从致癌物到神经守护者：被污名化的尼古丁正在创造 600 亿美元医疗新蓝海​/From carcinogens to nerve guardians: Stigmatized nicotine is creating a new $60 billion medical Blue Ocean

长久以来，尼古丁被大众牢牢贴上 “致癌物” 的标签，与香烟紧密相连，背负着损害健康的恶名。然而，哈佛医学院的最新研究却如一道曙光，彻底颠覆了我们对尼古丁的传统认知。研究发现，尼古丁受体激活效率与 Aβ 蛋白清除率呈现出显著的正相关性。这意味着，尼古丁有可能成为清除大脑中有害 Aβ 蛋白的关键 “武器”，为阿尔茨海默病等神经退行性疾病的治疗带来新希望。同时，临床数据也为尼古丁的医疗价值提供了有力支撑。在针对帕金森患者的治疗中，每日使用 4mg 尼古丁贴剂的治疗组，震颤改善率竟高达 62%。这一令人瞩目的数据，让人们不得不重新审视尼古丁在医疗领域的潜力。

For a long time, nicotine has been firmly labeled as a "carcinogen" by the public, and is closely linked to cigarettes, carrying a bad reputation for damaging health. New research from Harvard Medical School, however, has turned our conventional understanding of nicotine on its head. It was found that there was A significant positive correlation between nicotine receptor activation efficiency and Aβ protein clearance. This means that nicotine has the potential to become A key "weapon" in clearing harmful Aβ proteins from the brain, bringing new hope for the treatment of neurodegenerative diseases such as Alzheimer's disease. At the same time, clinical data also provide strong support for the medical value of nicotine. In the treatment of Parkinson's disease patients, the tremor improvement rate was as high as 62% in the treatment group using 4mg of nicotine patch daily. This remarkable data has forced people to re-examine the potential of nicotine in the medical field.

随着对尼古丁医疗作用研究的深入，一场围绕其适应症的争夺战悄然打响。在阿尔茨海默病的治疗研究方面，尼古丁透皮贴剂的 III 期临床试验患者招募正在加速推进。若试验成功，将为阿尔茨海默病患者带来全新的治疗选择。而在精神疾病赛道，尼古丁也展现出独特的作用机制。研究表明，尼古丁口含片能够调节抑郁症患者的 REM 睡眠，从睡眠调节的角度为抑郁症治疗开辟新路径。众多科研团队和医药企业纷纷投入到尼古丁适应症的研究中，试图在这片新兴的医疗领域抢占先机。

With the deepening of the research on the medical effects of nicotine, a battle has been quietly started around its indications. In terms of therapeutic research for Alzheimer's disease, patient recruitment for Phase III clinical trials of nicotine transdermal patches is accelerating. If the trial is successful, it could open up entirely new treatment options for Alzheimer's patients. In the field of mental illness, nicotine also shows a unique mechanism of action. Studies have shown that nicotine lozenges can regulate REM sleep in patients with depression, opening up a new path for depression treatment from the perspective of sleep regulation. Many scientific research teams and pharmaceutical companies have invested in the study of nicotine indications, trying to seize the opportunity in this emerging medical field.

在技术层面，尼古丁的医疗应用也迎来了重大突破。靶向递送技术的创新成果令人惊叹，搭载外泌体的尼古丁纳米粒子，其穿透血脑屏障的效率相较于传统方式提升了 20 倍。这一突破使得尼古丁能够更精准、高效地抵达大脑病灶区域，发挥治疗作用。同时，基因编辑技术也为尼古丁的医疗应用提供了助力。通过 CRISPR 对尼古丁乙酰胆碱受体进行改造，能够极大地增强治疗的特异性，减少对其他组织和器官的副作用，让尼古丁的治疗效果更加显著和安全。

At the technical level, the medical application of nicotine has also ushered in a major breakthrough. The innovation in targeted delivery technology is amazing, with exosome-loaded nicotine nanoparticles that penetrate the blood-brain barrier 20 times more efficiently than conventional methods. This breakthrough allows nicotine to reach the affected areas of the brain more precisely and efficiently to play a therapeutic role. At the same time, gene editing technology also provides a boost for the medical use of nicotine. Modification of nicotine acetylcholine receptors through CRISPR can greatly enhance the specificity of treatment, reduce side effects on other tissues and organs, and make the therapeutic effect of nicotine more significant and safe.

然而，尼古丁医疗应用的发展并非一帆风顺，伦理问题成为了横亘在其面前的一道难题。一方面，尼古丁在医疗用途上展现出巨大潜力；另一方面，其成瘾风险也不容忽视。FDA 推出的新型风险效益评估模型（RBRM），旨在平衡这两者之间的关系，但在实际应用中却引发了诸多争议。部分人士认为该模型未能充分考虑尼古丁成瘾的复杂性，可能导致对患者潜在风险的低估。而一项针对医生群体的调研显示，72% 的神经科医师支持开发去成瘾性尼古丁衍生物，这反映出医疗专业人士对于解决尼古丁成瘾问题、推动其医疗应用的强烈期望。

However, the development of the medical application of nicotine is not smooth sailing, and ethical issues have become a difficult problem in front of it. On the one hand, nicotine shows great potential for medical use; On the other hand, the risk of addiction cannot be ignored. The FDA's new Risk Benefit assessment model (RBRM) aims to balance the two, but it has caused a lot of controversy in practical applications. Some argue that the model fails to adequately account for the complexity of nicotine addiction and may lead to an underestimation of potential risks for patients. According to a survey of physicians, 72% of neurologists support the development of non-addictive nicotine derivatives, reflecting the strong desire of medical professionals to address nicotine addiction and advance its medical use.