Synthetic nicotine has arrived

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<jats:p>The introduction of a new product line of the popular disposable electronic cigarette brand Puffbar, advertised as containing synthetic nicotine, has drawn attention to the increasing use of synthetic nicotine in marketed products and its uncertain regulatory status. A search of the Truth Tobacco Industry Documents revealed that the industry considered using synthetic nicotine already in the 1960s, efforts that were abandoned due to high costs and insufficient purity. Recent patents revealed renewed efforts to develop more efficient strategies for the synthesis of nicotine. Nicotine exists as two stereoisomers, <jats:italic>S</jats:italic>-nicotine and <jats:italic>R</jats:italic>-nicotine. While <jats:italic>S</jats:italic>-nicotine is the prevalent (>99%) form of nicotine in tobacco, a market-leading form of synthetic nicotine contains both stereoisomers at equal amounts, raising concerns about inaccurate labelling and the poorly understood health effects of <jats:italic>R</jats:italic>-nicotine. Other manufacturers, including a leading vendor of pharmaceutical grade nicotine, developed stereospecific strategies to synthesise pure <jats:italic>S</jats:italic>-nicotine, now added to electronic cigarette products marketed in the USA and UK. While <jats:italic>S</jats:italic>-nicotine and <jats:italic>R</jats:italic>-nicotine can be differentiated by enantioselective High Performance Liquid Chromatography (HPLC), differentiation of synthetic (fossil-derived) from tobacco-derived <jats:italic>S</jats:italic>-nicotine will require development of methods to measure carbon isotope (<jats:sup>14</jats:sup>C or <jats:sup>13</jats:sup>C) content. Vendors claim that the FDA has no authority to regulate synthetic nicotine as a tobacco product, allowing them to circumvent the premarket tobacco product application process. However, legal analysis suggests that FDA may have the authority to regulate synthetic nicotine as a drug. Alternatively, Congress needs to include nicotine from any source within the legal definition of tobacco products.</jats:p>






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Jordt, Sven-Eric (n.d.). Synthetic nicotine has arrived. Tobacco Control. 10.1136/tobaccocontrol-2021-056626 Retrieved from

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Sven Eric Jordt

Associate Professor in Anesthesiology

Research in the Jordt laboratory focuses on the mechanisms that enable humans and animals to sense touch, pain and irritation. These fundamental sensations originate in peripheral sensory neurons which contain signaling pathways that translate environmental physical and chemical stimuli into neural activity. Our aims are to identify the molecular components of these pathways and to understand how sensory neurons become activated and sensitized during injury, inflammation and chronic painful conditions. The lab uses molecular, genetic and physiological techniques with a focus on models that closely mimic human conditions.

Current projects focus on:

1)   Ion channels and New Targets in Pain: The Jordt lab investigates the role of Transient Receptor Potential (TRP) ion channels, a group of ion channels that activate sensory neurons and pain sensations in response to thermal (hot, cold) and chemical stimuli. TRP channels were identified through their interactions with natural products such as capsaicin (in chili peppers), mustard oil (in mustard and wasabi) and menthol (in peppermint), and were shown to be involved in many painful conditions, including arthritis, diabetes and infections. The Jordt lab is studying the actions of TRP channel inhibitors in pain models and investigates mechanisms through which natural products such as menthol and eucalyptol inhibit acute and inflammatory pain.

2)   Allergies, Asthma and Itch: Sensory neurons mediate the sensations of itch, irritation and respiratory discomfort in allergic conditions. Research in the Jordt laboratory has revealed that blocking sensory nerves by targeting their receptors alleviates asthmatic conditions and also diminishes itch and inflammation in allergic contact dermatitis. We developed a unique model of poison ivy contact dermatitis we study to identify novel treatments to suppress itch in conditions unresponsive to antihistamines.

3)   Chemical Exposure Injuries and Tear Gas Agents: Supported by the National Institute of Environmental Health Sciences (NIEHS) and the NIH Countermeasures Against Chemical Threats Program (CounterACT)since 2006, the Jordt laboratory has made key contributions to research understanding the injury mechanisms following toxic chemical exposures. We identified TRPA1 as a target of chlorine gas and many other toxic exposures eliciting incapacitating pain, inflammation and organ injury. The Jordt laboratory is actively working with federal agencies and industry partners to identify additional targets and develop countermeasures that improve health outcomes following chemical exposures. Other studies focus on tear gas agents (CS, CN) and their potentially toxic effects, a topic Dr. Jordt has been interviewed on frequently by the public press.

4)   Tobacco Regulatory Science: Menthol cigarettes are increasingly popular, especially with adolescent beginning smokers. Applying our expertise in chemical sensory biology the Jordt lab demonstrated that menthol reduces the irritation sensed when inhaling smoke and increases markers of nicotine uptake. These effects are mediated by TRPM8, the cold/menthol receptor in sensory neurons innervating the respiratory system. This work is funded by programs from the FDA Center for Tobacco Products (CTP) and the National Institute on Drug Abuse (NIDA) through a Tobacco Center of Regulatory Science (TCORS) in collaboration with Yale University, also supporting studies on flavor additives in electronic cigarettes and smokeless tobacco. 

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