotoxic compound would be missed if the toxicity of the highest dose did not exceed 50%. Cell growth measured by cell counts as a percentage of controls can underestimate toxicity. For example, if we seed half a million cells per culture, and the controls double to 1 million during the experiment, a culture that truly has no growth will still have a cell count 50% of the control. Measurement of population doublings (PDs) more accurately assesses cell growth. To assess the use of PD in dose selection, we examined previous data from this lab and data from new experiments with "true," primary DNA damaging clastogens, and with clastogens, including drugs, thought to act indirectly, through cytotoxicity-associated mechanisms. We compared aberration results where the highest doses scored were based on 50% reductions in final cell counts with results obtained when the highest doses were based on PD. The PD method allows detection of true clastogens, including those that are active in a range with some toxicity, and reduces the number of toxicity-related "false"-positive results.

Genotoxicity of naturally occurring indole compounds: correlation between covalent DNA binding and other genotoxicity tests.

3-Methylindole (3MI), melatonin (Mel), serotonin (Ser), and tryptamine (Tryp) were evaluated in vitro for their potential to induce DNA adducts, DNA strand breaks, chromosomal aberrations (Abs), inhibition of DNA synthesis, and mutations. All compounds produced DNA adducts in calf thymus DNA in the presence of rat liver S9. In cultured rat hepatocytes, all produced DNA adducts but none induced DNA strand breaks. In Chinese hamster ovary cells, 3MI and Mel produced DNA adducts, Abs, and inhibition of DNA synthesis with and without S9, except that Mel without S9 did not form adducts. Ser formed DNA adducts, was an equivocal Abs inducer, and suppressed DNA synthesis. Tryp induced neither adducts nor Abs, but did suppress DNA synthesis with S9. Ser and Tryp were less cytotoxic than 3MI and Mel. Mel, Ser, and Tryp failed to induce mutations in Salmonella and E. coli strains with or without S9. 3MI and Mel produced DNA adducts but not mutations in Salmonella TA100 with S9. 3MI and its metabolite indole 3-carbinol also did not induce mutations in a shuttle vector system in human cells. The lack of correlation between DNA adducts and other genotoxicity endpoints for these indole compounds may be due to the higher sensitivity of the (32)P-postlabeling adduct assay or it may indicate that the indole-DNA adducts per se are not mutagenic and are not able to induce strand breaks or alkali-labile lesions. The indole-induced Abs may result from cytotoxicity and suppression of DNA synthesis with minimal if any contribution from DNA adducts.