Kurzgesagt – In a Nutshell 

Sources – Vaping

We thank the following experts for their input and critical reading:

– Dr. Konstantinos E. Farsalinos

University of Patras, Greece


– Dr. Jamie Hartmann-Boyce

University of Massachusetts Amherst, USA

– Vaping is kind of amazing – finally a less bad alternative to smoking. It delivers one of the most popular drugs in the world: Nicotine. 

We talk about specifically nicotine containing vapes in this video. Nicotine-less vapes or vapes with other active substance are not covered in this video, though some of the specific findings about vaping regardless of the active substance applies to them in general as well.  

– It may improve your attention, concentration, memory, reaction time and endurance. It can reduce anxiety and stress and help you relax and enhance your mood. Nicotine also suppresses hunger, making it easier to maintain or lose weight.

It is important to keep in mind that the evidence on the overall benefit of nicotine is not very strong. There are many confounding effects such as the accompanying harmful chemicals in traditional cigarettes which cause cognitive deficits, long term vs acute effects, and also it is difficult for smokers to differentiate the cognitive enhancing effects of nicotine itself from its stabilizing effect of the withdrawal symptoms upon reuptake. 

Following is a recent review on the biological effects of nicotine. 

#Sansone L, Milani F, Fabrizi R, Belli M, Cristina M, Zagà V, de Iure A, Cicconi L, Bonassi S, Russo P. Nicotine: From Discovery to Biological Effects. Int J Mol Sci. 2023 

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10572882/

Quote: “The biological effects of nicotine are diverse, and include both negative effects on the cardiovascular system and addiction (now classified as Substance Use Disorders) [2], as well as positive effects such as enhancing cognitive function in individuals with Alzheimer’s disease [86]. A significant portion of the clinical phenotype observed in Alzheimer’s disease (AD) occurs through nAChRs. Degeneration of cholinergic neurons, combined with aberrant nAChR expression and activation partially through amyloid-beta peptide (Aβ)-nAChR leads to the upregulation of pro-inflammatory pathways and subsequently progressive cognitive decline in AD. Interestingly, the cholinergic anti-inflammatory pathway is also mediated through α7-nAChR, in particular. Thus, agonists of these receptors will likely exert pro-cognitive benefits through multiple mechanisms, including stimulating the cholinergic pathway, modulating inflammation, and buffering the effects of amyloid. Despite this promising theoretical use, trials thus far have been complicated by adverse effects or minimal improvement [14,87–89].”

#Valentine G, Sofuoglu M. Cognitive Effects of Nicotine: Recent Progress. Curr Neuropharmacol. 2018 

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6018192/

Quote: “Preclinical models and human studies have demonstrated that nicotine has cognitive-enhancing effects, including improvement of fine motor functions, attention, working memory, and episodic memory. These cognitive-enhancing effects of nicotine may be an important factor in vulnerability to TUD (tobacco use disorder), especially in individuals with cognitive deficits, including a majority of individuals with primary psychiatric disorders. Accumulating evidence suggest that both α7 and β2 nAChRs participate in the cognitive effects of nicotine. The α7 subunit may modulate a sensory filtering function associated with schizophrenia, and the β2 subunit appears to mediate attention, working memory, and behavioral flexibility functions. The neurotransmitters that contribute to nicotine’s cognitive effects include DA, glutamate, serotonin, norepinephrine, GABA, and ACh. Imaging studies have been instrumental in identifying brain regions where nicotine is active, and research on the dynamics of large-scale networks after activation by, or withdrawal from, nicotine hold promise for improved understanding of the complex actions of nicotine on human cognition.”

The evidence on the endurance is rather mixed: while some studies show some parameters are affected positively upon nicotine administration through ways other than smoking, others didn’t find meaningful improvements. 

#Zandonai et al. The effects of oral smokeless tobacco administration on endurance performance. Journal of Sport and Health Science. 2018. 

https://www.sciencedirect.com/science/article/pii/S2095254616301284#s0105

Quote#1: “Nicotine reduces heart rate variability, increases perception of mental fatigue and workload, and affects the perceived readiness level among amateur football players who are non-smokers and non-snus users.17 It also impairs myocardial perfusion during heart stimulation in healthy non-smokers18 and reduces stroke volume during submaximal intensity exercise.19 Therefore, the use of nicotine may negatively affect exercise capacity.20

Furthermore, data describing the possible effects of smokeless tobacco on endurance performance in healthy subjects are scant. One study has suggested that nicotine, administered by patch, significantly increases time to exhaustion (TTE) by ~17% during endurance performance.21

However, even if no effect on fatigue perception was detected when compared with placebo, the authors suggested that nicotine prolongs TTE via a central mechanism. Indeed, stimulation of nicotinic cholinergic receptors (nAChR) releases a variety of neurotransmitters in the brain.22 One of them, dopamine, has direct effects on brain microcirculation and underlies blood flow changes of brain functions.23”

Quote#2: “Despite an increase in cerebral and muscular tissue oxygenation, snus use in healthy, non-smoker participants did not modify perception of effort and did not increase TTE during continuous exercise performed at 65%Wmax. Further research is necessary to test the perception of effort and TTE at higher exercise intensities (and maybe systematically modulating the levels of nicotine concentrations). In general, our results showed that snus could not be considered an ergogenic substance at submaximal exercise level.”

#Bartik et al. The Effect of High Nicotine Dose on Maximum Anaerobic Performance and Perceived Pain in Healthy Non-Smoking Athletes: Crossover Pilot Study. 2023. 

https://www.mdpi.com/1660-4601/20/2/1009

Quote: “The systematic review of physiological function changes after nicotine application revealed that the majority of 28 evaluated studies reported a significant increase in heart rate, blood pressure, and blood flow [45]. However, only one of six studies that evaluated endurance abilities reported an improvement in the monitored parameters. Several studies reported no significant ergogenic effect of lower nicotine dose (2 and 4 mg) on maximum anaerobic power by the Wingate test [46,47,48]. Conversely, the study of Johnson et al. [49] reported a positive effect after administration of 5 mg oral-dispersible nicotine strip in two repeated 30 s Wingate tests with 3 min rest between bouts. Peak and average power output were significantly greater following nicotine administration compared to placebo. Similarly, significant increases were also seen in heart rate and blood pressure following nicotine administration compared to placebo. No significant impact on pre-exercise side effect score, reaction time, rate of perceived exertion, or post-exercise blood lactate levels was observed.

Based on the above-mentioned findings, when a nicotine dose of 2–4 mg did not lead to an improvement in anaerobic performance, while intake of 5 mg increased bouts of peak and average power output during the Wingate test, we decided to assess the effect of an even higher dose (8 mg of nicotine) on maximum anaerobic performance and the subjective perception of pain and perceived exertion. Considering a high dose of nicotine administered, there has not been a similar research study conducted. This is the pilot study that reports the effect of 8 mg dose of nicotine on performance and perceived pain.”

Nicotine can suppress appetite but it doesn’t mean that it can be used as a weight loss tool. 

#Schwartz A, Bellissimo N. Nicotine and energy balance: A review examining the effect of nicotine on hormonal appetite regulation and energy expenditure. Appetite. 2021 

https://pubmed.ncbi.nlm.nih.gov/33848592/

Quote: “Nicotine has been shown to decrease appetite, food intake (FI) and body weight, but the mechanisms are unclear. The purpose of this review was to examine research on the effects of nicotine on energy balance by exploring physiological mechanisms and hormone regulation related to FI, subjective appetite and energy expenditure (EE). We searched PubMed and MEDLINE, and included articles investigating the effects of nicotine on central appetite regulation, FI, leptin, peptide-YY (PYY), ghrelin, glucagon-like peptide-1 (GLP-1), adiponectin, cholecystokinin (CCK), orexin, and EE. A total of 65 studies were included in the qualitative synthesis and review. Our findings suggest that the decrease in appetite and FI may be attributed to nicotinic alterations of neuropeptide Y (NPY) and pro-opiomelanocortin (POMC) but the effect of nicotine on FI remains unclear. Furthermore, nicotine increases resting EE (REE) and physical activity EE (PAEE) in both smokers and non-smokers; and these increases may be a result of the catecholaminergic effect of nicotine. Decreases in body weight and appetite experienced by nicotine users results from increased EE and changes in the central hypothalamic regulation of appetite. There is not enough evidence to implicate a relationship between peripheral hormones and changes in appetite or FI after nicotine use. Although nicotine increases REE and PAEE, the effect of nicotine on other components of EE warrants further research. We conclude that further research evaluating the effect of nicotine on appetite hormones, FI and EE in humans is warranted.”

– Compared to other stimulants, nicotine's effect doesn't come at the same high price for our bodies. It is also crystal clear that vaping is way, way less harmful than smoking. Smoking delivers, well, hot smoke and extremely toxic particles directly into your lungs, causing serious damage all over your body right away. But we will purely focus on nicotine vapes in this video. 

#NHS. Vaping myths and the facts. Retrieved August 2024.

https://www.nhs.uk/better-health/quit-smoking/vaping-to-quit-smoking/vaping-myths-and-the-facts/

Quote: “Vaping is not completely harmless. We only recommend it for adult smokers, to support quitting smoking and staying quit.”

– Well we should find out quickly. While in the West smoking is slowly falling out of fashion, especially among teens vaping has become a growing epidemic. 

#GBD 2019 Tobacco Collaborators. Spatial, temporal, and demographic patterns in prevalence of smoking tobacco use and attributable disease burden in 204 countries and territories, 1990–2019: a systematic analysis from the Global Burden of Disease Study 2019. The Lancet 2021.

https://www.thelancet.com/pb/assets/raw/Lancet/infographics/tobacco/Tobacco_infographics_global.pdf

#Tarasenko et al. Electronic cigarette use among adolescents in 17 European study sites: findings from the Global Youth Tobacco Survey. Eur J Public Health. 2022
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8807119/

Quote: “In light of the growing concerns of increasing e-cigarette use among children and adolescents and the mounting evidence on the health risks associated with the use of these products,4,10,11 we examined the current prevalence of e-cigarette use and changes overtime in youth aged 11–17 years in 17 European study sites. We found in the last 4–6 years, the percentage of students aged 11–17 years currently using e-cigarettes had doubled in Georgia and Italy, and nearly doubled in Latvia. The prevalence of current e-cigarette use increased in Romania and San Marino. The finding of upward trend is similar to reports from other countries. A systematic review and meta-analyses of 27 publications (36 surveys) from 13 countries has shown ENDS ever use among youth aged < 20 years increased in New Zealand, Poland, the Republic of Korea and the USA.20 In the UK, 4.9% of youth aged 11–18 years were currently using e-cigarettes in 2019 vs. 2.4% in 2015.21”

#eClinicalMedicine. E-cigarette use among adolescents: Are we doing enough? EClinicalMedicine. 2022

https://www.thelancet.com/action/showPdf?pii=S2589-5370%2822%2900353-4
Quote: “Data on adolescent e-cigarette use in Asian countries, South America, and low-income countries such as India and Africa are scarce, but available data suggest that the prevalence might be lower in some Asian countries (eg, 3.5% in China) and Brazil (2.1%), than in Europe or the USA. Although most adolescents have never tried e-cigarettes, and there have been promising reductions in underage combustible cigarette smoking, the recent rise in the use of e-cigarettes among youths in some countries has sparked health warnings from respiratory health experts.”

– In 2023, in the UK 20% of children have tried vaping at least once. 

According to the report by Action on Smoking and Health (ASH) based on the data from ASH Smokefree GB Youth Survey 2023 over 2600 11-17 years olds, 20.5% of them tried vaping. 

#Action on Smoking and Health (ASH). Use of e-cigarettes (vapes) among young people in Great Britain. 2023.

https://ash.org.uk/uploads/Use-of-vapes-among-young-people-GB-2023-v2.pdf?v=1697209531

Quote: “In 2023 20.5% of children had tried vaping, up from 15.8% in 2022 and 13.9% in 2020 before the first COVID lockdown. The majority had only vaped once or twice (11.6%), while 7.6% were currently vaping (3.9% less than once a week, 3.6% more than once a week) and the remainder (1.3% in 2023) saying they no longer vape.”

Following paper shows that disposable vapes seem to reverse the declines in nicotine in the UK and nicotine use appears to be rising, primarily due to sharp increases in vaping among 18 to 24-year-olds, the youngest group studied in the paper. This was also the group with the continued decline in smoking whereas it has been stagnated or reversed in adults ≥45. 

#Tattan-Birch et al. Trends in vaping and smoking following the rise of disposable e-cigarettes: a repeat cross-sectional study in England between 2016 and 2023. Lancet. 2024. 

https://www.thelancet.com/journals/lanepe/article/PIIS2666-7762(24)00091-7/fulltext

Quote: “Pre-disposables, vaping and smoking prevalence had been stable or declining across all age groups. However, post-disposables, the odds of current vaping increased by 99% per year among 18 to 24-year-olds (odds ratio [OR] = 1.99; 95% confidence interval [CI] = 1.71 to 2.31), compared with 39% (OR = 1.39; 95% CI = 1.26 to 1.52) in 25 to 44-year-olds and 23% (OR = 1.23; 95% CI = 1.12 to 1.35) in those aged 45 or older. Smoking rates continued to decline — albeit modestly — in 18 to 24-year-olds (OR = 0.88, 95% CI = 0.77 to 1.00) and 25 to 44-year-olds (OR = 0.93, 95% CI = 0.86 to 1.00), but increased among those aged 45 or older (OR = 1.12, 95% CI = 1.05 to 1.20). As a result, post-disposables, the overall prevalence of inhaled nicotine use increased across all age groups. Trends were similar for daily use, but post-disposables increases in vaping were greatest among people who had never regularly smoked (e.g., 18 to 24-year-olds: OR = 2.50, 95% CI = 1.82 to 3.43).”

– In the US 8% of all students are currently vaping regularly. One in four of them do it daily, and almost all of them use vapes with flavors. 

According to the data from the 2023 National Youth Tobacco Survey (NYTS) released by FDA and Centers for Disease Control and Prevention (CDC), over 2 million students currently using e-cigarettes. 

Survey was conducted on a nationally representative sample of 22,069 U.S. students attending private or public schools in grades 6-12. 

#FDA. Results from the Annual National Youth Tobacco Survey. 2024. 

https://www.fda.gov/tobacco-products/youth-and-tobacco/results-annual-national-youth-tobacco-survey

Quote: “Current Use

• 7.7% of students (2.13 million) reported current use of e-cigarettes 

• 10.0% (1.56 million) high school students and 4.6% (550,000) middle school students reported current use of e-cigarettes

Frequency of Use

• More than 1 in 4 (25.2%) of current youth e-cigarette users use an e-cigarette product every day   

• More than 1 in 3 (34.7%) youth e-cigarette users report using e-cigarettes at least 20 of the last 30 day

Flavored E-Cigarette Use

• Almost 9 out of 10 current e-cigarette users (89.4%) used flavored e-cigarettes, with fruit flavors being the most popular, followed by candy, desserts, or other sweets; mint; and menthol 

Over half (57.9%) of students currently using e-cigarettes reported using flavors with “ice” or “iced” in the name”

– A vape is basically a small tank of liquid, heated up by a metallic coil, that vaporises it. 

There are various different versions but the basic working mechanism is pretty much similar. 

#Cao Y et al. Toxicity of electronic cigarettes: A general review of the origins, health hazards, and toxicity mechanisms. Sci Total Environ. 2021 

https://www.sciencedirect.com/science/article/abs/pii/S004896972100543X
Quote: “E-cigarette is an electronic product with similar characteristics to traditional cigarettes in terms of look, smoke, taste, and feel. It allows users to an aerosol converted from heated nicotine (extracted from tobacco), flavorings and other chemicals. There are several different types of e-cigarettes, including Vape Pen, Box Mod, Mech Mod, Pod Mod, HnB and E-hookah, etc. Vape Pen is a pen type e-cigarette. Box Mod is a boxshaped e-cigarette, named after its shape like a box. Mech Mod is a mechanical smoke, an e-cigarette device that does not contain a control chip, and its safety depends on the knowledge of the player. Pod Mod is a closed e-cigarette with replaceable cartridges. HnB is a heat-notburn smoking device and E-hookah is an electronic hookah. The major components of an electronic cigarette include a tobacco pipe containing a nicotine solution, an evaporation device, a battery, and a mouthpiece (see Fig. 1). The atomizer is powered by a battery rod, which transforms the liquid nicotine in the cartridge into a mist so that the user has a smoking-like feel during inhalation.”

– The major ingredient in most vape juice is propylene glycol and glycerol, the main chemicals in smoke machines, which are also used in countless chemical processes. From food like candy and baking mixes, to cosmetics, paints or plastics. Then there are the nicotine salts containing the magic and dozens of different flavour molecules.

#National Academies of Sciences, Engineering, and Medicine; Health and Medicine Division; Board on Population Health and Public Health Practice; Committee on the Review of the Health Effects of Electronic Nicotine Delivery Systems; Eaton DL, Kwan LY, Stratton K, editors. Public Health Consequences of E-Cigarettes. Washington (DC): National Academies Press (US); 2018 Jan 23. 5, Toxicology of E-Cigarette Constituents. 

https://www.ncbi.nlm.nih.gov/books/NBK507184/

Quote: “In general, e-cigarettes often contain ingredients such as propylene glycol (PG) and glycerol, mixed with concentrated flavors and, optionally, a variable percentage of nicotine. Quantitative and qualitative studies have identified a wide variety of chemical components in the cartridges, refill solutions, and aerosols of e-cigarettes. Herrington and Myers (2015) have detected approximately 60 to 70 compounds (unidentified and identified) in each liquid tested, only varying by several constituents throughout the liquid. Kucharska and colleagues (2016) have identified 113 chemicals in 50 brands of liquids. Even more compounds are observed in the aerosol over their respective solution because some chemicals are generated during the vaporization process. An aerosol generated from a single product tested by Herrington and Myers (2015) showed 18 additional compounds observed in the solution.

[...]

E-cigarettes use humectants as solvent carriers in e-liquids to produce aerosols that simulate combustible tobacco cigarette smoke. In addition to these humectants, water is a common ingredient of e-liquids. PG and glycerol (commonly referred to as a “vegetable glycerin” in liquid formulations) are the most common vaporizing solvents used in e-cigarettes. Hutzler and colleagues (2014) analyzed 28 liquids of 7 manufacturers purchased in Germany and detected both PG and glycerol in all samples. Both PG and glycerol are also commonly used as humectant ingredients in manufactured cigarettes to control and maintain the moisture content of the cut tobacco filler (Uryupin et al., 2013). ” PG = propylene glycol

#Public Health Statement for Propylene Glycol. Agency for Toxic Substances and Disease Registry. 2014 

https://wwwn.cdc.gov/TSP/PHS/PHS.aspx?phsid=1120&toxid=240

Quote: “Propylene glycol is a synthetic liquid substance that absorbs water. Propylene glycol is also used to make polyester compounds, and as a base for deicing solutions. Propylene glycol is used by the chemical, food, and pharmaceutical industries as an antifreeze when leakage might lead to contact with food. The Food and Drug Administration (FDA) has classified propylene glycol as an additive that is "generally recognized as safe" for use in food. It is used to absorb extra water and maintain moisture in certain medicines, cosmetics, or food products. It is a solvent for food colors and flavors, and in the paint and plastics industries. Propylene glycol is also used to create artificial smoke or fog used in fire-fighting training and in theatrical productions. Other names for propylene glycol are 1,2-dihydroxypropane, 1,2-propanediol, methyl glycol, and trimethyl glycol.”

#Chemical Safety Facts. Glycerol / Glycerin. 2022

https://www.chemicalsafetyfacts.org/chemicals/glycerol-glycerin/

Quote: “Glycerol is a common ingredient in pharmaceuticals, where it can help improve the smoothness and taste of medicines. It is added to cough syrups to help prevent throat irritation which leads to coughing, and it is used to make tablets easier to swallow.

Glycerol is added to personal care products to protect the skin from irritants and bring moisture to the surface of skin and hair.

A variety of food and beverages contain glycerol to help retain moisture, and add smoothness, bulk and sweetness.

The FDA has approved glycerol for use as a food additive and for use in cosmetics and skin care products.”

– The scary answer is that we don’t really know. Studies found that vape liquids can be thousands of very different mixes of many dozens of substances. The majority were not even mentioned on the label. This seems almost unbelievable, but the vaping industry is much less regulated than you’d think.

Following study found almost 20,000 e-liquids in the Dutch market in 2017, in 245 unique flavor descriptions.

#Havermans A, Krüsemann EJZ, Pennings J, de Graaf K, Boesveldt S, Talhout R. Nearly 20 000 e-liquids and 250 unique flavour descriptions: an overview of the Dutch market based on information from manufacturers. Tob Control. 2021 

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7803909/

Quote: “Flavour-related information about all products in the Dutch section of the European Common Entry Gate (EU-CEG) system29 was extracted on 30 November 2017. Only information from the category ‘refillable e-liquids and cartridges’ (not ‘devices’ or ‘individual parts’) was selected for this study. When there were multiple presentations of the same product (eg, one e-liquid marketed in different packages), one presentation was randomly selected. This was the case for 3922 products. Eight products were excluded due to incomplete information. E-liquids with the same flavour description, but different nicotine concentrations were considered different products and therefore separately included. The final dataset consisted of 19 266 products.”

#Herrington JS, Myers C. Electronic cigarette solutions and resultant aerosol profiles. J Chromatogr A. 2015 

https://pubmed.ncbi.nlm.nih.gov/26422308/

Quote: “This novel application provided detectable levels of over one hundred fifteen volatile organic compounds (VOCs) and semivolatile organic compounds (SVOCs) from a single 40 mL puff. The aerosol profiles from four commercially available e-cigarettes were compared to their respective solution profiles with the same GC–MS method. Solution profiles produced upwards of sixty four unidentified and identified (some only tentatively) constituents and aerosol profiles produced upwards of eighty two compounds. Results demonstrated distinct analyte profiles between liquid and aerosol samples. Most notably, formaldehyde, acetaldehyde, acrolein, and siloxanes were found in the aerosol profiles; however, these compounds were never present in the solutions. These results implicate the aerosolization process in the formation of compounds not found in solutions; have potential implications for human health; and stress the need for an emphasis on electronic cigarette aerosol testing.”

#National Academies of Sciences, Engineering, and Medicine; Health and Medicine Division; Board on Population Health and Public Health Practice; Committee on the Review of the Health Effects of Electronic Nicotine Delivery Systems; Eaton DL, Kwan LY, Stratton K, editors. Public Health Consequences of E-Cigarettes. Washington (DC): National Academies Press (US); 2018 Jan 23. 5, Toxicology of E-Cigarette Constituents.

https://www.ncbi.nlm.nih.gov/books/NBK507184/

Quote: “In general, e-cigarettes often contain ingredients such as propylene glycol (PG) and glycerol, mixed with concentrated flavors and, optionally, a variable percentage of nicotine. Quantitative and qualitative studies have identified a wide variety of chemical components in the cartridges, refill solutions, and aerosols of e-cigarettes. Herrington and Myers (2015) have detected approximately 60 to 70 compounds (unidentified and identified) in each liquid tested, only varying by several constituents throughout the liquid. Kucharska and colleagues (2016) have identified 113 chemicals in 50 brands of liquids. Even more compounds are observed in the aerosol over their respective solution because some chemicals are generated during the vaporization process. An aerosol generated from a single product tested by Herrington and Myers (2015) showed 18 additional compounds observed in the solution.”

#Larcombe A, Allard S, Pringle P, Mead-Hunter R, Anderson N, Mullins B. Chemical analysis of fresh and aged Australian e-cigarette liquids. Med J Aust. 2022 

https://pubmed.ncbi.nlm.nih.gov/34528266/

Quote: “The measured levels of propylene glycol and glycerol often diverged from those recorded on the e-liquid label. All e-liquids contained one or more potentially harmful chemicals, including benzaldehyde, menthol, trans-cinnamaldehyde, and polycyclic aromatic hydrocarbons. Nicotine or nicotyrine were detected in a small proportion of e-liquids at extremely low concentrations.”

Also the companies were not necessarily obliged by law to list all the chemicals they use as flavors in the labels. Some are counted as trade secrets since the recipes are not copyrighted. 

#Government of Canada. Industry Guide to Vaping Products Subject to the Canada Consumer Product Safety Act. 2024. 

https://www.canada.ca/en/health-canada/services/consumer-product-safety/reports-publications/industry-professionals/vaping-products-canada-consumer-product-safety-act/document.html

Quote: ”4.2.2.1 Flavour Ingredients

If any ingredient or combination of ingredients is added to a vaping substance solely to produce a particular flavour or combination of flavours, those ingredients must be denoted only by the single term "flavour" in the English list of ingredients, and by the single term "arôme" in the French list of ingredients (see subsection 47(2)). The use of common names within the list of ingredients is not permitted for ingredients that are added solely to produce a particular flavour.

4.2.2.2 Order of Ingredients in the List of Ingredients

Any ingredients that are present in a vaping substance in a concentration of 1% or more must be set out in descending order of their proportion in the list of ingredients (see paragraph 61(1)(a)). Any ingredients that are present in a vaping substance in a concentration of less than 1% may be set out in any order immediately following the ingredients present at a concentration of 1% or more (see paragraph 61(1)(b)). The percentage is obtained from the ratio of the weight of an ingredient to the volume of the vaping substance (see subsection 61(2)). The concentration of an ingredient is not required to be displayed within the list of ingredients.

As discussed in the preceding section, "flavour" and "arôme" is to appear only once in the English list of ingredients and only once in the French list, respectively, even if multiple ingredients are added solely to produce a particular flavour or flavours. The total proportion of all flavour ingredients must be calculated in order to determine the placement of the term "flavour" and "arôme" in the list of ingredients (see subsection 61(3)).”

#Barhdadi S, Mertens B, Van Bossuyt M, Van De Maele J, Anthonissen R, Canfyn M, Courselle P, Rogiers V, Deconinck E, Vanhaecke T. Identification of flavouring substances of genotoxic concern present in e-cigarette refills. Food Chem Toxicol. 2021 

https://pubmed.ncbi.nlm.nih.gov/33217530/

Quote: “Besides specific requirements for certain ingredients, the manufacturers of e-liquids are also obliged to notify their products before they are placed on the EU market (EU, 2015/2183). In this notification, a list of ingredients should be provided with toxicological information on all ingredients (EC, 2015). However, the listing highly depends on the goodwill of the manufacturers. Some manufacturers are not eager to provide the required information, because of confidentiality issues. In the Decision (EU) 2015/2183, it is stated that ingredients present at a level below 0.1% in the final product formulation may be deemed confidential or a trade secret. Consequently, these ingredients are often described collectively in the notification by an umbrella term such as e.g. ‘strawberry flavouring’. In most cases, the complete composition of the e-liquid thus remains unclear to the authorities (and even to the manufacturers), especially when natural extracts are used (tobacco extracts, essential oils, herbal extracts, or non-chemically synthetized flavourings), as their composition is not always known and may vary from batch to batch depending on biological and geographical origins (Bhattacharya and Preedy, 2016). It is thus highly likely that e-liquids contain substances with unknown toxicological properties or known toxic substances that exceed certain safety limits. In those cases, the use of e-liquids might cause adverse human health effects.”

– We know that many official substances in vapes are technically safe. Kinda. They’re used in cosmetics, medicine or food and have been extensively tested. Most are safe to eat or put on your skin. But this is not the same as breathing them in.

#National Academies of Sciences, Engineering, and Medicine; Health and Medicine Division; Board on Population Health and Public Health Practice; Committee on the Review of the Health Effects of Electronic Nicotine Delivery Systems; Eaton DL, Kwan LY, Stratton K, editors. Public Health Consequences of E-Cigarettes. Washington (DC): National Academies Press (US); 2018 Jan 23. 5, Toxicology of E-Cigarette Constituents.

https://www.ncbi.nlm.nih.gov/books/NBK507184/

Quote: “Although few studies have examined the effects of flavoring substances administered by inhalation, there are some chemicals that, although approved for ingestion, have established adverse health effects when inhaled. Table 5-4 presents an overview of common flavorings and their inhalation toxicity. Examples of such chemicals include diacetyl, acetylpropionyl, acetoin, cinnamaldehyde, and benzaldehyde; these are reviewed in details below.”

https://www.ncbi.nlm.nih.gov/books/NBK507184/table/tab_5-4/?report=objectonly

On top of this, these chemicals can be found in higher concentrations in e-liquids than they are found in food and cosmetic products. 

#Omaiye EE, McWhirter KJ, Luo W, Tierney PA, Pankow JF, Talbot P. High concentrations of flavor chemicals are present in electronic cigarette refill fluids. Sci Rep. 2019 

https://pubmed.ncbi.nlm.nih.gov/30792477/

Quote: “We characterized the flavor chemicals in a broad sample of commercially available electronic cigarette (EC) refill fluids that were purchased in four different countries. Flavor chemicals in 277 refill fluids were identified and quantified by gas chromatography-mass spectrometry, and two commonly used flavor chemicals were tested for cytotoxicity with the MTT assay using human lung fibroblasts and epithelial cells. About 85% of the refill fluids had total flavor concentrations >1 mg/ml, and 37% were >10 mg/ml (1% by weight). Of the 155 flavor chemicals identified in the 277 refill fluids, 50 were present at ≥1 mg/ml in at least one sample and 11 were ≥10 mg/ml in 54 of the refill fluids. Sixty-one% (170 out of 277) of the samples contained nicotine, and of these, 56% had a total flavor chemical/nicotine ratio >2. Four chemicals were present in 50% (menthol, triacetin, and cinnamaldehyde) to 80% (ethyl maltol) of the samples. Some products had concentrations of menthol (“Menthol Arctic”) and ethyl maltol (“No. 64”) that were 30 times (menthol) and 100 times (ethyl maltol) their cytotoxic concentration. One refill fluid contained cinnamaldehyde at ~34% (343 mg/ml), more than 100,000 times its cytotoxic level. High concentrations of some flavor chemicals in EC refill fluids are potentially harmful to users, and continued absence of any regulations regarding flavor chemicals in EC fluids will likely be detrimental to human health.”

Quote: “Although cinnamaldehyde has been approved by the Food and Drug Administration (21CFR182.60) for use as a flavoring agent22 and given FEMA GRAS status, some in the flavor industry and the Research Institute for Fragrance Materials have recommended that cinnamaldehyde not exceed 1% when used in skin cosmetic products23,24. Cinnamaldehyde is usually found in body care and household products, such as detergents, creams and lotions, soaps and perfumes, in the range 0.001–0.8%25. Moreover, cinnamaldehyde is used in food products at concentrations ranging from 7.7 ppm (0.00077%) in ice creams to a 700 ppm (0.07%) in candy and up to a 6,400 ppm (0.64%) in fruits and juices23,26,27. In our refill fluid samples, two products had cinnamaldehyde concentrations of 118 mg/ml (11.8% or 118,000 ppm) and 343 mg/ml (34.3% or 343,000 ppm). We have previously reported that the cinnamaldehyde concentrations in a different set of refill fluid samples often exceeded 1% (range = 0.00022–14%) for cinnamon flavored refill fluids10,11. Our current study further shows, in agreement with our earlier work11 that cinnamaldehyde is more widely used in EC refill fluids than would be expected based on the names of the EC products. For example, cinnamaldehyde was found previously in fruity flavors, such as a product named “Blueberry Hills”, and in the current study was found in 70 of 277 (25%) products, even though only two products indicated “cinnamon” in their name. Cinnamaldehyde at concentrations found in EC products has also been shown to impair the function of immune cells in the respiratory system13.”

#Larcombe A, Allard S, Pringle P, Mead-Hunter R, Anderson N, Mullins B. Chemical analysis of fresh and aged Australian e-cigarette liquids. Med J Aust. 2022 

https://pubmed.ncbi.nlm.nih.gov/34528266/

Quote: “The high frequency of detection and the high concentrations of these chemicals have concerning health implications. Menthol enhances the addictive properties of nicotine23 and inhibits nicotine metabolism.20 Menthol was detected in most e-liquids, but only a small proportion were labelled as being “menthol”- or “ice”-flavoured. Conversely, one “menthol” e-liquid contained no menthol, and may have instead contained potentially carcinogenic analogues such as pulegone, or synthetic “coolants” such as N-ethyl-p-menthane-3-carboxamide.”

#Barhdadi S, Mertens B, Van Bossuyt M, Van De Maele J, Anthonissen R, Canfyn M, Courselle P, Rogiers V, Deconinck E, Vanhaecke T. Identification of flavouring substances of genotoxic concern present in e-cigarette refills. Food Chem Toxicol. 2021 

https://pubmed.ncbi.nlm.nih.gov/33217530/

Quote: “Some argue that by using food grade flavourings in e-cigarettes, the risks are minimized (Costigan and Meredith, 2015). However, this is not necessarily true as the safety assessment of food flavourings is based on concentrations to which the consumer is orally exposed and these may significantly differ from the concentrations to which consumers are

exposed via inhalation. The large surface area in the lungs and the absence of an epithelial barrier comparable to the gastrointestinal mucosa or the stratum corneum barrier function of the skin usually results in a higher percentage of absorption after inhalatory exposure and

consequently, a higher internal dose. Also, the kinetic processes for a compound after oral exposure are different compared to those after inhalation. Hence, it is important to execute a separate risk assessment for inhalatory exposure to flavourings present in e-liquids based on their concentration in the aerosol emissions and their toxicity both at the first site of contact and after systemic uptake via the lungs (ECHA, 2012).”

– Cinnamaldehyde, found in cinnamon oil, kills cells and causes genetic damage when inhaled. 

#Clapp PW, Pawlak EA, Lackey JT, Keating JE, Reeber SL, Glish GL, Jaspers I. Flavored e-cigarette liquids and cinnamaldehyde impair respiratory innate immune cell function. Am J Physiol Lung Cell Mol Physiol. 2017 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5582929/

Quote: “E-liquids were then analyzed via mass spectrometry to identify individual flavoring components. Three cinnamaldehyde-containing e-liquids exhibited dose-dependent broadly immunosuppressive effects. Quantitative mass spectrometry was used to determine concentrations of cinnamaldehyde in each of the three e-liquids, and cells were subsequently challenged with a range of cinnamaldehyde concentrations. Cinnamaldehyde alone recapitulated the impaired function observed with e-liquid exposures, and cinnamaldehyde-induced suppression of macrophage phagocytosis was reversed by addition of the small-molecule reducing agent 1,4-dithiothreitol. We conclude that cinnamaldehyde has the potential to impair respiratory immune cell function, illustrating an immediate need for further toxicological evaluation of chemical flavoring agents to inform regulation governing their use in e-liquid formulations.”

#Larcombe A, Allard S, Pringle P, Mead-Hunter R, Anderson N, Mullins B. Chemical analysis of fresh and aged Australian e-cigarette liquids. Med J Aust. 2022 Jan 17;216(1):27-32. doi: 10.5694/mja2.51280. Epub 2021 Oct 6. PMID: 34528266.

https://pubmed.ncbi.nlm.nih.gov/34528266/

Quote: “trans-Cinnamaldehyde impairs innate immune cell function in the lung,3 suppresses bronchial airway epithelial cell ciliary motility and mitochondrial function,7 inhibits microsomal CYP2A6, impairs neutrophil, macrophage and natural killer cell function, and reduces oxidative burst when heated and inhaled.10”

#Behar RZ, Luo W, Lin SC, Wang Y, Valle J, Pankow JF, Talbot P. Distribution, quantification and toxicity of cinnamaldehyde in electronic cigarette refill fluids and aerosols. Tob Control. 2016 

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5503843/

Quote: “In summary, cinnamaldehyde was present in 51% of 39 refill fluids at concentrations that would be cytotoxic and genotoxic in multiple assays. Refill fluid flavours containing cinnamaldehyde included tobacco, fruit, sweet, cinnamon and flavoured tobacco. Cinnamon Ceylon or cinnamaldehyde aerosols produced at 5 V were more cytotoxic than those produced at 3 V, and aerosols made with Cinnamon Ceylon contained chemicals not seen in the parent refill fluid or the 3 Vaerosol. The hPF and hESC were able to recover normal morphology and grow after short exposures to cinnamaldehyde with hESC being more robust. MTT IC50 concentrations of cinnamaldehyde caused rounding up of hPF accompanied by depolymerisation of microtubules. In the live cell imaging assay, the MTT NOAEL concentration of cinnamaldehyde reduced growth, increased motility and increased death of treated hESC colonies. MTT NOAEL concentrations of cinnamaldehyde also induced DNA damage in hESC and hPF, an effect that was reversible in hESC. These data support the idea that inhaling heated refill fluids containing cinnamaldehyde adversely affects the health of embryonic and respiratory cells. The relatively widespread use of cinnamaldehyde in refill fluids at concentrations that are toxic in vitro suggests a need for regulation and caution in use of refill fluid products. Additional in vitro exposures using an air–liquid interface model as well as animal and human studies could be performed in the future to verify the responses observed in this study.”

There were also studies that did not present it as genotoxic though, but other other substances to cause mutations and chromosome damage in experimental studies.  

#Barhdadi S, Mertens B, Van Bossuyt M, Van De Maele J, Anthonissen R, Canfyn M, Courselle P, Rogiers V, Deconinck E, Vanhaecke T. Identification of flavouring substances of genotoxic concern present in e-cigarette refills. Food Chem Toxicol. 2021 

https://pubmed.ncbi.nlm.nih.gov/33217530/

Quote: “E-cigarettes have become very popular, a trend that has been stimulated by the wide variety of available e-liquid flavours. Considering the large number of e-liquid flavours (>7000), there is an urgent need to establish a screening strategy to prioritize the flavouring substances of highest concern for human health. In the present study, a prioritization strategy combining analytical screening, in silico tools and literature data was developed to identify potentially genotoxic e-liquid flavourings. Based on the analysis of 129 e-liquids collected on the Belgian market, 60 flavourings with positive in silico predictions for genotoxicity were identified. By using literature data, genotoxicity was excluded for 33 of them whereas for 5, i.e. estragole, safrole, 2-furylmethylketon, 2,5-dimethyl4-hydroxyl-3(2H)-furanone and transhexanal, there was a clear concern for in vivo genotoxicity. A selection of 4 out of the remaining 22 flavourings was tested in two in vitro genotoxicity assays. Three out of the four tested flavourings induced gene mutations and chromosome damage in vitro, whereas equivocal results were obtained for the fourth compound. Thus, although there is a legislative framework which excludes the use of CMR compounds in e-liquids, flavourings of genotoxic concern are present and might pose a health risk for e-cigarette users.”

– Benzaldehyde found in almonds or apples has a fruity taste and is common in cherry, berry, chocolate or mint flavoured vapes. As a gas, it irritates the respiratory tract. 

It is important to note that the toxicity is also dependent on the concentration. Not all chemicals that were found to be toxic in previous studies with different conditions are toxic in the concentrations found in vapes. However, this still can come into play in long term exposure where even small amounts can be harmful over time.  

#Kosmider L, Sobczak A, Prokopowicz A, Kurek J, Zaciera M, Knysak J, Smith D, Goniewicz ML. Cherry-flavoured electronic cigarettes expose users to the inhalation irritant, benzaldehyde. Thorax. 2016 

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4937616/
Quote: “Benzaldehyde was detected in 108 out of 145 examined products (levels above LLOQ). The highest yields of benzaldehyde were observed in cherry-flavored products (5.129 – 141.2 μg/30 puffs). Benzaldehyde yields in aerosol generated from cherry-flavored nicotine solutions were significantly higher than in other products (χ2(7)=43.70, p<0.0001; Kruskal-Wallis Test). Benzaldehyde yields in non-cherry flavored products were within the range of 0.025 to 10.27 μg/30 puffs (Table 1). The benzaldehyde doses inhaled using 30 puffs from flavored e-cigarettes were often higher than doses inhaled from a conventional cigarette. The estimated median daily inhaled dose of benzaldehyde from cherry-flavored e-cigarettes was 70.3 μg, which would be over one thousand times lower than the PEL dose for benzaldehyde concentrations in the workplace (Figure 1).”

#!SIDSP* OECD/SIDS. Screening Information Data Set (SIDS) of OECD High Production Volume Chemicals Programme. 1994

https://hpvchemicals.oecd.org/UI/handler.axd?id=cbba08a9-5eda-4930-92ad-540207d26a84

– What is worse is that we don’t know what many substances in vape juice do if heated up. The longer you inhale and the hotter the coil gets, the more chemicals in the juice change. Molecules merge or break down, creating new compounds with unknown consequences. 

#Government of Canada. Industry Guide to Vaping Products Subject to the Canada Consumer Product Safety Act. 2024. 

https://www.canada.ca/en/health-canada/services/consumer-product-safety/reports-publications/industry-professionals/vaping-products-canada-consumer-product-safety-act/document.html

Quote: “5.3.5 Thermal Degradation of Products

Under intended conditions of use, users of vaping products inhale the emissions (i.e., aerosol) generated by vaping products and not the vaping substance in liquid form. For a typical vaping device, the vaping substance is heated to form a vapour, which is drawn through the device and condenses into an aerosol that is then inhaled. The heat used to vapourize the vaping substance may alter the proportion of different ingredients in the aerosol compared to the liquid, trigger additional chemical reactions and may result in thermal decomposition of the diluent or other constituents. For example, it is known that the thermal degradation of propylene glycol and glycerol during vaping can lead to the emission of thermal degradants such as formaldehyde, acetaldehyde, and acrolein, among other potential toxicants. Studies have demonstrated that these thermal degradants are produced as a result of the so-called 'dry hit' or 'dry puff' phenomenaFootnote10 as well as under other conditions that are still pleasant to the user. It is recommended that vaping device manufacturers establish limits on operating parameters for devices such that the generation of harmful emissions due to thermal decomposition is as low as reasonably achievable.”

#Niu, J., Zhu, J. Thermal reaction products and formation pathways of two monoterpenes under in situ thermal desorption conditions that mimic vaping coil temperatures. Sci Rep 13, 21650 (2023). 

https://www.nature.com/articles/s41598-023-49174-2

Quote: “Thermal degradation in vaping has been confirmed to generate more transformed chemical products leading to increased unpredictable toxicity10,12. For example, soluble components of e-cigarettes are linked to dose-dependent loss of lung endothelial barrier function13. Benzene, a well known carcinogen14, has been found to be the common thermal degradant from many components in vaping liquids upon vaporization10,15,16,17. Other inhalation hazards (irritants and carcinogens) can also be generated from the thermal degradation including furans and aldehydes from saccharides (a sweet flavour for appealing children in vaping liquid)18, formaldehyde and dihydroxyacetone from PG and GLY10,15, and methacrolein and methyl vinyl ketone from tetrahydrocannabinol19. Therefore, consumers of vaping products are exposed from not only the vaporised vaping liquid components but also numerous thermal reaction products (RPs) of these components.”

– When propylene glycol and glycerol are heated too much, they decompose and turn into harmful molecules. This can happen when the liquid runs out or the coil gets too hot. You will probably notice this because your vape will taste weird or burned – if this happens you should stop right away.

#Beard JM, Collom C, Liu JY, Obiako P, Strongin RM, Zavala J, Sayes CM. In vitro toxicity and chemical analysis of e-cigarette aerosol produced amid dry hitting. Toxicology. 2024 

https://pubmed.ncbi.nlm.nih.gov/38876198

Quote: “Dry hitting, a phenomenon produced by e-cigarettes with refillable cartridges when the liquid in the coil is low, is a common occurrence among regular vapers despite being an unintended consequence of the device. This phenomenon's hazard to public health is still unknown and needs further investigation. Lung cells cultured at the air-liquid interface were exposed to vaped aerosol consisting of 3 % w/v ethyl maltol in propylene glycol for three-second puffs every 30 seconds for 80 total puffs with either dry hit or saturated conditions. Cytotoxicity was measured colorimetrically. The thermal degradation of the heating coils and wicks was visualized using scanning electron microscopy. The chemical byproducts in the aerosol were analyzed using proton nuclear magnetic resonance and inductively coupled plasma mass spectrometry. The results revealed a highly significant increase in cytotoxicity from dry hit treatments. Imaging showed thermal decomposition of the cotton wick after dry hitting, which was confirmed by energy dispersive x-ray spectroscopy with less oxygen in the dry hit cotton. Chemical byproducts were found via unique peaks in the dry hit condensate in the aromatic and alkene regions. Saturated condensate showed higher concentrations of detected metal species than dry-hit condensate. E-cigarette users should avoid dry hitting by refilling tanks or cartridges preemptively or by using disposable coils to avoid increased toxicity during vaping.”

#Jiang H, Ahmed CMS, Martin TJ, Canchola A, Oswald IWH, Garcia JA, Chen JY, Koby KA, Buchanan AJ, Zhao Z, Zhang H, Chen K, Lin YH. Chemical and Toxicological Characterization of Vaping Emission Products from Commonly Used Vape Juice Diluents. Chem Res Toxicol. 2020 

https://par.nsf.gov/servlets/purl/10180924

Quote: “3.1. PG and VG.
The chemical compositions of PG and VG oil changed significantly after vaping. We observed a series of oligomers in unvaped PG oil but only C6H14O3 in its vaping emissions

(Figure 1). A dimer C6H12O4 was detected in both unvaped and vaped VG. Oligomers were also reported in particles emitted from PG and VG vaping previously by Escobar et al.24 Various carbonyls were generated from the vaping emissions of PG, including acetaldehyde, acetone, propionaldehyde, 1,3-dihydroxypropanone, and 2-oxopropanal (Table S2). Seven different carbonyls were detected from vaping emissions of VG, including formaldehyde, acetaldehyde, acetone, 1,2-dihydroxypropanone, oxalaldehyde, 2-oxopropanal, and pentane-2,4-dione (Table S3). The production of carbonyls from the vaping of PG and VG may contribute to the increased cellular toxicity (i.e., left-shift in the concentration-response curve) as measured by the XTT assay (Figure 2A). Note that VG has higher viscosity, which causes thicker cloud production during vaping.18 The fluid starvation in the wick may lead to the “dry puff” conditions (i.e., overheating of the coil) and result in increased production of carbonyls.8 Thus, the vaping emission products from neat (100%) VG may not represent the vaping scenarios when blends of PG and VG mixture are used as vaping liquids. “

#Jaegers, N.R., Hu, W., Weber, T.J. et al. Low-temperature (< 200 °C) degradation of electronic nicotine delivery system liquids generates toxic aldehydes. Sci Rep 11, 7800 (2021). 

https://www.nature.com/articles/s41598-021-87044-x

Quote: “Herein, we have examined the low-temperature thermal degradation of propylene glycol and glycerol, the primary constituents of ENDS liquids. Monitoring the low-temperature degradation pathway over an extended period of time has enabled the detection of converted chemical species by natural abundance 13C NMR and 1H NMR which may well represent the types of species present in ENDS vapors and aerosols at these temperatures. The results demonstrate that the degradation of ENDS liquids is strongly dependent on the oxygen availability, both in the presence and absence of a catalyst surface, evidenced by the strong effect of the Ogas/C ratio. When oxygen is available, the ENDS liquids decompose at temperatures below 200 °C and form numerous chemical species via a radical-mediated mechanism initiated by molecular oxygen. Among the species formed, formic and acrylic acids are generated which represent health risks upon inhalation29,30. Further, the formation of hemi- and formal acetals is abundant, signifying the generation of both formaldehyde and acetaldehyde in ENDS aerosols. The dangers of formaldehyde in heated nicotine products has been well-established31, though subsequent discussion has suggested that such dangers in e-cigarettes are over-stated. These new results show clearly the presence of such aldehydes in ENDS liquids thermally degraded at low temperatures. “

Saliba NA, El Hellani A, Honein E, Salman R, Talih S, Zeaiter J, Shihadeh A. Surface Chemistry of Electronic Cigarette Electrical Heating Coils: Effects of Metal Type on Propylene Glycol Thermal Decomposition. J Anal Appl Pyrolysis. 2018 

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6428435/

Quote: “ECIG heating filament wires were found to have a strong catalytic effect. Carbonyl formation initiated at temperatures lower than 250°C in the presence of the metallic wires, compared to 460°C without them. Carbonyl formation was found to be a function of the material of construction, and whether the wire was new or aged. New nichrome wires were the least reactive, but when aged they exhibited the highest reactivity. Carbonyls were formed via dehydration or oxidation reactions of PG.”

#Jensen, R. P. et al. Solvent Chemistry in the Electronic Cigarette Reaction Vessel. Sci. Rep. (2017).

https://www.nature.com/articles/srep42549#Abs1

Quote: “In this investigation we used NMR for e-cigarette aerosol product identification with no aerosol sample processing, apart from dilution in DMSO-d6. As had been proposed, a main finding was that the e-cigarette solvents PG and GLY afford products that are fully consistent with prior studies of their pyrolysis and combustion. In addition, the results herein suggest NMR as a viable alternative to DNPH trapping cartridges for monitoring challenging, reactive toxins such as acrolein. Finally, (i) the sensitivity of PG and GLY to thermal oxidation, (ii) the catalysis of their dehydration reactions by acids and/or metals, and (iii) the variability in the heat transfer efficiencies of individual clearomizers and heating coils should be taken into account when considering strategies to minimize toxin production and inter-laboratory inconsistencies in evaluating these devices.”

– And it gets worse. When the metal coil is heated up, it releases metal particles. 

#Government of Canada. Industry Guide to Vaping Products Subject to the Canada Consumer Product Safety Act. 2024. 

https://www.canada.ca/en/health-canada/services/consumer-product-safety/reports-publications/industry-professionals/vaping-products-canada-consumer-product-safety-act/document.html

Quote: “Studies have suggested that factors such as coil type and composition, vaping device power setting, device type, and user behaviour could contribute to the release of certain elements, including toxic metals, from the device to the aerosol, which would subsequently be inhaled by the userFootnote11. In general, the amounts of toxic metals such as cadmium and lead that are released into the aerosol generated by a vaping device are lower than those found in mainstream cigarette smokeFootnote12. However, vaping devices and parts could be a potential source of exposure to a wide variety of elements that may be toxic when inhaled (including essential elements such as manganese and zinc)Footnote13 Footnote14. It is recommended that manufacturers control the presence of harmful elements in vaping devices and vaping parts so that their transmission to aerosol under normal use conditions is minimized.”

– Studies found aluminium, boron, calcium, iron, copper, magnesium, zinc, lead, chromium, nickel, and manganese in the vapor – all of which vary from really bad news to straight up toxic and can cause lung irritation, chronic bronchitis and shortness of breath in the short term. Nickel can also cause cancer when breathed in. 

#Canchola A, Langmo S, Meletz R, Lum M, Lin YH. External Factors Modulating Vaping-Induced Thermal Degradation of Vitamin E Acetate. Chem Res Toxicol. 2023 

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9846828/

Quote: “In addition to potentially toxic organic products, there is also the potential for the release of metals into the e-liquid and e-cigarette emissions at potentially toxic concentrations. e-Cigarette devices often contain various transition metals, including Ni, Fe, Cu, Cr, etc.12−15 A recent study by Williams et al.16 detected particles containing metals such as Sn, Ag, Fe, Ni, Al, and Cr in e-cigarette aerosol emissions. In a similar study, McDaniel et al.12 found various levels of transition metals, including Cr, Cu, and Ni, in e-cigarette aerosols and leached into the e-liquid. These metals pose a risk of metal toxicity to vape users upon inhalation,17 and recent studies have suggested a potential catalytic role in the thermal degradation of e-liquids, particularly at low temperatures.7,18,19”

#Fowles J, Barreau T, Wu N. Cancer and Non-Cancer Risk Concerns from Metals in Electronic Cigarette Liquids and Aerosols. Int J Environ Res Public Health. 2020 

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7142621/

Quote: “Metals that comprise the heating elements and tanks of e-cigarette devices have the potential to be released into the liquids or the aerosols during use. Metal contaminants in e-liquids, or e-cigarette aerosols, have been quantified in a number of recent studies and include lead, cadmium, chromium, cobalt, arsenic, antimony, manganese, tin, nickel, zinc, copper, aluminum, iron, tungsten, and barium [15,16,17,18,19,20,21,22,23,24]. A recent case report of an e-cigarette user with giant cell interstitial pneumonia concluded that the presence of cobalt in liquid from the device was consistent with a ‘hard metal’ lung injury [25]. Some of these metals (e.g., nickel and chromium) are known respiratory irritants and/or allergens.”

#National Academies of Sciences, Engineering, and Medicine; Health and Medicine Division; Board on Population Health and Public Health Practice; Committee on the Review of the Health Effects of Electronic Nicotine Delivery Systems; Eaton DL, Kwan LY, Stratton K, editors. Public Health Consequences of E-Cigarettes. Washington (DC): National Academies Press (US); 2018 Jan 23. 5, Toxicology of E-Cigarette Constituents. Available from: 

https://www.ncbi.nlm.nih.gov/books/NBK507184/

Quote#1: “A small number of studies have investigated the role of e-cigarette aerosols in metal exposure. Most of these studies have evaluated one or two devices to measure metals in e-cigarette emissions and assess which metals are in higher concentrations compared with other metals, as well as to compare metals found in e-cigarette emissions and tobacco smoke. For example, Saffari and colleagues (2014) used quartz filters to study emission rates of a European tank-style device and found evidence of several metals. The authors detected boron (mean emission rate, ng/h: 964), cadmium (0.480), chromium (28.1), lanthanum (3.21), lead (96.2), nickel (131), potassium (7,765), silver (20.9), titanium (50.2), and zinc (1,142), but did not identify aluminum, copper, iron, or tin. However, the particle-sampling method the authors used in this study could have failed to distinguish metals during the aerosol phase. A study by Goniewicz and colleagues (2014) assessed metal concentrations in aerosols from a pharmaceutical nicotine inhaler and 12 e-cigarettes. Metals, including cadmium (concentrations varied from undetectable to 0.22 µg/150 puffs), lead (0.03 to 0.57 µg/150 puffs), and nickel (0.11 to 0.29 µg/150 puffs), were found in most of the samples tested. Mikheev and colleagues (2016) used quartz filters and inductively coupled plasma mass spectrometry to study metals in aerosols from a tank-style device and cigalike products. The authors measured antimony (0.05 to 0.50 ng/mg), arsenic (0.01 to 0.70 ng/mg), chromium (0.40 to 5.0 ng/mg), copper (0.05 to 5.0 ng/mg), nickel (0.05 to 5.0 ng/mg), tin (0.02 to 0.50 ng/mg), and zinc (1.50 to 50.0 ng/mg) in most samples, but did not measure lead. In another study, Williams and colleagues (2013) detected aluminum, iron, nickel, silver, and tin in particles greater than 1 µm from one brand's 22 cigalike cartomizers; nanoparticles (less than 100 nm) had chromium, nickel, and tin. The authors also used inductively coupled plasma optical emission spectrometry to identify lead (0.017 µg/10 puffs).”

Quote#2: “Few studies have measured the toxic characteristics of metals in e-cigarette aerosols, although in principle, metal toxicity would not necessarily change compared with metal exposure from other sources. In one of the few studies testing this metal e-cigarette toxicity, an in vitro study of copper nanoparticles from e-cigarette aerosols, it was found that copper nanoparticles increased mitochondrial oxidative stress and DNA fragmentation, supporting their critical toxic role (Lerner et al., 2016). Metals have also been involved as one possible reason explaining cellular damage, generation of ROS, and activation of global defense systems observed in vitro experiments (Bharadwaj et al., 2017; Lerner et al., 2015a).”

#Shehata SA, Toraih EA, Ismail EA, Hagras AM, Elmorsy E, Fawzy MS. Vaping, Environmental Toxicants Exposure, and Lung Cancer Risk. Cancers (Basel). 2023 

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10526315/

Quote: “Increased use of E-cigarettes and ECs has raised numerous adverse health concerns involving the risks of heavy metals exposure via Els and vapors [145]. Current studies have confirmed that many heavy metals are present in both EC liquids and vapors at potentially harmful levels, which endangers both user and passive vaping [146]. Several metal levels have been detected in ECs, ELs, and human biological samples collected from vaping users [147]. The most commonly found metals were arsenic (As), copper (Cu), cadmium (Cd), chromium (Cr), lead (Pb), nickel (Ni), iron (Fe), and zinc (Zn) [148]. The source of these metals is commonly from the metal coils incorporated in the clearomizer of the ECs device or from e-liquids [149]. Mikheev et al. found that the previous metal presence in nanoparticle size was less than 2.5 µm [150]. Hence, the ultrafine size range is more dangerous to the lungs than larger ones due to their ready access to the alveolar region and rapid absorption systemically [151]. Heavy metal exposure in ECs is linked to significant health threats, such as neurotoxic and carcinogenic effects [152]. Chronic inhalation of lead nanoparticles is linked with respiratory and central nervous system pathological changes [153]. Co-exposure to several heavy metals in ECs caused oxidative stress as indicated by increases in the generation of ROS and the expression of ferritin light chain mRNA and heme oxygenase-1 mRNA and protein [141]. Heavy metals prompt apoptosis and evoke oxidative stress and DNA damage in lung cells [141].”

#Traboulsi, H.; Cherian, M.; Abou Rjeili, M.; Preteroti, M.; Bourbeau, J.; Smith, B.M.; Eidelman, D.H.; Baglole, C.J. Inhalation Toxicology of Vaping Products and Implications for Pulmonary Health. Int. J. Mol. Sci. 2020

https://www.mdpi.com/1422-0067/21/10/3495

Quote: “E-liquids can contain traces of many inorganic elements and toxic metals such as sodium, bromine, gold, scandium, iron, and cobalt. The concentrations are much less than the respective ones in cigarette smoke, and thus, the risk associated with exposures could be very low. However, long-term studies are required to evaluate if these metals can accumulate in the lung and cause adverse effect after long-periods of exposure [92]. Moreover, in e-cigarettes, heating coils are usually made of nichrome (combination of nickel (Ni) and chromium (Cr)) and stainless steel. Toxic metals from heated coils can leach into vaping aerosols [91] and is the reason why Ni and Cr are present in e-cigarette aerosols but not the e-liquids [93,94]. This suggests that the Cr and Ni emission are higher than smoke from tobacco cigarettes. Analysis of cigarette smoke showed that emission levels were not quantifiable. However, Cr and Ni levels in e-cigarette aerosol were 50 ng in the first 100 puffs [91]. Ni and Cr are toxic for human and classified as a group 1 carcinogen by the International Agency for Research on Cancer (IARC); inhalation of these metals is associated with chronic bronchitis and reduced lung function [95]. In addition to Ni and Cr, copper and zinc are also detected in e-cigarette aerosols (0.2 µg generated from 100 puffs). Cadmium (Cd), a metal present in tobacco, is also found in aerosols but not in e-liquids. Analysis of four different e-cigarettes showed that the concentration of Cd in the e-cigarette aerosol is lower than in tobacco smoke (0.002 µg/15 puffs vs 0.056 µg/15 puffs, respectively) [96]. Cadmium accumulates in the lung of smokers, and although there is an association between Cd exposure and an increased risk of lung cancer, studies are inconclusive due to confounding factors such as the presence of other metals [97].”

#Traboulsi, H.; Cherian, M.; Abou Rjeili, M.; Preteroti, M.; Bourbeau, J.; Smith, B.M.; Eidelman, D.H.; Baglole, C.J. Inhalation Toxicology of Vaping Products and Implications for Pulmonary Health. Int. J. Mol. Sci. 2020

https://www.mdpi.com/1422-0067/21/10/3495

Quote: “Although there is an existing body literature that suggests e-cigarettes could have a role in smoking cessation or reduction (reviewed in Section 3), the long-term health effects of vaping remain largely unknown. Furthermore, e-cigarette use by a previous never smoker may not be without harm, particularly if initiation occurs at a young age, given that young individuals have a longer time to accrue disease, or in individuals with existing pulmonary comorbidities. Available data summarized above indicates that e-cigarette use is associated with adverse cellular events that could lead to pulmonary alterations. Of concern are the increasing number of studies, presented below, showing that chronic e-cigarette use can have adverse clinical effects that are both similar yet different when compared to traditional cigarettes. As e-cigarettes are a relatively new product, there is uncertainity about the overall health effects of vaping. This lack of consensus is due to many factors, including the rapidly evolving e-cigarette technology, diversity of e-liquid composition, and the absence of standardization in e-cigarette products, all of which makes it challenging to compare results across studies. This is unlike traditional cigarettes, where the health consequences are well known and manufactured products are relatively uniform. There is however, a general agreement among many from the public health community, such as the Canadian Cancer Society and Canadian Thoracic Society, that while e-cigarettes could be helpful for smoking cessation in some individuals, they are not without harm [164,165]. From toxicologic analysis, risks are lower than those of traditional tobacco smoke, but the clinical impact is not known for individuals continuing to use e-cigarettes for the long term.”

– The elephant in the room is that we don’t know exactly how bad vaping is, since it has only been around for about ten years. Also, most studies on health effects in humans focused on smokers who switched to vapes. We do know for sure that smoking is orders of magnitudes more harmful. Switching to vaping will reduce your risks for diseases massively. If you smoke, please switch to vaping. But these studies also muddy the water a bit.

#Traboulsi, H.; Cherian, M.; Abou Rjeili, M.; Preteroti, M.; Bourbeau, J.; Smith, B.M.; Eidelman, D.H.; Baglole, C.J. Inhalation Toxicology of Vaping Products and Implications for Pulmonary Health. Int. J. Mol. Sci. 2020, 21, 3495. 

https://doi.org/10.3390/ijms21103495

Quote: “E-cigarette use is still a relatively new phenomenon, having become widely popular in the last decade. Consequently, strong associations—and causality—between e-cigarette use and chronic pulmonary diseases are yet to be established. Nonetheless, there is emerging data to suggest a link between e-cigarettes and chronic lung diseases such as asthma and COPD [197,198].”

#Banks E, Yazidjoglou A, Brown S, Nguyen M, Martin M, Beckwith K, Daluwatta A, Campbell S, Joshy G. Electronic cigarettes and health outcomes: systematic review of global evidence. Report for the Australian Department of Health. National Centre for Epidemiology and Population Health, Canberra: April 2022. 

https://www.nhmrc.gov.au/sites/default/files/documents/attachments/ecigarettes/Electronic_cigarettes_and_health_outcomes_%20systematic_review_of_evidence.pdf

Quote: “Reliable evidence relating to common clinical health outcomes such as cancer, cardiovascular disease and mental health problems requires high-quality large-scale short and long-term studies and statistical comparisons between those exposed and not exposed to e-cigarettes. It also requires studies where the effects of e-cigarettes can be reliably distinguished from those of tobacco smoking and that are independent of competing interests. Studies must also relate directly to the outcomes of interest and be capable of providing evidence relevant to causality. Overall, across 20 outcomes groups, there were 143 studies relating to primary clinical disease outcomes (Appendix 5). Studies were generally small and short-term and did not permit reliable conclusions to be drawn regarding the relationship of e-cigarette use to these outcomes. In this review, we have also included commentary on physiological and other outcome types and other study types for completeness. However, these should not be interpreted as providing reliable evidence on the causal relationship of e-cigarettes to clinical disease outcomes. ”

#Allbright K, Villandre J, Crotty Alexander LE, Zhang M, Benam KH, Evankovich J, Königshoff M, Chandra D. The paradox of the safer cigarette: understanding the pulmonary effects of electronic cigarettes. Eur Respir J. 2024 

https://pubmed.ncbi.nlm.nih.gov/38609098/

Quote: “The basic science data on the pulmonary effects of e-cigarettes is preliminary and evolving rapidly. Independent studies suggest that e-cigarette aerosol is cytotoxic to pulmonary cells, induces acute and chronic inflammation, impairs immune responses against viral and bacterial pathogens, impairs mucociliary clearance, induces oxidative stress, causes DNA damage and increases airway hyperresponsiveness in vitro and in vivo. Adding nicotine to the e-liquid increased mucociliary dysfunction, oxidative stress, emphysema and airway hyperreactivity. In preliminary studies, flavouring compounds have been implicated in lung damage induced by e-cigarettes. Specifically, cinnamon, tobacco and mint/menthol flavourings enhanced cytotoxicity and induce lung inflammation compared with other flavourings or the absence of flavouring. In addition, cinnamon flavourings have been found to impair antipathogen immune responses, reduce mucociliary clearance and enhance oxidative stress. Similarly, tobacco flavouring has been found to induce oxidative stress, airway hyperresponsiveness and DNA damage. Finally, mint/menthol flavouring has been associated with increased DNA damage. The available data suggest that puff-for-puff, e-cigarette aerosol is less harmful than combustion cigarette smoke in terms of cytotoxicity and lung inflammation. This reduced harm of e-cigarettes may not fully translate into reduced morbidity and mortality in the community due to the gateway effect, re-entry effect, dual-use and known and unknown toxicities of e-cigarettes. In aggregate, we label these phenomena the paradox of the safer cigarette.”

– If you smoke, switching to vaping will reduce your risks for diseases massively. If you smoke, please switch to vaping. But these studies also muddy the water a bit.

Before we cite the publications that suggest vaping is less harmful than smoking, it is important to note once again that vaping on its own is not harmless. And there are still publications that do not take the switch from smoking to vaping granted as safer. 

#Banks E, Yazidjoglou A, Brown S, Nguyen M, Martin M, Beckwith K, Daluwatta A, Campbell S, Joshy G. Electronic cigarettes and health outcomes: systematic review of global evidence. Report for the Australian Department of Health. National Centre for Epidemiology and Population Health, Canberra: April 2022. 

https://www.nhmrc.gov.au/sites/default/files/documents/attachments/ecigarettes/Electronic_cigarettes_and_health_outcomes_%20systematic_review_of_evidence.pdf

Quote: “The current worldwide evidence indicates that use of electronic cigarettes (e-cigarettes) increases the risk of certain adverse health outcomes. There is conclusive evidence that nicotine e-cigarettes and their constituents can cause poisoning, injuries and burns, and immediate toxicity through inhalation, including seizures, and moderate evidence they cause less serious adverse events, such as throat irritation and nausea. There is conclusive evidence that e-cigarettes cause acute lung injury (EVALI), largely linked to e-liquids containing THC and vitamin E acetate, although around 1 in 8 cases in the largest study to date were from reported use of nicotine-only products. Their environmental impacts include waste, fires and indoor airborne particulate matter, which, in turn, are likely to have adverse health impacts, the extent of which cannot be determined. Nicotine is highly addictive and there is clear evidence of widespread use and addiction, particularly among youth, in many countries. There is insufficient evidence regarding ceasing smoking and switching completely to e-cigarettes with respect to exacerbations of respiratory disease or changes in respiratory symptoms, lung function and other respiratory measures. There is limited or insufficient evidence that use of ENDS in non-smokers leads to acute reductions in lung function and other respiratory measures. Among smokers, there is moderate evidence that use of ENDS increases heart rate, systolic blood pressure, diastolic blood pressure and arterial stiffness acutely after use.”

#Vaping substantially less harmful than smoking, largest review of its kind finds. 2022. King's College London. News Centre. 

https://www.kcl.ac.uk/news/vaping-substantially-less-harmful-than-smoking-largest-review-of-its-kind-finds

Quote: “New research from the Institute of Psychiatry, Psychology & Neuroscience (IoPPN) at King’s College London has found that the use of vaping products rather than smoking leads to a substantial reduction in exposure to toxicants that promote cancer, lung disease and cardiovascular disease.

The independent report, commissioned by the Office for Health Improvement and Disparities in the Department of Health and Social Care, represents the most comprehensive review of the risks of vaping to date. It found that, while vaping is not risk free (particularly for people who have never smoked), it poses a small fraction of the health risks of smoking in the short to medium term.

The report reviewed many aspects of vaping, including who is vaping and what products, the effects on health (both absolute and compared with smoking) and public perceptions of harm. The authors examined studies of biomarkers of exposure (measures of potentially harmful substance levels in the body) as well as biomarkers of potential harm (measures of biological changes in the body) due to vaping or smoking.

The strongest evidence, and where there was a greater volume of research, came from biomarkers of exposure. An exploration of the available studies found that levels of tobacco specific nitrosamines, volatile organic compounds and other toxicants implicated in the main diseases caused by smoking were found at significantly lower levels in vapers. Among vapers, overall levels of nicotine were lower or similar to smokers.”

#Vaping and quitting smoking. Government of Canada. 2023. 

https://www.canada.ca/en/health-canada/services/smoking-tobacco/vaping/quit-smoking.html

Quote: “Though vaping products are relatively new and research into their long-term effects is ongoing, researchers have already established that switching completely to vaping nicotine is less harmful than continuing to smoke.

The best available evidence indicates that adults who smoke, who then switch completely to vaping:

Immediately reduce their exposure to the harmful chemicals found in cigarette smoke; 

See general health improvements in the short term as a result of no longer smoking cigarettes; 

May be more likely to quit smoking than those who use nicotine replacement therapy (NRT) or counseling to quit; 

Do not currently report serious unwanted effects while using vaping products to quit; and,

May have a higher startup cost but save money in the long run (cost per equivalent puff).”

#Zamora Goicoechea J, Boughner A, Cirion Lee JJ, Mahajan A, Yeo K, Sproga M, Patel T, Saitta C, Russell C, Coughlan M, Caponnetto P, Polosa R. A Global Health Survey of People Who Vape but Never Smoked: Protocol for the VERITAS (Vaping Effects: Real-World International Surveillance) Study. JMIR Res Protoc. 2024 

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11009848/

Quote: “Under normal operational conditions (without overheating or dry burning coils), ECs present a significant reduction in exposure to harmful constituents compared to CCs [15-17]. No discernible negative health effects solely attributed to EC use (commonly known as “vaping”) have been conclusively established [18-20]. Analytical chemistry and toxicology studies of vaporized chemicals suggest no imminent health risks, although concerns persist about potential long-term respiratory implications [21-23]. Hence, further investigation into the prolonged health impact of persistent vaping is warranted.”

#Action on Smoking and Health Press Release. Four in ten smokers wrongly believe that vaping is as or more harmful as smoking. 2023.  

https://ash.org.uk/media-centre/news/press-releases/four-in-ten-smokers-wrongly-believe-that-vaping-is-as-or-more-harmful-as-smoking

Quote: “Earlier this year the Government announced a national ‘swap to stop’ campaign to offer 1 million smokers a free vaping starter kit together with behavioural support, to help them quit smoking. [2] Vaping combined with behavioural support is nearly twice as effective as medicinal nicotine replacement therapy, [3] so this evidence-based strategy could play a significant role in delivering the government’s smokefree 2030 ambition.

However, the success of ‘swap to stop’ is threatened by growing concerns among smokers that vaping is as or more risky then smoking.

Among the 1.8 million smokers who are yet to try vaping 43% believe e-cigarettes are as harmful or more than smoking up from 27% in 2019. Among the 2.9 million smokers who have tried vaping but stopped, 44% believe vaping is as harmful or more than smoking up from 25% in 2019. The most accurate risk perceptions are among the 2.7 million ex-smokers who vape and 2.9 million ex-smokers who are ex-vapers, 75% and 45% of whom correctly believe that vaping is less harmful than smoking.”

#NHS. Using e-cigarettes to stop smoking. 2022.

https://www.nhs.uk/live-well/quit-smoking/using-e-cigarettes-to-stop-smoking/

Quote: “In the UK, e-cigarettes are tightly regulated for safety and quality.

Vaping is not completely risk-free, but it poses a small fraction of the risk of smoking cigarettes. The long-term risks of vaping are not yet clear.

E-cigarettes do not produce tar or carbon monoxide, two of the most harmful elements in tobacco smoke.

The liquid and vapour contain some potentially harmful chemicals also found in cigarette smoke, but at a much lower level.”

#Michael Joseph Blaha. 5 Vaping Facts You Need to Know. Johns Hopkins Medicine. Retrieved August 2024.

https://www.hopkinsmedicine.org/health/wellness-and-prevention/5-truths-you-need-to-know-about-vaping

Quote: “1: Vaping is less harmful than smoking, but it’s still not safe.

E-cigarettes heat nicotine (extracted from tobacco), flavorings and other chemicals to create an aerosol that you inhale. Regular tobacco cigarettes contain 7,000 chemicals, many of which are toxic. While we don’t know exactly what chemicals are in e-cigarettes, Blaha says “There’s almost no doubt that vaping exposes you to fewer toxic chemicals than smoking traditional cigarettes.”

However, there has been an outbreak of lung injuries and deaths associated with vaping. In February 2020, the Centers for Disease Control and Prevention (CDC) confirmed 2,807 cases of e-cigarette or vaping use-associated lung injury (EVALI) and 68 deaths attributed to that condition.

“These cases appear to predominantly affect people who modify their vaping devices or use black market modified e-liquids. This is especially true for vaping products containing THC,” explains Blaha.”

– What if you never smoked and started to vape? In the short term, a significant portion of vapers develop poor breathing symptoms: coughing, extra mucus production, shortness of breath, wheezing, throat and chest pain. But the truth is we simply don’t know what will happen in the long term. 

#Varella MH, Andrade OA, Shaffer SM, Castro G, Rodriguez P, Barengo NC, Acuna JM. E-cigarette use and respiratory symptoms in residents of the United States: A BRFSS report. PLoS One. 2022 

https://pubmed.ncbi.nlm.nih.gov/36454742/

Quote: “Our data revealed that 2.5% and 4.2% of the sample subjects were every day or some days e-cigarette users, respectively. Overall, respiratory symptoms (cough, phlegm production, or shortness of breath) was reported in approximately 28% of the sample, much higher frequency than those symptoms previously reported [9–11]. Compared to never users, e-cigarette use was associated with up to 50% increased odds of respiratory symptoms; the highest odds were found for those using some day, followed by former users of e-cigarette.”

#Ghosh A, Coakley RD, Ghio AJ, Muhlebach MS, Esther CR Jr, Alexis NE, Tarran R. Chronic E-Cigarette Use Increases Neutrophil Elastase and Matrix Metalloprotease Levels in the Lung. Am J Respir Crit Care Med. 2019 

https://pubmed.ncbi.nlm.nih.gov/31390877/

Quote: “Conclusions: We conclude that vaping induces nicotine-dependent protease release from resident pulmonary immune cells. Thus, chronic vaping disrupts the protease–antiprotease balance by increasing proteolysis in lung, which may place vapers at risk of developing chronic lung disease. These data indicate that vaping may not be safer than tobacco smoking.”

#Godfred O Antwi, Darson L Rhodes, Association between E-cigarette use and chronic obstructive pulmonary disease in non-asthmatic adults in the USA, Journal of Public Health, Volume 44, Issue 1, March 2022. 

https://doi.org/10.1093/pubmed/fdaa229

Quote: “Results: Significant associations between e-cigarette use and COPD among former combustible cigarette smokers and those who reported never using combustible cigarettes were found. Compared with never e-cigarette users, the odds of having COPD were significantly greater for daily e-cigarette users (OR = 1.53; 95% CI: 1.11–2.03), occasional users (OR = 1.43, 95% CI: 1.13–1.80) and former users (OR = 1.46 95% CI: 1.28–1.67).

Conclusions: Findings from this study indicate a potential link between e-cigarette use and COPD. Further research to explore the potential effects of e-cigarette on COPD is recommended.”

#Allbright K, Villandre J, Crotty Alexander LE, Zhang M, Benam KH, Evankovich J, Königshoff M, Chandra D. The paradox of the safer cigarette: understanding the pulmonary effects of electronic cigarettes. Eur Respir J. 2024 

https://pubmed.ncbi.nlm.nih.gov/38609098/

Quote: “Even in the absence of nicotine, e-cigarette aerosols can impact mucociliary clearance. For example, a 5-day exposure to either PG-only aerosol or VG-only aerosol increased mucus concentration of tracheal secretions in sheep [70, 71]. Likewise, exposure to PG-only aerosol decreased ciliary beating and increased mucus concentrations in human bronchial epithelial cells in vitro, probably by disrupting the function of large conductance, Ca2+ and voltage-activated potassium channels [71].”

#Alqahtani MM, Alenezi FK, Almeshari MA, Alanazi AM, Taleb ZB, Kalan MEE, Martinasek MP, McNab RJ, Culbreth R, Alotaibi M, Aljohani H, Goodfellow LT, Ismaeil TT, Algarni SS, Alotaibi TF, Alqahtani MK, Al-Ajel H, Alwadeai KS, Almutairi NS, Ford E. E-cigarette use and respiratory symptoms in adults: A systematic review and meta-analysis. Tob Induc Dis. 2023 https://pubmed.ncbi.nlm.nih.gov/38098748/

Quote: “Overall, our review found that e-cigarette users reported presence of respiratory symptoms. In our comprehensive analysis, those who exclusively used e-cigarettes displayed significant occurrences of different respiratory issues such as coughing, phlegm production, breathing difficulties, wheezing, dry mouth, chest discomfort, and irritation in the throat. Moreover, our analysis encompassed several studies that examined respiratory symptoms in individuals who used both e-cigarettes and cigarettes; the results indicated significant instances of cough, phlegm, shortness of breath, wheezing, dry mouth, chest pain, and throat irritation. The meta-analysis revealed the following incidences of respiratory symptoms among transitioning e-cigarette users: cough, phlegm, shortness of breath, any respiratory symptoms, wheezing, oropharyngeal symptoms, dry mouth symptoms, nasopharyngeal symptoms, chest pain symptoms, and throat irritation symptoms. These data suggest a significant impact of e-cigarette usage on respiratory health, underlining the need for further investigation.”

#Gotts J E, Jordt S, McConnell R, Tarran R. What are the respiratory effects of e-cigarettes? BMJ 2019.

https://www.bmj.com/content/366/bmj.l5275

Fig 1 . Reported effects of vaping on the human pulmonary system

– The first larger scale study on vaping with non-smokers only started in 2024 – it will take years before we can say anything with confidence.

#Zamora Goicoechea J, Boughner A, Cirion Lee JJ, Mahajan A, Yeo K, Sproga M, Patel T, Saitta C, Russell C, Coughlan M, Caponnetto P, Polosa R. A Global Health Survey of People Who Vape but Never Smoked: Protocol for the VERITAS (Vaping Effects: Real-World International Surveillance) Study. JMIR Res Protoc. 2024 

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11009848/

Quote:”Research into the respiratory health effects of regular vaping is limited [11,36,37]. Previous research investigating the health status of individuals who used to smoke faces challenges due to unknown health effects caused by prior smoking. Consequently, studies involving individuals who solely vape with no established smoking history are essential to identify potential harms attributed to vaping. A small prospective study of daily EC users who never smoked CCs demonstrated no significant alterations in lung function, inflammation, or structural abnormalities observed in lung scans [30]. Moreover, consistent respiratory symptoms were not reported in this study [30]. However, large longitudinal studies focusing on well-characterized EC users, with and without a history of CC smoking, are necessary to establish the long-term effects of regular vaping on respiratory health.

This proposed study aims to be the first investigation exploring the association between respiratory health effects and the use of ECs in a large group of individuals who exclusively vape, with no established CC smoking history. Additionally, the research will delve into potential confounding factors that could influence any association identified between vaping and respiratory symptoms.”

– Your lungs are made from very sensitive tissue and were never meant to deal with trillions of aerosols, chemicals and metals. What goes into your lungs generally stays in them forever, which is why smokers’ lungs are dark and dirty.  

#Why does smoking make your lungs go black? 2022

https://www.ucl.ac.uk/culture-online/case-studies/2022/sep/why-does-smoking-make-your-lungs-go-black#:~:text=One%20of%20these%20toxins%20is,immune%20cells%20to%20fight%20them.

Quote: “One single puff of cigarette smoke has thousands of chemicals. When someone breathes this in all these chemical go straight into their lungs. Some of these chemicals are toxins which means they are harmful to the body. One of these toxins is called sticky tar. This sticky tar is black in colour and after years of smoking it builds up inside the lungs and causes them to become black too.  Also, the lungs recognise the toxins and send immune cells to fight them. This fighting between our cells and the toxins causes something called inflammation which means swelling. If the person keeps smoking for more years the inflammation will become scar tissue which is dark and stiff compared to healthy lungs. “

– It seems that vaping activates the immune system, which tries to clean up the aerosols. This causes inflammation and fluid seeps into the lungs, while the cells guarding their entry produce extra mucus you have to cough out. Some of them may even die. 

#Allbright K, Villandre J, Crotty Alexander LE, Zhang M, Benam KH, Evankovich J, Königshoff M, Chandra D. The paradox of the safer cigarette: understanding the pulmonary effects of electronic cigarettes. Eur Respir J. 2024 

https://pubmed.ncbi.nlm.nih.gov/38609098/

Quote: “In summary, the majority of available data suggest that e-cigarette aerosol can induce acute and chronic inflammation in the lungs in vivo and in vitro, although less so than combustion cigarette smoke. Addition of cinnamon, tobacco, mint and mango flavouring in e-liquids may exacerbate inflammatory responses. Lung inflammation is central in the pathogenesis of most chronic lung diseases, including COPD, asthma, interstitial lung diseases and lung cancer. The exacerbation of lung inflammatory processes with e-cigarette

use therefore has the potential to drive and exacerbate associated clinical disease including COPD, asthma, interstitial lung disease and neoplastic diseases. More research is needed in these areas, but studies thus far suggest that e-cigarette use might worsen asthma pathogenesis by increasing inflammatory cell recruitment to the lungs and increase goblet cell hyperplasia [49].

[...]

In summary, consistent in vitro and in vivo data suggest that e-cigarette aerosol impedes mucociliary function, and the nicotine in e-liquid may potentiate these effects. There is evidence to suggest that e-cigarettes and combustion tobacco products cause similar levels of mucociliary dysfunction. Impaired antipathogen immune responses (summarised earlier) and reduced mucociliary function can increase susceptibility to lung infections. These effects may be especially relevant to patients with bronchiectasis, chronic bronchitis and COPD, and to immunocompromised individuals. ”

#Stephen R Broderick, M.D.. What Does Vaping Do to Your Lungs? John Hopkins Medicine. Retrieved August 2024. 

https://www.hopkinsmedicine.org/health/wellness-and-prevention/what-does-vaping-do-to-your-lungs#:~:text=Vaping%2DRelated%20Lipoid%20Pneumonia,inflammatory%20response%20in%20the%20lungs.

Quote: “Unlike the classic pneumonia caused by infection, lipoid pneumonia develops when fatty acids (the building blocks of fat) enter the lungs. Vaping-related lipoid pneumonia is the result of inhaling oily substances found in e-liquid, which sparks an inflammatory response in the lungs. Symptoms of lipoid pneumonia include:

Chronic cough

Shortness of breath

Coughing up blood or blood-tinged mucus

“There’s isn’t a good treatment for lipoid pneumonia, other than supportive care, while the lungs heal on their own,” says Broderick. “The single-most important thing you can do is identify what is causing it — in this case vaping — and eliminate it.””

#Sinha I, Goel R, Bitzer ZT, Trushin N, Liao J, Sinha R. Evaluating electronic cigarette cytotoxicity and inflammatory responses in vitro. Tob Induc Dis. 2022 

https://pmc.ncbi.nlm.nih.gov/articles/PMC9081552/

Quote: "Our data indicate that PG:VG at 60:40 was not toxic to BEAS-2B while 70:30 ratio was growth inhibitory (Figure 1 A). Similar findings were reported elsewhere25. Even though we did not find any effect of PG:VG on H460 cells, others have reported growth inhibition on various lung cancer cell lines25,26,31. We believe that for investigating impact of e-cigarettes in lungs, it is better to experiment on near normal bronchial epithelial cells and so we performed other assays using BEAS-2B cells. Menthol flavor with added nicotine was more toxic compared to nicotine alone when added directly to human bronchial epithelial cells (Figure 1 B). This finding is in accordance with a previous study32. Aerosolized Smoothol in presence of nicotine showed significant growth inhibition of BEAS-2B cells (Figure 1 C). However, the aerosols from ‘rainbow candy’ and vanilla flavors showed moderate growth inhibition (Figure 1 D)."

– Vaping also may cause stress all over your body: it may increase your heart rate and blood pressure, lower blood oxygen or stiffen and clog up your blood vessels. It may create oxidative stress, which has all sorts of bad effects on your organs and may potentially cause many different diseases over time. Does this increase your risk of strokes, heart diseases, lung diseases or cause cancer? Again, we don’t know. Maybe it causes damage, but something else will kill you before vaping does. Maybe it will make you sick. But all we have right now is: Maybe. 

#Allbright K, Villandre J, Crotty Alexander LE, Zhang M, Benam KH, Evankovich J, Königshoff M, Chandra D. The paradox of the safer cigarette: understanding the pulmonary effects of electronic cigarettes. Eur Respir J. 2024 

https://pubmed.ncbi.nlm.nih.gov/38609098/

Quote: “In summary, most in vitro and in vivo studies suggest that e-cigarette use induces oxidative stress in the lung, causes DNA damage, and probably increases the risk of lung cancer. Nicotine seems to potentiate these changes, as may certain flavourings such as tobacco and menthol. Unfortunately, given the long latency of lung cancer with most inhalational exposures, such as traditional cigarette smoke, it is likely to be many years before epidemiological studies can assess lung cancer risk reliably in e-cigarette users.”

#McClelland ML, Sesoko CS, MacDonald DA, Davis LM, McClelland SC. The Immediate Physiological Effects of E-Cigarette Use and Exposure to Secondhand E-Cigarette Vapor. Respir Care. 2021 

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10027181/

Quote: “The immediate physiological effects of vaping with mint-flavored e-cigarettes with 5% nicotine and exposure to the vapor have significant effects on several health variables. The notion that vaping or being exposed to vapor is safer than cigarette smoking may not necessarily be accurate. Our results indicate that vaping with mint-flavored e-cigarettes with 5% nicotine increases heart rate, breathing frequency, and oral temperature and decreases SpO2 after 20 min of vape use. These short-term effects can have significant long-term health effects, especially if sustained. These findings have important implications for health care professionals who should be assessing for vape use in their patients and providing education on the negative health effects of use both in the short and long term.”

#Marques, P., Piqueras, L. & Sanz, MJ. An updated overview of e-cigarette impact on human health. Respir Res 22, 151 (2021). 

https://doi.org/10.1186/s12931-021-01737-5
Quote: “In this line, a study compared the acute impact of CS vs. e-cigarette vaping with equivalent nicotine content in healthy smokers and non-smokers. Both increased markers of oxidative stress and decreased NO bioavailability, flow-mediated dilation, and vitamin E levels showing no significant differences between tobacco and e-cigarette exposure (reviewed in [20]). Inasmuch, short-term e-cigarette use in healthy smokers resulted in marked impairment of endothelial function and an increase in arterial stiffness (reviewed in [20]). Similar effects on endothelial dysfunction and arterial stiffness were found in animals when they were exposed to e-cigarette vapor either for several days or chronically (reviewed in [20]). In contrast, other studies found acute microvascular endothelial dysfunction, increased oxidative stress and arterial stiffness in smokers after exposure to e-cigarettes with nicotine, but not after e-cigarettes without nicotine (reviewed in [20]). In women smokers, a study found a significant difference in stiffness after smoking just one tobacco cigarette, but not after use of e-cigarettes (reviewed in [20]).”

#Antoniewicz L, Brynedal A, Hedman L, Lundbäck M, Bosson JA. Acute Effects of Electronic Cigarette Inhalation on the Vasculature and the Conducting Airways. Cardiovasc Toxicol. 2019
https://pubmed.ncbi.nlm.nih.gov/30963443/
Quote: "The use of electronic cigarettes has increased exponentially since its introduction onto the global market in 2006. However, short- and long-term health effects remain largely unknown due to the novelty of this product. The present study examines the acute effects of e-cigarette aerosol inhalation, with and without nicotine, on vascular and pulmonary function in healthy volunteers. Seventeen healthy subjects inhaled electronic cigarette aerosol with and without nicotine on two separate occasions in a double-blinded crossover fashion. Blood pressure, heart rate, and arterial stiffness measured by pulse wave velocity and pulse wave analysis were assessed at baseline, and then at 0 h, 2 h, and 4 h following exposure. Dynamic spirometry and impulse oscillometry were measured following vascular assessments at these time points, as well as at 6 h following exposure. e-Cigarette aerosol with nicotine caused a significant increase in heart rate and arterial stiffness. Furthermore, e-cigarette aerosol-containing nicotine caused a sudden increase in flow resistance as measured by impulse oscillometry, indicating obstruction of the conducting airways. Both aerosols caused an increase in blood pressure. The present study indicates that inhaled e-cigarette aerosol with nicotine has an acute impact on vascular and pulmonary function. Thus, chronic usage may lead to long-term adverse health effects. Further investigation is warranted."

– What is new about vaping is the sheer amount of nicotine it delivers into your system. For most people it is kind of hard to smoke 20+ cigarettes a day because smoking is pretty harsh. As vaping is less aggressive and doesn’t smell bad, you can do it inside and constantly, for hours. It is easy to go through an entire vape a day. Vapes are now a far more effective nicotine delivery system than cigarettes. They shower your brain in extremely high nicotine doses, which makes them extremely addictive.

The amount of nicotine in vapes varies across products and it is possible to find anything from nicotine-less to 90 mg/ml. In some rare cases it can be even more. Not all vapes have more nicotine than cigarettes or better at delivering nicotine. Amount of absorbed nicotine also depends on the user. One point that is quite evident is that the later generations of e-cigarettes are better at delivering nicotine compared to the first generations. 

Prochaska JJ, Vogel EA, Benowitz N. Nicotine delivery and cigarette equivalents from vaping a JUULpod. Tob Control. 2022 

https://pubmed.ncbi.nlm.nih.gov/33762429/

Quote: “With patented nicotine salt technology, JUUL dominates the e-cigarette market. We reviewed studies of JUUL's nicotine pharmacokinetic profile and studies quantifying nicotine in a JUULpod, emitted in the aerosol and absorbed by users. Examined in eight studies, JUUL's peak nicotine levels were half to three-quarters that of a combustible cigarette in industry-conducted studies with JUUL-naïve users, while comparable to or greater than combustible cigarettes in independent studies of experienced e-cigarette users. JUUL Labs reports each 5% (nicotine-by-weight) cartridge contains approximately 40 mg nicotine per pod and is 'approximately equivalent to about 1 pack of cigarettes.' In five independent studies, nicotine in the liquid in a JUULpod ranged from 39.3 to 48.3 mg. Seven studies measured nicotine delivery via vaping-machine generated aerosols, varying in puffing regimes and equipment. One study estimated 68% transfer efficiency to the aerosol, measuring 28.8 mg nicotine per JUULpod. The other studies reported nicotine values ranging from 72 to 164 µg/puff. At 200 puffs, this is 14.4-32.8 mg of nicotine per pod with equivalence to 13-30 cigarettes. A study measuring nicotine levels in JUUL users during a 5-day controlled switch found equivalence to 18 cigarettes. One JUULpod appears capable of delivering the nicotine equivalent to smoking about a pack of cigarettes, with variability. In JUUL-naïve smokers, JUUL's nicotine boost was lower than that of combustible cigarettes; while in experienced users, JUUL was comparable. Minimising harshness and adaptive to user experience, JUUL's design facilitates initiation to a high nicotine, and ultimately, highly addictive vaping product.”

#NHS. Vaping myths and the facts. Retrieved August 2024.

https://www.nhs.uk/better-health/quit-smoking/vaping-to-quit-smoking/vaping-myths-and-the-facts/

Quote: “A UK standard disposable vape delivers a similar amount of nicotine as 20 cigarettes.

A UK-regulated disposable vape with the highest legal nicotine level (20mg/ml) contains 2ml of liquid and 40mg of nicotine. This delivers, on average, about 20mg of nicotine to the user. A pack of 20 cigarettes contains 200 to 300mg of nicotine. This delivers, on average, 20 to 30mg of nicotine to the smoker.”

#Sharp rise in vapers using high-strength nicotine in England. UCL News. 2024.
https://www.ucl.ac.uk/news/2024/jun/sharp-rise-vapers-using-high-strength-nicotine-england
Quote: “The study, published in the journal Addiction and funded by Cancer Research UK, found that a third of vapers (32.5%) used high-strength nicotine in January 2024 compared to just 3.8% on average between July 2016 and June 2021.

The biggest increases were among 18- to 24-year-old vapers (from 3.9% to 53.1%) and vapers who mainly used disposables (2.6% to 49.0%), but large rises were also seen in older age groups and among current smokers and recent ex-smokers.”

#St Helen G, Havel C, Dempsey DA, Jacob P 3rd, Benowitz NL. Nicotine delivery, retention and pharmacokinetics from various electronic cigarettes. Addiction. 2016
https://pmc.ncbi.nlm.nih.gov/articles/PMC4749433
Quote: "E-cigarettes can deliver levels of nicotine that are comparable to or higher than typical tobacco cigarettes, with similar systemic retention. Although the average maximum plasma nicotine concentration in experienced e-cigarettes users appears to be generally lower than what has been reported from tobacco cigarette use, the shape of the pharmacokinetic curve is similar, suggesting addictive potential."

#NIH, National Cancer Institute. Vaping Pods Produce High Nicotine Levels in Young Users. 2018.
https://www.cancer.gov/news-events/cancer-currents-blog/2018/youth-vaping-high-nicotine-levels
Quote: "Pod-type e-cigarettes have skyrocketed in popularity over the last several years. Just one brand—Juul—now makes up about 70% of the e-cigarette market in the United States, according to recent consumer data, said Dr. Grana.

Pod systems differ substantially from earlier generations of e-cigarettes, Dr. Goniewicz explained. Earlier products used electricity to heat a cartridge of liquid, which usually contained nicotine in a so-called free-base form. This form of nicotine can cause a harsh sensation when inhaled, which may make it unappealing to young users, he added.

In contrast, pods work by vaporizing nicotine salts—a compact substance that allows the pods to be made small enough to fit in the palm of a hand. Nicotine salts are known to quickly deliver a high concentration of nicotine to the body without an unpleasant, harsh sensation. Dr. Goniewicz and his colleagues wanted to get an idea of how products incorporating these salts might be affecting young users.

They recruited 506 young people aged 12–21 who visited one of three outpatient clinics in Long Island, New York, in 2017 or 2018. All study participants completed an anonymous questionnaire about their use of e-cigarettes and other tobacco products. They also provided a urine sample.

Thirty-eight of the participants reported that they used pods daily or on some days and did not smoke conventional cigarettes. Their exclusive use of pods was confirmed by testing their urine samples for a biomarker of tobacco combustion.

The pod users had evidence of high levels of nicotine in their body. The median concentration of cotinine, a molecule that is formed during the breakdown of nicotine, in the participants’ urine samples was more than 50% higher than the urinary cotinine levels reported in a previous study of youth tobacco smoking."

#Yingst JM, Foulds J, Veldheer S, Hrabovsky S, Trushin N, Eissenberg TT, Williams J, Richie JP, Nichols TT, Wilson SJ, Hobkirk AL. Nicotine absorption during electronic cigarette use among regular users. PLoS One. 2019
https://pmc.ncbi.nlm.nih.gov/articles/PMC6657878
Quote: "This study evaluated the nicotine delivery of e-cigarettes and compared the nicotine delivery of two classes of e-cigarettes, first-generation and advanced devices, to the nicotine delivery of cigarettes. We found that advanced e-cigarette devices were associated with a greater maximum concentration of nicotine and a greater nicotine boost compared with first-generation devices. These results support prior research showing that first-generation devices deliver less nicotine than advanced devices [13, 22]. Even among the current sample of experienced users, vaping with their personal devices, the nicotine delivery of advanced devices exceeds that of first-generation devices. This may help to explain users’ preferences for second-generation advanced devices over first-generation devices [5, 22, 29]. In addition, while many studies of nicotine absorption measure baseline blood nicotine and then again immediately after a period of vaping (e.g. 5 minutes)[10, 18, 19], the present study was able to assess nicotine absorption during vaping and more accurately assess the Tmax by taking 5 blood samples while the participants were actively vaping (1, 2, 4, 6, and 8 minutes after starting vaping, as well as immediately after they finished vaping, at minutes 10, 12 and 15. We found that the average Tmax for e-cigarette users overall was at 11.5 minutes, with no differences between the users of first-generation and advanced users."

#Farsalinos, K., Spyrou, A., Tsimopoulou, K. et al. Nicotine absorption from electronic cigarette use: comparison between first and new-generation devices. Sci Rep 4, 4133 (2014).
https://doi.org/10.1038/srep04133
Quote: "A wide range of electronic cigarette (EC) devices, from small cigarette-like (first-generation) to new-generation high-capacity batteries with electronic circuits that provide high energy to a refillable atomizer, are available for smokers to substitute smoking. Nicotine delivery to the bloodstream is important in determining the addictiveness of ECs, but also their efficacy as smoking substitutes. In this study, plasma nicotine levels were measured in experienced users using a first- vs. new-generation EC device for 1 hour with an 18 mg/ml nicotine-containing liquid. Plasma nicotine levels were higher by 35–72% when using the new- compared to the first-generation device. Compared to smoking one tobacco cigarette, the EC devices and liquid used in this study delivered one-third to one-fourth the amount of nicotine after 5 minutes of use. New-generation EC devices were more efficient in nicotine delivery, but still delivered nicotine much slower compared to tobacco cigarettes. The use of 18 mg/ml nicotine-concentration liquid probably compromises ECs' effectiveness as smoking substitutes; this study supports the need for higher levels of nicotine-containing liquids (approximately 50 mg/ml) in order to deliver nicotine more effectively and approach the nicotine-delivery profile of tobacco cigarettes."

#Cho YJ, Mehta T, Hinton A, Sloan R, Nshimiyimana J, Tackett AP, Roberts ME, Brinkman MC, Wagener TL. E-Cigarette Nicotine Delivery Among Young Adults by Nicotine Form, Concentration, and Flavor: A Crossover Randomized Clinical Trial. JAMA Netw Open. 2024
https://pubmed.ncbi.nlm.nih.gov/39120901/
Quote: "Conclusions and Relevance  In this crossover randomized clinical trial among young adult e-cigarette users, salt-based (vs freebase) nicotine e-liquids increased nicotine intake and yielded more positive subjective effects ratings and intense puffing behaviors, suggesting higher abuse potential. Restricting the level of acidic additives and menthol flavoring may reduce the addictiveness of e-cigarettes."

#Voos N, Goniewicz ML, Eissenberg T. What is the nicotine delivery profile of electronic cigarettes? Expert Opin Drug Deliv. 2019
https://pmc.ncbi.nlm.nih.gov/articles/PMC6814574
Quote: "Although some e-cigarette liquids do not contain nicotine, the majority of users use an e-cigarette with a liquid that does (in 2015, 99.0% of e-cigarette products sold contained nicotine) [28,29]. One systematic review examined the chemicals in e-cigarette cartridges and refill solutions in studies published between 2007 and 2013 [30]. Of the studies examined, six looked at the nicotine content of cartridges (used in first generation devices). These studies found the nicotine content to be between 0 and 21.8 mg/cartridge. Six studies examined the nicotine content in refill solutions and found nicotine content to vary between 0 and 87.2 mg/ml [30]."

– For teens this may be very bad. During your teenage years your brain is developing and your nicotine receptors are especially active. They are directly linked with your reward system and thus, how you feel about yourself and your life. Nicotine may change brain development by overstimulating the nicotine receptors. 

#Government of Canada. Risks of vaping. Retrieved October 2024.
https://www.canada.ca/en/health-canada/services/smoking-tobacco/vaping/risks.html
Quote: "Effects of nicotine on kids and teens

While vaping products can help people quit smoking and switching completely to vaping is less harmful than continuing to smoke, it is not harmless and not intended for young people.

Kids and teens are especially susceptible to the harmful effects of nicotine because brain development continues throughout adolescence and into early adulthood. Footnote6

Evidence suggests the developing brain may be more sensitive to the effects of nicotine compared to adults.

Youth may also become dependent on nicotine with lower levels of exposure than adults. Footnote7 Once a young person shows symptoms of dependence and addiction to nicotine, it can be hard to stop vaping."

#Leslie FM. Unique, long-term effects of nicotine on adolescent brain. Pharmacol Biochem Behav. 2020 

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7484459/

Quote: “Mechanistic analyses have shown that adolescent nicotine induces profound and long-lasting neuronal and molecular alterations in regions that are critical for emotional regulation (Slawecki et al., 2005; Holliday et al., 2016; Jobson et al., 2019). In particular, the behavioral alterations are accompanied by increased firing frequency and bursting of neurons in the VTA and prefrontal cortex (Jobson et al., 2019). A selective downregulation of dopamine D1 receptor expression in the prefrontal cortex has also been observed, which may have may have occurred in response to elevated sub-cortical dopaminergic firing and bursting. Clinical studies have previously shown that striatal levels of the D1 receptor are negatively associated with major depression, particularly in those with anger attacks (Dougherty et al., 2006; Cannon et al., 2009). Although the Jobson study did not suggest possible therapeutic approaches to treatment of adolescent nicotine-induced mood disorders, an earlier study has shown that both nicotine and the antidepressants, fluoxetine and buproprion, could reduce the associated negative emotional states (Iñiguez et al., 2009).”

#Elatfy A, Vrahimis S, Conti A, Baldacchino A. Chronic tobacco smoking and neurocognitive impairments in adolescents and young adults: a systematic review and meta-analysis. Front Psychiatry. 2024 

https://pubmed.ncbi.nlm.nih.gov/38716120/

Quote: “Chronic exposure to nicotine during adolescence has also been shown to be associated with an increase in the probability of an individual developing major psychiatric disorders and neurocognitive impairments in later life. Most commonly, adolescent, and young adult chronic tobacco smokers experience a level of progressive attentional deficit (29). Specific neurocognitive disturbances seen in studies include changes to working memory and attention, with a notable reduction in the activation of the prefrontal cortex (PFC) (30, 31). There are also specific psychiatric conditions that are associated with chronic nicotine exposure in adolescence, including major depressive disorder, schizophrenia, and addiction to other substances (32–38).”

#Keeley RJ, Prillaman ME, Scarlata M, Vrana A, Tsai PJ, Gomez JL, Bonaventura J, Lu H, Michaelides M, Stein EA. Adolescent nicotine administration increases nicotinic acetylcholine receptor binding and functional connectivity in specific cortico-striatal-thalamic circuits. Brain Commun. 2022 

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9683397/
Quote: “Nicotine exposure is associated with regional changes in brain nicotinic acetylcholine receptors subtype expression patterns as a function of dose and age at the time of exposure. Moreover, nicotine dependence is associated with changes in brain circuit functional connectivity, but the relationship between such connectivity and concomitant regional distribution changes in nicotinic acetylcholine receptor subtypes following nicotine exposure is not understood. Although smoking typically begins in adolescence, developmental changes in brain circuits and nicotinic acetylcholine receptors following chronic nicotine exposure remain minimally investigated. Here, we combined in vitro nicotinic acetylcholine receptor autoradiography with resting state functional magnetic resonance imaging to measure changes in [3H]nicotine binding and α4ß2 subtype nicotinic acetylcholine receptor binding and circuit connectivity across the brain in adolescent (postnatal Day 33) and adult (postnatal Day 68) rats exposed to 6 weeks of nicotine administration (0, 1.2 and 4.8 mg/kg/day). Chronic nicotine exposure increased nicotinic acetylcholine receptor levels and induced discrete, developmental stage changes in regional nicotinic acetylcholine receptor subtype distribution. These effects were most pronounced in striatal, thalamic and cortical regions when nicotine was administered during adolescence but not in adults. Using these regional receptor changes as seeds, resting state functional magnetic resonance imaging identified dysregulations in cortico-striatal-thalamic-cortical circuits that were also dysregulated following adolescent nicotine exposure. Thus, nicotine-induced increases in cortical, striatal and thalamic nicotinic acetylcholine receptors during adolescence modifies processing and brain circuits within cortico-striatal-thalamic-cortical loops, which are known to be crucial for multisensory integration, action selection and motor output, and may alter the developmental trajectory of the adolescent brain. This unique multimodal study significantly advances our understanding of nicotine dependence and its effects on the adolescent brain.”

Below are a few review and summary papers on the interaction of nicotine with the reward mechanisms.

#Xiao, C., Zhou, Cy., Jiang, Jh. et al. Neural circuits and nicotinic acetylcholine receptors mediate the cholinergic regulation of midbrain dopaminergic neurons and nicotine dependence. Acta Pharmacol Sin 41, 1–9 (2020). 

https://www.nature.com/articles/s41401-019-0299-4

Quote: “Cigarette smoking causes the most preventable diseases worldwide [1]. Nicotine is a bioactive compound in cigarettes that exerts rewarding effects by activating nicotinic acetylcholine receptors (nAChRs) in the central nervous system. Repetitive nicotine intake modifies plasticity in the central nervous system, leading to nicotine dependence [2]. Among the brain regions responsive to nicotine, the midbrain contains dopaminergic (DA) neurons, which have been implicated in a wide range of physiological functions, including reward processing, reinforcement learning, aversion avoidance, and motivation [3, 4]. Therefore, the midbrain is unique in that it is the target of nicotine for the development and maintenance of nicotine dependence.”

#Wills et al. Neurobiological Mechanisms of Nicotine Reward and Aversion. 2022. 

https://pharmrev.aspetjournals.org/content/74/1/271

Quote: “Neuronal nicotinic acetylcholine receptors (nAChRs) regulate the rewarding actions of nicotine contained in tobacco that establish and maintain the smoking habit. nAChRs also regulate the aversive properties of nicotine, sensitivity to which decreases tobacco use and protects against tobacco use disorder. These opposing behavioral actions of nicotine reflect nAChR expression in brain reward and aversion circuits. nAChRs containing α4 and β2 subunits are responsible for the high-affinity nicotine binding sites in the brain and are densely expressed by reward-relevant neurons, most notably dopaminergic, GABAergic, and glutamatergic neurons in the ventral tegmental area. High-affinity nAChRs can incorporate additional subunits, including β3, α6, or α5 subunits, with the resulting nAChR subtypes playing discrete and dissociable roles in the stimulatory actions of nicotine on brain dopamine transmission. nAChRs in brain dopamine circuits also participate in aversive reactions to nicotine and the negative affective state experienced during nicotine withdrawal. nAChRs containing α3 and β4 subunits are responsible for the low-affinity nicotine binding sites in the brain and are enriched in brain sites involved in aversion, including the medial habenula, interpeduncular nucleus, and nucleus of the solitary tract, brain sites in which α5 nAChR subunits are also expressed. These aversion-related brain sites regulate nicotine avoidance behaviors, and genetic variation that modifies the function of nAChRs in these sites increases vulnerability to tobacco dependence and smoking-related diseases. Here, we review the molecular, cellular, and circuit-level mechanisms through which nicotine elicits reward and aversion and the adaptations in these processes that drive the development of nicotine dependence.”

#Mahajan SD, Homish GG, Quisenberry A. Multifactorial Etiology of Adolescent Nicotine Addiction: A Review of the Neurobiology of Nicotine Addiction and Its Implications for Smoking Cessation Pharmacotherapy. Front Public Health. 2021 https://www.frontiersin.org/journals/public-health/articles/10.3389/fpubh.2021.664748/full

Quote: “Nicotine is the primary pharmacologic component of tobacco, and its highly addictive nature is responsible for its widespread use and significant withdrawal effects that result in challenges to smoking cessation therapeutics. Nicotine addiction often begins in adolescence and this is at least partially attributed to the fact that adolescent brain is most susceptible to the neuro-inflammatory effects of nicotine. There is increasing evidence for the involvement of microglial cells, which are the brain's primary homeostatic sensor, in drug dependence and its associated behavioral manifestations particularly in the adolescent brain. A hallmark of neuro-inflammation is microglial activation and activation of microglia by nicotine during adolescent development, which may result in long-term addiction to nicotine. This non-systematic review examines multifactorial etiology of adolescent nicotine addiction, neurobiology of nicotine addiction and the potential mechanisms that underlie the effects of nicotine on inflammatory signaling in the microglia, understanding how nicotine affects the adolescent brain. We speculate, that modulating homeostatic balance in microglia, could have promising therapeutic potential in withdrawal, tolerance, and abstinence-related neural adaptations in nicotine addiction, in the adolescent brain. Further, we discuss nicotine addiction in the context of the sensitization-homeostasis model which provides a theoretical framework for addressing the potential role of microglial homeostasis in neural adaptations underlying nicotine abuse.”

#Govind AP, Vezina P, Green WN. Nicotine-induced upregulation of nicotinic receptors: underlying mechanisms and relevance to nicotine addiction. Biochem Pharmacol. 2009 

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2728164/

Quote: “Nicotine, like ACh, is a nicotinic receptor agonist. The binding of nicotine and ACh to nicotinic receptors cause a conformational change that either opens or closes the receptors’ ion channels, thereby changing the receptors’ functional state. Before binding agonist, the receptor is in the resting state and is nonfunctional. With agonist binding, receptors rapidly activate by opening the ion channel through the receptor. Activation is a metastable event. If the receptor remains bound by agonist, activation is quickly followed by a second conformational change into a nonfunctional state termed desensitization in which the channel is closed [74]. Normally, receptors rapidly recover from the desensitized state and enter the resting state when nicotine is removed. Several lines of evidence indicate that chronic exposure to nicotine causes some of the nicotinic receptors in the brain to undergo long-lasting state changes. These conformational changes are distinguished from activation and desensitization by much slower kinetics (on the order of hours to days). ”

– Again, the science is pretty annoying here with loads of caveats. 

Most of what we know comes from animal studies since ethical human trials with addictive substances are difficult to design, control and follow up long term. There are also multiple confounding parameters like sex differences, use of other drugs, environmental and social factors, or existing psychological conditions making the substance use and addiction studies difficult.

The following review paper is one of the recent and extensive summary of the status quo of the current research and we relied on that for this section of the video about neurobiological effects of adolescent nicotine exposure.

Leslie FM. Unique, long-term effects of nicotine on adolescent brain. Pharmacol Biochem Behav. 2020 

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7484459/

Quote: ”Adolescence is a time of major plasticity of those brain systems that regulate motivated behavior and cognition (Yuan et al., 2015). It is also the age of peak onset of nicotine use (Miech et al., 2017). Although there has been a decline in teen use of cigarettes in recent years, there has been a huge increase in nicotine vaping (Cullen et al., 2019; Miech et al., 2019). As a result, it is critically important to understand the impact of nicotine on this phase of brain development. Given ethical constraints on conducting experimental drug studies on human teens, this necessitates the use of animal studies.

As outlined in this review, preclinical studies have consistently shown unique effects of nicotine on adolescent brain. There is an increased number and activity of nAChRs in brain regions that are important for reward (Doura et al., 2007; Kota et al., 2007) , and an increase in nicotine-induced DA release in limbic regions of adolescent brain (Azam et al., 2007; Corongiu et al., 2020). There are significant age differences in many of the acute behavioral effects of nicotine. Some behavioral effects, such as nicotine reward, are greater in adolescents than adults (Adriani et al., 2003; Torres et al., 2008; Gellner et al., 2016). In contrast, other behavioral effects, such as aversion, are greater in adults (O’Dell et al., 2006, Shram et al., 2006; Torres et al., 2008).”

– Nicotine in teens has been linked to cognitive deficits, hyperactivity, reduced impulse control, deficits in attention and cognition, and mood disorders. But there is a chicken and egg problem – did nicotine cause this or are people with a tendency for emotional dysregulation just more likely to use it? 

Currently all we have is associations from observational types of studies. To establish causality between all these conditions and vaping, definitely more research is needed. Below we listed some example papers. 

The following paper reviews the effects of nicotine exposure specifically in adolescence. 

Leslie FM. Unique, long-term effects of nicotine on adolescent brain. Pharmacol Biochem Behav. 2020 

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7484459/

Quote: “There is a strong association between teen use of tobacco products and anxiety and depression (Patton et al., 1998; Jamner et al., 2003; McKenzie et al., 2010; Leventhal et al., 2016; Cho et al., 2018). Whereas many studies suggest that tobacco use is preceded by emotional dysregulation, and may be a form of self-medication (Gehricke et al., 2007; Weinstein et al., 2008), there is substantial evidence for a bidirectional association between smoking/vaping and depression (Chaiton et al., 2009; Lechner et al., 2017; Esmaeelzadeh, 2018). Other predictors of teen and young adult smoking include anhedonia, aggression, low hedonic capacity and lower distress tolerance (Roberts et al., 2010; Audrain-McGovern et al., 2012; Trujillo et al., 2016; Stone et al., 2017; Trucco et al., 2018).”

Quote#2: “deBry & Tiffany (2008) proposed a Tobacco-Induced Neurotoxicity of Adolescent Cognitive Development (TINACD) theory which postulates that smoking during early adolescence, a period of major neurodevelopment of brain structures regulating inhibitory control, leads to increased impulsivity and inattention. In particular, the prefrontal cortex, which plays a critical role in integrating emotional and motivational states to regulate top-down attentional processes, is still actively maturing during adolescence and is a target for aberrant nicotine effects. Prefrontal cortical activity, working memory and attentional performance are all reduced in teen smokers during withdrawal (Jacobsen et al., 2005; 2007), although male smokers are significantly more impaired during tests of selective and divided attention than female smokers and nonsmokers. Cognitive performance has also been shown to be influenced negatively by adolescent nicotine exposure in animal studies (Schochet et al., 2005; 2008; Counotte et al., 2011). “

Grant JE, Lust K, Fridberg DJ, King AC, Chamberlain SR. E-cigarette use (vaping) is associated with illicit drug use, mental health problems, and impulsivity in university students. Ann Clin Psychiatry. 2019 

https://pubmed.ncbi.nlm.nih.gov/30699215/

Quote: “In summary, this study found e-cigarette use to be relatively common in university students, and use was associated with several issues such as poorer academic performance, greater likelihood of using other substances, and greater rates of anxiety, ADHD, and PTSD. E-cigarette use was also associated with higher rates of impulsivity on the Barratt Impulsivity Scale. The strongest associations with e-cigarette use, which were significant in conservative regression modelling controlling for potential confounds, were illicit drug use (both lifetime and current on the DAST), alcohol use (Audit), male gender, being an undergraduate, and being single. The results indicate that longitudinal assessment of the relationships between these clinical variables and e-cigarette consumption are warranted. Effects of e-cigarette consumption on brain development and mental health merit further study.”

#Goriounova and Mansvelder. Nicotine Exposure during Adolescence Leads to Short- and Long-Term Changes in Spike Timing-Dependent Plasticity in Rat Prefrontal Cortex. 2012. 

https://www.jneurosci.org/content/32/31/10484

Quote: “Novelty-seeking and risk-taking behavior during adolescence has been linked to late development of brain areas involved in cognitive control, such as the medial prefrontal cortex (mPFC) (Gogtay et al., 2004; Casey et al., 2005). Adolescence also marks a period of increased vulnerability to initiation and subsequent abuse of drugs, including tobacco smoking (Chassin et al., 2000). Indeed, 70% of adolescents report experimenting with smoking cigarettes (Escobedo et al., 1993; Currie et al., 2008). This early exposure of prefrontal brain areas to nicotine can compromise normal development and have long-lasting consequences for cognitive performance. In adolescents, chronic smoking is associated with disturbances in working memory and attention as well as reduced PFC activation (Jacobsen et al., 2005, 2007; Musso et al., 2007). In rats, adolescent nicotine treatment results in a lasting impairment in attention and enhanced impulsive behavior during adulthood, 5 weeks after exposure (Counotte et al., 2009).”

#Gentzke at al. Tobacco Product Use and Associated Factors Among Middle and High School Students — National Youth Tobacco Survey, United States, 2021. Centers for Disease Control and Prevention. 2022. 

https://www.cdc.gov/mmwr/volumes/71/ss/pdfs/ss7105a1-H.pdf

Quote: “Furthermore, although peer use and curiosity were the most commonly cited reasons for initiating e-cigarette use among ever users in 2021, among youths who currently used e-cigarettes, the most commonly cited reasons for use were attributable to feelings of anxiety, stress, or depression and the “high or buzz” associated with nicotine use. This is particularly concerning given the bidirectional association between nicotine use and mental health disorders such as depression and anxiety; studies found that youths with mental health disorders were at increased risk for cigarette smoking, but also that youth nicotine exposure was associated with the development of mental health disorders (3,13).”

#Symmes A, Winters KC, Fahnhorst T, Botzet A, Lee S, August G, Realmuto G. The Association Between Attention-Deficit Hyperactivity Disorder and Nicotine Use Among Adolescents and Young Adults. J Child Adolesc Subst Abuse. 2015

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4306279/

Quote: “Previous research indicates that youth with ADHD are more susceptible to nicotine use compared to those without ADHD and one explanation for this association is the self-medication theory. The present study examines nicotine use in a prospective sample derived from a community sampling procedure rather than a clinical setting. Nicotine use was measured through young adulthood (mean ages: 18, 20 and 22) and three groups were compared based on childhood status: ADHD-only, ADHD-extemalizers and control groups. Results indicated that at all three data points, individuals with childhood ADHD plus an externalizing disorder reported higher nicotine use on all variables compared to the ADHD group absent of an externalizing disorder and the comparison group of non-ADHD youth. The group differences were significant even after controlling for possible confounding variables (age, gender, and current treatment with psychostimulant medication). Study results are discussed in light of the self-medication hypothesis and of the importance of including nicotine prevention programs for adolescents and young adults with ADHD and externalizing problems.”

– There have been studies that suggest nicotine is a gateway drug making it more likely to develop other addictions. But this has been largely rejected. Instead it seems people who are generally more likely to take risks, tend to do more risky things. They are more likely to get addicted to smoking, alcohol or cannabis, hard drugs or gambling. This doesn’t make vaping any less addictive, it just means that it is probably not the cause of other addictions.

Even though gate-away effect does not seem viable given the increase in vaping and decrease in tobacco smoking, there are also studies finding bidirectional effects or confounding effects due to similar risk factors for both. 

#Government of Canada. Risks of vaping. Retrieved October 2024.
https://www.canada.ca/en/health-canada/services/smoking-tobacco/vaping/risks.html
Quote: "There are also concerns about the appeal of vaping products among youth and their potential to promote tobacco use. There is limited evidence that vaping product use increases the risk of ever using combustible tobacco cigarettes (smoking cigarettes) among youth and young adults. Footnote8, Footnote9 However, recent data suggests that, thus far, smoking rates, for both youth and adults, continue to decline and are at an all-time low. The 2021 Canadian Community Health Survey indicated that smoking among Canadians aged 15 years and older was 12 percent. Footnote10"

#Delnevo CD. e-Cigarette and Cigarette Use Among Youth: Gateway or Common Liability? JAMA Netw Open. 2023

https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2802772

Quote: “Third, the most recent data from the 2022 NYTS not only highlighted concerning rates of e-cigarette use (14.1%), it also documented the lowest rate of cigarette smoking (2.0%) ever recorded for high school–aged youths.7 This is notable, considering that in 2009, around the time when e-cigarettes were introduced in the US, the cigarette smoking prevalence was 23.2%. At the population level, e-cigarettes do not appear to be a gateway to cigarette smoking. While cross-sectional surveys, like the NYTS, are limited in exploring trajectories, studies like PATH are well suited to do so. The analysis by Sun and colleague2 clearly points to very few youths reporting continued cigarette smoking regardless of baseline e-cigarette use. Collectively, concerns about a gateway effect and a potential increase in youth cigarette use following the introduction of e-cigarettes to the US market are not supported by the data. Moreover, future research and policy efforts should give more attention to the common liability theory and consider that in the context of a complex tobacco marketplace, increased diversity in the types of products, brands, and flavors fundamentally provides more opportunities for youths to experiment with tobacco and nicotine products.”

#Beard et al. Association of quarterly prevalence of e-cigarette use with ever regular smoking among young adults in England: a time–series analysis between 2007 and 2018.

2022.
https://onlinelibrary.wiley.com/doi/10.1111/add.15838

Quote: “Prevalence of e-cigarette use among the youth population in England does not appear to be associated with substantial increases or decreases in the prevalence of smoking uptake. Small associations cannot be ruled out.”

#Pesola et al. Effects of reduced-risk nicotine-delivery products on smoking prevalence and cigarette sales: an observational study. 2023
https://www.journalslibrary.nihr.ac.uk/phr/RPDN7327/#/abstract

Quote: “We detected some indications that alternative nicotine products are competing with cigarettes rather than promoting smoking and that regulations that allow their sales are associated with a reduction rather than an increase of smoking, but the findings are inconclusive because of insufficient data points and issues with the assumptions of the pre-specified statistical analyses.”

#Owotomo O, Stritzel H, McCabe SE, Boyd CJ, Maslowsky J. Smoking Intention and Progression From E-Cigarette Use to Cigarette Smoking. Pediatrics. 2020 https://publications.aap.org/pediatrics/article/146/6/e2020002881/77089/Smoking-Intention-and-Progression-From-E-Cigarette?autologincheck=redirected

Quote: “E-cigarette use was associated with higher odds of cigarette smoking only among adolescents who had no previous intention to smoke conventional cigarettes, suggesting adolescent e-cigarette users can progress to cigarette smoking even when they have no previous intentions to do so. Pediatricians should continue to screen for and counsel adolescents against e-cigarette use to prevent onset of cigarette smoking.60  Indeed, abstinence from e-cigarette use should be framed as an adolescent smoking prevention strategy.”

#Khouja JN, Suddell SF, Peters SE, et alIs e-cigarette use in non-smoking young adults associated with later smoking? A systematic review and meta-analysis. Tobacco Control 2021;30:8-15.

https://tobaccocontrol.bmj.com/content/30/1/8.citation-tools

Quote: “Data synthesis Of 9199 results, 17 studies were included in the meta-analysis. There was strong evidence for an association between e-cigarette use among non-smokers and later smoking (OR: 4.59, 95% CI: 3.60 to 5.85) when the results were meta-analysed in a random-effects model. However, there was high heterogeneity (I2 =88%).

Conclusions Although the association between e-cigarette use among non-smokers and subsequent smoking appears strong, the available evidence is limited by the reliance on self-report measures of smoking history without biochemical verification. None of the studies included negative controls which would provide stronger evidence for whether the association may be causal. Much of the evidence also failed to consider the nicotine content of e-liquids used by non-smokers, meaning it is difficult to make conclusions about whether nicotine is the mechanism driving this association.”

#Martinelli T, Candel MJJM, de Vries H, et al. Exploring the gateway hypothesis of e-cigarettes and tobacco: a prospective replication study among adolescents in the Netherlands and FlandersTobacco Control 2023;32:170-178.

https://tobaccocontrol.bmj.com/content/32/2/170

Quote: “Findings Consistent with prior findings, baseline e-cigarette use was associated with higher odds of tobacco smoking at 6-month (OR=1.89; 95% CI 1.05 to 3.37) and 12-month (OR=5.63; 95% CI 3.04 to 10.42) follow-ups. More frequent use of e-cigarettes at baseline was associated with more frequent smoking at follow-ups. Baseline tobacco smoking was associated with subsequent e-cigarette use (OR=3.10; 95% CI 1.58 to 6.06 at both follow-ups).

Conclusion Our study replicated the positive relation between e-cigarette use and tobacco smoking in both directions for adolescents. This may mean that the gateway works in two directions, that e-cigarette and tobacco use share common risk factors, or that both mechanisms apply.”

#Chang YP, Seo YS. E-cigarette use and concurrent risk behaviors among adolescents. Nurs Outlook. 2021 

https://pubmed.ncbi.nlm.nih.gov/33121761/

Quote: “Purpose: Although electronic cigarette (e-cigarette) use is on the rise among adolescents, its relationship with risk behaviors is unclear. This study aimed to examine whether e-cigarette use was related to other risk behaviors and whether age and sex play a role in those associations.

Methods: Data from the 2017 Youth Risk Behavior Surveillance System was used. Weighted logistic regression analysis was conducted to examine the relationships among variables of interest.

Fundings: The results showed that e-cigarette users, compared to nonusers, had higher odds of using other types of substances, as well as being involved in other risk behaviors including driving-related behaviors, sexual activity-related behaviors, and violence-related behaviors. Furthermore, some of these relationships are moderated by age and sex.

Discussion: Our findings suggest that e-cigarette use is linked to other risk behaviors among adolescents. Policy makers and educators should address multiple risk behaviors as part of comprehensive tobacco-free policies and youth substance use prevention programs.”

#Demissie Z, Everett Jones S, Clayton HB, King BA. Adolescent Risk Behaviors and Use of Electronic Vapor Products and Cigarettes. Pediatrics. 2017 

https://pubmed.ncbi.nlm.nih.gov/28115539/

Quote: “Results: In 2015, 73.5% of high school students did not smoke cigarettes or use EVPs, 3.2% smoked cigarettes only, 15.8% used EVPs only, and 7.5% were dual users. Frequency of cigarette smoking and EVP use was greater among dual users than cigarette-only smokers and EVP-only users. Cigarette-only smokers, EVP-only users, and dual users were more likely than nonusers to engage in several injury, violence, and substance use behaviors; have ≥4 lifetime sexual partners; be currently sexually active; and drink soda ≥3 times/day. Only dual users were more likely than nonusers not to use a condom at last sexual intercourse.

Conclusions: EVP use, alone and concurrent with cigarette smoking, is associated with health-risk behaviors among high school students.”

#Balogh KN, Mayes LC, Potenza MN. Risk-taking and decision-making in youth: relationships to addiction vulnerability. J Behav Addict. 2013 

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3840427/

Quote: “Impulsivity and sensation-seeking in addictions Impulsivity and sensation-seeking are elevated in those with substance or behavioral addictions as measured by self-report assessments (Grant et al., 2010). Inadequate impulse control and heightened risk-taking may both contribute to addiction vulnerability. As biological developmental changes during adolescence increase sensation-seeking and possibly decrease self-control, youth may engage in behaviors that can become problematic or pathological, especially those who score high on impulsivity and sensation-seeking (Brezing et al., 2010). Prospective studies suggest that excessive impulsivity during adolescence predicts problematic gambling behavior later in life (Dussault et al., 2011; Michalczuk et al., 2011).

Other important constructs, such as compulsivity, may also contribute to difficulties in self-control and relate to risk-taking and decision-making (Leeman & Potenza, 2012). This and other possible risk factors (e.g., stress (Sinha, 2008)) warrant consideration and have been reviewed in detail elsewhere.”

– Where the science is pretty solid, is that most people have a bad time when quitting nicotine. Nicotine is one of the most addictive substances we know and comes with a wide range of really unpleasant physical withdrawal symptoms. 

#Adams TN, Morris J. Smoking. [Updated 2023 May 22]. 

https://www.ncbi.nlm.nih.gov/books/NBK537066/

Quote: “Daily cigarette smokers keep smoking because they are physically addicted to nicotine - a substance that is naturally found in tobacco leaves. Because nicotine is one of the most addictive substances known to man, tobacco smoking is often very difficult to quit, often requiring repeated attempts at quitting involving various cessation methods. Five nicotine-based medications (gum, lozenges, inhaler, nasal spray, patch) and 2 non-nicotine-based medications (varenicline and bupropion SR) have been shown to aid in long-term smoking cessation. Recent evidence includes a potential role for cytisine and naltrexone. For patients willing to quit, a combination of counseling and one or more medications has proven more effective than just counseling or medication alone.[25][26][27]”

#Leslie FM. Unique, long-term effects of nicotine on adolescent brain. Pharmacol Biochem Behav. 2020 

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7484459/

Quote: “Abrupt cessation of tobacco use in dependent smokers results in withdrawal symptoms that include both somatic and affective components. Somatic symptoms include bradycardia, insomnia, and gastrointestinal discomfort, whereas negative affective symptoms include anger, anxiety, craving, depression, difficulty concentrating, impatience, insomnia, and restlessness (Hughes, 2007a). There is limited research on withdrawal from e-cigarettes, but recent analysis of the US Population Assessment of Tobacco and Health Survey and a clinical trial by the same investgators indicated that withdrawal symptoms were mild in never smokers (Hughes & Callas, 2019; Hughes et al., 2020), whereas another study of self-reported dependence symptoms suggested there were similarities to tobacco dependence but with some unique indicators (Soule et al., 2020). Some clinical studies of cessation of tobacco use in teenagers indicate that they may be especially sensitive to withdrawal, exhibiting symptoms of dependence soon after smoking initiation and before the establishment of daily smoking habits (DiFranza et al., 2007; Dierker & Mermelstein, 2010; Zhan et al., 2012). A recent study has reported that teen e-cigarette users are more likely to report dependence signs and be daily users if they use high nicotine content pods, such as Juul (Boykan et al., 2019a).”

– You can be on edge and experience intense craving for nicotine, unpleasant mood swings and anxiety. You can have difficulty sleeping, fatigue and headaches and trouble concentrating. It can be harder to experience joy and to deal with stress. And it can make depression worse. Without nicotine your suppressed appetite comes back and since some people compensate by eating more, they put on weight.

#National Cancer Institute. Handling Nicotine Withdrawal and Triggers When You Decide To Quit Tobacco. 2022

https://www.cancer.gov/about-cancer/causes-prevention/risk/tobacco/withdrawal-fact-sheet#what-are-some-of-the-nicotine-withdrawal-symptoms-associated-with-quitting-tobacco

Quote: “Because the nicotine in tobacco is highly addictive, people who quit may experience nicotine withdrawal symptoms, especially if they have smoked or used other tobacco products heavily for many years. Although many of the examples in this fact sheet refer to smoking, the tips are relevant for those who are quitting the use of any tobacco product.

Common nicotine withdrawal symptoms include:

nicotine cravings 

anger, frustration, and irritability

difficulty concentrating

insomnia

restlessness

anxiety

depression

hunger or increased appetite

Other, less common nicotine withdrawal symptoms include headaches, fatigue, dizziness, coughing, mouth ulcers, and constipation (1, 2).”

– All of this makes quitting nicotine extremely hard. On top comes psychological addiction, that can be intense, since vaping is extremely habit forming. 

#Centre for Addiction and Mental Health. Nicotine dependence. Retrieved August 2024. 

https://www.camh.ca/en/health-info/mental-illness-and-addiction-index/nicotine-dependence#:~:text=In%20addition%20to%20physical%20factors,can%20be%20difficult%20to%20change.

Quote: “In addition to physical factors involved in nicotine dependence, there are psychological factors. People develop conditioned signals, or “triggers,” for tobacco use. For example, some people always smoke after a meal or when they feel anxious. These triggers lead to behaviour patterns that can be difficult to change.”

#American Cancer Society. Dealing with the Mental Part of Tobacco Addiction. Retrieved August 2024. 

https://www.cancer.org/cancer/risk-prevention/tobacco/guide-quitting-smoking/getting-help-with-the-mental-part-of-tobacco-addiction.html

Quote: “The emotional and mental dependence (addiction) make it hard to stay away from nicotine after you quit. To quit and stay quit, people who use tobacco must deal with both the physical and mental dependence. Fortunately, there are counseling services, self-help materials, mobile apps for your cell phone or tablet, and support services available to help you get through this time. And just like the physical symptoms, the emotional changes get better over time.”

– The good news is that these symptoms are entirely reversible. It takes about 72 hours for the nicotine to leave your body and the worst withdrawal symptoms fade out or stop entirely in a few weeks. 

#National Cancer Institute. Handling Nicotine Withdrawal and Triggers When You Decide To Quit Tobacco. 2022

https://www.cancer.gov/about-cancer/causes-prevention/risk/tobacco/withdrawal-fact-sheet#what-are-some-of-the-nicotine-withdrawal-symptoms-associated-with-quitting-tobacco

Quote: “The good news is that there is much you can do to reduce nicotine cravings and manage common withdrawal symptoms. Also, it may help to know that nicotine withdrawal symptoms do subside over time. They are usually worst during the first week after quitting, peaking during the first 3 days. From that point on, the intensity of symptoms usually drops over the first month. However, everyone is different, and some people have withdrawal symptoms for several months after quitting (3, 4).”

#Ian McLaughlin. Nicotine Withdrawal. 2015. 

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4542051/

Quote: “An aversive abstinence syndrome manifests 4–24 h following cessation of chronic use of nicotine-containing products. Symptoms peak on approximately the 3rd day and taper off over the course of the following 3–4 weeks.

[...]

The Diagnostic and Statistical Manual of Mental Disorders (DSM-5) reports 7 primary symptoms associated with nicotine withdrawal: irritability/anger/frustration, anxiety, depressed mood, difficulty concentrating, increased appetite, insomnia, and restlessness (American Psychiatric Association 2013). The syndrome might also include constipation, dizziness, nightmares, nausea, and sore throat. For practical purposes, nicotine withdrawal symptoms are classified as affective, somatic, and cognitive. Affective symptoms include anxiety, anhedonia, depression, dysphoria, hyperalgesia, and irritability. Somatic manifestations include tremors, bradycardia, gastrointestinal discomfort, and increased appetite. Cognitive symptoms manifest as difficulty concentrating and impaired memory (Heishman et al. 2010).”