(A) Biobank Engine, a tool to search case-control association results from the UK Biobank hospital in-patient health-related outcomes summary information data, was utilized to obtain insight into the genetic mechanism of cannabis-associated cardiovascular disease. Schematic of the stratification of the UK Biobank dataset phenotypes for analysis. To determine the population-level/clinical impact of cannabis on cardiovascular events, patient data acquired from the UK Biobank were analyzed. To identify the relevant study population, self-reported patient surveys collected as part of the UK Biobank dataset were utilized to stratify the UK Biobank population. A total of 157,331UK Biobank participants were surveyed on whether they have ever used cannabis. A subset of 34,878 individuals who responded “yes” were subsequently surveyed for the frequency of cannabis use, and 11,914 responded that they utilized cannabis more than 1 time per month. On the other hand, 122,445 individuals responded “no” to ever taking cannabis. Among these individuals, cannabis use was associated with an increased incidence of MI in a logistic regression model with normalized age, sex, and body mass index (odds ratio 1.16 (95% confidence interval 1.00–1.34); p < 0.05). Cannabis users also showed a higher incidence of premature MI (under the age of 50) than non-users (0.53% versus 0.45%).
(B) Investigating inflammatory cytokine release in response to smoking marijuana. Twenty recreational marijuana smokers were recruited to smoke a single marijuana cigarette, and serial blood draws were performed to assess the Δ9-THC levels in blood. Inflammatory cytokine production was assayed using the Olink proteomic platform. Participants were asked to abstain from using marijuana for 24 h before testing. Two participants did not consent to subsequent testing and were excluded from the Olink analysis. Plasma was isolated from n = 18 individuals (13 males/5 females) using sodium citrate tubes at 15 min intervals from 0 min to 180 min after smoking. An Olink inflammation panel with 92 cytokines implicated in inflammation and oxidative stress was used to analyze the blood samples at 0, 90, and 180 min. The Olink panel revealed that several circulating cytokines were upregulated in marijuana smokers as implicated in atherosclerosis.