Acrolein and other toxicant exposures in relation to cardiovascular disease among marijuana and tobacco smokers in a longitudinal cohort of HIV-positive and negative adults

Abstract

Background Marijuana smoke contains some of the same toxicants present in tobacco smoke. Marijuana smoking is prevalent among HIV+ individuals, but few studies have characterized smoke-related toxicants or associated health outcomes in exclusive marijuana users. Methods This longitudinal study included 245 participants over age 40 (76% HIV+). 33 plasma and 28 urine metabolites of nicotine, ∆-9-trans-tetrahydrocannabinol, polycyclic aromatic hydrocarbons, and volatile organic compounds were assayed by liquid or gas chromatography/mass spectrometry. Exposures and health outcomes were assessed from surveys and medical records. Findings At baseline, 18% of participants were marijuana-only smokers, 20% tobacco-only smokers, and 24% dual marijuana-tobacco smokers (median (IQR) age 53 (47–60) years, 78% male, 54% white race). Marijuana smoking was independently associated with elevated plasma naphthalenes, 2-hydroxyfluorene sulfate, 4-vinylphenol sulfate, and o-cresol sulfate (p< 0·05) and urine acrylonitrile and acrylamide metabolites ( p< 0·05), but levels were lower than those associated with tobacco smoking. Acrolein metabolite N-Acetyl-S-(3-hydroxypropyl)- l -cysteine (3HPMA) was significantly elevated in plasma and urine in tobacco-only and dual but not marijuana-only smokers, and correlated with nicotine metabolites ( p< 0·05). The highest tertile of 3HPMA was associated with increased cardiovascular disease diagnoses independent of tobacco smoking, traditional risk factors, and HIV status (odds ratio [95% CI] 3·34 [1·31–8·57]; p = 0·012). Interpretation Smoke-related toxicants, including acrylonitrile and acrylamide metabolites, are detectable in exclusive marijuana smokers, but exposures are lower compared with tobacco or dual smokers. Acrolein exposure is increased by tobacco smoking but not exclusive marijuana smoking in HIV+ and HIV- adults, and contributes to cardiovascular disease in tobacco smokers. Funding U.S. NIH.

Mechanisms of acrolein induces toxicity in human umbilical vein endothelial cells: Oxidative stress, DNA damage response, and apoptosis

“…9,12 Among them, tobacco smoking is typically the largest source of acrolein exposure. [13][14][15] Human exposure to acrolein via cigarette smoking can occur at extremely high levels (>50 ppm acrolein/ cigarette). 15,16 Smoking has been implicated as a major risk factor for CVDs, it is included in the FDA's list of harmful and potentially harmful constituents of tobacco products as a cardiovascular toxicant.…”

Co-use of cigarettes and cannabis among people with HIV: Results from a randomized controlled smoking cessation trial

“…In addition, factors that influence cannabis use and cigarette cessation simultaneously, such as reasons for use, are in need of further study. Given that co-use of tobacco and cannabis may result in greater nicotine dependence ( Weinberger et al., 2021 ) and cardiovascular toxicity ( Lorenz et al., 2021 ; Smith et al., 2020 ) than use of tobacco or cannabis alone, there is a need for additional research assessing cigarette cessation intervention effects on co-use and the development of integrated treatments that explicitly target both cannabis and tobacco.…”

“…Moreover, co-use of cigarettes/cannabis is associated with greater nicotine dependence compared to cigarette smoking alone ( Weinberger et al., 2021 ) and cigarettes/cannabis co-use may undermine cigarette smokers’ motivation to quit cigarettes and quit success ( Driezen et al., 2022 ; Goodwin et al., 2022 ; Schauer et al., 2017 ; Strong et al., 2018 ; Vogel et al., 2018 ; Weinberger, Delnevo, et al., 2020 ; Weinberger, Pacek, et al., 2020 ; Weinberger et al., 2018 ), though other work suggests that cannabis use may not hinder cigarette smoking cessation after adjusting for other factors ( Rabin et al., 2016 ; Westmaas et al., 2021 ). Still, co-use of cigarettes/cannabis is associated with higher toxicant levels (e.g., acrylonitrile, acrylamide) indicative of cardiovascular disease risk compared to use of cannabis alone, though there are mixed reports on whether such toxicant levels may be similar ( Lorenz et al., 2021 ) or higher ( Smith et al., 2020 ) for cigarette/cannabis co-users compared to cigarette smokers who do not use cannabis.…”

Attenuation of Cardiomyopathy Induced in Sub-Chronic Exposure of Acrolein by Sulforaphane via Indirect PPARy Expression Promoter

“…1,2 It is implicated in causing chronic cardiac disease, among other organ effects, by reacting with nucleophiles such as DNA and protein molecules to cause oxidative stress and myocardial damage. 3,4 The heart is usually a known target for assault by numerous agents, including ACL, because it is one of the most energy-demanding organs. In this regard, cardiomyopathy becomes the likely outcome of most drugs' assault on the heart leading to failure.…”