Researchers tested the iSENZIA™ heated herbal system and found it delivers nicotine with far fewer harmful chemicals than cigarettes, sparking debate on whether it could offer smokers a safer alternative.
Study: Assessment of heated herbal products’ tobacco harm reduction potential: pre-clinical and clinical studies. Image credit: Olga Vasilyeva/Shutterstok.com
A recent study in Frontiers in Toxicology assessed pre-clinical and clinical study findings to understand the potential for heated herbal products to reduce tobacco harm. This study indicates the potential of the iSENZIA™ heated herbal system (HHS) in producing satisfactory levels of nicotine with reduced harmful effects compared to cigarettes.
Effect of smoking on health
Smoking is associated with multiple diseases, including lung cancer, emphysema, reproductive/developmental toxicity, and cardiovascular disease. Cigarette smoking leads to more than 7 million preventable deaths per year globally. Most diseases caused by smoking stem from inhaling the burned tobacco fumes that contain around 7,000 chemicals. Among these, nicotine is an addictive compound, and whilst not risk-free, it is not thought to be directly responsible for the major health harms of cigarette smoking.
Clinicians have urged cigarette smokers to quit or reduce smoking to lower their exposure to harmful and potentially harmful constituents (HPHCs) present in cigarettes, which would decrease their risk of multiple diseases.
Although many smokers attempt to quit cigarette smoking every year, only a few are successful. For individuals who are unwilling or uninterested in quitting, tobacco harm reduction (THR) approaches aim to reduce the harms associated with smoking. In 2001, the US Institute of Medicine (IoM) introduced the THR concept in the ‘Clearing the Smoke’ report to reduce exposure to harmful toxicants that could decrease overall morbidity and mortality.
THR can be achieved by decreasing cigarette consumption, lowering the risk associated with tobacco use, or reducing the prevalence of use. Therefore, the production of novel nicotine and tobacco products that yield nicotine without emitting HPHCs and other toxicants linked to smoking-related diseases is necessary.
Heated tobacco products vs. heated herbal products
Recent studies have highlighted the use of heated tobacco products (HTPs) as an alternative to nicotine-containing products for adult smokers. HTPs electrically heat a tobacco-based substrate in a controlled manner to generate a nicotine-containing aerosol. Since the heating temperature is considerably lower than that required to burn cigarettes, the levels of HPHCs and other toxicants present in HTP aerosols are significantly less than those in cigarette smoke.
In contrast to HTP, heated herbal products (HHPs) electronically heat a non-tobacco, nicotine-containing substrate, generating an aerosol containing nicotine. Few studies have assessed the impact of HHPs on health.
About the study
The current study explored the preclinical and clinical studies conducted to assess a novel heated herbal system (HHS) called iSENZIA™. This system comprises the PULZE™ 2.0 device and iSENZIA™ sticks. The preclinical studies considered two iSENZIA™ sticks: Forest Berry and Summer Watermelon.
The clinical study involved 25 candidates. The study cohort comprised 40% males, and all subjects were White. All participants smoked non-mentholated cigarettes as their usual brand.
Study findings
Preclinical studies' findings indicated the generation of aerosols from the iSENZIA™ HHS, and six of the nine World Health Organization (WHO) Study Group on Tobacco Product Regulation (TobReg 9) analytes were below the limits of quantification (LOQ). The levels of the three quantifiable analytes (acetaldehyde, acrolein, and carbon monoxide) were approximately 96-99% lower than those measured in 1R6F reference cigarette smoke.
Compared to the 1R6F reference cigarette smoke, iSENZIA™ HHS aerosol nicotine yield for Forest Berry and Summer Watermelon was significantly lower by 65% and 67%, respectively. Furthermore, a lower aerosol collected mass (ACM) was measured for the iSENZIA™ HHS aerosols, compared to total particulate matter (TPM) in 1R6F reference cigarette whole smoke by approximately 18% for both flavor variants.
Cytotoxicity assay revealed that more puffs are required to induce toxicity, compared to 1R6F reference cigarette smoke. Similarly, greater mutagenicity and genotoxicity were observed in the reference cigarette smoke compared to the iSENZIA™ HHS variant aerosols. However, the micronucleus assay was positive for both iSENZIA aerosols and cigarette smoke, though iSENZIA aerosols showed much lower genotoxic potency.
For the clinical study, any test product used in the controlled puffing sessions revealed a rapid increase in plasma nicotine levels. On average, participants took 9.3 puffs from each of the iSENZIA™ stick variants and 10.3 puffs from their usual brand cigarettes. Compared to usual brand cigarettes, each of the iSENZIA™ HHS flavor variants exhibited a significantly lower value for area under the plasma nicotine concentration-time curve (AUC) and mean maximum plasma nicotine concentration.
No statistically significant difference was observed between the iSENZIA™ HHS flavor variants and usual brand cigarettes regarding the median time to reach the maximum plasma nicotine concentration. Cigarettes produced the most significant reduction in urge to smoke (highest Emax); iSENZIA variants reduced urge less (by ~36-38%) and reached their maximum effect later (higher TEmax).
In product evaluation, participants reported lower satisfaction, psychological reward, and relief for iSENZIA variants compared to cigarettes. Intent-to-use-again rates were 52% (Forest Berry) and 44% (Summer Watermelon), versus 76% for the usual brand cigarettes.
This study reported no serious and infrequent adverse effects (AEs). Mild dizziness and nausea were found to be the most reported AEs.
Conclusions
Pre-clinical and clinical study findings indicate that aerosol from the iSENZIA™ HHS contains significantly lower levels of HPHCs and toxicants than cigarette smoke. The lower levels significantly reduce biological impact, supporting reduced exposure and lower biological activity, but long-term harm reduction is not yet established.
Because nicotine delivery and product evaluation measures were lower than for cigarettes, the authors suggest iSENZIA may have lower abuse liability while still supporting adult smokers who would otherwise continue to smoke. Taken together, these findings support reduced-exposure and lower-abuse-liability potential for iSENZIA versus cigarettes; long-term health impact and switching effectiveness remain to be established.
The authors also note limitations: a small and narrow demographic sample, a single laboratory puffing regimen, a limited analyte panel, and no long-term or real-world outcomes. They emphasize the need for broader chemistry, long-term biomarker studies, and switching data. Imperial Brands PLC funded the study, and most authors are employees of the company that manufactures iSENZIA.
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