A critical appraisal of the harm reduction argument for heat-not-burn tobacco products

[ABSTRACT]. Heat-not-burn products (HNBs) are efficient nicotine delivery devices that heat tobacco instead of burning it, as conventional cigarettes do. Since heating yields less carbon monoxide and other tobacco pyrolysis–derived toxicants, tobacco companies claim that HNBs are less harmful than conventional cigarettes are. Although this hypothesis is plausible, no long-term clinical trials and/or observational studies are available to corroborate it. To overcome barriers to the entry of tobacco products to the market, manufacturers of HNBs argue that they are a new wave of harm reduction alternatives. Nonetheless, even if HNBs were in fact less harmful than conventional cigarettes, they would still have the potential to cause nicotine addiction (a major health hazard) and other harms to smokers’ health. HNBs deliver nicotine, provide users a tobacco aroma and flavor and some rituals of smoking, and are supposedly safer than conventional cigarettes. Owing to these features, HNBs are likely to enhance smoking appeal and initiation among young persons and discourage smokers’ attempts to quit. In other words, if HNBs were freely available on the market, they would increase the prevalence of smoking. However, HNBs may constitute a harm reduction alternative for nicotine-dependent smokers who are unable or unwilling to quit smoking. Given these facts, approval of HNBs for use under medical supervision (prescription only), along with strict restrictions on advertising, is a balanced regulatory option that would reconcile the therapeutic needs of nicotine-addicted patients with the public heath goal of achieving a smoke-free generation in the near future.

[RESUMEN]. Los productos de tabaco calentado (PTC) son dispositivos eficientes para la administración de nicotina que calientan el tabaco en vez de quemarlo (como sucede con los cigarrillos convencionales). Al calentar el tabaco se produce menos monóxido de carbono y se liberan menos sustancias tóxicas derivadas de la pirólisis del tabaco; por tanto, las empresas tabacaleras sostienen que los PTC son menos nocivos que los cigarrillos convencionales. Aunque esta hipótesis es verosímil, no hay ningún ensayo clínico ni estudios de observación a largo plazo que la corroboren. Para superar las barreras a la entrada de los productos de tabaco en el mercado, los fabricantes de PTC sostienen que estos productos son una nueva ola de alternativas menos dañinas. Sin embargo, aunque los PTC fueran realmente menos nocivos que los cigarrillos convencionales, seguirían teniendo el potencial de causar adicción a la nicotina (un riesgo grave para la salud), así como otros perjuicios para la salud de los fumadores. Los PTC administran nicotina y brindan a los consumidores el aroma y el sabor del tabaco, así como algunos de los rituales del acto de fumar, a la vez que son supuestamente más seguros que los cigarrillos convencionales. Precisamente por estas características, los PTC pueden volverse una forma de fumar atractiva que incite a los jóvenes a comenzar a usarlos y disuada a los fumadores de dejar de hacerlo. Es decir, si los PTC estuviesen disponibles sin restricciones en el mercado, aumentaría la prevalencia del consumo de tabaco. Sin embargo, los PTC pueden ser una alternativa menos dañina para los fumadores adictos a la nicotina que no pueden o no quieren dejar de fumar. Por todo ello, aprobar los PTC para su uso bajo supervisión médica (únicamente con prescripción), junto con restricciones estrictas en cuanto a su promoción publicitaria, es una opción regulatoria en la que se equilibrarían las necesidades terapéuticas de los pacientes adictos a la nicotina con el objetivo de salud pública de conseguir una generación sin tabaco en un futuro próximo.

[RESUMO]. Os cigarros aquecidos são aparelhos eficientes de liberação de nicotina que aquecem o tabaco em vez de queimá-lo como os cigarros convencionais. Como o aquecimento produz menos monóxido de carbono e outros produtos tóxicos derivados da queima do tabaco, as empresas de tabaco alegam que os cigarros aquecidos são menos prejudiciais que os convencionais. Apesar de esta hipótese ser plausível, não existem estudos clínicos e/ou observacionais de longo prazo para corroborá-la. Para vencer os obstáculos à entrada no mercado dos produtos derivados do tabaco, os fabricantes dos cigarros aquecidos argumentam que eles fazem parte de um novo ciclo de alternativas para redução de danos. No entanto, mesmo se os cigarros aquecidos forem de fato menos prejudiciais que os convencionais, eles continuam tendo o potencial de causar dependência da nicotina (um sério risco à saúde) e outros danos à saúde dos fumantes. Os cigarros aquecidos liberam nicotina, dispensando o aroma e o sabor do tabaco e proporcionando ao usuário alguns dos rituais do ato de fumar, e supostamente seriam mais seguros que os cigarros convencionais. Devido a essas características, eles podem tornar o ato de fumar mais atraente e fazer os jovens começarem a fumar e desincentivar os fumantes a parar de fumar. Em outras palavras, se forem comercializados livremente no mercado, aumentariam a prevalência do tabagismo. Porém, os cigarros aquecidos podem ser uma alternativa para a redução de danos em fumantes dependentes da nicotina que não conseguem ou relutam em parar de fumar. Diante destes fatos, a aprovação dos cigarros aquecidos para uso sob supervisão médica (com prescrição), aliada a restrições rigorosas à publicidade do produto, é uma opção regulamentar ponderada que conciliaria as necessidades terapêuticas dos pacientes dependentes de nicotina com a meta de saúde pública de ter uma geração que não fuma em um futuro próximo.

Traditional use and safety of herbal medicines

In the European Union, traditional herbal medicines that are regarded as "acceptably safe, albeit not having a recognized level of efficacy" fit into a special category of drugs ("traditional herbal medicine products") for which requirements of non-clinical and clinical studies are less rigorous. A regulation proposal published by the Brazilian National Health Surveillance (Anvisa) defines a similar drug category ("traditional phytotherapeutic products") for registration purposes. Regarding herbal medicines, both agencies seem to be lenient regarding proof of efficacy, and consider long-standing folk use as evidence of safety and a waiver of a thorough toxicological evaluation. Nonetheless, several herbal products and constituents with a long history of folk usage are suspected carcinogenic and/or hepatotoxic. Herbal products have also been shown to inhibit and/or induce drug-metabolizing enzymes. Since herbal medicines are often used in conjunction with conventional drugs, kinetic and clinical interactions are a cause for concern. A demonstration of the safety of herbal medicines for registration purposes should include at least in vitro and in vivo genotoxicity assays, long-term rodent carcinogenicity tests (for drugs intended to be continuously used for > 3 months or intermittently for > 6 months), reproductive and developmental toxicity studies (for drugs used by women of childbearing age), and investigation of the effects on drug-metabolizing enzymes.

Modulation of expression and activity of cytochrome P450s and alteration of praziquantel kinetics during murine schistosomiasis

In this study, we investigated the expression and activity of liver cytochrome P450s (CYPs) and praziquantel (PZQ) kinetics in mice infected with Schistosoma mansoni. Swiss Webster (SW) mice of both genders were infected (100 cercariae) on postnatal day 10 and killed on post-infection days (PIDs) 30 or 55. Non-infected mice of the same age and sex served as controls. Regardless of mouse sex, infection depressed the activities of CYP1A [ethoxy/methoxy-resorufin-O-dealkylases (EROD/MROD)], 2B9/10 [pentoxy/benzyloxy-resorufin-O-dealkylases (PROD, BROD)], 2E1 [p-nitrophenol-hydroxylase (PNPH)] and 3A11 [erythromycin N-demethylase (END)] on PID 55 but not on PID 30. On PID 55, infection decreased liver CYP mRNA levels (real-time reverse transcription-polymerase chain reaction). On PID 30, whereas mRNA levels remained unaltered in males, they were depressed in females. Plasma PZQ (200 and 400 mg/kg body weight intraperitoneally) levels were measured (high-performance liquid chromatography) at different post-treatment intervals. In males and females, infection delayed the PZQ clearance on PID 55, but not on PID 30. Therefore, it can be concluded that schistosomiasis down-modulated CYP expression and activity and delayed PZQ clearance on PID 55, when a great number of parasite eggs were lodged in the liver. On PID 30, when egg-laying was initiated by the worms, no change of CYP expression and activity was found, except for a depression of CYP1A2 and 3A11 mRNAs in female mice.