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Bernhard-Michael(Bernd)Mayer,PhD
Professor&ChairDepartmentofPharmacology&Toxicology
InstituteofPharmaceuticalSciences,UniversityofGraz,Humboldtstraße46,A-8010Graz,Austria
NicotineToxicityandAddiction– DebunkingofTwoPopularMyths
PotentialConflictofInterestsØ
Ihavebeenadvocatingelectroniccigarettesfortobaccoharmreductionsince2006.Ø
Ihavewrittenhonoredexpertopinionsforpharmaceuticalandvapeindustries.Ø
Iservedasunpaidexpertwitnessinpolicydecision-makingontheregulationofvaping(since
2014).Ø
Iservedashonoredexpertwitnessinapatentcaseone-liquids(USA,2017).Ø
Iamfinancially,legallyandpersonallyindependentofmyclientsandreceivednofundingfrom
thetobaccoorvapeindustry.
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Cancer
COPD
otherrespiratorydiseases
strokeandmyocardialinfarction
prematuredeath(~10yreducedlifespan)
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Perceptionoftheroleofnicotineincancercausedbysmoking
bycourtesyofJoeGitchell
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FourCrucialMisconceptions inTobacco Control
1. smoking=abuseofnicotine[med.:nicotineabusus]
2. smokingcessation=therapyofnicotinedependence
3. electroniccigarette=tobaccoproduct(WHO,FDA)
4. goalofpublichealth=tobacco-freeworld
X
X
X
smoke
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Harmreductionshelf– Condoms andNicotineProducts
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EstablishedBiological EffectsofNicotine
Ø slight,short-termincreases
inbloodpressureandheartrate(similartocaffeineorexercise);
Ø angiogenesis (growthofnewbloodvessels);
Ø inhibitionofinflammationassociatedwithimmunesuppression;
Ø psychoactive,enhancedcognitiveperformance;
Ø
activationofdopaminergicreward-pathwaysassociatedwithpleasure(basisfordependence
incombinationwithtobaccosmoke;seelater);
Ø numerousothereffectsobservedinvitro
andinrodentsbutnotinhumans.
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PotentialBenefitsofNicotineConsumption
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improvedcognitiveperformance(self-treatmentofschizophrenicpatientsbysmoking?);
Ø protectionagainstneurodegenerativediseases
(M.Alzheimer,M.Parkinson);
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protectionagainstulcerativecolitis,anastyinflammatoryboweldisease.
PotentialRisksofNicotineConsumption
Ø Pregnancy: Noevidenceforadversebirthoutcomes
inclinicalstudies(observationofchildrenforupto2years);
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CardiovascularDiseases:potentialhealthriskforpatientswithseverecoronaryarterydisease,e.g.survivedmyocardialinfarction(controversial);
Ø Cancer: nicotine
isnotcancerogenic,butacceleratedgrowthofestablished
tumorswasobservedinanimalstudies(duetoangiogenesis);noclinicaldata.
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Myth#1– Nicotine ishighlytoxic,60mgwillkillanadult
Thetoxicityofnicotinehasbeenoverestimatedfor>100yearsbecauseofanuntenableestimateofthelethaldosebasedonself-experiments
thatwereperformedinViennaaround
1850andledtothe60-mgestimatepublishedbyRudolfKobertinatextbookin1905.
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Ø Rapidmetabolism
anddistributionofnicotinekeepsplasmalevelsfarbelowtoxictresholdswhenappliedatsmallamountsatatime(smoking,vaping).
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firstsignsofoverdosing(headache,dizziness)resultinstopofconsumption;
Ø veryslowresorptionofnicotinethroughskin(nicotinepatch:tmax
~12hours,cmax
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CaveatØ
Smallchildrenareathigherrisk(accordingtolowerbodyweight).
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Therefore,nicotinecontainingliquidshavetobekeptoutofthereachofchildren.(liketoiletcleaners,guns,medicinalproducts,tobaccocigarettes,alcoholicdrinks,matchesetc)
20"shots"à10ml(TPD2version)
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SummaryoftheHardFactsonToxicity (beyonddispute)
Ø Inhalationofnicotine(via smokingorvaping)isnottoxic.
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Unintentionalswallowingofafewdrops(orevenafewml)ofliquidiscompletelyharmless.
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Therearenoadverseeffectsofliquidsunintentionallyspilledonskin.
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Mostsuicideattemptsbyingestinglargeamountsofconcentratednicotinesolutionswereunsuccessfulduetovomitting.
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Myth#2- Nicotine ishighlyaddictive
Smokersdon'tdieoftheirdependence butofthesmoke!
Ø Ifatall,animalsdonotself-administer
nicotineasreadilyasharddrugslikecocaineorheroin.
Ø Therewardingeffectsofnicotinearemarkedlypotentiated
byotherconstituents oftobaccosmoke.
Ø Thelong-termefficiencyofNRTforsmokingcessation
isclosetoplacebo(>95%failureafter12months).
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Never-smokerstreatedforupto6monthswithnicotinepatchesdidnotbecomedependent.
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Basedontheseandotherfacts,KarlFagerströmrenamedhisfamousandwidelyappliedtestfornicotinedependenceto"Fagerströmtestforcigarettedependence".
Factsarguingagainstasignificantaddictivepotentialofpurenicotine:
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DeterminantsofCigaretteDependence(adaptedfromFagerström,2012)
Ø drug-inducedpleasurereward(nicotine
incombinationwithotherconstituents oftobaccosmoke);
Ø throathit(via
activationofnicotinergicreceptorsonsensoryC-fibersintheupperairways);
Ø habitandconditioning(smoking-associatedbehavior).
NicotineTob.Res. 14,1382-90,2012
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E-cigarettesprovidenicotine+throathit+behavior.