nicotine toxicity and addiction –debunking of two popular...
TRANSCRIPT
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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
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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
Ø improvedcognitiveperformance(self-treatmentofschizophrenicpatientsbysmoking?);
Ø protectionagainstneurodegenerativediseases (M.Alzheimer,M.Parkinson);
Ø protectionagainstulcerativecolitis,anastyinflammatoryboweldisease.
PotentialRisksofNicotineConsumption
Ø Pregnancy: Noevidenceforadversebirthoutcomes inclinicalstudies(observationofchildrenforupto2years);
Ø 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).
Ø firstsignsofoverdosing(headache,dizziness)resultinstopofconsumption;
Ø veryslowresorptionofnicotinethroughskin(nicotinepatch:tmax ~12hours,cmax
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CaveatØ Smallchildrenareathigherrisk(accordingtolowerbodyweight).
Ø Therefore,nicotinecontainingliquidshavetobekeptoutofthereachofchildren.(liketoiletcleaners,guns,medicinalproducts,tobaccocigarettes,alcoholicdrinks,matchesetc)
20"shots"à10ml(TPD2version)
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SummaryoftheHardFactsonToxicity (beyonddispute)
Ø Inhalationofnicotine(via smokingorvaping)isnottoxic.
Ø Unintentionalswallowingofafewdrops(orevenafewml)ofliquidiscompletelyharmless.
Ø Therearenoadverseeffectsofliquidsunintentionallyspilledonskin.
Ø 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).
Ø Never-smokerstreatedforupto6monthswithnicotinepatchesdidnotbecomedependent.
Ø 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.