Thomas Eissenberg

A Clinical Laboratory Model for Evaluating the Acute Effects of Electronic “Cigarettes”: Nicotine Delivery Profile and Cardiovascular and Subjective Effects

Background: Electronic “cigarettes” are marketed to tobacco users as potential reduced exposure products (PREP), albeit with little information regarding electronic cigarette user toxicant exposure and effects. This information may be obtained by adapting clinical laboratory methods used to evaluate other PREPs for smokers. Methods: Thirty-two smokers participated in four independent Latin-square ordered conditions that differed by product: own brand cigarette, “NPRO” electronic cigarettes (NPRO EC; 18 mg cartridge), “Hydro” electronic cigarettes (Hydro EC; 16 mg cartridge), or sham (unlit cigarette). Participants took 10 puffs at two separate times during each session. Plasma nicotine and carbon monoxide (CO) concentration, heart rate, and subjective effects were assessed. Results: Own brand significantly increased plasma nicotine and CO concentration and heart rate within the first five minutes of administration whereas NPRO EC, Hydro EC, and sham smoking did not. Own brand, NPRO EC, and Hydro EC (but not sham) significantly decreased tobacco abstinence symptom ratings and increased product acceptability ratings. The magnitude of symptom suppression and increased acceptability was greater for own brand than for NPRO EC and Hydro EC. Conclusions: Under these acute testing conditions, neither of the electronic cigarettes exposed users to measurable levels of nicotine or CO, although both suppressed nicotine/tobacco abstinence symptom ratings. Impact: This study illustrates how clinical laboratory methods can be used to understand the acute effects of these and other PREPs for tobacco users. The results and methods reported here will likely be relevant to the evaluation and empirically based regulation of electronic cigarettes and similar products. Cancer Epidemiol Biomarkers Prev; 19(8); 1945–53. ©2010 AACR.

Electronic cigarette nicotine delivery can exceed that of combustible cigarettes: a preliminary report

Introduction Electronic cigarettes (ECIGs) aerosolise a liquid that usually contains propylene glycol and/or vegetable glycerine, flavourants and the dependence-producing drug, nicotine, in various concentrations. This laboratory study examined the relationship between liquid nicotine concentration and plasma nicotine concentration and puffing behaviour in experienced ECIG users. Methods Sixteen ECIG-experienced participants used a 3.3-Volt ECIG battery attached to a 1.5-Ohm dual-coil ‘cartomiser’ loaded with 1 mL of a flavoured propylene glycol/vegetable glycerine liquid to complete four sessions, at least 2 days apart, that differed by nicotine concentration (0, 8, 18 or 36 mg/mL). In each session, participants completed two 10-puff ECIG-use bouts (30 s puff interval) separated by 60 min. Venous blood was sampled to determine plasma nicotine concentration. Puff duration, volume and average flow rate were measured. Results Immediately after bout 1, mean plasma nicotine concentration was 5.5 ng/mL (SD=7.7) for 0 mg/mL liquid, with significantly (p<0.05) higher mean concentrations observed for the 8 (mean=17.8 ng/mL, SD=14.6), 18 (mean=25.9 ng/mL, SD=17.5) and 36 mg/mL (mean=30.2 ng/mL; SD=20.0) concentrations; a similar pattern was observed for bout 2. For bout 1, at 36 mg/mL, the mean post- minus pre-bout difference was 24.1 ng/mL (SD=18.3). Puff topography data were consistent with previous results and revealed few reliable differences across conditions. Discussion This study demonstrates a relationship between ECIG liquid nicotine concentration and user plasma nicotine concentration in experienced ECIG users. Nicotine delivery from some ECIGs may exceed that of a combustible cigarette. The rationale for this higher level of nicotine delivery is uncertain.

Waterpipe tobacco and cigarette smoking: direct comparison of toxicant exposure.

BACKGROUND Waterpipe (hookah, shisha) tobacco smoking has spread worldwide. Many waterpipe smokers believe that, relative to cigarettes, waterpipes are associated with lower smoke toxicant levels and fewer health risks. For physicians to address these beliefs credibly, waterpipe use and cigarette smoking must be compared directly. PURPOSE The purpose of this study is to provide the first controlled, direct laboratory comparison of the toxicant exposure associated with waterpipe tobacco and cigarette smoking. METHODS Participants (N=31; M=21.4 years, SD=2.3) reporting monthly waterpipe use (M=5.2 uses/month, SD=4.0) and weekly cigarette smoking (M=9.9 cigarettes/day, SD=6.4) completed a crossover study in which they each smoked a waterpipe for a maximum of 45 minutes, or a single cigarette. Outcome measures included expired-air carbon monoxide (CO) 5 minutes after sessions end, and blood carboxyhemoglobin (COHb), plasma nicotine, heart rate, and puff topography. Data were collected in 2008-2009 and analyzed in 2009. RESULTS On average, CO increased by 23.9 ppm for waterpipe use (SD=19.8) and 2.7 ppm for cigarette smoking (SD=1.8), while peak waterpipe COHb levels (M=3.9%, SD=2.5) were three times those observed for cigarette smoking (M=1.3%, SD=0.5; ps<0.001). Peak nicotine levels did not differ (waterpipe M=10.2 ng/mL, SD=7.0; cigarette M=10.6 ng/mL, SD=7.7). Significant heart rate increases relative to pre-smoking were observed at 5, 10, 15, 20, 25, and 35 minutes during the cigarette session and at 5-minute intervals during the waterpipe session (ps<0.001). Mean total puff volume was 48.6 L for waterpipe use as compared to 1.0 L for cigarette smoking (p<0.001). CONCLUSIONS Relative to cigarette smoking, waterpipe use is associated with greater CO, similar nicotine, and dramatically more smoke exposure. Physicians should consider advising their patients that waterpipe tobacco smoking exposes them to some of the same toxicants as cigarette smoking and therefore the two tobacco-smoking methods likely share some of the same health risks.

Electronic cigarettes: review of use, content, safety, effects on smokers and potential for harm and benefit

AIMS We reviewed available research on the use, content and safety of electronic cigarettes (EC), and on their effects on users, to assess their potential for harm or benefit and to extract evidence that can guide future policy. METHODS Studies were identified by systematic database searches and screening references to February 2014. RESULTS EC aerosol can contain some of the toxicants present in tobacco smoke, but at levels which are much lower. Long-term health effects of EC use are unknown but compared with cigarettes, EC are likely to be much less, if at all, harmful to users or bystanders. EC are increasingly popular among smokers, but to date there is no evidence of regular use by never-smokers or by non-smoking children. EC enable some users to reduce or quit smoking. CONCLUSIONS Allowing EC to compete with cigarettes in the market-place might decrease smoking-related morbidity and mortality. Regulating EC as strictly as cigarettes, or even more strictly as some regulators propose, is not warranted on current evidence. Health professionals may consider advising smokers unable or unwilling to quit through other routes to switch to EC as a safer alternative to smoking and a possible pathway to complete cessation of nicotine use.

Waterpipe tobacco smoking: an emerging health crisis in the United States.

OBJECTIVE To examine the prevalence and potential health risks of waterpipe tobacco smoking. METHODS A literature review was performed to compile information relating to waterpipe tobacco smoking. RESULTS Waterpipe tobacco smoking is increasing in prevalence worldwide; in the United States, 10-20% of some young adult populations are current waterpipe users. Depending on the toxicant measured, a single waterpipe session produces the equivalent of at least 1 and as many as 50 cigarettes. Misconceptions about waterpipe smoke content may lead users to underestimate health risks. CONCLUSION Inclusion of waterpipe tobacco smoking in tobacco control activities may help reduce its spread.

Electronic Cigarettes: Effective Nicotine Delivery After Acute Administration

INTRODUCTION Electronic cigarettes (ECs) are marketed as nicotine delivery devices. Two studies with EC-naïve participants suggest that ECs deliver little or no nicotine. In those studies, standard-sized ECs were used, though experienced EC users often use larger devices that house higher voltage and/or longer lasting batteries. Whether user experience and device characteristics influence EC nicotine delivery is uncertain. The purpose of the present study was to examine the effects of ECs in experienced users who were using their preferred devices. METHODS Eight EC users (3 women) who had been using ECs for at least 3 months, completed one 5-hr session using devices they provided and the flavor/strength nicotine cartridges they selected. Sessions consisted of 4 phases: baseline, 10 puffs (30-s interpuff interval) from the device, 1-hr ad lib puffing period, and a 2-hr rest period (no puffing). Outcome measures in each phase included plasma nicotine concentration, heart rate, and subjective ratings of nicotine/product effects and abstinence symptoms. RESULTS Relative to baseline, plasma nicotine and heart rate increased significantly within 5 min of the first puff and remained elevated throughout the ad lib puffing period. Increases in ratings of direct effects of nicotine and product were observed as well as decreases in abstinence symptoms. CONCLUSIONS User experience and/or device characteristics likely influence EC nicotine delivery and other effects. Systematic manipulation of these and other variables could elucidate conditions that produce intended effects.

Electronic nicotine delivery systems: a research agenda

Electronic nicotine delivery systems (ENDS, also called electronic cigarettes or e-cigarettes) are marketed to deliver nicotine and sometimes other substances by inhalation. Some tobacco smokers report that they used ENDS as a smoking cessation aid. Whether sold as tobacco products or drug delivery devices, these products need to be regulated, and thus far, across countries and states, there has been a wide range of regulatory responses ranging from no regulation to complete bans. The empirical basis for these regulatory decisions is uncertain, and more research on ENDS must be conducted in order to ensure that the decisions of regulators, health care providers and consumers are based on science. However, there is a dearth of scientific research on these products, including safety, abuse liability and efficacy for smoking cessation. The authors, who cover a broad range of scientific expertise, from basic science to public health, suggest research priorities for non-clinical, clinical and public health studies. They conclude that the first priority is to characterize the safety profile of these products, including in long-term users. If these products are demonstrated to be safe, their efficacy as smoking cessation aids should then be tested in appropriately designed trials. Until these studies are conducted, continued marketing constitutes an uncontrolled experiment and the primary outcome measure, poorly assessed, is user health. Potentially, this research effort, contributing to the safety and efficacy of new smoking cessation devices and to the withdrawal of dangerous products, could save many lives.

Initial tobacco use episodes in children and adolescents: current knowledge, future directions

Approximately three-quarters of adult tobacco users report that their first tobacco use occurred between ages 11 and 17, while many adults who do not regularly use tobacco report that they experimented with it as adolescents. Surprisingly little is known about the effects of these initial tobacco use episodes and their influence on adult tobacco use patterns. In particular, understanding the role that nicotine plays in these early tobacco use experiences may be important in understanding the development of regular tobacco use and concomitant nicotine dependence. One goal of this review is to summarize current knowledge regarding the effects of initial tobacco use episodes in adolescents and to discuss nicotine exposure in initial tobacco use episodes. Another goal is to outline a research agenda designed to learn more about initial tobacco use episodes and the effects of nicotine in children. An ethical rationale and some potential methods for this research agenda are presented.

The clinical pharmacology of buprenorphine: extrapolating from the laboratory to the clinic

This paper will review clinical pharmacology studies on buprenorphine, a mixed opioid agonist-antagonist currently approved as a treatment for opioid dependence. The focus is on studies characterizing buprenorphines pharmacodynamic actions, including its safety, abuse liability, withdrawal suppression and withdrawal precipitation capacity, physical dependence potential, cross-tolerance and duration of action as well as a review of the pharmacological profile of buprenorphine/naloxone combinations. The findings from these clinical pharmacology studies are synthesized and presented in a framework designed to (1) inform clinicians about the advantages and disadvantages of buprenorphine as an opioid maintenance agent, and (2) provide information about dosing procedures that may optimize the use of buprenorphine in the clinic.

Patterns of waterpipe use and dependence: implications for intervention development.

Despite the dramatic increase of tobacco smoking via waterpipe in Arab societies, and the apparent potential of waterpipe use to produce tobacco-related disease, little is known about the pharmacological effects of this method of tobacco smoking, particularly its ability to support dependence. This review focuses on recent waterpipe research and current theories of dependence in an attempt to identify patterns of waterpipe use and features likely to reveal dependence. Recent work indicates that, relative to cigarette smoking, this form of tobacco use is characterized by more intermittent use, later age of onset, greater spread among women and lower interest in quitting or appreciation of addictive properties. Waterpipe use is associated with classic features of tobacco/nicotine dependence, as well as features unique to this tobacco use method. However, even shared features of dependence, such as craving and addiction-induced socio-cognitive behavioral changes, can be displayed differently in waterpipe users, indicating the need for waterpipe-specific research approaches. Preliminary evidence suggests that an important step toward dependence involves a transition from social to individual patterns of waterpipe use. Surveillance and research into factors affecting use and cessation of this tobacco use method should pave the way for the development of effective prevention and intervention strategies to curb the burgeoning waterpipe use epidemic.