Cigarettes with different nicotine levels affect sensory perception and levels of biomarkers of exposure in adult smokers.

INTRODUCTION: Few clinical studies involving cigarettes have provided a comprehensive picture of smoke exposure, test article characterization, and insights into sensory properties combined. The purpose of these pilot studies was to determine whether cigarettes with different levels of nicotine but similar tar levels would affect sensory experience or smoking behavior so as to significantly alter levels of selected biomarkers of exposure (BOE). METHODS: In 2 confined, double-blind studies, 120 adult smokers switched from Marlboro Gold cigarettes at baseline to either 1 of 2 lower nicotine cigarettes or 1 of 2 higher nicotine cigarettes and then to the other cigarette after 5 days. Urinary excretion of exposure biomarkers (nicotine equivalents [NE], total and free 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol [NNAL], 1-hydroxypyrene, and 3-hydroxypropyl mercapturic acid) as well as carboxyhemoglobin and plasma cotinine were measured at baseline, Day 5, and Day 10. Daily cigarette consumption was monitored and sensory characteristics were rated for each cigarette. RESULTS: With higher nicotine yield, urine NE, urine total NNAL, and plasma cotinine increased while nonnicotine BOE decreased without changes in cigarette consumption. In contrast, with lower nicotine yield, urine NE, urine total NNAL, and plasma cotinine dropped while nonnicotine BOE and cigarettes per day increased. Higher nicotine cigarettes were rated harsher and stronger than at baseline while lower nicotine cigarettes were less strong. All 4 test cigarettes were highly disliked. CONCLUSIONS: These studies demonstrate that abrupt increases or decreases in nicotine and the resulting sensory changes impact BOE through changes in intensity or frequency of smoking.

Commentary: Cigarette dependence in menthol and non-menthol young adult cigarette smokers.

FDA's Proposed Final Rule to ban menthol cigarettes asserts that "menthol cigarettes contribute to greater nicotine dependence in youth and young adults than non-menthol cigarettes." However, none of the publications referenced included young adults. To provide empirical evidence on the subject, we examine smoking frequency and Heaviness of Smoking Index (HSI) dependence among 2,194 young adult (ages 18-25 years) menthol and non-menthol smokers from 31 online survey samples. Unpaired t-tests examined if daily smoking or the proportion of daily smokers who are low or high dependence on the HSI vary by menthol cigarette smoking status. Young adult menthol smokers were less likely to be daily smokers than young adult non-menthol smokers. There were no differences in the percentages of daily menthol and non-menthol smokers categorized as low or high dependence on the HSI. Smoking menthol cigarettes, therefore, does not appear to be associated with greater cigarette dependence among young adults than smoking non-menthol cigarettes.

Heaviness of smoking index in menthol and non-menthol smokers.

BACKGROUND: It has been hypothesized that menthol in cigarettes increases dependence. Several studies suggest that menthol and non-menthol smokers have similar or lower levels of dependence, but those studies are not without limitations. The Heaviness of Smoking Index (HSI) is a widely accepted, validated measure of cigarette dependence. OBJECTIVES: This report aims to provide further evidence regarding dependence among menthol and non-menthol smokers, as indicated by daily smoking and as measured by the HSI. METHODS: Survey data from 27,131 adult smokers were analyzed to compare the percent of menthol and non-menthol smokers who are daily smokers, and the percentage who are low or high HSI dependence. Logistic regressions were also conducted to determine if menthol use predicts daily smoking, and low or high dependence after controlling for demographic differences. RESULTS: Comparisons among weighted samples of adult smokers demonstrate that menthol smokers were consistently more likely to be non-daily smokers, more likely to be in the low dependence category, and less likely to be in the high dependence category on the HSI as compared to non-menthol smokers. Logistic regression confirmed that when controlling for age, gender, race/ethnicity, and education, relative to non-menthol smokers, menthol smokers had no difference in odds of being in the low dependence HSI category and significantly lower odds of being a daily smoker, and of being in the high dependence category. CONCLUSIONS: These analyses support the conclusion that, based on the HSI, menthol smokers are not more cigarette dependent than non-menthol smokers, and may be less dependent.

Biomarkers of potential harm among adult smokers and nonsmokers in the total exposure study.

INTRODUCTION: There is overwhelming medical and scientific consensus that cigarette smoking causes lung cancer, heart disease, emphysema, and other serious diseases in smokers. In the Total Exposure Study, 29 biomarkers of potential harm (BOPH) were measured in a cross-sectional sample of 3,585 adult smokers (AS) and 1,077 nonsmokers (NS). The BOPH included markers of oxidative stress, inflammation, platelet activation, endothelial function, lipid metabolism, hematology, metabolism, the cardiovascular system, lung function, kidney function, and liver function. METHODS: Multiple stepwise regression was used to examine the effect of demographic factors (age, gender, body mass index [BMI], and race) and smoking (number of cigarettes smoked per day or nicotine equivalents [NE] per 24 hr and smoking duration) on each BOPH. RESULTS: As compared with NS, AS had >10% higher levels of 8-epi-prostaglandin F(2α) (8-epi-PG F(2α), 42%), 11-dehydrothromboxane B2 (11-DHTB, 29%), white blood cell (WBC) count (19%), high-sensitivity C-reactive protein (15%), triglycerides (16%), and alkaline phosphatase (11%) and had 18% lower total bilirubin. Multiple stepwise regression revealed that although NE (milligrams per 24 hours) was statistically significant for 18 of the 29 BOPH, it was the most important factor only for WBCs and 11-DHTB. Smoking duration was the most important factor for forced expiratory volume in 1 second. In contrast, BMI was the most important factor for 12 BOPH. CONCLUSIONS: These results contribute to the understanding of the relationship between tobacco smoking and potential biological effects.

A comprehensive evaluation of the toxicology of cigarette ingredients: aromatic and aliphatic alcohol compounds.

CONTEXT: Various aromatic and aliphatic alcohol compounds are found in tobacco and tobacco smoke. OBJECTIVE: A battery of tests was used to compare the toxicity of mainstream smoke from experimental cigarettes containing eight aromatic and aliphatic alcohol compounds that were added individually to experimental cigarettes at three different levels. The lowest target inclusion level was 100 ppm and the highest level was 24,400 ppm. MATERIALS AND METHODS: Mainstream smoke from each of the cigarette types was evaluated using analytical chemistry and assays to measure in vitro cytotoxicity (neutral red uptake) and Salmonella (five strains) mutagenicity. For three of the compounds (benzyl alcohol, propyl paraben, and rum flavor), 90-day smoke inhalation studies with 6-week recovery periods were also performed using rats. RESULTS: Inclusion of eugenol produced several dose-related reductions in concentrations of selected smoke constituents. Cytotoxicity and mutagenicity were unaffected by any of the test ingredients, except for dose-related reductions in cytotoxicity of the gas vapor phase produced by the inclusion of eugenol. The three smoke inhalation studies showed a few sporadic differences between the groups and there were no differences in the patterns of recovery for any of the ingredients. CONCLUSIONS: Despite using exaggerated inclusion levels of the eight aliphatic and aromatic alcohol compounds in experimental cigarettes, there was minimal toxicological response, which is consistent with published reports of studies using mixtures of compounds added to tobacco.

The relationship between nicotine dependence scores and biomarkers of exposure in adult cigarette smokers.

BACKGROUND: Tobacco dependence is a multidimensional phenomenon. The Fagerström Test for Nicotine Dependence (FTND) is a widely administered six-item questionnaire used as a measure of nicotine dependence. It has been suggested that this test may not represent the entire spectrum of factors related to dependence. Also the relationship of this test with biomarkers of exposure to cigarette smoke has not been extensively studied. METHODS: Data from a multi-center, cross-sectional, ambulatory study of US adult smokers (the Total Exposure Study, TES) was analyzed. The FTND score and a number of additional questions related to smoking behavior, from an adult smoker questionnaire (ASQ) completed by 3585 adult smokers in the TES were analyzed. The 24-h urine nicotine equivalents, serum cotinine and blood carboxyhemoglobin were measured as biomarkers of exposure (BOE) to nicotine and carbon monoxide. Cigarette butts returned were collected during the 24-h urine collection period. RESULTS: The FTND showed moderate correlations with BOE, while selected questions from ASQ although statistically significant, had weaker correlations. FTND scores showed substantially weaker correlations without the question about cigarettes smoked per day (CPD). CPD and time to first cigarette (TTFC) had the most impact on BOE. CONCLUSION: Additional questions from ASQ did not appear to contribute towards refining the FTND test. The correlation of the FTND scores with nicotine and carbon monoxide seems to be primarily driven by CPD. CPD and TTFC were the most important factors correlating with exposure.

Factors affecting exposure to nicotine and carbon monoxide in adult cigarette smokers.

Exposure to cigarette smoke among smokers is highly variable. This variability has been attributed to differences in smoking behavior as measured by smoking topography, as well as other behavioral and subjective aspects of smoking. The objective of this study was to determine the factors affecting smoke exposure as estimated by biomarkers of exposure to nicotine and carbon monoxide (CO). In a multi-center cross-sectional study of 3585 adult smokers and 1077 adult nonsmokers, exposure to nicotine and CO was estimated by 24h urinary excretion of nicotine and five of its metabolites and by blood carboxyhemoglobin, respectively. Number of cigarettes smoked per day (CPD) was determined from cigarette butts returned. Puffing parameters were determined through a CreSS® micro device and a 182-item adult smoker questionnaire (ASQ) was administered. The relationship between exposure and demographic factors, smoking machine measured tar yield and CPD was examined in a statistical model (Model A). Topography parameters were added to this model (Model B) which was further expanded (Model C) by adding selected questions from the ASQ identified by a data reduction process. In all the models, CPD was the most important and highest ranking factor determining daily exposure. Other statistically significant factors were number of years smoked, questions related to morning smoking, topography and tar yield categories. In conclusion, the models investigated in this analysis, explain about 30-40% of variability in exposure to nicotine and CO.

Does dual use jeopardize the potential role of smokeless tobacco in harm reduction?

INTRODUCTION: The use of smokeless tobacco as part of a strategy to reduce the harm from cigarette smoking is a topic of debate within the tobacco control and public health communities. One concern voiced regarding endorsement of such a tactic is the possibility of actually increasing harm should current smokers adopt dual cigarette/smokeless tobacco use (dual use), which could lead to unintended consequences by perpetuating cigarette smoking, diminishing tobacco cessation, or increasing tobacco-related harm. METHODS: Here, we review the available literature on health effects and trajectories of use among dual users from a variety of U.S. and European epidemiological studies. RESULTS: These data suggest that there are not any unique health risks associated with dual use of smokeless tobacco products and cigarettes, which are not anticipated or observed from cigarette smoking alone. Furthermore, studies show that dual users smoke fewer cigarettes than exclusive smokers, and studies of tobacco use patterns over time (tobacco use trajectory data) indicate that dual users are more likely than exclusive cigarette smokers to cease smoking. CONCLUSIONS: Overall, the concern about dual use appears to be contradicted by the evidence in the literature that dual use of smokeless tobacco and cigarettes may result in reduction in smoking-related harm as smoking intensity is decreased and smoking cessation increases.

Measures of dependence in menthol and nonmenthol smokers - A comprehensive narrative review.

Introduction. More than a decade ago, concerns were raised that menthol in cigarettes might enhance addiction to smoking. This article provides a comprehensive review of published studies examining cigarette dependence among menthol and nonmenthol smokers. The purpose of the review is to evaluate the scientific evidence to determine if menthol increases cigarette dependence. Materials and Methods. The published literature was searched in 2019 for studies that provide evidence on cigarette dependence among menthol compared to nonmenthol smokers. Included in this review are published studies that compare menthol and nonmenthol smokers based on widely accepted and validated measures of dependence, or other established predictors of dependence (age of smoking initiation [first cigarette]/age of progression [regular/daily smoking]) and indicators of dependence (smoking frequency, cigarettes smoked per day, time to first cigarette after waking, night waking to smoke, smoking duration). Results and Conclusion. Based on a review of the available studies, including those with adjusted results and large representative samples, reliable and consistent empirical evidence supports a conclusion that menthol smokers are not more dependent than nonmenthol smokers and thus menthol in cigarettes does not increase dependence.

The relationship between smoking machine derived tar yields and biomarkers of exposure in adult cigarette smokers in the US.

UNLABELLED: Comprehensive data on human exposure to smoke constituents from different machine-measured tar yield cigarettes is limited. METHODS: This study used a stratified, cross-sectional, multi-center design to estimate biomarkers of exposure (BOE) from nicotine, 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK), pyrene, CO, acrolein, and 1,3-butadiene and their relationship to tar yield categories of cigarette in adult smokers in the U.S. 3625 adults smokers were enrolled into four tar categories < or =2.9 mg (T1), 3.0-6.9 mg (T2), 7.0-12.9 mg (T3), and > or =13.0mg (T4). Biomarkers were measured in blood (carboxyhemoglobin, 4-aminobiphenyl-hemoglobin (4-ABP-Hb)-adducts, serum cotinine) and 24h urine (nicotine and five metabolites, calculated as nicotine equivalents (NE), NNAL, 1-OH-pyrene, 3-HPMA, MHBMA and DHBMA). Data were analyzed using analysis of covariance (ANCOVA). RESULTS: Tar was a significant factor for most biomarkers in the ANCOVA models. The largest least square mean differences between tar categories was 35% for NE per day, 28% for NE per cigarette, 36% for serum cotinine, 42% for NNAL per day, 29% for NNAL per cigarette, 26% for 1-OHP, 24% for COHb, 14% for 3-HPMA and 40% for 4-ABP-Hb. Variability in BOE ranged from 41% to 154% CV. CONCLUSIONS: There was a statistically significant effect of machine-measured tar yield on most BOE, which were generally lower with lower tar yield.

Environmental tobacco smoke (ETS) evaluation of a third-generation electrically heated cigarette smoking system (EHCSS).

This sub-study of a randomized, controlled, forced-switching, open-label, parallel-group, clinical study compared environmental tobacco smoke (ETS) produced when 60 male and female adult smokers switched to a third-generation electrically heated cigarette smoking system (EHCSS), continued to smoke a conventional cigarette (CC), or stopped smoking (No-smoking). Concentrations of air constituents including respirable suspended particulate (RSP), carbon monoxide (CO), ammonia and total volatile organic compounds (TVOCs) and ETS markers including solanesol-related particulate matter (Sol-PM), ultraviolet absorbing particulate matter (UVPM), fluorescent particulate matter (FPM), nicotine and 3-ethenyl pyridine (3-EP) were measured in a ventilated, furnished conference room over a 2-h period on separate occasions for each smoking condition. When the EHCSS was used, concentrations of CO and most ETS markers were in the same range as during no-smoking. Concentrations of ammonia were reduced by 41% and concentrations of other selected constituents of ETS were reduced by 87-99% in the air of a room in which EHCSS cigarettes were smoked as compared to concentrations in the same room when conventional cigarettes were smoked. Switching from conventional cigarette smoking to the EHCSS resulted in substantial reductions in concentrations of several markers of environmental tobacco smoke.

12-week clinical exposure evaluation of a third-generation electrically heated cigarette smoking system (EHCSS) in adult smokers.

This randomized, controlled, forced-switching, open-label, parallel-group, single-center study in 90 male and female adult smokers evaluated six biomarkers of tobacco smoke exposure over a 12-week period of unrestricted smoking in the participants' normal life setting. Baseline biomarker levels were measured, then participants were randomly assigned to switch to an electrically heated cigarette smoking system (EHCSS, Series K) or to continue smoking a conventional cigarette (CC) of similar tar yield (Federal Trade Commission method) for 12 weeks. Compared to Baseline, adult smokers who switched to the EHCSS for 12 weeks in their normal life setting had significantly reduced nicotine equivalents (-33%), total NNAL (a biomarker for NNK, -63%), 1-OHP (a surrogate biomarker for polycyclic aromatic hydrocarbons, -38%), carboxyhemoglobin (a biomarker for carbon monoxide, -23%), 3-HPMA (a biomarker for acrolein, -25%) and S-PMA (a biomarker for benzene, -49%), whereas exposure was stable in the CC control group.

Short-term clinical exposure evaluation of a third-generation electrically heated cigarette smoking system (EHCSS) in adult smokers.

This randomized, controlled, forced-switching, open-label, parallel-group, single-center study in 100 male and female adult smokers evaluated 12 biomarkers of tobacco smoke exposure. We measured exposure to the following smoke constituents: nicotine, pyrene, tobacco-specific nitrosamines, three aromatic amines, carbon monoxide, benzene, acrolein, crotonaldehyde, and 1,3-butadiene. After baseline exposure determination, adult smokers of a conventional cigarette (CC) were switched to an electrically heated cigarette smoking system (EHCSS, Series K), continued smoking the CC, or stopped smoking (No-smoking) for 8 days in a controlled, confined, clinical setting. In the EHCSS group, the mean decrease from Baseline to Day 8 in the biomarkers of exposure ranged from 16% to 77% at Day 8 compared to Baseline. After adjusting for the residual effect (carryover effects due to long elimination half-life and non-tobacco confounding sources of exposure), the mean percent decrease from Baseline for all 12 biomarkers ranged from 47% to 90%. In conclusion, switching for 8 days from a conventional cigarette to the EHCSS substantially reduced exposure of adult smokers to several constituents of both the particulate and gas phases of cigarette smoke.

Second-hand exposure to aerosolized intravenous anesthetics propofol and fentanyl may cause sensitization and subsequent opiate addiction among anesthesiologists and surgeons.

We hypothesize that aerosolization of anesthetics administered intravenously to patients in the operating room may be an unintended source of exposure to physicians. This may lead to inadvertent sensitization, which is associated with an increased risk for developing addiction. This may contribute to the over-representation of certain specialties among physicians with addiction. We retrospectively reviewed the de-identified demographic information of all licensed physicians treated for substance abuse in the State of Florida since 1980, to determine if medical specialty was associated with addiction in this group of individuals. Then, to identify the potential for exposure, two mass spectrometry assays were developed to detect two intravenously administered drugs, fentanyl and propofol, in air. Since 1980, 7.6% of licensed Florida physicians underwent treatment for addiction. Addiction in anesthesiologists was higher than expected. Opiate abuse was greater in anesthesiologists and surgeons compared to other specialties. Aerosolized fentanyl was detected in the air of the cardiothoracic operating room, in patients' expiratory circuits, and in the headspace above sharps boxes, but not in adjoining hallways. Aerosolized propofol was detected in the expirations of a patient undergoing transurethral prostatectomy. While access and stress may place anesthesiologists and surgeons at greater risk for substance abuse, an additional risk factor may be unintended occupational exposure to addictive drugs. This report provides preliminary evidence of detection of aerosolized intravenous anesthetics using two newly developed analytical methods. We conclude that the potential exists for chronic exposure to low levels of airborne intravenously administered drugs. Further studies are under way to determine the significance of this exposure.

Fentanyl abuse and dependence: further evidence for second hand exposure hypothesis.

We have proposed a novel hypothesis regarding the potential role of occupational or second-hand exposure in physician substance use, abuse, and addiction. While only 5.6% of licensed physicians in Florida are anesthesiologists, nearly 25% of physicians followed for substance abuse/dependence are anesthesiologists. When we sort by drug of choice, anesthesiologists have more opioid abuse and dependence than other physicians and appropriate controls. Abuse of one opioid, fentanyl, appears to be increasing and has been noted among the State of Florida's causes of opioid deaths. Fentanyl and sufentanyl are commonly administered highly potent opioid analgesics, as much as 80-800 times as potent as morphine. We have recent data from the State of Florida impaired physicians database, which has allowed us to categorize all fentanyl abusing and/ or dependent physicians. Just knowing that a physician abuses fentanyl gives you a good clue as to their specialty; 75% are anesthesiologists! While drug abuse researchers, oncologists and others who handle drugs of abuse everyday, have no greater incidence of opioid abuse or dependence, anesthesiologists are at the top of every list. Can this be due to just access and stress? We have proposed an alternative hypothesis of second hand exposure. To test this hypothesis, we developed a sensitive LC/MS/MS assay to measure the intravenous anesthetic and analgesic agents, propofol and fentanyl in air. Not only did we detect propofol and fentanyl in cardiovascular surgery operating room air, we also found the highest concentrations were close to the patient's mouth where anesthesiologists work for hours. Like tobacco, second hand opioid exposure can sensitize and change the brain making abuse, dependence and behavioral disorders more likely. Thus environmental exposure and sensitization may be an important risk factor in physician addiction. Second hand exposure may affect treatment outcome and explain anesthesiologist's inability to return to work in the operating room. We are developing an animal model for second hand exposure and additional studies of the operating room and cardiac anesthesiologists are underway.

Is speeding a form of gambling in adolescents?

Speeding is a major contributor to motor vehicle accidents, which are the leading cause of death in adolescents. This study compares the extent to which adolescents with gambling behavior and substance use reported driving over the posted speed limits ("speeding"). Florida adolescents ages 13-17 (n = 1051) were surveyed, and asked about gambling activities, problems related to gambling, substance use, demographic questions, and speeding. Of the 562 respondents who were drivers, the gender distribution was 52.1% male and 47.9% female. Of those respondents, 76.9% were Caucasian, 6.8% were African American, 10.1% were Hispanic, and 6.1% were Native American/Asian/Other. Simple correlation analysis revealed that self-reported speeding is significantly related to gambling behavior and substance use. When a linear regression model was used, four factors showed the most significant influence on self-reported speeding: past year gambling tendency, age, trouble with the police due to drinking, and tranquilizer usage. Gambling behavior and high-risk speeding (driving ≥ 10 mph over speed limit) also were noted to be positively correlated. Our data indicate a relationship between risky driving, gambling, and other risk-taking behaviors in adolescents, and support the hypothesis that speeding may be a form of gambling behavior in this age group.

A Well-Mixed Computational Model for Estimating Room Air Levels of Selected Constituents from E-Vapor Product Use.

Concerns have been raised in the literature for the potential of secondhand exposure from e-vapor product (EVP) use. It would be difficult to experimentally determine the impact of various factors on secondhand exposure including, but not limited to, room characteristics (indoor space size, ventilation rate), device specifications (aerosol mass delivery, e-liquid composition), and use behavior (number of users and usage frequency). Therefore, a well-mixed computational model was developed to estimate the indoor levels of constituents from EVPs under a variety of conditions. The model is based on physical and thermodynamic interactions between aerosol, vapor, and air, similar to indoor air models referred to by the Environmental Protection Agency. The model results agree well with measured indoor air levels of nicotine from two sources: smoking machine-generated aerosol and aerosol exhaled from EVP use. Sensitivity analysis indicated that increasing air exchange rate reduces room air level of constituents, as more material is carried away. The effect of the amount of aerosol released into the space due to variability in exhalation was also evaluated. The model can estimate the room air level of constituents as a function of time, which may be used to assess the level of non-user exposure over time.

Body mass index and marijuana use.

Though marijuana has been reported to stimulate appetite, we searched for a correlation between obesity and decreased marijuana use. We examined charts of all females referred for morbid obesity/weight management in a 12-month period. BMI and substance use data were collected from 297 charts. While 29% of the sample with BMI < 30 (n = 7) used marijuana in the past year, only 21% of those with BMI 30-39 (n = 84), 16% of those with BMI 40-49 (n = 110) and 14% (n = 96) of those with BMI > 50 used marijuana in the past year. Linear regression revealed a negative correlation between BMI group and percent marijuana use (R-squared = 0.96; P = 0.0173). These findings provide support for overeating as competition for drugs and alcohol in brain reward sites.

Naltrexone augments the effects of nicotine replacement therapy in female smokers.

BACKGROUND: There is increased recognition that gender differences may influence outcomes and may modify vulnerability to tobacco addiction, severity of course and response to different treatments. We hypothesized that naltrexone, which has been used to successfully treat opioid and alcohol dependence, when combined with nicotine replacement therapy (NRT) and psychosocial therapy (PT) may enhance smoking cessation rates in women. METHODS: Forty-four adult female smokers meeting DSM-IV criteria for nicotine dependence with expired carbon monoxide content of > or = 15 ppm were randomly assigned in a double blind placebo controlled clinical trial of naltrexone 50 mg + NRT patch + psychosocial therapy (N + NRT + PT)(N = 12) or placebo + NRT patch + psychosocial therapy (P + N + PT)(N=12) for 12 weeks. RESULTS: Twelve weeks of treatment was completed by 54.5%. Smoking cessation among females who completed the 12 weeks for N + NRT + PT was 91.7% (11/12) and for P + NRT + PT was 50% (6/12). CONCLUSION: Naltrexone combined with NRT and psychosocial therapy appears to have a positive cessation effect on women and may be a new treatment option for recidivist female smokers.

Occupational exposure and addictions for physicians: case studies and theoretical implications.

Risk of addiction through occupational exposure to drugs of abuse is an important but relatively neglected public health problem. Stress and access may have much less of a role in addiction among certain populations than originally was thought. Risk of addition may be increased dramatically by unintentional exposure in the workplace to potent substances that sensitize the brain. Everyone knows that second-hand inhalation of crack vapors is a very dangerous proposition, but rarely has alarm been raised about exposing anesthesiologists to second-hand fentanyl. Additional studies of the relationship between exposure in the workplace and addiction are necessary. These studies should include biological measures, such as blood levels in exposed workers, and sensitive assays that quantitatively assess levels of exposure in the workplace.