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Smarter, Faster, Harder

HowWillMedicalStudentsandDoctorsBeAffectedby'CognitiveEnhancing'Drugs? MeherLadNeilHarrison Posted:09/13/2012StudBMJ2012BMJPublishingGroup

Introduction Medicalschoolishardwork.Therearelonghoursforweeksonend,andwehavetokeepprovingourselvesevenafterwe qualifyasdoctors.Thereisaconstantpressuretopassexams,engageinextracurricularactivities,conductresearch projects,andpublish,tobecompetitiveforfuturejobs.Thisisastrainonanystudentsmotivation,concentration,andfocus. Itisperhapsnosurprisethatmanystudentsturntoaidssuchascoffee,revisioncourses,tutors,orevenspecialdiets.In recentyears,somestudentshavebeenusinganumberofcognitiveenhancingdrugsofflicence.Thereareclaimsthat thesecanincreaseconcentrationandmemoryandallowprolongedperiodsofattentionwhileyouareworking.[13] CognitiveEnhancers,Neuroenhancers,orNootropics Thesearethetermsforagroupofdrugsintendedforuseinmedicalandpsychiatricdisorderssuchasattentiondeficit hyperactivitydisorder,fatigue,shiftworksleepdisorder,andnarcolepsy(seeTable).Methylphenidate(Ritalin),Adderall (mixedamphetaminesalts),andmorerecentlymodafinil(Provigil)havegainedareputationamongsomestudentsas cognitiveenhancers.USgovernmentaldatashowthat1.6millionpeopleusedoneofthesewithoutprescriptionin2007.[1]At someUSuniversities,7%ofstudentsregularlyusethesedrugswhilestudying,and1625%haddonesointhepastyear.[2,3] Evidencealsosuggeststhatthisisatrendthatislikelytogrowinthefuture.[3]DatafromtheUnitedKingdomhavenotbeen aswelldocumented.
Table1.

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Butarethesedrugseffective?Evidenceshowsthatinhealthypeopletheyseemtoenhanceelementsofexecutivefunction, anumbrellatermforhighlevelcognitiveprocessesincludingworkingmemory,planning,attention,problemsolving,and multitasking[4]Workingmemoryhasbeenshowntobeenhancedbymethylphenidate,adrugthatincreasestheconcentration ofdopamineandnoradrenalinebypreventingtheirreuptake.[5]Bothofthesechemicalsareinvolvedinavarietyofbrain functionsandareimportantmediatorsofconcentration.Neuroimaginghasshownthatmethylphenidatereducestheactivation oftheareasofthebraininvolvedinworkingmemoryduringnoveltasks,implyingareducedworkingmemoryload.[6] Interestingly,inthisstudy,thepeoplewhodidworseonthecognitivetaskbeforereceivingthedrugbenefitedthemost.A similareffecthasbeenobservedforthedrugbromocriptine.[7] Anewerdrug,modafinil,hasbeenshowntoinhibitinappropriateimpulsiveresponsesandimproveperformancewhenfatigue setsin.[8]Thisdruginhibitsdopamineandnoradrenalinereuptakebutalsoseemstohaveeffectsonhistamine,orexins,and serotonin,whichmayexplainwhyitpromoteswakefulness. Theacetylcholinesteraseinhibitordonepezil,whichislicensedforuseinslowingtheprogressionofAlzheimersdisease,has beenshowntoenhancetheperformanceofpilotsafterflightsimulatortraining.[9]Acetylcholinemightbeinvolvedinmemory, andincreasingitsconcentrationseemstobenefitpatientswithAlzheimersdiseaseandalsohealthypeople.Otherdrugsare beinginvestigated.[10,11] AreTheseDrugsSafe? Althoughthebenefitsofthesedrugsfortreatmentoftheirintendedmedicalconditionsarewelldocumented,wemustalso considertheirsideeffects.Peoplewithattentiondeficithyperactivitydisorderornarcolepsymayconsideritreasonableto enduremildsideeffectstoincreasetheirqualityoflifeoverall.Butisthisjustifiableinpeoplewhojustwanttopasstheir exams? Someoftheshorttermsideeffectsthatareknownfortheamphetaminebaseddrugsincludedecreasedappetite,drymouth,

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andsleepingproblems.Thesearewelltoleratedbymostpeopleandaresignificantinlessthan10%ofpeople.[6]Themain worry,however,isthattheremaybeunknowneffectsthatbecomeevidentonlyaftermanyyearsofuse.Itisstillnotknown howcognitiveenhancersaffectneuralplasticityinthelongterm.Theappetitesuppressantfenfluramineseemedawonder drugwhenitwasreleased,butitwasremovedyearslaterwhenitwasdiscoveredthatithadseriouscardiacsideeffects.[12] Wemayalsonotbeabletopickupthemoresubtlesideeffectsthesedrugsmayhave.Forexample,dotheeffectsthey haveontheneurotransmittersystemsalterourpersonalities,mood,orlibido?Althoughthereisanestablishedsideeffect profileforpatientstakingthesedrugsfortheirlicenseduse,thereisapaucityofdataabouthealthypeopleusingthemas cognitiveenhancers. UsesofCognitiveEnhancers Thepotentialofcognitiveenhancershasbeenexploitedinthepastandislikelytobeagain.Amphetamineswerewidelyused inthesecondworldwarbyGerman,British,Japanese,andAmericansoldierstokeepawakeandalert,andsoldierswere sometimeslegallyrequiredtotakethesedrugsforthesakeofmilitaryperformance.[1]Itisconceivablethatinthefuturethis maybearequirementinotherfieldsofwork.Aneurosurgeoncouldbenefitfromhisorherconcentrationbeingaugmented whileperforminghighrisksurgery,forexample,andlonghaulpilotsmightneeddrugstohelpstayfocusedinlongflights.A recentrandomisedcontrolledtrialshowedthatsleepdepriveddoctorsbenefitedfrompharmacologicalenhancementin situationsrequiringflexiblethinkinganddecisionmaking.[13]Cosmeticsurgery,sportsmedicine,andfertilitytreatmenthave enhancedhumanabilitiesandshapeddesiresgreatlyinthepastdecade,andperhapscognitiveenhancementwilldothe same. Theuseofcognitiveenhancingdrugshasdirectimplicationsforpatientcare.Whatifmorbidityandmortalityratesofpatients areshowntodeclinewhendoctorscognitionisenhanced?Willwebeobligedtotaketheminthefuture?Itmaybethatthe publiccoulddemandcognitivelyenhanceddoctors. Somescientistsbelievethatcognitiveenhancementisalreadyarealityformanypeoplewhoarewillingtoenhancetheir cognition,andthatothersmaybefallingbehind.[1416]MichaelGazzaniga,aneuroscientistattheUniversityofCalifornia, commented,Ifwecanboostourabilitiestomakeupfortheonesmothernaturedidntgiveus,whatiswrongwiththat?Itis necessarytothinkofthewaysthatwecanmoveforward.Cantheuseofcognitiveenhancersbefair?Ifnotforeveryone, thencantheybeusedforspecialpopulations?Whatroledohealthprofessionalshavetoplayinbeingthegatekeepersof thesedrugs? DoctorsasGatekeepers Aplausiblescenariointhefutureisasfollows.Astudentispreparingforhisorherlastexamandfeelsthattofinishlearning thecurriculumheorsheneedstopullanallnighter.Thestudenthasreadaboutanarticleaboutanewdrugthatpromotes wakefulnessinshiftworkersandthinksitcouldbeusefulduringrevision.Soheorshevisitsthegeneralpractitionerand requestsmodafinil.Howshouldthedoctorrespond?Somegeneralpractitionerswehavespokentosaidtheywould recommendsleephygiene(thatis,methodstoalterbehaviouralandenvironmentalfactorsthatinterferewithsleep,suchas drinkingcoffeeatnightornappinginthedaytime)duringexamsandtoavoidthecrammingthatsomanystudentsendure.On theotherhand,othersmightgiveaoneoffprescription.Itisclearthatopinionisdividedandtherearenostudiesdescribing doctorsviewsonthesubject. Theroleofthedoctorisimportantincognitiveenhancementbecausedoctorswillbethegatekeepersforthesedrugsiftheir useisacceptedinsociety.Isitethicalforageneralpractitionertoprescribeaoneoffdoseofsuchdrugs?Whathappensif suchvisitsbecomearegularoccurrence?AnarticlepublishedinNaturebyagroupofeminentneuroscientistsaskedfora responsibleuseofcognitiveenhancersinthehealthy.[15]Theyarguethatthisispossibleifthesedrugsareproperly regulated,andaninitialstepwouldbeforphysicians,educators,andregulatorstodeveloppoliciesfortheiruse.Othersteps includebuildinganinformationbaseabouttheireffects,developingguidelinesfortheiruse,increasingpublicunderstanding, andcreatingappropriatelegislationsothattheycanbeusedsafely. ReachingaVerdict Onepotentialwaytoreconciletheuseofcognitiveenhancingdrugscomesfromphilosophy.Itcouldbearguedthatthese drugsdotoourmindsinternallywhatexternaldevicessuchastheinternetandsmartphonesdoeveryday.DavidChalmers, inTheExtendedMindHypothesis,hasarguedthatitisarbitrarytosaythatthemindiscontainedwithintheconfinesofthe skull.Insteadhesaysthattheconceptofthemindshouldbeexpandedtoincludeexternalobjectsiftheyservethesame functionasinternalprocesses.[17]Forexample,yourmindcanbeextendedtoanotebookthatstoresinformationabout

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differentmedicalconditionsinthesamewayanotherpersonrememberssuchinformation.Similarly,itcanbearguedthat cognitiveenhancingdrugsdointernallywhatanotherpersonsnotebookorinnatememorymightdo. Shouldtheuseofcognitiveenhancersbeallowed,ordotheycreateanunfairplayingfieldwhenitcomestoexamsandjob opportunities?Theverdictisstillunclear.Thesedrugsarenotcurrentlylicensedforcognitiveenhancement,however,and theiracquisitionanduseforsuchpurposesisillegal.Itisunclearwhetherthisservesasadeterrent.Thelongterm pharmacologicaleffectsandpotentialforharmarealsounknown.Aretheserisksworthtakingtogainthecompetitiveedge?

References

1. StixG.Turbochargingthebrain.ScientAmMag2009301:4655. 2. BabcockQ,ByrneT.Studentperceptionsofmethylphenidateabuseatapublicliberalartscollege.JAmCollHealth 200049:1435. 3. MaherB.Pollresults:lookwhosdoping.Nature2008452:6745. 4. SahakianB,MoreinZamirS.Professorslittlehelper.Nature2007450:11579. 5. MehtaMA,OwenAM,SahakianBJ,MavvadatN,PickardJD,RobbinsTW.Methylphenidateenhancesworking memorybymodulatingdiscretefrontalandparietalloberegionsinthehumanbrain.JNeurosci200020:65RC. 6. ElliottR,SahakianBJ,MatthewsK,BannerjeaA,RimmerJ,RobbinsTW.Effectsofmethylphenidateonspatial workingmemoryandplanninginhealthyyoungadults.Psychopharmacology1997131:196206. 7. KimbergDY,DEspositoM,FarahMJ.Effectsofbromocriptineonhumansubjectsdependonworkingmemory capacity.Neuroreport19978:3581. 8. TurnerDC,RobbinsTW,ClarkL,AronAR,SahakianBJ.Cognitiveenhancingeffectsofmodafinilinhealthy volunteers.Psychopharmacology2003165:2609. 9. YesavageJA,MumenthalerMS,TaylorJL,FriedmanL,OHaraR,SheikhJ.Donepezilandflightsimulator performance:effectsonretentionofcomplexskills.Neurology200259:123. 10. Lynch,G.Memoryenhancement:thesearchformechanismbaseddrugs.NatureNeuroscience20025:10358. 11. HallSS.Thequestforasmartpill.ScientAm2003289:5465. 12. ConnollyHM,CraryJL,McGoonMD,HensrudDD,EdwardsBS,EdwardsWD,etal.Valvularheartdiseaseassociated withfenfluraminephentermine.NEnglJMed1997337:5818. 13. SugdenC,HousdenCR,AggarwalR,SahakuianBJ,DarziA.Effectofpharmacologicalenhancementonthecognitive andclinicalpsychomotorperformanceofsleepdepriveddoctors:arandomizedcontrolledtrial.AnnSurg2012255:222 7. 14. FarahMJ,IllesJ,CookDeeganR,GardnerH,KandelE,KingP,etal.Neurocognitiveenhancement:whatcanwedo andwhatshouldwedo?NeuroethicsPublications20049. 15. GreelyH,SahakianB,HarrisJ,KesslerRC,GazzanigaM,CampbellPB,etal.Towardsresponsibleuseofcognitive enhancingdrugsbythehealthy.Nature2008456:7025. 16. GillM,HaerichP,WestcottK,GoldenickL,TuckerJA.Cognitiveperformancefollowingmodafinilversusplaceboin sleepdeprivedemergencyphysicians:adoubleblindrandomizedcrossoverstudy.AcadEmergMed200613:15865. 17. ChalmersDJ.Philosophyofmind:classicalandcontemporaryreadings.OxfordUniversityPress,2002.

Competinginterests Nonedeclared. Provenanceandpeerreview Notcommissionedexternallypeerreviewed. StudBMJ2012BMJPublishingGroup

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