Free Radicals in Cannabis Smoke.

Cannabis use and cancer.

IntroductionThere is increasing evidence that cannabis smoking, combined with tobacco, increases the risk of emphysema and bullous lung disease (BLF Report 2012). The aim of this retrospective case study was...

Pulmonary alveolar macrophages were obtained by bronchopulmonary lavage from male rats after 30 consecutive days of in vivo exposure to marijuana and tobacco smoke. No significant differences were found between either group of experimental animals and controls in the number of cells recovered, the protein content per 10(6) cells, or the percentage of cells that adhered to plastic surfaces. The ability of macrophages to phagocytize viable bacteria was not affected by exposure to either marijuana or tobacco smoke in that both treatment groups ingested Staphylococcus aureus over a 60-min period as well as did control cells. Differences were found between the groups, however, with respect to cellular metabolism. Marijuana smoke inhalation caused a small decrease in the amount of oxygen consumed by macrophages during phagocytosis, as compared with control cells. This may have been reflected in the even greater decrease in superoxide formation observed during particle engulfment by these treated cells. Tobacco smoke, on the other hand, increased oxygen consumption and was without effect on superoxide release. Neither tobacco nor marijuana smoke treatment had an effect on the direct oxidation of glucose via the hexose monophosphate shunt. Our results indicate that, despite several metabolic alterations in response to marijuana and tobacco smoke, alveolar macrophages were not compromised with respect to their ability to ingest a particulate challenge.

Recent increases in marijuana use and legalization without adequate knowledge of the risks necessitate the characterization of the billions of nanoparticles contained in each puff of smoke. Tobacco smoke offers a benchmark given that it has been extensively studied. Tobacco and marijuana smoke particles are quantitatively similar in volatility, shape, density and number concentration, albeit with differences in size, total mass and chemical composition. Particles from marijuana smoke are on average 29% larger in mobility diameter than particles from tobacco smoke and contain 3.4× more total mass. New measurements of semi-volatile fractions determine over 97% of the mass and volume of the particles from either smoke source are comprised of semi-volatile compounds. For tobacco and marijuana smoke, respectively, 4350 and 2575 different compounds are detected, of which, 670 and 536 (231 in common) are tentatively identified, and of these, 173 and 110 different compounds (69 in common) are known to cause negative health effects through carcinogenic, mutagenic, teratogenic, or other toxic mechanisms. This study demonstrates striking similarities between marijuana and tobacco smoke in terms of their physical and chemical properties.

The relationship of tobacco and marijuana smoking characteristics

The primary depolymerization processes of hydrolytic lignin (HL) are examined, focusing on the formation of intermediate oligomers and bulky environmentally persistent free radicals (EPFRs). Fragmentation of HL was conducted in a continuous atomization (CA) fast flow reactor, where HL, dissolved in a 9:1 acetone-to-water solution, was dispersed. Results indicated that HL fragmentation occurs significantly faster in the gas phase in comparison to the literature rate of formation of major biofuel-phenolic compounds. In other words, the formation of phenolic compounds occurs at much lower rate constants being the limiting stage for lignin depolymerization. The critical role of surface associated reactions for formation of biofuel compounds developed in our previous work was highlighted. Using spin trapping with electron paramagnetic resonance (EPR) spectroscopy, it was shown that intermediate EPFRs, as hydroxyl radical generators, may act as biologically active intermediates in aqueous environments relevant to anthropogenic activities, wildfires, tobacco smoke, and other combustion processes. The addition of a highly hydroxylated 5% CuO/SiO2 catalyst at concentrations of 1-3% (relative to an initial lignin concentration of 1 g/L in a 9:1 acetone-to-water mixture) did not significantly alter EPFR yields. However, an increasing trend in EPFR yield was observed with catalyst concentrations at 5%. A mechanistic scheme for the formation of CuO-surface-associated EPFRs is discussed.

The chemical composition of tobacco smoke has been extensively examined, and the presence of known and suspected carcinogens in such smoke has contributed to the link between tobacco smoking and adverse health effects. The consumption of marijuana through smoking remains a reality and, among youth, seems to be increasing. There have been only limited examinations of marijuana smoke, including for cannabinoid content and for tar generation. There have not been extensive studies of the chemistry of marijuana smoke, especially in direct comparison to tobacco smoke. In this study, a systematic comparison of the smoke composition of both mainstream and sidestream smoke from marijuana and tobacco cigarettes prepared in the same way and consumed under two sets of smoking conditions, was undertaken. This study examined the suite of chemicals routinely analyzed in tobacco smoke. As expected, the results showed qualitative similarities with some quantitative differences. In this study, ammonia was found in mainstream marijuana smoke at levels up to 20-fold greater than that found in tobacco. Hydrogen cyanide, NO, NO x , and some aromatic amines were found in marijuana smoke at concentrations 3-5 times those found in tobacco smoke. Mainstream marijuana smoke contained selected polycyclic aromatic hydrocarbons (PAHs) at concentrations lower than those found in mainstream tobacco smoke, while the reverse was the case for sidestream smoke, with PAHs present at higher concentrations in marijuana smoke. The confirmation of the presence, in both mainstream and sidestream smoke of marijuana cigarettes, of known carcinogens and other chemicals implicated in respiratory diseases is important information for public health and communication of the risk related to exposure to such materials.

Both the gaseous and the particulate phases of tobacco and cannabis smoke contain a similar range of harmful chemicals. However, differing patterns of inhalation mean that smoking a 'joint' of cannabis results in exposure to significantly greater amounts of combusted material than with a tobacco cigarette. The histopathological effects of cannabis smoke exposure include changes consistent with acute and chronic bronchitis. Cellular dysplasia has also been observed, suggesting that, like tobacco smoke, cannabis exposure has the potential to cause malignancy. These features are consistent with the clinical presentation. Symptoms of cough and early morning sputum production are common (20-25%) even in young individuals who smoke cannabis alone. Almost all studies indicate that the effects of cannabis and tobacco smoking are additive and independent. Public health education should dispel the myth that cannabis smoking is relatively safe by highlighting that the adverse respiratory effects of smoking cannabis are similar to those of smoking tobacco, even although it remains to be confirmed that smoking cannabis alone leads to the development of chronic lung disease.

Impact of cannabis smoking in patients with COPD: A retrospective cross-sectional study in a safety- net hospital.

A chemical spin trap, 5,5-dimethyl-1-pyrroline-N-oxide (DMPO), in conjunction with electron paramagnetic resonance (EPR) spectroscopy was employed to measure the production of hydroxyl radical (·OH) in aqueous suspensions of 5% Cu(II)O/silica (3.9% Cu) particles containing environmentally persistent free radicals (EPFRs) of 2-monochlorophenol (2-MCP). The results indicate: (1) a significant differences in accumulated DMPO-OH adducts between EPFR containing particles and non-EPFR control samples, (2) a strong correlation between the concentration of DMPO-OH adducts and EPFRs per gram of particles, and (3) a slow, constant growth of DMPO-OH concentration over a period of days in solution containing 50 μg/mL EPFRs particles + DMPO (150 mM) + reagent balanced by 200 μL phosphate buffered (pH = 7.4) saline. However, failure to form secondary radicals using standard scavengers, such as ethanol, dimethylsulfoxide, sodium formate, and sodium azide, suggests free hydroxyl radicals may not have been generated in solution. This suggests surface-bound, rather than free, hydroxyl radicals were generated by a surface catalyzed-redox cycle involving both the EPFRs and Cu(II)O. Toxicological studies clearly indicate these bound free radicals promote various types of cardiovascular and pulmonary disease normally attributed to unbound free radicals; however, the exact chemical mechanism deserves further study in light of the implication of formation of bound, rather than free, hydroxyl radicals.

Effects of ‘Crack’ Cocaine on Pulmonary Alveolar Permeability

In the current study, electron paramagnetic resonance (EPR) spectroscopy was employed to measure environmentally persistent free radicals (EPFRs) in the total particulate matter (TPM) of mainstream and sidestream TPM of conventional cigarettes and the TPM of e-cigarettes. Comparable concentrations of EPFRs were detected in both sidestream (8.05 ± 1.32) × 104 pmol/g and mainstream TPM (7.41 ± 0.85) × 104 pmol/g of conventional cigarettes. TPM exposure to air resulted in long-lived oxygen centered, secondary radicals with EPR g values of 2.0041 for mainstream and 2.0044 for sidestream. Surprisingly, despite no combustion process, the TPM from e-cigarettes (menthol flavor of NJOY and V2 brands) also contain EPFRs with g values of 2.0031-2.0033, characteristic of carbon centered radicals, while the radical signal in the vanilla flavor of V2 brand was remarkably similar to semiquinones in cigarette smoke with a higher g value (2.0063). The radical concentration in e-cigarettes was much lower as compared to tobacco TPM. Although the production of ROS generated by e-cigarettes is comparatively lower than ROS generated by conventional cigarettes, EPFRs in e-cigarettes appear to be more potent than those in tobacco TPM with respect to hydroxyl radical generation yield per unit EPFR. EPFRs in e-cigarette TPM may be a potential source of health impacts.

A global toxicogenomic analysis investigating the mechanistic differences between tobacco and marijuana smoke condensates in vitro

Environmentally persistent free radicals (EPFRs) can be detected in ambient PM2.5, cigarette smoke, and soils and are formed through combustion and thermal processing of organic materials. The hazards of EPFRs are largely unknown. In this study, we assess the developmental toxicity of EPFRs and the ability of TEMPOL (4-Hydroxy-2,2,6,6-tetramethylpiperidine 1-oxyl) to protect against such hazards using zebrafish embryos. Particles containing EPFRs were acquired by dosing dichlorobenzene (DCB) vapor on the Cab-o-sil/5% CuO particles at 230 °C in vacuo (referred to as DCB-230). The particles were suspended in ultrapure water to make 1 mg/mL of stock solution from which series dilution was undertaken to obtain 10, 20, 30, 40, 50, 60, 80, and 100 µg/mL final test solutions, which were then placed in individual wells with a 4 h postfertilization (hpf) zebrafish embryo. Plates were run in duplicate to obtain a sample size of 24 animals per concentration; 12 embryos were exposed per concentration per plate. Statistical analysis of the morphology endpoints was performed. We investigated overt toxicity responses to DCB-230 in a 22-endpoint battery that included developing zebrafish from 24–120 hpf. Exposure to concentrations greater than 60 µg/mL of DCB-230 induced high mortality in the developmental zebrafish model. Exposure to EPFRs induced developmental hazards that were closely related to the concentrations of free radicals and EPFRs. The potential protective effects of TEMPOL against EPFRs’ toxicity in zebrafish were investigated. Exposure to EPFRs plus TEMPOL shifted the concentration to an induced 50% adverse effect (EC50), from 23.6 to 30.8 µg/mL, which verifies TEMPOL’s protective effect against EPFRs in the early phase of zebrafish development.

Environmentally persistent free radicals (EPFRs) are produced during biochar pyrolysis and, depending on biochar application, can be either detrimental or beneficial. High levels of EPFRs may interfere with cellular metabolism and be toxic, because EPFR-generated reactive oxygen species (e.g., hydroxyl radicals (•OH)) attack organic molecules. However, •OH can be useful in remediating recalcitrant organic contaminants in soils. Understanding the (system-specific) safe range of EPFRs produced by biochars requires knowing both the context of their use and their overall significance in the existing suite of environmental radicals, which has rarely been addressed. Here we place EPFRs in a broader environmental context, showing that biochar can have EPFR concentrations from 108-fold lower to 109-fold higher than EPFRs from other environmental sources, depending on feedstock, production conditions, and degree of environmental aging. We also demonstrate that •OH radical concentrations from biochar EPFRs can be from 104-fold lower to 1017-fold higher than other environmental sources, depending on EPFR type and concentration, reaction time, oxidant concentration, and extent of environmental EPFR persistence. For both EPFR and •OH concentrations, major uncertainties derive from the range of biochar properties and the range of data reporting practices. Controlling feedstock lignin content and pyrolysis conditions are the most immediate options for managing EPFRs. Co-application of compost to provide organics may serve as a postpyrolysis method to quench and reduce biochar EPFRs.