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Psychopharmacological Neuroenhancement: Evidence on Safety and Efficacy

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Cognitive Enhancement

Part of the book series: Trends in Augmentation of Human Performance ((TAHP,volume 1))

Abstract

A number of experts from diverse disciplines have been calling for an evidence-based approach to the evaluation of the risks and benefits of pharmacological cognitive enhancement. If these drugs can be shown to have positive effects in healthy individuals, then this adds urgency to the question of how to regulate their potential use for enhancement purposes. If no evidence of neuroenhancement effects can be found in the existing literature, then this should be made known to healthy individuals who are ready to accept the risk of consuming psychopharmaceuticals.

This paper summarizes the results of a systematic review of the literature that contributes to this quest by collecting and analyzing the available evidence for the most cited neuroenhancement drugs. Based on meta-analyses, it can be shown that expectations regarding the effectiveness of these drugs exceed their actual effects, as has been demonstrated in single- or double-blind randomized controlled trials. According to these data, it seems that the strongest reason not to use prescription drugs for enhancement purposes at the moment is the lack of evidence both for their effectiveness and their long-term safety in healthy people.

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References

  • Babkoff H, Krueger G (1992) Use of stimulants to ameliorate the effects of sleep loss during sustained performance. Mil Psychol 4:191–205

    Article  Google Scholar 

  • Babkoff H, Kelly T, Matteson L, Gomez S, Lopez A, Hauser S, Naitoh P, Assmus J (1992) Pemoline and methylphenidate: interaction with mood, sleepiness, and cognitive performance during 64 hours of sleep deprivation. Mil Psychol 4:235–265

    Article  Google Scholar 

  • Baranski J, Pigeau RA (1997) Self-monitoring cognitive performance during sleep deprivation: effects of modafinil, d-amphetamine and placebo. J Sleep Res 6:84–91

    Article  PubMed  CAS  Google Scholar 

  • Baranski J, Pigeau R, Dinich P, Jacobs I (2004) Effects of modafinil on cognitive and meta-cognitive performance. Hum Psychopharmacol Clin Exp 19:323–332

    Article  CAS  Google Scholar 

  • Beglinger LJ, Gaydos BL, Kareken DA, Tangphao-Daniels O, Siemers ER, Mohs RC (2004) Neuropsychological test performance in healthy volunteers before and after donepezil administration. J Psychopharmacol 18:102–108

    Article  PubMed  CAS  Google Scholar 

  • Beglinger LJ, Tangphao-Daniels O, Kareken DA, Zhang L, Mohs R, Siemers ER (2005) Neuropsychological test performance in healthy elderly volunteers before and after donepezil administration: a randomized, controlled study. J Clin Psychopharmacol 25:159–165

    Article  PubMed  CAS  Google Scholar 

  • Bishop C, Roehrs T, Rosenthal L, Roth T (1997) Alerting effects of methylphenidate under basal and sleep-deprived conditions. Exp Clin Psychopharmacol 5:344–352

    Article  PubMed  CAS  Google Scholar 

  • Bray CL, Cahill KS, Oshier JT, Peden CS, Theriaque DW, Flotte TR, Stacpoole PW (2004) Methylphenidate does not improve cognitive function in healthy sleep-deprived young adults. J Investig Med 52:192–201

    Article  PubMed  CAS  Google Scholar 

  • Brumaghim JT, Klorman R (1998) Methylphenidate’s effects on paired-associate learning and event-related potentials of young adults. Psychophysiology 35:73–85

    Article  PubMed  CAS  Google Scholar 

  • Caldwell JA, Smythe NK, Caldwell JL, Hall KK, Norman DN et al (1999) The effects of modafinil on aviator performance during 40 hours of continuous wakefulness: a UH-60 helicopter simulator study. USAARL Report No. 99-17. United States Air Force Research Laboratory, Fort Rucker

    Google Scholar 

  • Caldwell JA, Caldwell JL, Smythe NK, Hall KK (2000) A double-blind, placebo-controlled investigation of the efficacy of modafinil for sustaining the alertness and performance of aviators: a helicopter simulator study. Psychopharmacology (Berl) 150:272–282

    Article  CAS  Google Scholar 

  • Caldwell JA, Caldwell JL, Smith JK, Brown DL (2004) Modafinil’s effects on simulator performance and mood in pilots during 37 h without sleep. Aviat Space Environ Med 75:777–784

    PubMed  Google Scholar 

  • Clark CR, Geffen GM, Geffen LB (1986) Role of monoamine pathways in attention and effort: effects of clonidine and methylphenidate in normal adult humans. Psychopharmacology (Berl) 90:35–39

    CAS  Google Scholar 

  • Dinges DF, Arora S, Darwish M, Niebler GE (2006) Pharmacodynamic effects on alertness of single doses of armodafinil in healthy subjects during a nocturnal period of acute sleep loss. Curr Med Res Opin 22:159–167

    Article  PubMed  CAS  Google Scholar 

  • Dumont GJ, de-Visser SJ, Cohen AF, van-Gerven JM (2005) Biomarkers for the effects of selective serotonin reuptake inhibitors (SSRIs) in healthy subjects. Br J Clin Pharmacol 59:495–510

    Article  PubMed  CAS  Google Scholar 

  • Eddy D, Storm W, French J, Barton E, Cardenas R (2005) An assessment of modafinil for vestibular and aviation-related effects. Report AFRL-HE-BR-TR-2005-0129, United States Air Force Research Laboratory, Brooks City-Base

    Google Scholar 

  • Egger M, Smith GD, Altman DG et al (2001) Systematic reviews in health care: meta-analysis in context. BMJ Books, London

    Book  Google Scholar 

  • FitzGerald DB, Crucian GP, Mielke JB, Shenal BV, Burks D, Womack KB, Ghacibeh G, Drago V, Foster PS, Valenstein E et al (2008) Effects of donepezil on verbal memory after semantic processing in healthy older adults. Cogn Behav Neurol 21:57–64

    Article  PubMed  Google Scholar 

  • Fitzpatrick P, Klorman R, Brumaghim JT, Keefover RW (1988) Effects of methylphenidate on stimulus evaluation and response processes: evidence from performance and event-related potentials. Psychophysiology 25:292–304

    Article  PubMed  CAS  Google Scholar 

  • Gilbert JG, Donnelly KJ, Zimmer LE, Kubis JF (1973) Effect of magnesium pemoline and methylphenidate on memory improvement and mood in normal aging subjects. Int J Aging Hum Dev 4:35–51

    Article  PubMed  CAS  Google Scholar 

  • Gill M, Haerich P, Westcott K, Godenick KL, Tucker JA (2006) Cognitive performance following modafinil versus placebo in sleep-deprived emergency physicians: a double-blind randomized crossover study. Acad Emerg Med 13:158–165

    Article  PubMed  Google Scholar 

  • Gobbi G, Slater S, Boucher N, Debonnel G, Blier P (2003) Neurochemical and psychotropic effects of bupropion in healthy male subjects. J Clin Psychopharmacol 23:233–239

    PubMed  CAS  Google Scholar 

  • Greely H, Sahakian B, Harris J, Kessler RC, Gazzaniga M, Campbell P, Farah MJ (2008) Towards responsible use of cognitive-enhancing drugs by the healthy. Nature 456:702–705

    Article  PubMed  CAS  Google Scholar 

  • Gron G, Kirstein M, Thielscher A, Riepe MW, Spitzer M (2005) Cholinergic enhancement of episodic memory in healthy young adults. Psychopharmacology 182:170–179

    Article  PubMed  Google Scholar 

  • Hart CL, Haney M, Vosburg SK, Comer SD, Gunderson E, Foltin RW (2006) Modafinil attenuates disruptions in cognitive performance during simulated night-shift work. Neuropsychopharmacology 31:1526–1536

    Article  PubMed  CAS  Google Scholar 

  • Higgins J, Green S (2006) Cochrane handbook for systematic reviews of interventions 4.2.6. Wiley, Chichester

    Google Scholar 

  • Hink RF, Fenton WH, Pfefferbaum A, Tinklenberg JR, Kopell BS (1978) The distribution of attention across auditory input channels: an assessment using the human evoked potential. Psychophysiology 15:466–473

    Article  PubMed  CAS  Google Scholar 

  • Kramer P (1993) Listening to Prozac. Penguin, New York

    Google Scholar 

  • Lagarde D, Batejat D, Van-Beers P, Sarafian D, Pradella S (1995) Interest of modafinil, a new psychostimulant, during a sixty-hour sleep deprivation experiment. Fund Clin Pharmacol 9:271–279

    Article  CAS  Google Scholar 

  • McManus P, Mant A, Mitchell PB, Montgomery WS, Marley J, Auland ME (2000) Recent trends in the use of antidepressant drugs in Australia, 1990–1998. Med J Aust 173:458–461

    PubMed  CAS  Google Scholar 

  • Mehta MA, Owen AM, Sahakian BJ, Mavaddat N, Pickard JD, Robbins TW (2000) Methylphenidate enhances working memory by modulating discrete frontal and parietal lobe regions in the human brain. J Neurosci 20:RC65

    PubMed  CAS  Google Scholar 

  • Olie JP, Elomari F, Spadone C, Lepine JP (2002) Antidepressants consumption in the global population in France. Encéphale 28:411–417

    PubMed  CAS  Google Scholar 

  • Peloquin LJ, Klorman R (1986) Effects of methylphenidate on normal children’s mood, event-related potentials, and performance in memory scanning and vigilance. J Abnorm Psychol 95:88–98

    Article  PubMed  CAS  Google Scholar 

  • Pigeau R, Naitoh P, Buguet A, McCann C, Baranski J, Taylor M, Thompson M, Mack I (1995) Modafinil, d-amphetamine and placebo during 64 hours of sustained mental work. I. Effects on mood, fatigue, cognitive performance and body temperature. J Sleep Res 4:212–228

    Article  PubMed  Google Scholar 

  • Racchi M, Mazzucchelli M, Porrello E, Lanni C, Govoni S (2004) Acetylcholinesterase inhibitors: novel activities of old molecules. Pharmacol Res 50:441–451

    Article  PubMed  CAS  Google Scholar 

  • Raymond CB, Morgan SG, Caetano PA (2007) Antidepressant utilization in British Columbia from 1996 to 2004: increasing prevalence but not incidence. Psychiatr Serv 58:79–84

    Article  PubMed  Google Scholar 

  • Repantis D, Schlattmann P, Laisney O, Heuser I (2009) Antidepressants for neuoenhancement in healthy individuals: a systemic review. Poiesis Prax 6:139–174

    Article  Google Scholar 

  • Repantis D, Laisney O, Heuser I (2010a) Acetylcholinesterase inhibitors and memantine for neuroenhancement in healthy individuals: a systemtic review. Pharmacol Res 61:473–481

    Article  PubMed  CAS  Google Scholar 

  • Repantis D, Schlattmann P, Laisney O, Heuser I (2010b) Modafinil and methylphenidate for neuroenhancement in healthy individuals: a systematic review. Pharmacol Res 62:187–206

    Article  PubMed  CAS  Google Scholar 

  • Roehrs T, Papineau K, Rosenthal L, Roth T (1999) Sleepiness and the reinforcing and subjective effects of methylphenidate. Exp Clin Psychopharmacol 7:145–150

    Article  PubMed  CAS  Google Scholar 

  • Roehrs T, Meixner R, Turner L, Johanson CE, Roth T (2004) Reinforcing and subjective effects of methylphenidate: dose and time in bed. Exp Clin Psychopharmacol 12:180–189

    Article  PubMed  CAS  Google Scholar 

  • Rogers RD, Blackshaw AJ, Middleton HC, Matthews K, Hawtin K, Crowley C, Hopwood A, Wallace C, Deakin JF, Sahakian BJ et al (1999) Tryptophan depletion impairs stimulus-reward learning while methylphenidate disrupts attentional control in healthy young adults: implications for the monoaminergic basis of impulsive behaviour. Psychopharmacology 146:482–491

    Article  PubMed  CAS  Google Scholar 

  • Schöne-Seifert B, Talbot D (2011) (Neuro-)enhancement. In: Helmchen H, Sartorius N (eds) Textbook of psychiatry. Springer, New York

    Google Scholar 

  • Smith D, Pernet A, Rosenthal JM, Bingham EM, Reid H, Macdonald IA, Amiel SA (2004) The effect of modafinil on counter-regulatory and cognitive responses to hypoglycaemia. Diabetologia 47:1704–1711

    Article  PubMed  CAS  Google Scholar 

  • Sonkusare SK, Kaul CL, Ramarao P (2005) Dementia of Alzheimer’s disease and other neurodegenerative disorders – memantine, a new hope. Pharmacol Res 51:1–17

    Article  PubMed  CAS  Google Scholar 

  • Spreen O, Strauss E (1998) A compendium of neuropsychological tests: administration, norms, and commentary. Oxford University Press, Inc., New York

    Google Scholar 

  • Strauss J, Lewis JL, Klorman R, Peloquin LJ, Perlmutter RA, Salzman LF (1984) Effects of methylphenidate on young adults’ performance and event-related potentials in a vigilance and a paired-associates learning test. Psychophysiology 21:609–621

    Article  PubMed  CAS  Google Scholar 

  • Talbot M (2009) A reporter at large brain gain. The underground world of neuroenhancing drugs. The New Yorker, April 27, 2009

    Google Scholar 

  • Taneja I, Haman K, Shelton RC, Robertson D (2007) A randomized, double-blind, crossover trial of modafinil on mood. J Clin Psychopharmacol 27:76–79

    Article  PubMed  CAS  Google Scholar 

  • Volkow ND, Wang GJ, Fowler JS, Gatley SJ, Logan J, Ding YS, Hitzemann R, Pappas N (1998) Dopamine transporter occupancies in the human brain induced by therapeutic doses of oral methylphenidate. Am J Psychiatry 155:1325–1331

    PubMed  CAS  Google Scholar 

  • Volkow ND, Wang GJ, Fowler JS, Logan J, Gatley SJ, Wong C, Hitzemann R, Pappas NR (1999a) Reinforcing effects of psychostimulants in humans are associated with increases in brain dopamine and occupancy of D(2) receptors. J Pharmacol Exp Ther 291:409–415

    PubMed  CAS  Google Scholar 

  • Volkow ND, Wang GJ, Fowler JS, Gatley SJ, Logan J, Ding Y, Dewey SL, Hitzemann R, Gifford AN, Pappas NR (1999b) Blockade of striatal dopamine transporters by intravenous methylphenidate is not sufficient to induce self-reports of ‘high’. J Pharmacol Exp Ther 288:14–20

    PubMed  CAS  Google Scholar 

  • Wesensten NJ, Belenky G, Kautz MA, Thorne DR, Reichardt RM, Balkin TJ (2002) Maintaining alertness and performance during sleep deprivation: modafinil versus caffeine. Psychopharmacology 159:238–247

    Article  PubMed  CAS  Google Scholar 

  • Wetzel CD, Squire LR, Janowsky DS (1981) Methylphenidate impairs learning and memory in normal adults. Behav Neural Biol 31:413–424

    Article  PubMed  CAS  Google Scholar 

  • Whitmore J, Hickey P, Doan B, Harrison R, Kisner J, Beltran T, McQuade J, Fischer J, Marks F (2006) A double-blind placebo controlled investigation of the efficacy of modafinil for maintaining alertness and performance in sustained military ground operations. Report AFRL-HE-BR-TR-2006-0005. United States Air Force Research Laboratory, Brooks-City-Base

    Google Scholar 

  • Yesavage JA, Mumenthaler MS, Taylor JL, Friedman L, O’Hara R, Sheikh J, Tinklenberg J, Whitehouse PJ (2002) Donepezil and flight simulator performance: effects on retention of complex skills. Neurology 59:123–125

    Article  PubMed  CAS  Google Scholar 

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Authors and Affiliations

  1. Department of Psychiatry, Charité-Universitätsmedizin Berlin, Campus Benjamin Franklin, Berlin, Germany

    Dimitris Repantis

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  1. Dimitris Repantis
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Correspondence to Dimitris Repantis .

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Editors and Affiliations

  1. , Department of Philosophy, University of Mainz, Jakob Welder-Weg 18, Mainz, 55099, Germany

    Elisabeth Hildt

  2. , Psychiatry and Psychotherapy, University Medical Center Mainz, Untere Zahlbacher Str. 8, Mainz, 55131, Germany

    Andreas G. Franke

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Repantis, D. (2013). Psychopharmacological Neuroenhancement: Evidence on Safety and Efficacy. In: Hildt, E., Franke, A. (eds) Cognitive Enhancement. Trends in Augmentation of Human Performance, vol 1. Springer, Dordrecht. https://doi.org/10.1007/978-94-007-6253-4_3

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