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      A State-of-the-Art Review on the Use of Modafinil as A Performance-enhancing Drug in the Context of Military Operationality

      1 , 2 , 3 , 1 , 4 , 1 , 1 , 4
      Military Medicine
      Oxford University Press (OUP)

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          ABSTRACT

          Introduction

          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?

          Method

          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.

          Results

          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.

          Discussion

          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.

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          Most cited references108

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          Review. The incentive sensitization theory of addiction: some current issues.

          We present a brief overview of the incentive sensitization theory of addiction. This posits that addiction is caused primarily by drug-induced sensitization in the brain mesocorticolimbic systems that attribute incentive salience to reward-associated stimuli. If rendered hypersensitive, these systems cause pathological incentive motivation ('wanting') for drugs. We address some current questions including: what is the role of learning in incentive sensitization and addiction? Does incentive sensitization occur in human addicts? Is the development of addiction-like behaviour in animals associated with sensitization? What is the best way to model addiction symptoms using animal models? And, finally, what are the roles of affective pleasure or withdrawal in addiction?
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            Mental fatigue impairs physical performance in humans.

            Mental fatigue is a psychobiological state caused by prolonged periods of demanding cognitive activity. Although the impact of mental fatigue on cognitive and skilled performance is well known, its effect on physical performance has not been thoroughly investigated. In this randomized crossover study, 16 subjects cycled to exhaustion at 80% of their peak power output after 90 min of a demanding cognitive task (mental fatigue) or 90 min of watching emotionally neutral documentaries (control). After experimental treatment, a mood questionnaire revealed a state of mental fatigue (P = 0.005) that significantly reduced time to exhaustion (640 +/- 316 s) compared with the control condition (754 +/- 339 s) (P = 0.003). This negative effect was not mediated by cardiorespiratory and musculoenergetic factors as physiological responses to intense exercise remained largely unaffected. Self-reported success and intrinsic motivation related to the physical task were also unaffected by prior cognitive activity. However, mentally fatigued subjects rated perception of effort during exercise to be significantly higher compared with the control condition (P = 0.007). As ratings of perceived exertion increased similarly over time in both conditions (P < 0.001), mentally fatigued subjects reached their maximal level of perceived exertion and disengaged from the physical task earlier than in the control condition. In conclusion, our study provides experimental evidence that mental fatigue limits exercise tolerance in humans through higher perception of effort rather than cardiorespiratory and musculoenergetic mechanisms. Future research in this area should investigate the common neurocognitive resources shared by physical and mental activity.
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              The human emotional brain without sleep--a prefrontal amygdala disconnect.

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                Author and article information

                Contributors
                (View ORCID Profile)
                Journal
                Military Medicine
                Oxford University Press (OUP)
                0026-4075
                1930-613X
                January 01 2022
                January 04 2022
                October 11 2021
                January 01 2022
                January 04 2022
                October 11 2021
                : 187
                : 1-2
                : 52-64
                Affiliations
                [1 ]VIPER Research Unit, Department of LIFE, Royal Military Academy, Brussels 1000, Belgium
                [2 ]Brain, Body and Cognition, Department of Psychology, Vrije Universiteit Brussel, Brussels 1050, Belgium
                [3 ]Clinical & Lifespan Psychology, Department of Psychology and Educational Sciences, Vrije Universiteit Brussel, Brussels 1050, Belgium
                [4 ]MFYS-BLITS, Department of Human Physiology, Vrije Universiteit Brussel, Brussels 1050, Belgium
                Article
                10.1093/milmed/usab398
                c9c2f3e3-8e78-49b6-ab79-4cfef419724e
                © 2021

                https://academic.oup.com/journals/pages/open_access/funder_policies/chorus/standard_publication_model


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