Dursun S M, Kutcher S
Department of Psychiatry, Dalhousie University, Queen Elizabeth II Health Sciences Centre, Halifax, Nova Scotia, Canada.
Med Hypotheses. 1999 Feb;52(2):101-9. doi: 10.1054/mehy.1997.0623.
Researchers interested in investigating the possible therapeutic effects and the mechanisms of action of nicotine in neuropsychiatric disorders face a social-scientific-ethical dilemma. This dilemma comprises three components: (1) the known addictive potential of nicotine makes careful evaluation of the therapeutic potential of this compound socially unattractive; (2) the potential misuse of scientifically determined data by the tobacco 'lobby' creates ethical concerns; and (3) the possible confusion between the differential effects of nicotine in human smokers versus non-smokers creates difficulties in study designs in voluntary human subjects. Therefore, it is imperative that, at the onset of this review, the authors stress that they do not advocate cigarette-smoking as a route of nicotine intake under any circumstances on the basis that controlled dosing of nicotine may be of potential benefit in some neuropsychiatric disorders. In this article, we review the psychopharmacology of nicotine and its effects in a variety of neuropsychiatric disorders including schizophrenia, depression, anxiety and Tourette's syndrome. Possible mechanisms of action of nicotine directly or indirectly via its interaction with other neurotransmitter systems (i.e. serotonin, dopamine and noradrenaline) in relation to its potential role in these disorders are discussed. It is postulated that new drugs may need to be developed that selectively interact with nicotinic receptors without addiction potential.
对尼古丁在神经精神疾病中的潜在治疗作用及作用机制进行研究的人员面临着社会科学伦理困境。这一困境包含三个方面：（1）尼古丁已知的成瘾潜力使得对该化合物治疗潜力的审慎评估在社会层面缺乏吸引力；（2）烟草“游说团体”对科学测定数据的潜在滥用引发了伦理担忧；（3）尼古丁在人类吸烟者与非吸烟者中不同作用的可能混淆给自愿参与研究的人体受试者的研究设计带来了困难。因此，在本综述开篇，作者必须强调，他们在任何情况下都不主张将吸烟作为尼古丁摄入途径，因为在某些神经精神疾病中，尼古丁的可控给药可能具有潜在益处。在本文中，我们综述了尼古丁的精神药理学及其在包括精神分裂症、抑郁症、焦虑症和图雷特综合征在内的多种神经精神疾病中的作用。讨论了尼古丁直接或通过与其他神经递质系统（即5-羟色胺、多巴胺和去甲肾上腺素）相互作用在这些疾病中发挥潜在作用的可能作用机制。据推测，可能需要研发出能选择性地与烟碱受体相互作用且无成瘾潜力的新药。
