Potential reduced exposure products (PREPs) for smokeless tobacco users: Clinical evaluation methodology

Abstract

Several potential reduced exposure products (PREPs) for smokeless tobacco (SLT) users are marketed in the United States, though their effects are largely unknown. These products include some that are low in tobacco-specific nitrosamines (TSNs), like Stonewall, a pressed tobacco tablet, and General snus, a moist snuff product produced in Sweden. Methodology assessing the toxicant exposure and effects of cigarette-like PREPs for smokers has been developed, and might be modified for use in evaluating PREPs for SLT users. This report describes two studies examining the toxicant exposure and effects of two PREPs for SLT users. Study 1 (n = 13) consisted of four 4.5-hr laboratory sessions where SLT products (own brand, Stonewall, General snus, and tobacco-free placebo) were used for four 30-min episodes and nicotine exposure and tobacco/nicotine abstinence symptoms were measured. Study 2 (n = 19) consisted of four 5-day ad libitum use periods when participants used own brand, Stonewall, General snus, or no SLT and urinary levels of metabolites of nicotine (cotinine) and the TSN 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNAL) and abstinence symptoms were measured. Compared with own brand, Stonewall was associated with lower levels of cotinine and NNAL, while General snus was associated with similar levels of cotinine and lower levels of NNAL. Abstinence symptoms generally did not differ across tobacco conditions. These results show that clinical laboratory methods can be used to evaluate the toxicant exposure and abstinence symptom suppression associated with PREPs for SLT users.

Evaluating the acute effects of oral, non-combustible potential reduced exposure products marketed to smokers

“…The reliability of these methods has been noted elsewhere17 and is evidenced here by the similarity of results across studies that used the same outcome measures and control conditions 14 16 17. The adaptability of these methods is evidenced by the fact that they are demonstrably useful for evaluating combustible PREPs for smokers,14 16–18 and non-combustible PREPs for smokeless tobacco users32 and smokers (the present study). In addition, our ability to test two versions of CS in this study demonstrates how the methods might be used to respond to changes in PREP design, although a within-subjects manipulation would likely have greater power than the relatively insensitive between-subjects factor reported here.…”

Animal models to assess the abuse liability of tobacco products: Effects of smokeless tobacco extracts on intracranial self-stimulation

“…Extending our ICSS model to this product is important because Camel Snus or other potential MTRPs can differ from conventional products in terms of their levels of behaviorally relevant non-nicotine constituents ( e.g. , acetaldehyde; Stepanov et al, 2008), subjective effects in humans (Cobb et al, 2009; Gray et al, 2008; Kotlyar et al, 2007). and relative market share (Delnevo et al, 2014).…”

Nicotine Absorption from Smokeless Tobacco Modified to Adjust pH

“…Questions were designed to assess the participant's perception of overall strength, amount swallowed, how well the product packed, increased salivation, burning sensations in the mouth, mouth tingling, and nausea [7,20]. The data were plotted on a curve of product ‘liking’ over time and an AUC was calculated to further analyze the data.…”