VIPER Research Unit, Department of LIFE, Royal Military Academy, Brussels 1000, Belgium.
Brain, Body and Cognition, Department of Psychology, Vrije Universiteit Brussel, Brussels 1050, Belgium.
Mil Med. 2022 Jan 4;187(1-2):52-64. doi: 10.1093/milmed/usab398.
Modafinil is an eugeroic drug that has been examined to maintain or recover wakefulness, alertness, and cognitive performance when sleep deprived. In a nonmilitary context, the use of modafinil as a nootropic or smart drug, i.e., to improve cognitive performance without being sleep deprived, increases. Although cognitive performance is receiving more explicit attention in a military context, research into the impact of modafinil as a smart drug in function of operationality is lacking. Therefore, the current review aimed at presenting a current state-of-the-art and research agenda on modafinil as a smart drug. Beside the question whether modafinil has an effect or not on cognitive performance, we examined four research questions based on the knowledge on modafinil in sleep-deprived subjects: (1) Is there a difference between the effect of modafinil as a smart drug when administered in repeated doses versus one single dose?; (2) Is the effect of modafinil as a smart drug dose-dependent?; (3) Are there individual-related and/or task-related impact factors?; and (4) What are the reported mental and/or somatic side effects of modafinil as a smart drug?
We conducted a systematic search of the literature in the databases PubMed, Web of Science, and Scopus, using the search terms "Modafinil" and "Cognitive enhance*" in combination with specific terms related to the research questions. The inclusion criteria were studies on healthy human subjects with quantifiable cognitive outcome based on cognitive tasks.
We found no literature on the impact of a repeated intake of modafinil as a smart drug, although, in users, intake occurs on a regular basis. Moreover, although modafinil was initially said to comprise no risk for abuse, there are now indications that modafinil works on the same neurobiological mechanisms as other addictive stimulants. There is also no thorough research into a potential risk for overconfidence, whereas this risk was identified in sleep-deprived subjects. Furthermore, eventual enhancing effects were beneficial only in persons with an initial lower performance level and/or performing more difficult tasks and modafinil has an adverse effect when used under time pressure and may negatively impact physical performance. Finally, time-on-task may interact with the dose taken.
The use of modafinil as a smart drug should be examined in function of different military profiles considering their individual performance level and the task characteristics in terms of cognitive demands, physical demands, and sleep availability. It is not yet clear to what extent an improvement in one component (e.g., cognitive performance) may negatively affect another component (e.g., physical performance). Moreover, potential risks for abuse and overconfidence in both regular and occasional intake should be thoroughly investigated to depict the trade-off between user benefits and unwanted side effects. We identified that there is a current risk to the field, as this trade-off has been deemed acceptable for sleep-deprived subjects (considering the risk of sleep deprivation to performance) but this reasoning cannot and should not be readily transposed to non-sleep-deprived individuals. We thus conclude against the use of modafinil as a cognitive enhancer in military contexts that do not involve sleep deprivation.
莫达非尼是一种促觉醒药物,已被研究用于在睡眠剥夺时维持或恢复觉醒、警觉和认知表现。在非军事环境中,莫达非尼作为益智药或智能药物的使用(即,在不睡眠剥夺的情况下提高认知表现)正在增加。尽管在军事环境中,认知表现受到了更多的关注,但缺乏关于莫达非尼作为智能药物在功能方面的影响的研究。因此,目前的综述旨在介绍莫达非尼作为智能药物的最新现状和研究议程。除了莫达非尼是否对认知表现有影响的问题外,我们还根据睡眠剥夺受试者中关于莫达非尼的知识,基于以下四个研究问题进行了检查:(1)莫达非尼作为智能药物在重复剂量给药与单次剂量给药之间是否存在差异?;(2)莫达非尼作为智能药物的效果是否存在剂量依赖性?;(3)是否存在个体相关和/或任务相关的影响因素?;以及(4)作为智能药物的莫达非尼有哪些报告的精神和/或躯体副作用?
我们在 PubMed、Web of Science 和 Scopus 数据库中进行了系统的文献搜索,使用了“莫达非尼”和“认知增强”这两个搜索词,并结合了与研究问题相关的特定术语。纳入标准是基于认知任务的量化认知结果,对健康人类受试者进行的研究。
我们没有发现关于重复摄入莫达非尼作为智能药物的影响的文献,尽管在使用者中,摄入是定期进行的。此外,尽管莫达非尼最初被认为没有滥用风险,但现在有迹象表明,莫达非尼作用于与其他成瘾性兴奋剂相同的神经生物学机制。也没有对过度自信的潜在风险进行彻底研究,而在睡眠剥夺的受试者中已经确定了这种风险。此外,最终的增强效果仅对初始表现水平较低的人或执行更困难任务的人有益,而且在时间压力下使用莫达非尼会产生不良影响,并可能对身体表现产生负面影响。最后,任务时间可能与服用的剂量相互作用。
应根据不同的军事人员的个人表现水平和任务特征,考虑认知需求、身体需求和睡眠可用性,将莫达非尼作为智能药物的使用进行检查。在一定程度上,一个组成部分(例如认知表现)的改善是否会对另一个组成部分(例如身体表现)产生负面影响还不清楚。此外,应该彻底研究定期和偶尔摄入的潜在滥用和过度自信风险,以描绘用户利益与不良副作用之间的权衡。我们发现目前存在风险,因为这种权衡对于睡眠剥夺的受试者来说是可以接受的(考虑到睡眠剥夺对表现的风险),但这种推理不能也不应轻易转移到非睡眠剥夺的个体。因此,我们反对在不涉及睡眠剥夺的军事环境中使用莫达非尼作为认知增强剂。