tobacco, nicotine and e-cigarettes · 2 table of contents tobacco, nicotine, and e-cigarettes...
TRANSCRIPT
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NationalInstituteonDrugAbuse(NIDA)
Tobacco,Nicotine,andE-Cigarettes
LastUpdatedJanuary2018
https://www.drugabuse.gov
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TableofContents
Tobacco,Nicotine,andE-Cigarettes
Introduction
Whatisthescopeoftobaccouseanditscosttosociety?
Howdoestobaccodeliveritseffects?
Isnicotineaddictive?
Whatarethephysicalhealthconsequencesoftobaccouse?
Whataretheeffectsofsecondhandandthirdhandtobaccosmoke?
Whataretherisksofsmokingduringpregnancy?
Howmanyadolescentsusetobacco?
Whatareelectroniccigarettes?
OtherTobaccoProducts
Aretheregenderdifferencesintobaccosmoking?
Dopeoplewithmentalillnessandsubstanceusedisordersusetobaccomoreoften?
Whataretreatmentsfortobaccodependence?
Howcanwepreventtobaccouse?
Whatresearchisbeingdoneontobaccouse?
References
WherecanIgetfurtherinformationabouttobacco/nicotine?
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Introduction
In2014,theNationmarkedthe50thanniversaryofthefirstSurgeonGeneral’sReportonSmokingandHealth.In1964,morethan40percentoftheadultpopulationsmoked.Oncethelinkbetweensmokinganditsmedicalconsequences—includingcancersandheartandlungdiseases—becameapartofthepublicconsciousness,educationeffortsandpublicpolicychangeswereenactedtoreducethenumberofpeoplewhosmoke.TheseeffortsresultedinsubstantialdeclinesinsmokingratesintheUnitedStates—tohalfthe1964level.
However,ratesofcigarettesmokingandothertobaccousearestilltoohigh,andsomepopulationsaredisproportionatelyaffectedbytobacco’shealthconsequences.Mostnotably,peoplewithmentaldisorders—includingsubstanceusedisorders—smokeathigherratesthanthegeneralpopulation.Additionally,peoplelivingbelowthepovertylineandthosewithlow
educationalattainmentaremorelikelytosmokethanthoseinthegeneralpopulation.AstobaccouseistheleadingpreventablecauseofmortalityintheUnitedStates, differentialratesofsmokinganduseofothertobaccoproductsisasignificantcontributortohealthdisparitiesamongsomeofthemostvulnerablepeopleinoursociety.
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Whatisthescopeoftobaccouseanditscosttosociety?
Approximatelyonefourthofthepopulationusestobaccoproducts,and19.4percentsmokecigarettes.Accordingtothe2016NationalSurveyonDrugUseandHealth(NSDUH),anestimated63.4millionpeopleaged12orolderusedatobaccoproductduringthepastmonth,including51.3millioncigarettesmokers. Smokingratescontinuetogodownyeartoyear;thepercentageofpeopleoverage18whosmokecigarettesdeclinedfrom20.9percentin2005to15.8percentin2016,accordingtothe2017NationalHealthInterviewSurvey.
However,smokingratesaresubstantiallyhigheramongsomeofthemostvulnerablepeopleinoursociety.The25percentofAmericanswithmentaldisorders,includingaddiction,accountfor40percentofthecigarettessmokedintheU.S. (see"Dopeoplewithmentalillnessandsubstanceusedisordersusetobaccomoreoften?").Morethan40percentofpeoplewithaGeneralEducationDevelopmentcertificate(GED)smoke—whichisthehighest
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prevalenceofanysocioeconomicgroup. Also,peoplewholiveinruralareas,particularlyintheSouthAtlanticstates,useallformsoftobaccoathigherratesthanpeoplewholiveinurbanareas.Thesedifferencescannotbefullyexplainedbydifferentlevelsofpovertyoraffluence.
Smokingamongyouthisathistoricallylowlevels.AccordingtotheNIDA-sponsoredMonitoringtheFuture(MTF)survey, in2015,anestimated4.7millionmiddleandhighschoolstudentsusedtobaccoproductsduringthepastmonth,accordingtodatafromtheNationalYouthTobaccoSurvey(NYTS) e-cigarettes)werethemostcommonlyusedtobaccoproductsamongmiddle(5.3percent)andhighschool(16.0percent)studentsin2015. E-cigarettesdeliversyntheticnicotineanddonotcontaintobacco;however,theyareclassifiedastobaccoproductsforregulatorypurposes.Thesefindingsareechoedbyotherstudies, includingthe MTFsurvey. Scientistshavenotyetdeterminedthemedicalconsequencesoflong-terme-cigaretteuseorthesecondhandeffectsofe-cigarettevapor(see"Whatareelectroniccigarettes?").
Between1964and2012,anestimated17.7milliondeathswererelatedtosmoking leadstomorethan480,000deathsannually. Ifcurrentsmokingratescontinue,5.6millionAmericanswhoarecurrentlyyoungerthan18willdieprematurelyfromsmoking-relateddisease.
Inadditiontothetremendousimpactofprematuredeathsrelatedtotobaccouse,theeconomiccostsarehigh.Expertsestimatethatbetween2009and2012,theannualsocietalcostsattributabletosmokingintheUnitedStateswerebetween$289and$332.5billion.Thisincludes$132.5to$175.9billionfordirectmedicalcareofadultsand$151billionforlostproductivityduetoprematuredeaths.In2006,lostproductivityduetoexposuretosecondhandsmokecostthecountry$5.6billion. About70percentofcurrentsmokers’excessmedicalcarecostscouldbepreventedbyquitting.
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Howdoestobaccodeliveritseffects?
Thesmokefromcombustibletobaccoproductscontainsmorethan7,000chemicals.Nicotineistheprimaryreinforcingcomponentoftobacco;itdrivestobaccoaddiction. Hundredsofcompoundsareaddedtotobaccotoenhanceitsflavorandtheabsorptionofnicotine. Cigarettesmokingisthemostpopularmethodofusingtobacco;however,manypeoplealsousesmokelesstobaccoproducts,suchassnuffandchewingtobacco,whichalsocontainnicotine(see"OtherTobaccoProducts").E-cigarettes,whichdelivernicotineintheabsenceofotherchemicalsintobacco,havebecomepopularinrecentyears(see"Whatareelectroniccigarettes?").
Thecigaretteisaveryefficientandhighlyengineereddrug-deliverysystem.Byinhalingtobaccosmoke,theaveragesmokertakesin1–2milligramsofnicotinepercigarette.Whentobaccoissmoked,nicotinerapidlyreachespeaklevelsinthebloodstreamandentersthebrain.Atypicalsmokerwilltake10puffsonacigaretteovertheroughly5minutesthatthecigaretteislit. Thus,apersonwhosmokesabout1pack(20cigarettes)dailygets200"hits"ofnicotinetothebraineachday.Amongthosewhodonotinhalethesmoke—suchascigarandpipesmokersandsmokelesstobaccousers—nicotineisabsorbedthroughmucousmembranesinthemouthandreachespeakbloodandbrainlevelsmoreslowly.
Immediatelyafterexposuretonicotine,thereisa"kick"causedinpartbythedrug’sstimulationoftheadrenalglandsandresultingdischargeofepinephrine(adrenaline).Therushofadrenalinestimulatesthebodyandcausesanincreaseinbloodpressure,respiration,andheartrate. Likeotherdrugs,nicotinealsoactivatesrewardpathwaysinthebrain—circuitrythatregulatesreinforcementandfeelingsofpleasure.
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Isnicotineaddictive?
Yes.Mostsmokersusetobaccoregularlybecausetheyareaddictedtonicotine.Addictionischaracterizedbycompulsivedrug-seekinganduse,eveninthefaceofnegativehealthconsequences.Themajorityofsmokerswouldliketostopsmoking,andeachyearabouthalftrytoquitpermanently.Yet,onlyabout6percentofsmokersareabletoquitinagivenyear. Mostsmokerswillneedtomakemultipleattemptsbeforetheyareabletoquitpermanently.Medicationsincludingvarenicline,andsomeantidepressants(e.g.bupropion),andnicotine-replacementtherapy,canhelpinmanycases(see"Whataretreatmentsfortobaccodependence?").
Atransientsurgeofendorphinsintherewardcircuitsofthebraincausesaslight,briefeuphoriawhennicotineisadministered.Thissurgeismuchbrieferthanthe"high"associatedwithotherdrugs.However,likeotherdrugsofabuse,nicotineincreaseslevelsoftheneurotransmitterdopamineintheserewardcircuits, whichreinforcesthebehavioroftakingthedrug.Repeatedexposurealtersthesecircuits'sensitivitytodopamineandleadstochangesinotherbraincircuitsinvolvedinlearning,stress,andself-control.Formanytobaccousers,thelong-termbrainchangesinducedbycontinuednicotineexposureresultinaddiction,whichinvolveswithdrawalsymptomswhennotsmoking,anddifficultyadheringtotheresolutiontoquit.
Thepharmacokineticpropertiesofnicotine,orthewayitisprocessedbythebody,contributetoitsaddictiveness. Whencigarettesmokeentersthelungs,nicotineisabsorbedrapidlyinthebloodanddeliveredquicklytothebrain,sothatnicotinelevelspeakwithin10secondsofinhalation.Buttheacuteeffectsofnicotinealsodissipatequickly,alongwiththeassociatedfeelingsofreward;thisrapidcyclecausesthesmokertocontinuedosingtomaintainthedrug'spleasurableeffectsandpreventwithdrawalsymptoms.
Withdrawaloccursasaresultofdependence,whenthebodybecomesusedtohavingthedruginthesystem.Beingwithoutnicotinefortoolongcancausearegularusertoexperienceirritability,craving,depression,anxiety,cognitiveandattentiondeficits,sleepdisturbances,andincreasedappetite.Thesewithdrawal
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symptomsmaybeginwithinafewhoursafterthelastcigarette,quicklydrivingpeoplebacktotobaccouse.
Whenapersonquitssmoking,withdrawalsymptomspeakwithinthefirstfewdaysofthelastcigarettesmokedandusuallysubsidewithinafewweeks. Forsomepeople,however,symptomsmaypersistformonths,andtheseverityofwithdrawalsymptomsappearstobeinfluencedbyaperson'sgenes.
Inadditiontoitspleasurableeffects,nicotinealsotemporarilyboostsaspectsofcognition,suchastheabilitytosustainattentionandholdinformationinmemory.However,long-termsmokingisassociatedwithcognitivedeclineandriskofAlzheimer'sDisease,suggestingthatshort-termnicotine-relatedenhancementdoesnotoutweighlong-termconsequencesforcognitivefunctioning. Inaddition,peopleinwithdrawalfromnicotineexperienceneurocognitivedeficitssuchasproblemswithattentionormemory. Theseneurocognitivewithdrawalsymptomsareincreasinglyrecognizedasacontributortocontinuedsmoking. Asmallresearchstudyalsosuggestedthatwithdrawalmayimpairsleepforseverelydependentsmokers,andthatthismayadditionallycontributetorelapse.
Inadditiontothedrug'simpactonmultipleneurotransmittersandtheirreceptors, manybehavioralfactorscanaffecttheseverityofwithdrawalsymptoms.Formanypeoplewhosmoke,thefeel,smell,andsightofacigaretteandtheritualofobtaining,handling,lighting,andsmokingthecigaretteareallassociatedwiththepleasurableeffectsofsmokingandcanmakewithdrawalorcravingworse. Learningprocessesinthebrainassociatethesecueswithnicotine-induceddopaminesurgesintherewardsystem —similartowhatoccurswithotherdrugaddictions.Nicotinereplacementtherapiessuchasgum,patches,andinhalers,andothermedicationsapprovedforthetreatmentofnicotineaddictionmayhelpalleviatethephysiologicalaspectsofwithdrawal
(see"Whataretreatmentsfortobaccodependence?");however,cravingsoftenpersistbecauseofthepowerofthesecues.Behavioraltherapiescanhelpsmokersidentifyenvironmentaltriggersofcravingsotheycanusestrategiestoavoidthesetriggersandmanagethefeelingsthatarisewhentriggerscannotbe.
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Arethereotherchemicalsthatmaycontributetotobaccoaddiction?
Researchisshowingthatnicotinemaynotbetheonlyingredientintobaccothataffectsitsaddictivepotential.
Smokingislinkedwithamarkeddecreaseinthelevelsofmonoamineoxidase(MAO),animportantenzymethatisresponsibleforthebreakdownofdopamine,aswellasareductioninMAObindingsitesinthebrain.Thischangeislikelycausedbysomeas-yet-unidentifiedingredientintobaccosmokeotherthannicotine,becauseweknowthatnicotineitselfdoesnotdramaticallyalterMAOlevels.AnimalresearchsuggeststhatMAOinhibitionmakesnicotinemorereinforcing,butmorestudiesareneededtodeterminewhetherMAOinhibitionaffectshumantobaccodependence.
Animalresearchhasalsoshownthatacetaldehyde,anotherchemicalintobaccosmokecreatedbytheburningofsugarsaddedassweeteners,dramaticallyincreasesthereinforcingpropertiesofnicotineandmayalsocontributetotobaccoaddiction.
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Whatarethephysicalhealthconsequencesoftobaccouse?
Cigarettesmokingharmsnearlyeveryorganinthebody, andsmokingistheleadingpreventablecauseofprematuredeathintheUnitedStates.Althoughratesofsmokinghavedeclined,itisestimatedthatitleadstoabout480,000deathsyearly. Smokersaged60andolderhaveatwofoldincreaseinmortalitycomparedwiththosewhohaveneversmoked,dyinganestimated6yearsearlier. Quittingsmokingresultsinimmediatehealthbenefits,andsomeorallofthereducedlifeexpectancycanberecovereddependingontheageapersonquits.
Althoughnicotineitselfdoesnotcausecancer,atleast69chemicalsintobaccosmokearecarcinogenic, andcigarettesmokingaccountsforatleast30percentofallcancerdeaths. Theoverallratesofdeathfromcanceraretwiceashighamongsmokersasnonsmokers,withheavysmokershavingafourtimesgreaterriskofdeathfromcancerthannonsmokers.
Foremostamongthecancerscausedbytobaccouseislungcancer.Cigarettesmokinghasbeenlinkedtoabout80to90percentofallcasesoflungcancer,theleadingcauseofcancerdeathforbothmenandwomen,anditisresponsibleforroughly80percentofdeathsfromthisdisease. Smokingincreaseslungcancerriskfivetotenfold,withgreaterriskamongheavysmokers. Smokingisalsoassociatedwithcancersofthemouth,pharynx,larynx,esophagus,stomach,pancreas,cervix,kidney,andbladder,aswellasacutemyeloid. Cigarettesmokingisnottheonlyformoftobaccouseassociatedwithcancers.Smokelesstobacco(see"OtherTobaccoProducts")hasbeenlinkedtocancerofthepharynx,esophagus,stomach,andlung,aswellastocolorectalcancer.
Inadditiontocancer,smokingcauseslungdiseasessuchaschronicbronchitisandemphysema,andithasbeenfoundtoexacerbateasthmasymptomsinadultsandchildren.Cigarettesmokingisthemostsignificantriskfactorforchronicobstructivepulmonarydisease(COPD). Survivalstatisticsindicatethatquittingsmokingresultsinrepairtomuchofthesmoking-inducedlung
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damageovertime.However,onceCOPDdevelops,itisirreversible;COPD-relatedlungdamageisnotrepairedwithtime.
Smokingalsosubstantiallyincreasestheriskofheartdisease,includingstroke,heartattack,vasculardisease,andaneurysm. Cardiovasculardiseaseisresponsiblefor40percentofallsmoking-relateddeaths. Smokingcausescoronaryheartdisease,theleadingcauseofdeathintheUnitedStates.Smokingisalsolinkedtomanyothermajorhealthconditions—includingdiabetes,rheumatoidarthritis,inflammation,andimpairedimmunefunction.Evenyoungsmokersaged26to41reportreducedhealth-relatedqualityoflifecomparedwithnonsmokingpeers,accordingtoacross-sectionalpopulationstudy.
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Whataretheeffectsofsecondhandandthirdhandtobaccosmoke?
Secondhandsmokeisasignificantpublichealthconcernanddriverofsmoke-freepolicies.Alsocalledpassiveorsecondarysmoke,secondhandsmokeincreasestheriskformanydiseases. Exposuretoenvironmentaltobaccosmokeamongnonsmokersincreaseslungcancerriskbyabout20percent.Secondhandsmokeisestimatedtocauseapproximately53,800deathsannuallyintheUnitedStates. Exposuretotobaccosmokeinthehomeisalsoariskfactorforasthmainchildren.
Smokingalsoleaveschemicalresidueonsurfaceswheresmokinghasoccurred,whichcanpersistlongafterthesmokeitselfhasbeenclearedfromtheenvironment.Thisphenomenon,knownas"thirdhandsmoke,"isincreasinglyrecognizedasapotentialdanger,especiallytochildren,whonotonlyinhalefumesreleasedbytheseresiduesbutalsoingestresiduesthatgetontheirhandsaftercrawlingonfloorsortouchingwallsandfurniture.Moreresearchisneededontherisksposedtohumansbythirdhandsmoke,butastudyinmiceshowedthatthirdhandsmokeexposurehasseveralbehavioralandphysicalhealthimpacts,includinghyperactivityandadverseeffectsontheliverandlungs.
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Whataretherisksofsmokingduringpregnancy?
Smokingduringpregnancyislinkedwitharangeofpoorbirthoutcomes—including:
Lowbirthweightandpretermbirth
Restrictedheadgrowth
Placentalproblems
Increasedriskofstillbirth
Increasedriskofmiscarriage
Healthanddevelopmentalconsequencesamongchildrenhavealsobeen
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linkedtoprenatalsmokeexposure,including:
Poorerlungfunction,persistentwheezing,andasthma,possiblythroughDNAmethylation
Visualdifficulties,suchasstrabismus,refractiveerrors,andretinopathy
Unfortunately,smokingbypregnantwomeniscommon.In2014,8.4percentofwomensmokedatanytimeduringpregnancy,withthoseaged20to24whowereAmericanIndianorAlaskaNativeshavinghigherrates,at13percentand18percent,respectively. Onefifthofwomenwhosmokedduringthefirst6monthsofpregnancyquitbytheirthirdtrimester.Overallcessationrateswerehighestforthosewiththehighesteducationalattainmentandprivateinsurance. Therefore,thereisaclearneedtoexpandsmokingcessationtreatmenttoyoungerwomenandtothoseoflowersocioeconomicstatus(seeBox:"SmokingCessationforPregnantWomen").
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Howmanyadolescentsusetobacco?
Mostpeoplewhousetobaccostartedduringadolescence,andthosewhobeginatayoungeragearemorelikelytodevelopnicotinedependenceandhavetroublequitting. Accordingtothe2017MonitoringtheFutureSurvey,9.7percentof12thgraders,5.0percentof10thgraders,and1.9percentof8thgradersusedcigarettesinthepastmonth. Analysesofthe2012NationalYouthTobaccoSurvey(NYTS)foundthat20.8percentofcurrentadolescenttobaccousersreportedwantingtousetobaccowithin30minutesofwaking—aclassicsymptomofnicotinedependence.Thisstudyalsofoundthat41.9percentreportedstrongcravingsfortobacco. Otherresearchhasfoundthatlightandintermittentsmokingamongadolescentsisassociatedwiththesamelevelofdifficultyquittingasdailysmoking.
Anyexposuretonicotineamongyouthisaconcern.Theadolescentbrainisstilldeveloping,andnicotinehaseffectsonthebrain’srewardsystemandbrainregionsinvolvedinemotionalandcognitivefunctions. Researchsuggeststhatthenicotine-relatedchangestotheseareasofthebrainduringadolescence
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mayperpetuatecontinuedtobaccouseintoadulthood. Thesechangesalsocontributetoahigherrateofothersubstanceusedisordersamongpeoplewhousetobaccoduringadolescence,sometimesreferredtoasa"gateway"effect.
Mentalhealth,beliefsaboutsmoking,perceptionofschoolmates’smoking,andothersubstanceuseareadditionalfactorsthatcaninfluenceanadolescent’sriskforsmokingandnicotinedependence. Emotionalproblems—includingdepression andrecentnegativelifeevents —areassociatedwithtobaccouseamongadolescents.Smokingamongpeersandwithinsocialgroupsisamajorenvironmentalfactorthatinfluencesadolescentsmoking;socialsmokingisamoreimportantmotivatorforadolescentscomparedtoadultsmokers.
Itiscommonforadolescentsmokingtofollowanintergenerationalpattern,whichhasgenetic,epigenetic,andenvironmentalinfluences. Datafromparentsandadolescentssuggeststhatcurrentparentalnicotinedependenceisstronglylinkedwithadolescentsmokinganddependence.Otherfactors—suchasparents’education,maritalstatus,andparentingbehavioralsoinfluenceteensmoking.
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Whatareelectroniccigarettes?
E-cigarettes(electronicnicotinedeliverysystems)emergedintheU.S.marketin2007andhaverapidlygrowninpopularity. E-cigarettes,ore-vaporizers,aredevicesthatheataliquidcontainingsolvents,flavors,andoftennicotine.Usersinhaletheresultingvapor.Avarietyofdesignsareavailable,somemimickingthelookoftraditionalcigarettes.Morethan7,000flavorsareavailablefore-cigarettes, someofwhichareespeciallyappealingtoyouth.Manyconveniencestores,drugstores,grocerystores,andotherphysicalandonlineretailoutletsselle-cigarettes,althoughasofAugust,2016,itisillegaltosellthemtopeopleunder18.Someconveniencestoresanddrugstorechainshavealsostoppedsellinge-cigarettestopromotepublichealth.
In2013,morethanonethirdofcigarettesmokerssaidtheyhadeverusede-cigarettes. Accordingtodatafromthe2014TobaccoProductsandRiskPerceptionsSurvey,currentcigarettesmokershadagreaterlikelihoodofusinge-cigarettes.Thisanalysisfoundthathalfofcigarettesmokershadeverusedane-cigaretteand20.7percentcurrentlyusedthesedevices.However,approximately10percentofadultswhousede-cigaretteshadneversmokedpreviously. Datafromthe2014NationalHealthInterviewSurveyindicatedthat0.4percentofadultswhohaveneversmokedand0.8percentofformersmokers(abstinent4ormoreyears)currentlyusee-cigarettes. Thesurveyalsofoundthat13percentofdailye-cigaretteuserswereformersmokerswhoquitduringthepastyear.
Aswithcigaretteuse,e-cigaretteuseishigheramongpeoplewithmentalhealthconditions—with3.1percentcurrentlyusingcomparedwith1.1percentofthosewithoutmentalillness. Itisalsoaconcernthatpregnantwomenareusinge-cigarettes,asnicotineexposureduringperiodsofdevelopmentalvulnerability(includingprenataldevelopment)hasadversehealthconsequences.
Usersreportthebeliefthate-cigaretteproductsarelessharmfulthantraditionalcigarettes, andmanyreportusingthemtohelpquitsmokingtraditionalcigarettes.Whileitisnotyetclearife-cigarettesareeffectivesmokingcessation
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aids,thedevicesaresometimesmarketedforthispurpose (see"Aree-cigarettesusefulforsmokingcessation?").Someresearchsuggeststhatolderadultsusethesedevicesasatobaccosubstitute,althoughnotalwaysasacessationmethod. Usersalsociteconvenienceandbeingconscientioustowardsothersasreasonsforusingtheseproducts.
Howdoesthefederalgovernmentregulatee-cigarettes?
TheU.S.FoodandDrugAdministration(FDA),whichregulatescigarettes,tobacco,andsmokelesstobacco,gainedtheauthorityin2016toalsoregulateelectronicnicotinedeliverysystems(suchase-cigarettesandvapepens),allcigars,hookah(waterpipe)tobacco,pipetobacco,andnicotinegels,amongothertobaccoproducts.Underthenewregulations,e-cigarettemanufacturersmustlistingredients,andvendorscannotselle-cigarettestopeopleunderage18.
Isittruethate-cigarettesaresaferthantraditionalcigarettes?
Itislikelythat,onbalance,e-cigarettesaresaferthantraditionalcigarettesfromthestandpointofphysicalhealth.However,asdiscussedabove,thenicotineine-cigarettescancauseaddictionandneurocognitiveimpairments.
Althoughforregulatorypurposese-cigarettesareclassifiedas“tobaccoproducts,”theydonotcontaintobaccoorproducethesametoxiccombustionproducts,liketar,thatcauselungcancerandotherdiseasesinusersandpeopleexposedtosecondhandsmoke.However,thevaporfrome-cigarettestypicallycontainsnicotineandarangeofotherchemicals. Becausetheseproductsarerelativelynew,evidenceontheshort-termeffectsofexposuretoe-cigaretteaerosolsislimited,andverylittleisknownaboutthelong-termhealtheffects.
Areviewofrecentliteraturefoundthatsomeofthechemicalsine-cigaretteliquid,propyleneglycolandglycerol,causethroatirritationand
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coughing. Otherresearchsuggeststhatvaporexposuremaybelinkedwithimpairedlungfunction. Chemicalanalysesthatcomparetheprofilesofelectronicandtraditionalcigaretteshavesuggestedthate-cigaretteshaveareducedcarcinogenicprofileandimpartalowerpotentialfordisease. However,toxicants,carcinogens,andmetalparticleshavebeendetectedintheliquidsandaerosolsofe-cigarettes,anditiscurrentlyunclearwhatrisktheyposewithrepeateduse. Aswithtraditionalcigarettes,useofe-cigarettesinvoluntarilyexposesnonuserstosecondhandandthirdhandaerosol.
Theresearchonsecondhandexposuretotheaerosolfrome-cigarettesislimited,butonestudyfoundthatfineparticulatematterconcentrationsduringanindooreventinalargeroomwithe-cigarettesmokerswerehigherthanthosereportedpreviouslyinvenuesthatallowedcigarettesmoking. Aninvitrostudyshowedthatexposinglungtissuesandcellstoe-cigaretteliquidinducedincreasedinflammatoryresponsesandoxidativestressmarkers. Anotherstudythatanalyzede-cigaretteflavoringsfoundthat39ofthe51flavorstestedpositivefordiacetyl,achemicalassociatedwithanirreversibleobstructivelungdiseasecalledbronchiolitisobliterans.Otherchemicals,2,3-pentanedioneandacetoin,associatedwithsevererespiratorydiseasesamongexposedpeople,werealsofoundinmanye-cigaretteflavorings.
Theamountofnicotineine-cigarettefluidvaries.Someresearchhasfoundthate-cigarettesdeliverlessnicotineonaveragethantraditionalcigarettes, butthatusersmaychangepuffingpatternstocompensate.Inexperiencede-cigaretteuserstakeinmodestnicotineconcentrations,butthosewhoregularlyusethesedevicesadjusttheirpuffingtoconsumesimilarlevelsofthedrugaswithtraditionalcigarettes. Newere-cigarettedevicescandeliversubstantialamountsofnicotine,andsomeusersareabletogetnicotineatlevelssimilarto orevengreaterthanatraditionalcigarette. Onestudyfoundequivalentlevelsofnicotine'smajormetaboliteinthebloodofsmokerswhousetraditionalande-cigarettes. Thus,allthenicotine-relatedconcernsoftraditionalcigarettes—addiction,effectsoncognitivefunction,andeffectsonprenataldevelopment—applytoe-cigarettesaswell.
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RisksofE-CigarettestoChildren
Youngchildrenmayaccidentallyingesttheconcentratednicotine(whichoftencontainsflavors)ine-cigaretteliquid. TheCentersforDiseaseControlandPreventionrecentlycomparedcallstopoisoncentersintheUnitedStatesrelatedtohumanexposurestoe-cigarettesandtraditionalcigarettes.ThestudyfoundthatbetweenSeptember2010andFebruary2014,theproportionofe-cigarettecallsamongallcigarette-relatedcallsincreasedfrom0.3percentto41.7percent. Mostofthee-cigaretteexposureswereamongchildrenundertheageof5years(51.1percent)andpeopleoverage20(42.0percent),whereasalmostalltraditionalcigaretteexposurecallsinvolvedyoungchildren. Dataindicatedthatagreaterproportionofe-cigaretteexposurecalls(57.8percent)resultedinadversehealtheffectsthantraditionalcigaretteexposure(36.0percent).Theseadversehealtheffectsincludedvomiting,nausea,andeyeirritation.
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Aree-cigarettesusefulforsmokingcessation?
Someresearchsuggestse-cigarettesmayhelppeoplequitsmokingcigarettes,whileotherdatasuggestthattheycanimpedequittingandthattheymayopenthedoortotraditionalcigaretteuseforpeoplewhomightnototherwisetrythem.Thus,muchmoreresearchisneededonthisquestion.
Onereviewofrecentstudiessuggestedthatthelikelihoodofquittingcigaretteswas28percentloweramongindividualswhousede-cigarettescomparedwiththosewhodidnotusethesedevices,regardlessofwhetheruserswereinterestedinquitting. ResearchfromtheUnitedKingdomsuggeststhatamongsmokerswhocontinuetousetraditionalcigarettes,dailyuseofe-cigaretteswasassociatedwithincreasedattemptstoquitandcutback,butnotwithsuccess. However,anotheranalysisestimatedthat,inEngland,16,000smokerswereabletoquitin2014whowouldnothavequitife-cigaretteshadnotbeenavailable. Areviewandmeta-analysisalsosuggestedthatusinge-cigarettesforaminimumof6monthswasassociatedwithquittingorreducingthenumberofcigarettesused.
E-cigarettesandTeens
Nationalsurveydatasuggestthate-cigaretteswerethemostcommonlyusednicotinedeliveryproductamongyouth. Areviewoftheliteraturefoundthatupto20percentofadolescentswhocurrentlyusee-cigaretteshadneversmokedatraditionalcigarette.
Amajorconcernisthate-cigarettes’flavors,design,andmarketingparticularlyappealtoyouth, andthatbyintroducingyoungpeopletonicotineandglamorizingasmoking-likebehavior,e-cigarettescouldopenthedoortocigaretteuseinapopulationthatisparticularlyvulnerabletoaddictionandthathasseenhistoricdeclinesincigarettesmoking.
Someresearchindicatesthate-cigaretteusemayleadtotheuseof
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traditionalcigarettesamongadolescentsandyoungadults. Accordingtodatafromthe2012NYTS,youthwhohadonlyusede-cigarettesreportedanincreasedintentiontosmoketraditionalcigarettescomparedwithpeerswhohadneverusedthesedevices.Thesurveyfoundnolinkbetweene-cigaretteuseandintentiontoquitsmokingamongyouthwhowerecurrentsmokers,indicatingthatthisagegroupdoesnotseetheseproductsprimarilyassmoking-cessationaids. Alongitudinalcohortstudyof16-to26-year-oldswhohadneversmokedtraditionalcigarettesfoundthat2.3percent(16participants)usede-cigarettesatthestartofthestudy.Afteraone-yearfollow-up,approximately69percent(11of16)oftheseparticipantsprogressedtosmokingtraditionalcigarettescomparedto18.9percent(128of678)amongthosewhoneverusedane-cigarette. Anotherstudyfoundthatpast-monthe-cigaretteusepredictedfuturecigaretteuse,butthatpast-monthcigaretteusedidnotpredictfuturee-cigaretteuse.
Manyyoungpeoplereportexperimentingwithe-cigarettesoutofcuriosity,becausetheflavorsappealtothem,orbecauseofpeerinfluences. Themajorityofyouthwhoreportede-cigaretteuseinonestudyhadfriendswhousedtheseproducts.Almosthalfofadolescentswhousede-cigarettessaidthattheydidnotbelievetheseproductswereassociatedwithhealthrisks. Youngpeoplealsoperceivede-cigarettesaseasytoobtain,"cool,"andabetteralternativetocigarettesbecausetheywerethoughttobehealthierandcouldbeusedanywhere.Amongyouthwhostoppedusinge-cigarettes,themajorunderlyingreasonswerehealthconcerns,lossofinterest,highcost,badtaste,andviewofe-cigarettesaslesssatisfyingthancigarettes.
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OtherTobaccoProducts
Whilecigarettesmokinghasdeclinedsignificantlyduringthepast40years,useofothertobaccoproductsisincreasing—particularlyamongyoungpeople. Theseinclude:
Cigars:tobaccowrappedinleaftobaccooranothertobacco-containingsubstanceinsteadofpaper,whichcanbeboughtindividually
Cigarillos:smallcigarsthatcostlessandarealsoavailableforpurchaseindividually
Hookahsorwaterpipes:pipeswithalong,flexibletubefordrawingsmokefromlit,flavoredtobaccothroughwatercontainedinabowl
Smokelesstobacco:productslikechewingtobaccoandsnuffthatareplacedinthemouthbetweentheteethandgums
Powdertobacco:mixturesthatareinhaledthroughthenose
In2014,almostone-quarterofhighschoolstudentsreportedpast-monthuseofatobaccoproduct—withe-cigarettes(13.4percent),hookahs(9.4percent),cigarettes(9.2percent),cigars(8.2percent),smokelesstobacco(5.5percent),andsnus(moistpowdertobacco)(1.9percent)asthemostpopular.
Cigars
In2016,anestimated12millionpeopleaged12orolder(4.6percentoftheadolescentandadultpopulation)smokedcigarsduringthepastmonth. Themajorityofadolescentsandyoungadultswhosmokedcigarsalsosmokecigarettes.
Cigarillos
DatafromtheTobaccoUseSupplementtotheCurrentPopulationSurveyandNSDUHsuggestthatyoungerandlesseconomicallyadvantagedmalesinitiate
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tobaccousewithcigarillos. From2002to2011,past-monthcigarettesmokingdeclinedformalesandfemalesofallagegroups.However,duringthissameperiod,ratesofcigarillouseamongmalesaged18to25remainedconstant(atapproximately9percent).
Hookahsorwaterpipes
Between2011and2014,useofhookahincreasedamongmiddleandhighschoolstudents,despitedecreaseduseofcigarettesandcigars,accordingtotheNYTS. Researchalsosuggeststhatratesofhookahusefortobaccosmokingincreaseduringthefirstmonthofcollege. Nationallyrepresentativedatafromcollegestudentsindicatethatdailycigaretteorcigarsmokers(aswellasmarijuanausers)weremorelikelytobefrequentwaterpipeusers.
Hookahusersmaymistakenlybelievethatitislessaddictiveordangerousthancigarettes;however,onesessionofhookahsmokingexposeduserstogreatersmokevolumesandhigherlevelsoftobaccotoxicants(e.g.,tar)thanasinglecigarette. Additionally,hookahsmokingislinkedwithnicotinedependenceanditsassociatedmedicalconsequences (see"Whatarethephysicalhealthconsequencesoftobaccouse?").Reviewsoftheliteratureonwaterpipeuserssuggestthatlikethosewhouseotherformsoftobacco,manyhavetriedtoquitbuthavebeenunsuccessfulontheirown. Thesefindingsindicatetheneedfortobaccocontrolpoliciesandpreventionandtreatmentinterventionsforthisformofnicotinedeliverythataresimilartothoseseenforcigarettes.
Smokelesstobacco
In2016,8.8millionpeopleaged12orolder(3.3percentofthispopulation)usedsmokelesstobaccoduringthepastmonth. Overall,useofsmokelesstobaccoamongadultsdecreasedfrom1992to2003buthasheldconstantsince. Longitudinaldatasuggestthatpeoplearemorelikelytoswitchfromsmokelesstobaccousetocigarettesmokingthanviceversa. Althoughsmokersmayattempttousesmokelessproductstocutdownorquit,researchsuggeststhatthisapproachisnoteffective. However,somearguethatusingsmokelesstobaccoinlieuofcigarettesmayhelpreducetheharmsassociatedwithsmokingtraditionalcigarettes.
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PolytobaccoUse
Someusersoftobaccoconsumeitinmultipleforms(polytobaccouse);thisbehaviorisassociatedwithgreaternicotinedependence andtheriskforothersubstanceusedisorder. AnalysesofadecadeofdatafromNSDUHfoundsteadyratesofpolytobaccousefrom2002to2011(8.7percentto7.4percent)amongpeopleage12andolder.However,useofsomeproductcombinations—suchascigarettesandsmokelesstobacco,cigarsandsmokelesstobacco,anduseofmorethantwoproducts—increasedoverthatperiod.
Amongindividualsyoungerthan26,ratesofpolytobaccouseincreaseddespitedeclinesinoveralltobaccouse.Polytobaccousewasassociatedwithbeingmale,havingrelativelylowincomeandeducation,andengaginginrisk-takingbehaviors. In2014,anestimated2.2millionmiddleandhighschoolstudentshadusedtwoormoretypesoftobaccoproductsduringthepastmonth,accordingtotheNYTS. Polytobaccousewascommon,evenamongstudentswhousedtobaccoproducts5daysorfewerduringthepastmonth. The2012NYTShadfoundthat4.3percentofstudentsusedthreeormoretypesoftobacco.Thisstudyalsoobservedthatmalegender,useofflavoredproducts,nicotinedependence,receptivitytotobaccomarketing,andperceivedpeerusewereallassociatedwithyouthpolytobaccouse.
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FlavoredTobaccoUseAmongAdolescentsandYoungAdults
Onespecificconcernaboute-cigarettesandtobaccoproductslikecigarillosandhookahsistheadditionofflavorings,whichmaymakethemparticularlyappealingtoyouth. TheFamilySmokingPreventionandTobaccoControlActof2009bannedthesaleofcigaretteswithflavorsotherthanmenthol,butotherflavoredtobaccoproducts(e.g.,smallcigars,cigarillos,andsmokelesstobacco)canstillbesold.Addingflavorstotobaccoproductsortothenicotinesolutionofe-cigarettescanmakethemmoreappealingtosomeusersbecausetheycanmasktheharshtaste. Althoughmoreresearchisneededonhowflavorsaffectlong-termuse,healthexpertshaveexpressedconcernsthatmanyoftheflavoringsusedintobaccoproductsarealsofoundincandiesandbeverages. Suchflavorsmaymakethemmoreappealingtoyouthandmaycontributetoincreaseduseoftheseproductsamongyoungpeople.
Approximately6.3percentofmiddleandhighschoolstudentsreportedusingeitherflavoredcigarettesorsmallcigars,accordingtothe2011NYTS. Datafromthe2014NYTSindicatethatofmiddleandhighschoolstudentswhocurrentlyusedtobacco,about70percent—anestimated3.26millionyouths—hadusedatleastoneflavoredtobaccoproductduringthepastmonth. Amongpast-monthusers,themostcommonlyusedflavoredproductsweree-cigarettes,hookahtobacco,andcigars. Itseemsthatyouthmaynotnecessarily“growoutof”usingflavoredtobaccoproducts.Amongyoungadultsaged18to34,nearlyone-fifth(18.5percent)ofthosewhousetobacco,consumedflavored(includingmenthol)products.
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Aretheregenderdifferencesintobaccosmoking?
Generally,mentendtousealltobaccoproductsathigherratesthanwomen. In2015,16.7percentofadultmalesand13.6percentofadultfemalessmokedcigarettes. Suchdifferencesmayrelatetoacombinationofphysiological(particularlyovarianhormones),cultural,andbehavioralfactors.
Resultsfromneuroimagingstudiessuggestthatsmokingactivatesmen’srewardpathwaysmorethanwomen's. Thisfindingisconsistentwiththeideathatmensmokeforthereinforcingeffectsofnicotine,whereaswomensmoketoregulatemoodorinresponsetocigarette-relatedcues.Astudyofstressresponsesandcravingamongmaleandfemalesmokerswhoweretryingtoquitfoundthatduringabstinence,lowerlevelsofthestresshormonecortisolpredictedrelapseinmen.However,highcortisollevelswerepredictiveofrelapseinwomen. Otherworkonabstinencefoundthatsmokingacigarettewithnicotine,ascomparedtoade-nicotinizedcigarette,alleviatedthe
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symptomsofwithdrawalandnegativemoodtoagreaterextentinmenthanwomen.Womenobtainedequalrelieffromcigaretteswithandwithoutnicotine,suggestingthattheyfoundthedruglessrewardingthanmen.
Cigarettecravingisamajorreasonwhysmokersfindithardtoquit,andthisstrongurgetosmokecanbeevokedbysensorycuesandstress.Researchsuggeststhatwomenexperiencestrongercravingthanmeninresponsetostress, butmenmaybemoreresponsivetoenvironmentalcues. Additionally,longitudinaldatafrominternationalsurveysconductedinfourindustrializedcountriesindicatedthatmenandwomendidnotdifferintheirdesiretoquit,planstoquit,orquitattempts.However,womenwere31percentlesslikelytoquitsuccessfully. Onereasonwhywomenmayhavedifficultyquittingispost-cessationweightgain.Thisconcernshouldbeaddressedinbehavioralcounselingandadjuncttreatmentsforallsmokers.
Theoveralllowercessationrateforwomenmayreflectsexdifferencesinresponsetoparticularmedications(see"Whataretreatmentsfortobaccodependence?").Forexample,vareniclinehasgreatershort-andimmediate-termefficacy(at3and6months)amongwomensmokers.However,womenandmenshowsimilar1-yearquitrateswhenusingvarenicline. Incontrast,acombinationofvareniclineplusbupropionwaslesseffectiveforcessationamongwomencomparedwithmen.
Anotherparticularconcernrelatedtotobaccouseamongwomenissmokingduringpregnancy(see"Whataretherisksofsmokingduringpregnancy?").
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Dopeoplewithmentalillnessandsubstanceusedisordersusetobaccomoreoften?
Thereissignificantcomorbiditybetweentobaccouseandmentaldisorders.Peoplewithmentalillnesssmokeattwotofourtimestherateofthegeneralpopulation.Amongpeoplewithamentalillness,36.1percentsmokedfrom2009to2011,comparedwith21.4percentamongadultswithnomentalillness. Smokingratesareparticularlyhighamongpatientswithseriousmentalillness(i.e.,thosewhodemonstrategreaterfunctionalimpairment).Whileestimatesvary,asmanyas70-85percentofpeoplewithschizophreniaandasmanyas50-70percentofpeoplewithbipolardisordersmoke.
Ratesofsmokingamongpeoplewithmentalillnesswerehighestforthoseyoungerthan45,thosewithlowlevelsofeducation,andthoselivingbelowthepovertylevel. LongitudinaldatafromNSDUH(2005–2013)indicatethatsmokingamongadultswithoutchronicconditionshasdeclinedsignificantly,butremainsparticularlyhighamongthosereportinganxiety,depression,andsubstanceusedisorders. Smokingisbelievedtobemoreprevalentamongpeoplewithdepressionandschizophreniabecausenicotinemaytemporarilylessenthesymptomsoftheseillnesses,suchaspoorconcentration,lowmood,andstress. Butitisimportanttonotethatsmokingcessationhasbeenlinkedwithimprovedmentalhealth—includingreduceddepression,anxiety,andstress,andenhancedmoodandqualityoflife.
AnalysesoflongitudinalNSDUHdataalsofoundahigherprevalenceofsmokelesstobaccouseamongindividualswithmentalhealthandsubstanceusedisorders. OtherresearchdrawingondatafromtheNationalEpidemiologicSurveyonAlcoholandRelatedConditionsfoundthatalltypesofsubstancedependencewereassociatedwithdependenceonnicotine. Smokingisalsohighlyprevalentamongpeopleintreatmentforsubstanceusedisorders, withmoststudiesfindingratesbetween65-85percentamongpatientsinaddictiontreatment.
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Additionally,smokerswithamentalhealthdisordertendtosmokemorecigarettesthanthoseinthegeneralpopulation.Theaveragenumberofcigarettessmokedduringthepastmonthwashigheramongthosewithamentalillnesscomparedwiththosewithoutone—331versus310cigarettes. Highcigaretteconsumptionisaparticularproblemforpeoplewithseriousmentalillness.Althoughadultswithseriousmentalillnesscomprisedonly6.9percentofpast-monthsmokers,theyconsumed8.7percentofallcigarettessold,accordingtodatafromthe2008–2012NSDUH.
HighPrevalenceofSmokingAmongPeoplewithSchizophrenia
Researchersareworkingtoidentifythebraincircuitsthatcontributetothehighprevalenceofsmokingamongpeoplewithschizophrenia.Schizophreniaisassociatedwithwidespreadreductionsinfunctionalconnectivitybetweenthedorsalanteriorcingulatecortexanddiversepartsofthelimbicsystem.Onereportidentified15circuitsforwhichthereductionoffunctionalconnectivitycorrelatedwithseverityofnicotineaddiction.
Peoplewithmentalandsubstanceusedisordersdonotquitsmokingatthesamerateasthoseinthegeneralpopulation.4Surveyresponsesfrompeoplewhohavesmokedatsomepointduringtheirlivesindicatedthatfewersmokerswithmentalillnesshadquitcomparedtothosewithoutpsychiatricdisorders:47.4percentoflifetimesmokerswithoutmentalillnesssmokedduringthepastmonth,comparedwith66percentofthosewithmentalillness. Havingamentaldisorderatthetimeofcessationisariskfactorforrelapsetosmoking,evenforthosewhohavesustainedabstinenceformorethanayear. Manysmokerswithmentalillnesswanttoquitforthesamereasonscitedbyothers(suchashealthandfamily),buttheymaybemorevulnerabletorelapserelatedtostressandnegativefeelings.
Thedisparityinsmokingprevalenceiscostinglives.Arecentstudyfoundthattobacco-relateddiseasesaccountedforapproximately53percentofdeathsamongpeoplewithschizophrenia,48percentamongthosewithbipolar
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disorder,and50percentamongthosewithdepression.
Sincethe1980s,manyprovidershavebelievedthatpeoplewithschizophreniasmoketoobtainrelieffromsymptomslikepoorconcentration,lowmood,andstress. Butresearchisnowshowingthatsmokingisassociatedwithworsebehavioralandphysicalhealthoutcomesinpeoplewithmentalillness,andquittingsmokingisshowingclearbenefitsforthispopulation. Comprehensivetobaccocontrolprogramsandenhancedeffortstopreventandtreatnicotineaddictionamongthosewithmentalillnesswouldreduceillnessanddeaths.Integratedtreatment—concurrenttherapyformentalillnessandnicotineaddiction—willlikelyhavethebestoutcomes.
Smokerswhoreceivementalhealthtreatmenthavehigherquitratesthanthosewhodonot. Moreover,evidence-basedtreatmentsthatworkinthegeneralpopulationarealsoeffectiveforpatientswithmentalillness.Forexample,peoplewithschizophreniashowedbetterquitrateswiththemedicationbupropion,comparedwithplacebo,andshowednoworseningofpsychiatricsymptoms. Acombinationofthemedicationvareniclineandbehavioralsupporthasshownpromiseforhelpingpeoplewithbipolarandmajordepressivedisordersquit,withnoworseningofpsychiatricsymptoms. Aclinicaltrialfoundthatacombinationofvareniclineandcognitivebehavioraltherapy(CBT)wasmoreeffectivethanCBTaloneforhelpingpeoplewithseriousmentalillnessstopsmokingforaprolongedperiod—after1yearoftreatmentandat6monthsaftertreatmentended.
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Whataretreatmentsfortobaccodependence?
Thereareeffectivetreatmentsthatsupporttobaccocessation,includingbothbehavioraltherapiesandFDA-approvedmedications.FDA-approvedpharmacotherapiesincludevariousformsofnicotinereplacementtherapyaswellasbupropionandvarenicline.Researchindicatesthatsmokerswhoreceiveacombinationofbehavioraltreatmentandcessationmedicationsquitathigherratesthanthosewhoreceiveminimalintervention.
Interventionssuchasbriefadvicefromahealthcareworker,telephonehelplines,automatedtextmessaging,andprintedself-helpmaterialscanalsofacilitatesmokingcessation. Cessationinterventionsutilizingmobiledevicesandsocialmediaalsoshowpromiseinboostingtobaccocessation. Itisimportantforcessationtreatmenttobeaspersonalizedaspossible,assomepeoplesmoketoavoidnegativeeffectsofwithdrawalwhileothersaremoredrivenbytherewardingaspectsofsmoking.
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Theprevalenceoftobaccouseanddependenceamongadolescents—aswellastheneurobiologicalimpactandmedicalconsequencesofnicotineexposure—suggestthatpediatricprimarycaresettingsshoulddelivertobaccocessationtreatmentstobothyouthandparentswhousetobacco. Currentclinicalguidancedoesnotrecommendmedicationsforadolescenttobaccocessationbecauseofalackofhigh-qualitystudies; however,acombinationofbehavioraltreatments—suchasmotivationalenhancementandCBT—hasshownpromiseforhelpingadolescentsquittobacco. Morewell-designedsmokingcessationstudiesneedtobeconductedwithadolescentsmokers,particularlyintheareaofpharmacologictreatmentsfornicotinedependence.
BehavioralTreatments
Behavioralcounselingistypicallyprovidedbyspecialistsinsmokingcessationforfourtoeightsessions. Bothin-personandtelephonecounselinghavebeenfoundbeneficialforpatientswhoarealsousingcessationmedications. Avarietyofapproachestosmokingcessationcounselingareavailable.
CognitiveBehavioralTherapy(CBT)—CBThelpspatientsidentifytriggers—thepeople,places,andthingsthatspurbehavior—andteachesthemrelapse-preventionskills(e.g.,relaxationtechniques)andeffectivecopingstrategiestoavoidsmokinginthefaceofstressfulsituationsandtriggers. AstudythatcomparedCBTandbasichealtheducationobservedthatbothinterventionsreducednicotinedependence. However,anotherstudyfoundthatamongsmokerstryingtoquitwiththenicotinereplacementtherapy(NRT)patch,patientswhoparticipatedinsixsessionsofintensivegroupCBThadbetterquitratesthanthosewhoreceivedsixsessionsofgeneralhealtheducation.
MotivationalInterviewing(MI)—InMI,counselorshelppatientsexploreandresolvetheirambivalenceaboutquittingsmokingandenhancetheirmotivationtomakehealthychanges.MIispatient-focusedandnonconfrontational,andproviderspointoutdiscrepanciesbetweenpatients’goalsorvaluesandtheircurrentbehaviors.Theyadjusttopatients’resistancetochangeandsupportself-efficacyandoptimism. StudiesofMIsuggestthatthisinterventionresultsinhigherquitratesthanbriefadvicetostopsmokingorusualcare.
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Mindfulness—Inmindfulness-basedsmokingcessationtreatments,patientslearntoincreaseawarenessofanddetachmentfromsensations,thoughts,andcravingsthatmayleadtorelapse. Inthistherapy,patientspurposelyattendtothethoughtsthattriggercravingsandurgesfortobaccoandcognitivelyreframethemasexpectedandtolerable.Patientslearntechniquesthathelpthemtoleratenegativeemotions—includingstressandcravings—withoutreturningtotobaccouseorotherunhealthybehaviors. Interestinmindfulness-basedtreatmentshasincreasedduringthepastdecade,andstudiesshowthatthisapproachbenefitsoverallmentalhealthandcanhelppreventrelapsetosmoking. However,well-controlledclinicaltrialsareneeded.
Telephonesupportandquitlines—Aspartoftobaccocontrolefforts,allstatesoffertoll-freetelephonenumbers(orquitlines)withsmokingcessationcounselorswhoprovideinformationandsupport(800-QUIT-NOWor800-784-8669).Studiesofquitlineinterventionsindicatethatsmokerswhocallquitlinesbenefitfromtheseservices, particularlywhenacounselorcallsthembackformultiplesessions. Thereislimitedevidenceontheoptimalnumberofcallsneeded,butsmokerswhoparticipatedinthreeormorecallshadagreaterlikelihoodofquitting,comparedwiththosewhoonlyreceivededucationalmaterials,briefadvice,orpharmacotherapyalone. Quitlineshavealsobeenshowntohelpsmokelesstobaccocessation. TheU.S.DepartmentofHealthandHumanServicesprovidesaSmokingQuitline(877-44U-QUITor877-448-7848),aswellasmoreinformationandtoolsforquitting(includingtextmessagesandothertelephone-basedsupport)athttps://smokefree.gov/.
Textmessaging,web-basedservices,andsocialmediasupport—Technology,includingmobilephones,internet,andsocialmediaplatformscanbeusedtoprovidesmokingcessationinterventions.Thesetechnologieshavethepowertoincreaseaccesstocarebyextendingtheworkofcounselorsandovercomingthegeographicalbarriersthatmaydeterpeoplefromenteringtreatment.
Areviewoftheliteratureontechnology-basedsmokingcessationinterventions(internet,personalcomputer,andmobiletelephone)foundthatthesesupportscanincreasethelikelihoodofadultsquitting,comparedwithnointerventionorself-helpinformation,andtheycanbeacost-effectiveadjuncttoothertreatments. Atechnologydoesnotnecessarilyhavetoberecentorhighly
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sophisticatedtohelpboostcessationrates.Forexample,studiessuggestthatadultswhoreceiveencouragement,advice,andquittingtipsviatext-message—acapabilityoneventhemostbasicmobiledevices—showimprovedquitratescomparedwithcontrolprograms.
Amongadulttobaccouserswhocalledastatequitline,mostselectedanintegratedphone/webcessationprograminfavorofaweb-onlyintervention. Participantswhochosetheweb-onlyoptiontendedtobeyoungerandhealthiersmokers,withahighersocioeconomicstatus.Theseparticipantstendedtointeractintenselywiththesiteonce,butdidnotre-engageasmuchasthosewhooptedforthephone/webcombination.Areviewofinternet-basedsmokingcessationprogramsforadultssuggestedthatinteractiveinternet-basedinterventionsthataretailoredtoindividualneedscanhelppeoplequitfor6monthsorlonger. Futureresearchshoulddeterminetheeffectivenessofdifferenttechnologiesforsmokingcessationsupportamongpopulationsthatmaybehardtoreach,includingthoseoflowsocioeconomicstatusandadultsolderthanage50.
Technology-basedcessationinterventionsareparticularlyrelevanttoyoungadultsaged18to25—about3.2millionofwhomsmokeddailyin2016. Asystematicreviewandmeta-analysisofpublishedrandomizedtrialsoftechnology-basedinterventions—includingcomputerprograms,internet,telephone,andtextmessaging—forsmokingcessationamongthispopulationfoundthattheyincreasedabstinenceby1.5timesthatofcomparisonsubjects. Researchersrecommendembeddingcessationinterventionsincommonlyusedsocialnetworkingplatforms, andtherehasbeensomeexploratoryworkinthisarea.ResultsofatrialwitharelativelysmallnumberofparticipantssuggestedthatFacebookwasanaccessible,low-costplatformforengagingyoungadultsconsideringcessation.However,thestudypointedtochallengesinmaintainingparticipation,retainingyoungpeopleintheprogram,andtheneedforgender-specificfeatures. Arandomizedcontrolledtrialhasbeendesignedtotestastage-basedsmokingcessationinterventiononFacebooktailoredforsmokersaged18to25.Participantswillberecruitedonline,randomlyassignedtoaFacebookgroupaccordingtotheirreadinesstoquit,andwillreceivetailoreddailymessagesandweeklycounseling.Thestudywillassesstheintervention’simpactonabstinencefromsmoking3,6,and12monthsaftertreatment,numberofcigarettessmoked,quitattemptslasting24
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hoursormore,andcommitmenttoabstinence.
SmokingCessationforPregnantWomen
Giventherisksassociatedwithsmokingduringpregnancy,butalsothechallengesfacedbyallsmokerswhentryingtoquit,researchershavestudiedanarrayofapproachestoimprovecessationratesforthispopulation.Manywomenaremotivatedtoquitduringpregnancy,butlikeothersmokers,mostwillneedassistance.
Studiesshowthatbehavioraltreatmentsareeffective,whereaspharmacotherapieshaveonlymarginalsuccess. Acombinationofincentivesandbehavioralcounselingismosteffectiveforpregnantwomen. Addingvoucherstoroutinecare(whichincludedfreenicotinereplacementtherapyfor10weeksandfourweeklysupportphonecalls)morethandoubledcessationratesduringpregnancy. Pooledresultsofbehavioralinterventionstudiesindicatethattreatmentreducedpretermbirthsandtheproportionofinfantsbornwithlowbirthweight,comparedwithusualcare. Thisfindingissupportedbyananalysisofpooledresultsfromstudieswitheconomicallydisadvantagedpregnantsmokers,whichfoundthatvoucher-basedincentivesimprovedsonographicallyestimatedfetalgrowth,birthweight,percentageoflow-birth-weightdeliveries,andbreastfeedingduration.
Medications
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NicotineReplacementTherapy(NRT)—AvarietyofformulationsofnicotineNRTsareavailableoverthecounter—includingthetransdermalpatch,spray,gum,andlozenges—andareequallyeffectiveforcessation. NRTsstimulatethebrainreceptorstargetedbynicotine,helpingrelievenicotinewithdrawalsymptomsandcravingsthatleadtorelapse. ManypeopleuseNRTtohelpthemgetthroughtheearlystagesofcessation,andthosewithmoreseverenicotineaddictioncanbenefitfromlonger-termtreatment.UseofNRTimprovessmokingcessationoutcomes,andaddingbehavioraltherapiesfurtherincreasesquitrates. Acombinationofcontinualnicotinedeliverythroughthetransdermalpatchandoneotherformofnicotinetakenasneeded(e.g.,lozenge,gum,nasalspray,inhaler)hasbeenfoundtobemoreeffectiveatrelievingwithdrawalsymptomsandcravingsthanasingletypeofNRT. ResearchersestimatethatNRTincreasesquitratesby50to70percent. Usingthepatchforupto24weekshasbeenshowntobesafe.
Bupropion—Bupropion(immediate-releaseandextended-release)wasoriginallyapprovedasanantidepressant.Itworksbyinhibitingthereuptakeofthebrainchemicalsnorepinephrineanddopamineaswellasstimulatingtheir
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release.Bupropionhasbeenfoundtoincreasequitratescomparedwithplaceboinbothshort-andlong-termfollow-upstudies andisindicatedforsmokingcessation.ItisequallyeffectivetoNRT.
Varenicline—Vareniclinehelpsreducenicotinecravingsbystimulatingthealpha-4beta-2nicotinicreceptorbuttoalesserdegreethannicotine.Vareniclinebooststheoddsofsuccessfullyquitting,comparedwithunassistedattempts. Vareniclineincreasedthelikelihoodofquittingcomparedwithplacebo,andsomestudiesfindthatitismoreeffectivethansingleformsofNRT andbupropion. Inaprimarycaresetting,44percentofpatientsonvarenicline,eitheraloneorcombinedwithcounseling,wereabstinentatthe2-yearfollow-up.Patientswhoparticipatedingrouptherapyandadheredtothemedicationweremorelikelytoremainabstinent. Researchalsosuggeststhatthismedicationmaybemoreeffectivethanbupropion.
Medicationcombinations—SomestudiessuggestthatcombiningNRTwithothermedicationsmayfacilitatecessation.Forexample,ameta-analysisfoundthatacombinationofvareniclineandNRT(especially,providinganicotinepatchpriortocessation)wasmoreeffectivethanvareniclinealone. Similarly,addingbupropiontoNRTalsoimprovedcessationrates. ForsmokerswhocouldnotcutdownsignificantlybyusingtheNRTpatch,combiningextended-releasebupropionandvareniclinewasmoreeffectivethanplacebo,particularlyformenandthosewhowereseverelynicotinedependent.
Otherantidepressants—Inadditiontobupropion,someotherantidepressantmedicationshavealsobeenfoundeffectiveforsmokingcessation,independentoftheirantidepressanteffects,andareconsideredsecond-linetreatments.AfewsmallstudiessuggestthatnortriptylineisequallyeffectiveasNRT. Althoughnortriptylinemayhavesideeffectsinsomepatients,thesmallstudiesforitsuseinsmokingcessationhavenotreportedany.Researchershavenotobservedanyimpactofselectiveserotoninreuptakeinhibitors(SSRIs)(e.g.,fluoxetine,paroxetine,andsertraline)onsmoking,eitheraloneorincombinationwithNRT.
PrecisionMedicine—Researchershavebeenexaminingwaystopersonalizetreatmentbasedonimportantindividualbiologicaldifferences,including
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geneticdifferences.Thefieldofpharmacogeneticsexamineshowgenesinfluencetherapeuticresponsetomedications,providingcriticalinformationtohelptailorpharmacotherapiestotheindividualformaximumbenefit.Forexample,peoplemetabolizenicotineatdifferentratesbecauseofvariationsinseveralgenes.Individualswhometabolizenicotinequicklysmokemore,showgreaterdependence,andhavemoredifficultyquitting. SuchgeneticvariationinfluencesthetherapeuticresponsestoNRTandothercessationmedications. Arecentstudycomparedratesofabstinence1weekaftertreatmentforslow,normal,andfastmetabolizersofnicotinewhowererandomlyassignedtoeitherplacebo,NRT,orvarenicline.Resultsindicatedthatvareniclineworkedbestfornormalnicotinemetabolizers,whereasNRTpatchesweremosteffectiveforslowmetabolizers.
Promisingmedicationsandongoingresearch—NIDAsupportsresearchtodevelopnewandimprovecurrenttreatmentoptionsforsmokingcessationbasedonagrowingunderstandingoftheneurobiologyofaddiction.Intheareaofmedications,researchisfocusingonthereceptorstargetedbynicotineandthebraincircuitsandregionsknowntoinfluencenicotineconsumption. Newerbraintargets—includingtheorexinandglutamatesignalingsystems—havealsoshownpromiseformedicationtreatment. Repurposingmedicationsalreadyonthemarketforotherindicationsmayalsoproveusefulinthesearchfornewsmokingcessationtherapies. Thisapproachhasbeensuccessfulinthepast,asbupropionwasanestablishedantidepressantbeforetheFDAapproveditasasmokingcessationmedication.OnecurrentcandidateisN-acetylcysteine,amedicationforacetaminophenoverdose,whichhasshownpromiseasatreatmentforvarioussubstanceusedisorders—includingnicotinedependence. Anotherapproachthatcouldpreventrelapseandthathasshownpromiseinearlystudiesisanicotinevaccine,whichwouldgenerateantibodiesthatkeepnicotinefromreachingthebrain.
TranscranialMagneticStimulation
Transcranialmagneticstimulation(TMS)isarelativelynewapproachbeingtestedtotreataddiction.Itisaphysiologicalinterventionthatnoninvasivelystimulatesneuralactivityintargetedareasofthebrainusingmagneticfields.MultipleTMSpulsesgivenconsecutivelyarereferredtoasrepetitiveTMS
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(rTMS).TheFDAhasapprovedtworTMSdevicesfordepressiontreatmentinadults.
ResearchonrTMSasatreatmentforsmokingcessationisinearlystagesbuthasshownpromise. Amongadultsmokerswhohadnotbeenabletoquitusingothertreatments,high-frequencyTMStreatmentsignificantlyreducedthenumberofcigarettessmoked.Combininghigh-frequencyTMSwithexposuretosmokingcuesimprovedeffectivenessandboostedtheoverallabstinencerateto44percentattheendofthetreatment.Sixmonthsaftertreatment,33percentofparticipantsremainedabstinentfromcigarettes. Futurerandomizedcontrolledclinicaltrialswithlargenumbersofpatientswillbeneededtoestablishitsefficacyforsmokingcessation.
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Howcanwepreventtobaccouse?
Themedicalconsequencesoftobaccouse—includingsecondhandexposure—maketobaccocontrolandsmokingpreventioncrucialpartsofanypublichealthstrategy.SincethefirstSurgeonGeneral’sReportonSmokingandHealthin1964,statesandcommunitieshavemadeeffortstoreduceinitiationofsmoking,decreaseexposuretosmoke,andincreasecessation.Researchersestimatethatthesetobaccocontroleffortsareassociatedwithavertinganestimated8millionprematuredeathsandextendingtheaveragelifeexpectancyofmenby2.3yearsandofwomenby1.6years. Butthereisalongwayyettogo:roughly5.6millionadolescentsunderage18areexpectedtodieprematurelyasaresultofanillnessrelatedtosmoking.
Preventioncantaketheformofpolicy-levelmeasures,suchasincreasedtaxationoftobaccoproducts;stricterlaws(andenforcementoflaws)regulatingwhocanpurchasetobaccoproducts;howandwheretheycanbepurchased;whereandwhentheycanbeused(i.e.,smoke-freepoliciesinrestaurants,bars,andotherpublicplaces);andrestrictionsonadvertisingandmandatoryhealthwarningsonpackages.Over100studieshaveshownthathighertaxesoncigarettes,forexample,producesignificantreductionsinsmoking,especiallyamongyouthandlower-incomeindividuals. Smoke-freeworkplacelawsandrestrictionsonadvertisinghavealsoshownbenefits.
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Preventioncanalsotakeplaceattheschoolorcommunitylevel.Merelyeducatingpotentialsmokersaboutthehealthriskshasnotproveneffective. Successfulevidence-basedinterventionsaimtoreduceordelayinitiationofsmoking,alcoholuse,andillicitdruguse,andotherwiseimproveoutcomesforchildrenandteensbyreducingormitigatingmodifiableriskfactorsandbolsteringprotectivefactors.Riskfactorsforsmokingincludehavingfamilymembersorpeerswhosmoke,beinginalowersocioeconomicstatus,livinginaneighborhoodwithhighdensityoftobaccooutlets,notparticipatinginteamsports,beingexposedtosmokinginmovies,andbeingsensation-seeking. Althougholderteensaremorelikelytosmokethanyoungerteens,theearlierapersonstartssmokingorusinganyaddictivesubstance,themorelikelytheyaretodevelopanaddiction.Malesarealsomorelikelytotakeupsmokinginadolescencethanfemales.
Someevidence-basedinterventionsshowlastingeffectsonreducingsmokinginitiation.Forinstance,communitiesutilizingtheintervention-deliverysystem,CommunitiesthatCare(CTC)forstudentsaged10to14showsustainedreductioninmalecigaretteinitiationupto9yearsaftertheendoftheintervention.
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Whatresearchisbeingdoneontobaccouse?
Newscientificdevelopmentscanimproveourunderstandingofnicotineaddictionandspurthedevelopmentofbetterpreventionandtreatmentstrategies.
GeneticsandEpigenetics
Anestimated50-75percentoftheriskfornicotineaddictionisattributabletogeneticfactors. Aclusterofgenes(CHRNA5-CHRNA3-CHRNB4)onchromosome15thatencodethe5,3,and4proteinsubunitsthatmakeupthebrainreceptorfornicotine areparticularlyimplicatedinnicotinedependenceandsmokingamongpeopleofEuropeandescent.VariationintheCHRNA5geneinfluencestheeffectivenessofcombinationNRT,butnotvarenicline. Otherresearchhasidentifiedgenesthatinfluencenicotinemetabolismandtherefore,thenumberofcigarettessmoked, responsivenesstomedication, andchancesofsuccessfullyquitting. Forexample,thetherapeuticresponsetovareniclineisassociatedwithvariantsfortheCHRNB2,CHRNA5,andCHRNA4genes,whilebupropion-relatedcessationislinkedwithvariationingenesthataffectnicotinemetabolism.
Smokingcanalsoleadtopersistentchangesingeneexpression(epigeneticchanges),whichmaycontributetoassociatedmedicalconsequencesoverthelongterm,evenfollowingcessation. Epigeneticchangesmayserveasapotentialbiomarkerforprenataltobaccosmokeexposure.Researchersfoundtobacco-specificchangesat26sitesontheepigenome,andthispatternpredictedprenatalexposurewith81percentaccuracy. Alargescalemeta-analysisofdataonepigeneticchangesassociatedwithprenatalexposuretocigarettesmokealsoidentifiedmanyepigeneticchangesthatpersistedintolaterchildhood. Moreresearchisneededtounderstandthelong-termhealthimpactsofthesechanges.
Neuroimaging
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Cutting-edgeneuroimagingtechnologieshaveidentifiedbrainchangesassociatedwithnicotinedependenceandsmoking.Usingfunctionalmagneticresonanceimaging(fMRI),scientistscanvisualizesmokers’brainsastheyrespondtocigarette-associatedcuesthatcantriggercravingandrelapse. Suchresearchmayleadtoabiomarkerforrelapseriskandformonitoringtreatmentprogress,aswellaspointtoregionsofthebraininvolvedinthedevelopmentofnicotineaddiction.
Aneuroimagingtechnologycalleddefault-modeorresting-statefMRI(rs-fMRI)revealsintrinsicbrainactivitywhenpeoplearealertbutnotperformingaparticulartask.Usingthistechnique,researchersareexaminingtheneurobiologicalprofileassociatedwithwithdrawalandhownicotineimpactscognition. Comparisonsbetweensmokersandnonsmokerssuggestthatchronicnicotinemayweakenconnectivitywithinbraincircuitsinvolvedinplanning,payingattention,andbehavioralcontrol—possiblycontributingtodifficultywithquitting. fMRIstudiesalsorevealtheimpactofsmokingcessationmedicationsonthebrain—particularlyhowtheymodulatetheactivityofdifferentbrainregionstoalleviatewithdrawalsymptomsandreducesmoking.AreviewofthesestudiessuggestedthatNRTenhancescognitionduringwithdrawalbymodulatingactivityindefault-networkregions,butmaynotaffectneuralcircuitsassociatedwithnicotineaddiction.
Someimagingtechniquesallowresearcherstovisualizeneurotransmittersandtheirreceptors,furtherinformingourunderstandingofnicotineaddictionanditstreatment. Usingthesetechniques,researchershaveestablishedthatsmokingincreasesthenumberofbrainreceptorsfornicotine.Individualswhoshowgreaterreceptorupregulationarelesslikelytostopsmoking. Combiningneuroimagingandgeneticsmayyieldparticularlyusefulinformationforimprovingandtailoringtreatment.Forexample,nonsmokingadolescentswithaparticularvariantintheCHRNA5-CHRNA3-CHRNB4genecluster(whichisassociatedwithnicotinedependenceandsmoking)showedreducedbrainactivityinresponsetorewardinthestriatumaswellastheorbitofrontalandanteriorcingulatecortex.Thisfindingsuggeststhatgeneticscaninfluencehowthebrainprocessesrewardswhichmayinfluencevulnerabilitytonicotinedependence. Neuroimaginggeneticsalsoshowsthatothergenes,includingonesthatinfluencedopamineneurotransmission,influencerewardsensitivityandriskforaddictiontonicotine.
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References
1. NationalCenterforChronicDiseasePreventionandHealthPromotion(US)OfficeonSmokingandHealth.TheHealthConsequencesofSmoking—50YearsofProgress:AReportoftheSurgeonGeneral.Atlanta(GA):CentersforDiseaseControlandPrevention(US);2014.http://www.ncbi.nlm.nih.gov/books/NBK179276/.
2. AgakuIT,KingBA,HustenCG,etal.Tobaccoproductuseamongadults—UnitedStates,2012-2013.MMWRMorbMortalWklyRep.2014;63(25):542-547.
3. StantonCA,KeithDR,GaalemaDE,etal.TrendsintobaccouseamongUSadultswithchronichealthconditions:NationalSurveyonDrugUseandHealth2005-2013.PrevMed.2016;92:160-168.doi:10.1016/j.ypmed.2016.04.008.
4. SmithPH,MazureCM,McKeeSA.SmokingandmentalillnessintheU.S.population.TobControl.2014;23(e2):e147-e153.doi:10.1136/tobaccocontrol-2013-051466.
5. KollinsSH,AdcockRA.ADHD,altereddopamineneurotransmission,anddisruptedreinforcementprocesses:implicationsforsmokingandnicotinedependence.ProgNeuropsychopharmacolBiolPsychiatry.2014;52:70-78.doi:10.1016/j.pnpbp.2014.02.002.
6. CookBL,WayneGF,KafaliEN,LiuZ,ShuC,FloresM.Trendsinsmokingamongadultswithmentalillnessandassociationbetweenmentalhealthtreatmentandsmokingcessation.JAMA.2014;311(2):172-182.doi:10.1001/jama.2013.284985.
7. CenterforBehavioralHealthStatisticsandQuality.Resultsfromthe2016NationalSurveyonDrugUseandHealth:DetailedTables.Rockville(MD):SAMHSA;2017.https://www.samhsa.gov/data/sites/default/files/NSDUH-DetTabs-2016/NSDUH-DetTabs-2016.pdf.AccessedSeptember14,2017.
8. NationalCenterforHealthStatistics.NationalHealthInterviewSurvey,1997-2016.CentersforDiseaseControlandPrevention;2017.https://www.cdc.gov/nchs/data/nhis/earlyrelease/earlyrelease201705_08.pdf.AccessedSeptember14,2017.
46
9. SubstanceAbuseandMentalHealthServicesAdministration.AdultswithMentalIllnessofSubstanceUseDisorderAccountfor40PercentofAllCigarettesSmoked.Rockville,MD:SAMHSA;2013.https://www.samhsa.gov/data/sites/default/files/spot104-cigarettes-mental-illness-substance-use-disorder/spot104-cigarettes-mental-illness-substance-use-disorder.pdf.AccessedOctober6,2017.
10. JamalA,HomaDM,O’ConnorE,etal.Currentcigarettesmokingamongadults-UnitedStates,2005-2014.MMWRMorbMortalWklyRep.2015;64(44):1233-1240.doi:10.15585/mmwr.mm6444a2.
11. RobertsME,DooganNJ,KurtiAN,etal.RuraltobaccouseacrosstheUnitedStates:Howruralandurbanareasdiffer,brokendownbycensusregionsanddivisions.HealthPlace.2016;39:153-159.doi:10.1016/j.healthplace.2016.04.001.
12. MiechR,SchulenbergJ,JohnstonL,BachmanJ,O’MalleyP,PatrickM.MonitoringtheFutureNationalAdolescentDrugTrendsin2017:FindingsReleased.AnnArbor,MI:InstituteforSocialResearch,TheUniversityofMichigan;2017.http://www.monitoringthefuture.org//pressreleases/17drugpr.pdf.AccessedJanuary2,2018.
13. SinghT,ArrazolaRA,CoreyCG,etal.TobaccoUseAmongMiddleandHighSchoolStudents--UnitedStates,2011-2015.MMWRMorbMortalWklyRep.2016;65(14):361-367.doi:10.15585/mmwr.mm6514a1.
14. WarnerKE.FrequencyofE-CigaretteUseandCigaretteSmokingbyAmericanStudentsin2014.AmJPrevMed.2016;51(2):179-184.doi:10.1016/j.amepre.2015.12.004.
15. ManteyDS,CooperMR,ClendennenSL,PaschKE,PerryCL.E-CigaretteMarketingExposureIsAssociatedWithE-CigaretteUseAmongUSYouth.JAdolescHealthOffPublSocAdolescMed.2016;58(6):686-690.doi:10.1016/j.jadohealth.2016.03.003.
16. GilreathTD,LeventhalA,Barrington-TrimisJL,etal.PatternsofAlternativeTobaccoProductUse:EmergenceofHookahandE-cigarettesasPreferredProductsAmongstYouth.JAdolescHealthOffPublSocAdolescMed.2016;58(2):181-185.doi:10.1016/j.jadohealth.2015.10.001.
17. ArrazolaRA,SinghT,CoreyCG,etal.Tobaccouseamongmiddleandhigh
47
schoolstudents-UnitedStates,2011-2014.MMWRMorbMortalWklyRep.2015;64(14):381-385.
18. HolfordTR,MezaR,WarnerKE,etal.Tobaccocontrolandthereductioninsmoking-relatedprematuredeathsintheUnitedStates,1964-2012.JAMA.2014;311(2):164-171.doi:10.1001/jama.2013.285112.
19. MaciosekMV,XuX,ButaniAL,PechacekTF.Smoking-attributablemedicalexpendituresbyage,sex,andsmokingstatusestimatedusingarelativeriskapproach.PrevMed.2015;77:162-167.doi:10.1016/j.ypmed.2015.05.019.
20. PicciottoMR,MineurYS.Moleculesandcircuitsinvolvedinnicotineaddiction:Themanyfacesofsmoking.Neuropharmacology.2014;76PtB:545-553.doi:10.1016/j.neuropharm.2013.04.028.
21. BalfourDJK.Theroleofmesoaccumbensdopamineinnicotinedependence.CurrTopBehavNeurosci.2015;24:55-98.doi:10.1007/978-3-319-13482-6_3.
22. NationalCancerPolicyForum,BoardonHealthCareServices,InstituteofMedicine.ReducingTobacco-RelatedCancerIncidenceandMortality:WorkshopSummary.Washington(DC):NationalAcademiesPress(US);2013.http://www.ncbi.nlm.nih.gov/books/NBK206891/.
23. HoffmannD,HoffmannI.Thechangingcigarette,1950-1995.JToxicolEnvironHealth.1997;50(4):307-364.doi:10.1080/009841097160393.
24. HukkanenJ,JacobP,BenowitzNL.Metabolismanddispositionkineticsofnicotine.PharmacolRev.2005;57(1):79-115.doi:10.1124/pr.57.1.3.
25. CentersforDiseaseControlandPrevention(CDC).Quittingsmokingamongadults—UnitedStates,2001-2010.MMWRMorbMortalWklyRep.2011;60(44):1513-1519.
26. NationalCancerInstitute.CigaretteSmoking:HealthRisksandHowtoQuit.NationalCancerInstitute.https://www.cancer.gov/about-cancer/causes-prevention/risk/tobacco/quit-smoking-pdq#section/_19.Published2016.AccessedSeptember14,2017.
27. CosgroveKP,EsterlisI,SandiegoC,PetrulliR,MorrisED.ImagingTobaccoSmokingwithPETandSPECT.CurrTopBehavNeurosci.2015;24:1-17.doi:10.1007/978-3-319-13482-6_1.
48
28. BrodyAL,MukhinAG,MamounMS,etal.Brainnicotinicacetylcholinereceptoravailabilityandresponsetosmokingcessationtreatment:arandomizedtrial.JAMAPsychiatry.2014;71(7):797-805.doi:10.1001/jamapsychiatry.2014.138.
29. ClausED,BlaineSK,FilbeyFM,MayerAR,HutchisonKE.Associationbetweennicotinedependenceseverity,BOLDresponsetosmokingcues,andfunctionalconnectivity.NeuropsychopharmacolOffPublAmCollNeuropsychopharmacol.2013;38(12):2363-2372.doi:10.1038/npp.2013.134.
30. JacksonKJ,MuldoonPP,DeBiasiM,DamajMI.Newmechanismsandperspectivesinnicotinewithdrawal.Neuropharmacology.2015;96(PtB):223-234.doi:10.1016/j.neuropharm.2014.11.009.
31. McLaughlinI,DaniJA,DeBiasiM.Nicotinewithdrawal.CurrTopBehavNeurosci.2015;24:99-123.doi:10.1007/978-3-319-13482-6_4.
32. AnsteyKJ,vonSandenC,SalimA,O’KearneyR.Smokingasariskfactorfordementiaandcognitivedecline:ameta-analysisofprospectivestudies.AmJEpidemiol.2007;166(4):367-378.doi:10.1093/aje/kwm116.
33. AshareRL,FalconeM,LermanC.Cognitivefunctionduringnicotinewithdrawal:Implicationsfornicotinedependencetreatment.Neuropharmacology.2014;76PtB:581-591.doi:10.1016/j.neuropharm.2013.04.034.
34. JasinskaAJ,ZorickT,BrodyAL,SteinEA.Dualroleofnicotineinaddictionandcognition:areviewofneuroimagingstudiesinhumans.Neuropharmacology.2014;84:111-122.doi:10.1016/j.neuropharm.2013.02.015.
35. JaehneA,UnbehaunT,FeigeB,etal.Sleepchangesinsmokersbefore,duringand3monthsafternicotinewithdrawal.AddictBiol.2015;20(4):747-755.doi:10.1111/adb.12151.
36. BrauerLH,BehmFM,LaneJD,WestmanEC,PerkinsC,RoseJE.Individualdifferencesinsmokingrewardfromde-nicotinizedcigarettes.NicotineTobResOffJSocResNicotineTob.2001;3(2):101-109.doi:10.1080/14622200110042000.
37. SteadLF,PereraR,BullenC,etal.Nicotinereplacementtherapyfor
49
smokingcessation.CochraneDatabaseSystRev.2012;11:CD000146.doi:10.1002/14651858.CD000146.pub4.
38. CarpenterMJ,JardinBF,BurrisJL,etal.Clinicalstrategiestoenhancetheefficacyofnicotinereplacementtherapyforsmokingcessation:areviewoftheliterature.Drugs.2013;73(5):407-426.doi:10.1007/s40265-013-0038-y.
39. SchnollRA,GoelzPM,Veluz-WilkinsA,etal.Long-termnicotinereplacementtherapy:arandomizedclinicaltrial.JAMAInternMed.2015;175(4):504-511.doi:10.1001/jamainternmed.2014.8313.
40. SteadLF,LancasterT.Combinedpharmacotherapyandbehaviouralinterventionsforsmokingcessation.CochraneDatabaseSystRev.2012;10:CD008286.doi:10.1002/14651858.CD008286.pub2.
41. SteadLF,KoilpillaiP,FanshaweTR,LancasterT.Combinedpharmacotherapyandbehaviouralinterventionsforsmokingcessation.CochraneDatabaseSystRev.2016;3:CD008286.doi:10.1002/14651858.CD008286.pub3.
42. HoggRC.ContributionofMonoamineOxidaseInhibitiontoTobaccoDependence:AReviewoftheEvidence.NicotineTobResOffJSocResNicotineTob.2016;18(5):509-523.doi:10.1093/ntr/ntv245.
43. HoffmanAC,EvansSE.Abusepotentialofnon-nicotinetobaccosmokecomponents:acetaldehyde,nornicotine,cotinine,andanabasine.NicotineTobResOffJSocResNicotineTob.2013;15(3):622-632.doi:10.1093/ntr/nts192.
44. NationalCancerInstitute.SEERStatFactSheets:CancerofAnySite.http://seer.cancer.gov/statfacts/html/all.html.
45. MüezzinlerA,MonsU,GellertC,etal.SmokingandAll-causeMortalityinOlderAdults:ResultsFromtheCHANCESConsortium.AmJPrevMed.2015;49(5):e53-e63.doi:10.1016/j.amepre.2015.04.004.
46. GoldmanDP,ZhengY,GirosiF,etal.ThebenefitsofriskfactorpreventioninAmericansaged51yearsandolder.AmJPublicHealth.2009;99(11):2096-2101.doi:10.2105/AJPH.2009.172627.
47. CentersforDiseaseControlandPrevention.WhatAretheRiskFactorsforLungCancer?https://www.cdc.gov/cancer/lung/basic_info/risk_factors.htm.
50
PublishedMay31,2017.AccessedDecember1,2017.
48. SchwartzAG,CoteML.EpidemiologyofLungCancer.AdvExpMedBiol.2016;893:21-41.doi:10.1007/978-3-319-24223-1_2.
49. LeePN.Epidemiologicalevidencerelatingsnustohealth—anupdatedreviewbasedonrecentpublications.HarmReductJ.2013;10:36.doi:10.1186/1477-7517-10-36.
50. ZuoL,HeF,SergakisGG,etal.Interrelatedroleofcigarettesmoking,oxidativestress,andimmuneresponseinCOPDandcorrespondingtreatments.AmJPhysiolLungCellMolPhysiol.2014;307(3):L205-L218.doi:10.1152/ajplung.00330.2013.
51. KelishadiR,PoursafaP.Areviewonthegenetic,environmental,andlifestyleaspectsoftheearly-lifeoriginsofcardiovasculardisease.CurrProblPediatrAdolescHealthCare.2014;44(3):54-72.doi:10.1016/j.cppeds.2013.12.005.
52. MorrisPB,FerenceBA,JahangirE,etal.CardiovascularEffectsofExposuretoCigaretteSmokeandElectronicCigarettes:ClinicalPerspectivesFromthePreventionofCardiovascularDiseaseSectionLeadershipCouncilandEarlyCareerCouncilsoftheAmericanCollegeofCardiology.JAmCollCardiol.2015;66(12):1378-1391.doi:10.1016/j.jacc.2015.07.037.
53. AthyrosVG,KatsikiN,DoumasM,KaragiannisA,MikhailidisDP.Effectoftobaccosmokingandsmokingcessationonplasmalipoproteinsandassociatedmajorcardiovascularriskfactors:anarrativereview.CurrMedResOpin.2013;29(10):1263-1274.doi:10.1185/03007995.2013.827566.
54. TianJ,VennAJ,BlizzardL,PattonGC,DwyerT,GallSL.Smokingstatusandhealth-relatedqualityoflife:alongitudinalstudyinyoungadults.QualLifeResIntJQualLifeAspTreatCareRehabil.2016;25(3):669-685.doi:10.1007/s11136-015-1112-6.
55. JacobsM,AlonsoAM,SherinKM,etal.Policiestorestrictsecondhandsmokeexposure:AmericanCollegeofPreventiveMedicinePositionStatement.AmJPrevMed.2013;45(3):360-367.doi:10.1016/j.amepre.2013.05.007.
56. Al-SayedEM,IbrahimKS.Second-handtobaccosmokeandchildren.
51
ToxicolIndHealth.2014;30(7):635-644.doi:10.1177/0748233712462473.
57. Martins-GreenM,AdhamiN,FrankosM,etal.CigaretteSmokeToxinsDepositedonSurfaces:ImplicationsforHumanHealth.PLOSONE.2014;9(1):e86391.doi:10.1371/journal.pone.0086391.
58. StoneWL,BaileyB,KhraishaN.Thepathophysiologyofsmokingduringpregnancy:asystemsbiologyapproach.FrontBiosciEliteEd.2014;6:318-328.
59. IonR,BernalAL.SmokingandPretermBirth.ReprodSciThousandOaksCalif.2015;22(8):918-926.doi:10.1177/1933719114556486.
60. EkbladM,KorkeilaJ,LehtonenL.Smokingduringpregnancyaffectsfoetalbraindevelopment.ActaPaediatrOsloNor1992.2015;104(1):12-18.doi:10.1111/apa.12791.
61. PhelanS.Smokingcessationinpregnancy.ObstetGynecolClinNorthAm.2014;41(2):255-266.doi:10.1016/j.ogc.2014.02.007.
62. HylandA,PiazzaKM,HoveyKM,etal.Associationsoflifetimeactiveandpassivesmokingwithspontaneousabortion,stillbirthandtubalectopicpregnancy:across-sectionalanalysisofhistoricaldatafromtheWomen’sHealthInitiative.TobControl.2015;24(4):328-335.doi:10.1136/tobaccocontrol-2013-051458.
63. PinelesBL,ParkE,SametJM.Systematicreviewandmeta-analysisofmiscarriageandmaternalexposuretotobaccosmokeduringpregnancy.AmJEpidemiol.2014;179(7):807-823.doi:10.1093/aje/kwt334.
64. ChhabraD,SharmaS,KhoAT,etal.Fetallungandplacentalmethylationisassociatedwithinuteronicotineexposure.Epigenetics.2014;9(11):1473-1484.doi:10.4161/15592294.2014.971593.
65. FernandesM,YangX,LiJY,CheikhIsmailL.Smokingduringpregnancyandvisiondifficultiesinchildren:asystematicreview.ActaOphthalmol(Copenh).2015;93(3):213-223.doi:10.1111/aos.12627.
66. CurtinSC,MatthewsTJ.SmokingPrevalenceandCessationBeforeandDuringPregnancy:DataFromtheBirthCertificate,2014.NatlVitalStatRepCentDisControlPrevNatlCentHealthStatNatlVitalStatSyst.2016;65(1):1-14.
52
67. WalkerJF,LoprinziPD.LongitudinalexaminationofpredictorsofsmokingcessationinanationalsampleofU.S.adolescentandyoungadultsmokers.NicotineTobResOffJSocResNicotineTob.2014;16(6):820-827.doi:10.1093/ntr/ntu005.
68. ApelbergBJ,CoreyCG,HoffmanAC,etal.Symptomsoftobaccodependenceamongmiddleandhighschooltobaccousers:resultsfromthe2012NationalYouthTobaccoSurvey.AmJPrevMed.2014;47(2Suppl1):S4-S14.doi:10.1016/j.amepre.2014.04.013.
69. RubinsteinML,RaitMA,SenS,ShiffmanS.Characteristicsofadolescentintermittentanddailysmokers.AddictBehav.2014;39(9):1337-1341.doi:10.1016/j.addbeh.2014.04.021.
70. SmithRF,McDonaldCG,BergstromHC,EhlingerDG,BrielmaierJM.Adolescentnicotineinducespersistingchangesindevelopmentofneuralconnectivity.NeurosciBiobehavRev.2015;55:432-443.doi:10.1016/j.neubiorev.2015.05.019.
71. LydonDM,WilsonSJ,ChildA,GeierCF.Adolescentbrainmaturationandsmoking:whatweknowandwherewe’reheaded.NeurosciBiobehavRev.2014;45:323-342.doi:10.1016/j.neubiorev.2014.07.003.
72. Cavazos-RehgPA,KraussMJ,SpitznagelEL,GruczaRA,BierutLJ.Youthtobaccousetypeandassociationswithsubstanceusedisorders.AddictAbingdonEngl.2014;109(8):1371-1380.doi:10.1111/add.12567.
73. KandelDB,GrieslerPC,HuM-C.IntergenerationalPatternsofSmokingandNicotineDependenceAmongUSAdolescents.AmJPublicHealth.2015;105(11):e63-e72.doi:10.2105/AJPH.2015.302775.
74. DierkerL,RoseJ,SelyaA,PiaseckiTM,HedekerD,MermelsteinR.Depressionandnicotinedependencefromadolescencetoyoungadulthood.AddictBehav.2015;41:124-128.doi:10.1016/j.addbeh.2014.10.004.
75. CheneyMK,OmanRF,VeselySK,AspyCB,TolmaEL.Prospectiveassociationsbetweennegativelifeeventsandyouthtobaccouse.AmJHealthBehav.2014;38(6):942-950.doi:10.5993/AJHB.38.6.16.
76. BonilhaAG,deSouzaEST,SicchieriMP,AchcarJA,CrippaJAS,Baddini-MartinezJ.Amotivationalprofileforsmokingamongadolescents.JAddict
53
Med.2013;7(6):439-446.doi:10.1097/01.ADM.0000434987.76599.c0.
77. VassolerFM,ByrnesEM,PierceRC.Theimpactofexposuretoaddictivedrugsonfuturegenerations:Physiologicalandbehavioraleffects.Neuropharmacology.2014;76PtB:269-275.doi:10.1016/j.neuropharm.2013.06.016.
78. KingBA,PatelR,NguyenKH,DubeSR.TrendsinawarenessanduseofelectroniccigarettesamongUSadults,2010-2013.NicotineTobResOffJSocResNicotineTob.2015;17(2):219-227.doi:10.1093/ntr/ntu191.
79. BrelandA,SouleE,LopezA,RamôaC,El-HellaniA,EissenbergT.Electroniccigarettes:whataretheyandwhatdotheydo?AnnNYAcadSci.2017;1394(1):5-30.doi:10.1111/nyas.12977.
80. KmietowiczZ.Marketfore-cigarettesincludes466brandsand7764uniqueflavours.BMJ.2014;348:g4016.
81. WeaverSR,MajeedBA,PechacekTF,NymanAL,GregoryKR,EriksenMP.UseofelectronicnicotinedeliverysystemsandothertobaccoproductsamongUSAadults,2014:resultsfromanationalsurvey.IntJPublicHealth.2016;61(2):177-188.doi:10.1007/s00038-015-0761-0.
82. DelnevoCD,GiovencoDP,SteinbergMB,etal.PatternsofElectronicCigaretteUseAmongAdultsintheUnitedStates.NicotineTobResOffJSocResNicotineTob.2016;18(5):715-719.doi:10.1093/ntr/ntv237.
83. CumminsSE,ZhuS-H,TedeschiGJ,GamstAC,MyersMG.Useofe-cigarettesbyindividualswithmentalhealthconditions.TobControl.2014;23Suppl3:iii48-iii53.doi:10.1136/tobaccocontrol-2013-051511.
84. EnglandLJ,BunnellRE,PechacekTF,TongVT,McAfeeTA.NicotineandtheDevelopingHuman:ANeglectedElementintheElectronicCigaretteDebate.AmJPrevMed.2015;49(2):286-293.doi:10.1016/j.amepre.2015.01.015.
85. ColemanBN,JohnsonSE,TessmanGK,etal.“It’snotsmoke.It’snottar.It’snot4000chemicals.Caseclosed”:Exploringattitudes,beliefs,andperceivedsocialnormsofe-cigaretteuseamongadultusers.DrugAlcoholDepend.2016;159:80-85.doi:10.1016/j.drugalcdep.2015.11.028.
86. RomO,PecorelliA,ValacchiG,ReznickAZ.AreE-cigarettesasafeand
54
goodalternativetocigarettesmoking?AnnNYAcadSci.2015;1340:65-74.doi:10.1111/nyas.12609.
87. CarrollChapmanSL,WuL-T.E-cigaretteprevalenceandcorrelatesofuseamongadolescentsversusadults:areviewandcomparison.JPsychiatrRes.2014;54:43-54.doi:10.1016/j.jpsychires.2014.03.005.
88. SouleEK,RosasSR,NasimA.Reasonsforelectroniccigaretteusebeyondcigarettesmokingcessation:Aconceptmappingapproach.AddictBehav.2016;56:41-50.doi:10.1016/j.addbeh.2016.01.008.
89. Callahan-LyonP.Electroniccigarettes:humanhealtheffects.TobControl.2014;23Suppl2:ii36-ii40.doi:10.1136/tobaccocontrol-2013-051470.
90. OhAY,KackerA.Doelectroniccigarettesimpartalowerpotentialdiseaseburdenthanconventionaltobaccocigarettes?ReviewonE-cigarettevaporversustobaccosmoke.TheLaryngoscope.2014;124(12):2702-2706.doi:10.1002/lary.24750.
91. WalleySC,JenssenBP,SectiononTobaccoControl.ElectronicNicotineDeliverySystems.Pediatrics.2015;136(5):1018-1026.doi:10.1542/peds.2015-3222.
92. LernerCA,SundarIK,YaoH,etal.Vaporsproducedbyelectroniccigarettesande-juiceswithflavoringsinducetoxicity,oxidativestress,andinflammatoryresponseinlungepithelialcellsandinmouselung.PloSOne.2015;10(2):e0116732.doi:10.1371/journal.pone.0116732.
93. SchroederMJ,HoffmanAC.Electroniccigarettesandnicotineclinicalpharmacology.TobControl.2014;23Suppl2:ii30-ii35.doi:10.1136/tobaccocontrol-2013-051469.
94. BeharE,SantosG-M,WheelerE,RoweC,CoffinPO.Briefoverdoseeducationissufficientfornaloxonedistributiontoopioidusers.DrugAlcoholDepend.2015;148:209-212.doi:10.1016/j.drugalcdep.2014.12.009.
95. EtterJ-F.Alongitudinalstudyofcotinineinlong-termdailyusersofe-cigarettes.DrugAlcoholDepend.2016;160:218-221.doi:10.1016/j.drugalcdep.2016.01.003.
96. LopezAA,HilerMM,SouleEK,etal.EffectsofElectronicCigaretteLiquidNicotineConcentrationonPlasmaNicotineandPuffTopographyin
55
TobaccoCigaretteSmokers:APreliminaryReport.NicotineTobResOffJSocResNicotineTob.2016;18(5):720-723.doi:10.1093/ntr/ntv182.
97. RamôaCP,HilerMM,SpindleTR,etal.Electroniccigarettenicotinedeliverycanexceedthatofcombustiblecigarettes:apreliminaryreport.TobControl.2016;25(e1):e6-e9.doi:10.1136/tobaccocontrol-2015-052447.
98. StHelenG,HavelC,DempseyDA,JacobP,BenowitzNL.Nicotinedelivery,retentionandpharmacokineticsfromvariouselectroniccigarettes.AddictAbingdonEngl.2016;111(3):535-544.doi:10.1111/add.13183.
99. Chatham-StephensK,LawR,TaylorE,etal.Notesfromthefield:callstopoisoncentersforexposurestoelectroniccigarettes--UnitedStates,September2010-February2014.MMWRMorbMortalWklyRep.2014;63(13):292-293.
100. KalkhoranS,GlantzSA.E-cigarettesandsmokingcessationinreal-worldandclinicalsettings:asystematicreviewandmeta-analysis.LancetRespirMed.2016;4(2):116-128.doi:10.1016/S2213-2600(15)00521-4.
101. BroseLS,HitchmanSC,BrownJ,WestR,McNeillA.Istheuseofelectroniccigaretteswhilesmokingassociatedwithsmokingcessationattempts,cessationandreducedcigaretteconsumption?Asurveywitha1-yearfollow-up.AddictAbingdonEngl.2015;110(7):1160-1168.doi:10.1111/add.12917.
102. WestR,ShahabL,BrownJ.Estimatingthepopulationimpactofe-cigarettesonsmokingcessationinEngland.AddictAbingdonEngl.2016;111(6):1118-1119.doi:10.1111/add.13343.
103. RahmanMA,HannN,WilsonA,MnatzaganianG,Worrall-CarterL.E-cigarettesandsmokingcessation:evidencefromasystematicreviewandmeta-analysis.PloSOne.2015;10(3):e0122544.doi:10.1371/journal.pone.0122544.
104. CardenasVM,EvansVL,BalamuruganA,FaramawiMF,DelongchampRR,WheelerJG.UseofelectronicnicotinedeliverysystemsandrecentinitiationofsmokingamongUSyouth.IntJPublicHealth.2016;61(2):237-241.doi:10.1007/s00038-015-0783-7.
105. ParkJ-Y,SeoD-C,LinH-C.E-CigaretteUseandIntentiontoInitiateorQuitSmokingAmongUSYouths.AmJPublicHealth.2016;106(4):672-678.
56
doi:10.2105/AJPH.2015.302994.
106. PrimackBA,SonejiS,StoolmillerM,FineMJ,SargentJD.ProgressiontoTraditionalCigaretteSmokingAfterElectronicCigaretteUseAmongUSAdolescentsandYoungAdults.JAMAPediatr.2015;169(11):1018-1023.doi:10.1001/jamapediatrics.2015.1742.
107. KongG,MoreanME,CavalloDA,CamengaDR,Krishnan-SarinS.ReasonsforElectronicCigaretteExperimentationandDiscontinuationAmongAdolescentsandYoungAdults.NicotineTobResOffJSocResNicotineTob.2015;17(7):847-854.doi:10.1093/ntr/ntu257.
108. Barrington-TrimisJL,BerhaneK,UngerJB,etal.PsychosocialFactorsAssociatedWithAdolescentElectronicCigaretteandCigaretteUse.Pediatrics.2015;136(2):308-317.doi:10.1542/peds.2015-0639.
109. U.S.FoodandDrugAdministration.Rules,Regulations&Guidance-FDA’sNewRegulationsforE-Cigarettes,Cigars,andAllOtherTobaccoProducts.https://www.fda.gov/TobaccoProducts/Labeling/RulesRegulationsGuidance/ucm394909.htmPublished2016.AccessedSeptember14,2017.
110. LautersteinD,HoshinoR,GordonT,WatkinsB-X,WeitzmanM,ZelikoffJ.ThechangingfaceoftobaccouseamongUnitedStatesyouth.CurrDrugAbuseRev.2014;7(1):29-43.
111. MesserK,WhiteMM,StrongDR,etal.TrendsinuseoflittlecigarsorcigarillosandcigarettesamongU.S.smokers,2002-2011.NicotineTobResOffJSocResNicotineTob.2015;17(5):515-523.doi:10.1093/ntr/ntu179.
112. ShepardsonRL,HustadJTP.HookahTobaccoSmokingDuringtheTransitiontoCollege:PrevalenceofOtherSubstanceUseandPredictorsofInitiation.NicotineTobResOffJSocResNicotineTob.2016;18(5):763-769.doi:10.1093/ntr/ntv170.
113. HaiderMR,SalloumRG,IslamF,OrtizKS,KatesFR,MaziakW.FactorsassociatedwithsmokingfrequencyamongcurrentwaterpipesmokersintheUnitedStates:FindingsfromtheNationalCollegeHealthAssessmentII.DrugAlcoholDepend.2015;153:359-363.doi:10.1016/j.drugalcdep.2015.05.015.
114. PrimackBA,CarrollMV,WeissPM,etal.SystematicReviewandMeta-AnalysisofInhaledToxicantsfromWaterpipeandCigaretteSmoking.Public
57
HealthRepWashDC1974.2016;131(1):76-85.doi:10.1177/003335491613100114.
115. WardKD,SiddiqiK,AhluwaliaJS,AlexanderAC,AsfarT.Waterpipetobaccosmoking:Thecriticalneedforcessationtreatment.DrugAlcoholDepend.2015;153:14-21.doi:10.1016/j.drugalcdep.2015.05.029.
116. RichardsonA,PearsonJ,XiaoH,StalgaitisC,ValloneD.Prevalence,harmperceptions,andreasonsforusingnoncombustibletobaccoproductsamongcurrentandformersmokers.AmJPublicHealth.2014;104(8):1437-1444.doi:10.2105/AJPH.2013.301804.
117. ChangJT,LevyDT,MezaR.TrendsandFactorsRelatedtoSmokelessTobaccoUseintheUnitedStates.NicotineTobResOffJSocResNicotineTob.2016;18(8):1740-1748.doi:10.1093/ntr/ntw090.
118. TamJ,DayHR,RostronBL,ApelbergBJ.AsystematicreviewoftransitionsbetweencigaretteandsmokelesstobaccoproductuseintheUnitedStates.BMCPublicHealth.2015;15:258.doi:10.1186/s12889-015-1594-8.
119. Ayo-YusufOA,BurnsDM.Thecomplexityof“harmreduction”withsmokelesstobaccoasanapproachtotobaccocontrolinlow-incomeandmiddle-incomecountries.TobControl.2012;21(2):245-251.doi:10.1136/tobaccocontrol-2011-050367.
120. FixBV,O’ConnorRJ,VoglL,etal.PatternsandcorrelatesofpolytobaccouseintheUnitedStatesoveradecade:NSDUH2002-2011.AddictBehav.2014;39(4):768-781.doi:10.1016/j.addbeh.2013.12.015.
121. NeffLJ,ArrazolaRA,CaraballoRS,etal.FrequencyofTobaccoUseAmongMiddleandHighSchoolStudents--UnitedStates,2014.MMWRMorbMortalWklyRep.2015;64(38):1061-1065.doi:10.15585/mmwr.mm6438a1.
122. LeeYO,HebertCJ,NonnemakerJM,KimAE.YouthtobaccoproductuseintheUnitedStates.Pediatrics.2015;135(3):409-415.doi:10.1542/peds.2014-3202.
123. FeirmanSP,LockD,CohenJE,HoltgraveDR,LiT.FlavoredTobaccoProductsintheUnitedStates:ASystematicReviewAssessingUseandAttitudes.NicotineTobResOffJSocResNicotineTob.2016;18(5):739-749.doi:10.1093/ntr/ntv176.
58
124. BrownJE,LuoW,IsabelleLM,PankowJF.Candyflavoringsintobacco.NEnglJMed.2014;370(23):2250-2252.doi:10.1056/NEJMc1403015.
125. KingBA,TynanMA,DubeSR,ArrazolaR.Flavored-little-cigarandflavored-cigaretteuseamongU.S.middleandhighschoolstudents.JAdolescHealthOffPublSocAdolescMed.2014;54(1):40-46.doi:10.1016/j.jadohealth.2013.07.033.
126. CoreyCG,AmbroseBK,ApelbergBJ,KingBA.FlavoredTobaccoProductUseAmongMiddleandHighSchoolStudents—UnitedStates,2014.MMWRMorbMortalWklyRep.2015;64(38):1066-1070.doi:10.15585/mmwr.mm6438a2.
127. VillantiAC,RichardsonA,ValloneDM,RathJM.FlavoredtobaccoproductuseamongU.S.youngadults.AmJPrevMed.2013;44(4):388-391.doi:10.1016/j.amepre.2012.11.031.
128. HigginsST,KurtiAN,RednerR,etal.AliteraturereviewonprevalenceofgenderdifferencesandintersectionswithothervulnerabilitiestotobaccouseintheUnitedStates,2004-2014.PrevMed.2015;80:89-100.doi:10.1016/j.ypmed.2015.06.009.
129. JamalA,KingBA,NeffLJ,WhitmillJ,BabbSD,GraffunderCM.CurrentCigaretteSmokingAmongAdults—UnitedStates,2005-2015.MMWRMorbMortalWklyRep.2016;65(44):1205-1211.doi:10.15585/mmwr.mm6544a2.
130. SieminskaA,JassemE.Themanyfacesoftobaccouseamongwomen.MedSciMonitIntMedJExpClinRes.2014;20:153-162.doi:10.12659/MSM.889796.
131. CosgroveKP,WangS,KimS-J,etal.Sexdifferencesinthebrain’sdopaminesignatureofcigarettesmoking.JNeurosciOffJSocNeurosci.2014;34(50):16851-16855.doi:10.1523/JNEUROSCI.3661-14.2014.
132. al’AbsiM,NakajimaM,AllenS,LemieuxA,HatsukamiD.Sexdifferencesinhormonalresponsestostressandsmokingrelapse:aprospectiveexamination.NicotineTobResOffJSocResNicotineTob.2015;17(4):382-389.doi:10.1093/ntr/ntu340.
133. PerkinsKA,KarelitzJL.Sexdifferencesinacutereliefofabstinence-inducedwithdrawalandnegativeaffectduetonicotinecontentincigarettes.NicotineTobResOffJSocResNicotineTob.2015;17(4):443-448.
59
doi:10.1093/ntr/ntu150.
134. WrayJM,GrayKM,McClureEA,CarpenterMJ,TiffanyST,SaladinME.Genderdifferencesinresponsestocuespresentedinthenaturalenvironmentofcigarettesmokers.NicotineTobResOffJSocResNicotineTob.2015;17(4):438-442.doi:10.1093/ntr/ntu248.
135. FergusonSG,FrandsenM,DunbarMS,ShiffmanS.Genderandstimuluscontrolofsmokingbehavior.NicotineTobResOffJSocResNicotineTob.2015;17(4):431-437.doi:10.1093/ntr/ntu195.
136. SmithPH,KaszaKA,HylandA,etal.Genderdifferencesinmedicationuseandcigarettesmokingcessation:resultsfromtheInternationalTobaccoControlFourCountrySurvey.NicotineTobResOffJSocResNicotineTob.2015;17(4):463-472.doi:10.1093/ntr/ntu212.
137. HarrisKK,ZopeyM,FriedmanTC.Metaboliceffectsofsmokingcessation.NatRevEndocrinol.2016;12(11):684.doi:10.1038/nrendo.2016.171.
138. McKeeSA,SmithPH,KaufmanM,MazureCM,WeinbergerAH.SexDifferencesinVareniclineEfficacyforSmokingCessation:AMeta-Analysis.NicotineTobResOffJSocResNicotineTob.2016;18(5):1002-1011.doi:10.1093/ntr/ntv207.
139. RoseJE,BehmFM.Combinationtreatmentwithvareniclineandbupropioninanadaptivesmokingcessationparadigm.AmJPsychiatry.2014;171(11):1199-1205.doi:10.1176/appi.ajp.2014.13050595.
140. CenterforBehavioralHealthStatisticsandQuality.BehavioralHealthTrendsintheUnitedStates:Resultsfromthe2014NationalSurveyonDrugUseandHealth.Rockville(MD):SAMHSA;2015.https://www.samhsa.gov/data/sites/default/files/NSDUH-FRR1-2014/NSDUH-FRR1-2014.pdf.AccessedSeptember14,2017.
141. ZiedonisD,HitsmanB,BeckhamJC,etal.Tobaccouseandcessationinpsychiatricdisorders:NationalInstituteofMentalHealthreport.NicotineTobResOffJSocResNicotineTob.2008;10(12):1691-1715.doi:10.1080/14622200802443569.
142. HeffnerJL,StrawnJR,DelBelloMP,StrakowskiSM,AnthenelliRM.Theco-occurrenceofcigarettesmokingandbipolardisorder:phenomenologyandtreatmentconsiderations.BipolarDisord.2011;13(5-6):439-453.
60
doi:10.1111/j.1399-5618.2011.00943.x.
143. CentersforDiseaseControlandPrevention(CDC).Vitalsigns:currentcigarettesmokingamongadultsaged≥18yearswithmentalillness-UnitedStates,2009-2011.MMWRMorbMortalWklyRep.2013;62(5):81-87.
144. AubinH-J,RollemaH,SvenssonTH,WintererG.Smoking,quitting,andpsychiatricdisease:areview.NeurosciBiobehavRev.2012;36(1):271-284.doi:10.1016/j.neubiorev.2011.06.007.
145. MinichinoA,BersaniFS,CalòWK,etal.Smokingbehaviourandmentalhealthdisorders—mutualinfluencesandimplicationsfortherapy.IntJEnvironResPublicHealth.2013;10(10):4790-4811.doi:10.3390/ijerph10104790.
146. WingVC,WassCE,SohDW,GeorgeTP.Areviewofneurobiologicalvulnerabilityfactorsandtreatmentimplicationsforcomorbidtobaccodependenceinschizophrenia.AnnNYAcadSci.2012;1248:89-106.doi:10.1111/j.1749-6632.2011.06261.x.
147. TaylorG,McNeillA,GirlingA,FarleyA,Lindson-HawleyN,AveyardP.Changeinmentalhealthaftersmokingcessation:systematicreviewandmeta-analysis.BMJ.2014;348:g1151.
148. GoodwinRD,ShefferCE,ChartrandH,etal.Druguse,abuse,anddependenceandthepersistenceofnicotinedependence.NicotineTobResOffJSocResNicotineTob.2014;16(12):1606-1612.doi:10.1093/ntr/ntu115.
149. GuydishJ,PassalacquaE,TajimaB,ChanM,ChunJ,BostromA.Smokingprevalenceinaddictiontreatment:areview.NicotineTobResOffJSocResNicotineTob.2011;13(6):401-411.doi:10.1093/ntr/ntr048.
150. CenterforBehavioralHealthStatisticsandQuality.SmokingandMentalIllness.Rockville(MD):SAMHSA;2013.https://www.samhsa.gov/data/sites/default/files/NSDUH093/NSDUH093/sr093-smoking-mental-illness.pdf.AccessedSeptember14,2017.
151. GlasheenC,HeddenSL,Forman-HoffmanVL,ColpeLJ.Cigarettesmokingbehaviorsamongadultswithseriousmentalillnessinanationallyrepresentativesample.AnnEpidemiol.2014;24(10):776-780.doi:10.1016/j.annepidem.2014.07.009.
61
152. MoranLV,SampathH,KochunovP,HongLE.Braincircuitsthatlinkschizophreniatohighriskofcigarettesmoking.SchizophrBull.2013;39(6):1373-1381.doi:10.1093/schbul/sbs149.
153. ÁlvarezGutiérrezFJ,FerrerGalvánM,RuizBernalA,etal.Predictorsof10-yearsmokingabstinenceinsmokersabstinentfor1yearaftertreatment.AddictAbingdonEngl.2016;111(3):545-551.doi:10.1111/add.13220.
154. TullochHE,PipeAL,ClydeMJ,ReidRD,ElsC.TheQuitExperienceandConcernsofSmokersWithPsychiatricIllness.AmJPrevMed.2016;50(6):709-718.doi:10.1016/j.amepre.2015.11.006.
155. CallaghanRC,VeldhuizenS,JeysinghT,etal.Patternsoftobacco-relatedmortalityamongindividualsdiagnosedwithschizophrenia,bipolardisorder,ordepression.JPsychiatrRes.2014;48(1):102-110.doi:10.1016/j.jpsychires.2013.09.014.
156. ProchaskaJJ,DelucchiK,HallSM.Ameta-analysisofsmokingcessationinterventionswithindividualsinsubstanceabusetreatmentorrecovery.JConsultClinPsychol.2004;72(6):1144-1156.doi:10.1037/0022-006X.72.6.1144.
157. MackowickKM,LynchM-J,WeinbergerAH,GeorgeTP.Treatmentoftobaccodependenceinpeoplewithmentalhealthandaddictivedisorders.CurrPsychiatryRep.2012;14(5):478-485.doi:10.1007/s11920-012-0299-2.
158. TsoiDT,PorwalM,WebsterAC.Interventionsforsmokingcessationandreductioninindividualswithschizophrenia.CochraneDatabaseSystRev.2013;(2):CD007253.doi:10.1002/14651858.CD007253.pub3.
159. StubbsB,VancampfortD,BobesJ,DeHertM,MitchellAJ.Howcanwepromotesmokingcessationinpeoplewithschizophreniainpractice?Aclinicaloverview.ActaPsychiatrScand.2015;132(2):122-130.doi:10.1111/acps.12412.
160. EvinsAE,CatherC,LafferA.Treatmentoftobaccousedisordersinsmokerswithseriousmentalillness:towardclinicalbestpractices.HarvRevPsychiatry.2015;23(2):90-98.doi:10.1097/HRP.0000000000000063.
161. EvinsAE,CatherC,PrattSA,etal.Maintenancetreatmentwithvareniclineforsmokingcessationinpatientswithschizophreniaandbipolardisorder:arandomizedclinicaltrial.JAMA.2014;311(2):145-154.
62
doi:10.1001/jama.2013.285113.
162. JainR,MajumderP,GuptaT.Pharmacologicalinterventionofnicotinedependence.BioMedResInt.2013;2013:278392.doi:10.1155/2013/278392.
163. WestR,RawM,McNeillA,etal.Health-careinterventionstopromoteandassisttobaccocessation:areviewofefficacy,effectivenessandaffordabilityforuseinnationalguidelinedevelopment.AddictAbingdonEngl.2015;110(9):1388-1403.doi:10.1111/add.12998.
164. SteadLF,KoilpillaiP,LancasterT.Additionalbehaviouralsupportasanadjuncttopharmacotherapyforsmokingcessation.CochraneDatabaseSystRev.2015;(10):CD009670.doi:10.1002/14651858.CD009670.pub3.
165. ColemanT,ChamberlainC,DaveyM-A,CooperSE,Leonardi-BeeJ.Pharmacologicalinterventionsforpromotingsmokingcessationduringpregnancy.CochraneDatabaseSystRev.2012;(9):CD010078.doi:10.1002/14651858.CD010078.
166. AubinH-J,LuquiensA,BerlinI.Pharmacotherapyforsmokingcessation:pharmacologicalprinciplesandclinicalpractice.BrJClinPharmacol.2014;77(2):324-336.doi:10.1111/bcp.12116.
167. CahillK,StevensS,PereraR,LancasterT.Pharmacologicalinterventionsforsmokingcessation:anoverviewandnetworkmeta-analysis.CochraneDatabaseSystRev.2013;(5):CD009329.doi:10.1002/14651858.CD009329.pub2.
168. ProchaskaJJ,BenowitzNL.ThePast,Present,andFutureofNicotineAddictionTherapy.AnnuRevMed.2016;67:467-486.doi:10.1146/annurev-med-111314-033712.
169. PbertL,FarberH,HornK,etal.State-of-the-artoffice-basedinterventionstoeliminateyouthtobaccouse:thepastdecade.Pediatrics.2015;135(4):734-747.doi:10.1542/peds.2014-2037.
170. BaileySR,CrewEE,RiskeEC,AmmermanS,RobinsonTN,KillenJD.Efficacyandtolerabilityofpharmacotherapiestoaidsmokingcessationinadolescents.PaediatrDrugs.2012;14(2):91-108.doi:10.2165/11594370-000000000-00000.
63
171. StantonA,GrimshawG.Tobaccocessationinterventionsforyoungpeople.CochraneDatabaseSystRev.2013;(8):CD003289.doi:10.1002/14651858.CD003289.pub5.
172. PenberthyJK,Ait-DaoudN,VaughanM,FanningT.Reviewoftreatmentforcocainedependence.CurrDrugAbuseRev.2010;3(1):49-62.
173. JhanjeeS.Evidencebasedpsychosocialinterventionsinsubstanceuse.IndianJPsycholMed.2014;36(2):112-118.doi:10.4103/0253-7176.130960.
174. RajaM,SahaS,MohdS,NarangR,ReddyLVK,KumariM.CognitiveBehaviouralTherapyversusBasicHealthEducationforTobaccoCessationamongTobaccoUsers:ARandomizedClinicalTrail.JClinDiagnResJCDR.2014;8(4):ZC47-ZC49.doi:10.7860/JCDR/2014/8015.4279.
175. WebbMS,deYbarraDR,BakerEA,ReisIM,CareyMP.Cognitive-behavioraltherapytopromotesmokingcessationamongAfricanAmericansmokers:arandomizedclinicaltrial.JConsultClinPsychol.2010;78(1):24-33.doi:10.1037/a0017669.
176. Lindson-HawleyN,ThompsonTP,BeghR.Motivationalinterviewingforsmokingcessation.CochraneDatabaseSystRev.2015;(3):CD006936.doi:10.1002/14651858.CD006936.pub3.
177. WitkiewitzK,BowenS,HarropEN,DouglasH,EnkemaM,SedgwickC.Mindfulness-basedtreatmenttopreventaddictivebehaviorrelapse:theoreticalmodelsandhypothesizedmechanismsofchange.SubstUseMisuse.2014;49(5):513-524.doi:10.3109/10826084.2014.891845.
178. deSouzaICW,deBarrosVV,GomideHP,etal.Mindfulness-basedinterventionsforthetreatmentofsmoking:asystematicliteraturereview.JAlternComplementMedNYN.2015;21(3):129-140.doi:10.1089/acm.2013.0471.
179. DanielssonA-K,ErikssonA-K,AllebeckP.Technology-basedsupportviatelephoneorweb:asystematicreviewoftheeffectsonsmoking,alcoholuseandgambling.AddictBehav.2014;39(12):1846-1868.doi:10.1016/j.addbeh.2014.06.007.
180. SteadLF,Hartmann-BoyceJ,PereraR,LancasterT.Telephonecounsellingforsmokingcessation.CochraneDatabaseSystRev.2013;(8):CD002850.
64
doi:10.1002/14651858.CD002850.pub3.
181. MushtaqN,BoeckmanLM,BeebeLA.Predictorsofsmokelesstobaccocessationamongtelephonequitlineparticipants.AmJPrevMed.2015;48(1Suppl1):S54-S60.doi:10.1016/j.amepre.2014.09.028.
182. ChenY-F,MadanJ,WeltonN,etal.Effectivenessandcost-effectivenessofcomputerandotherelectronicaidsforsmokingcessation:asystematicreviewandnetworkmeta-analysis.HealthTechnolAssessWinchEngl.2012;16(38):1-205,iii-v.doi:10.3310/hta16380.
183. HallAK,Cole-LewisH,BernhardtJM.Mobiletextmessagingforhealth:asystematicreviewofreviews.AnnuRevPublicHealth.2015;36:393-415.doi:10.1146/annurev-publhealth-031914-122855.
184. KeoleianV,PolcinD,GallowayGP.Textmessagingforaddiction:areview.JPsychoactiveDrugs.2015;47(2):158-176.doi:10.1080/02791072.2015.1009200.
185. NashCM,VickermanKA,KelloggES,ZbikowskiSM.UtilizationofaWeb-basedvsintegratedphone/Webcessationprogramamong140,000tobaccousers:anevaluationacross10freestatequitlines.JMedInternetRes.2015;17(2):e36.doi:10.2196/jmir.3658.
186. CivljakM,SteadLF,Hartmann-BoyceJ,SheikhA,CarJ.Internet-basedinterventionsforsmokingcessation.CochraneDatabaseSystRev.2013;(7):CD007078.doi:10.1002/14651858.CD007078.pub4.
187. ElfeddaliI,BolmanC,CandelMJJM,WiersRW,deVriesH.PreventingsmokingrelapseviaWeb-basedcomputer-tailoredfeedback:arandomizedcontrolledtrial.JMedInternetRes.2012;14(4):e109.doi:10.2196/jmir.2057.
188. GulliverA,FarrerL,ChanJKY,etal.Technology-basedinterventionsfortobaccoandotherdruguseinuniversityandcollegestudents:asystematicreviewandmeta-analysis.AddictSciClinPract.2015;10:5.doi:10.1186/s13722-015-0027-4.
189. Haines-SaahRJ,KellyMT,OliffeJL,BottorffJL.PictureMeSmokefree:aqualitativestudyusingsocialmediaanddigitalphotographytoengageyoungadultsintobaccoreductionandcessation.JMedInternetRes.2015;17(1):e27.doi:10.2196/jmir.4061.
65
190. RamoDE,ThrulJ,DelucchiKL,LingPM,HallSM,ProchaskaJJ.TheTobaccoStatusProject(TSP):StudyprotocolforarandomizedcontrolledtrialofaFacebooksmokingcessationinterventionforyoungadults.BMCPublicHealth.2015;15:897.doi:10.1186/s12889-015-2217-0.
191. CressmanAM,PupcoA,KimE,KorenG,BozzoP.Smokingcessationtherapyduringpregnancy.CanFamPhysicianMedFamCan.2012;58(5):525-527.
192. LeungLWS,DaviesGA.SmokingCessationStrategiesinPregnancy.JObstetGynecolCanJOGC.2015;37(9):791-797.doi:10.1016/S1701-2163(15)30149-3.
193. TappinD,BauldL,PurvesD,etal.Financialincentivesforsmokingcessationinpregnancy:randomisedcontrolledtrial.BMJ.2015;350:h134.
194. ChamberlainC,O’Mara-EvesA,OliverS,etal.Psychosocialinterventionsforsupportingwomentostopsmokinginpregnancy.CochraneDatabaseSystRev.2013;(10):CD001055.doi:10.1002/14651858.CD001055.pub4.
195. HigginsST,WashioY,HeilSH,etal.Financialincentivesforsmokingcessationamongpregnantandnewlypostpartumwomen.PrevMed.2012;55Suppl:S33-S40.doi:10.1016/j.ypmed.2011.12.016.
196. HeilSH,LinaresScottT,HigginsST.Anoverviewofprinciplesofeffectivetreatmentofsubstanceusedisordersandtheirpotentialapplicationtopregnantcigarettesmokers.DrugAlcoholDepend.2009;104Suppl1:S106-S114.doi:10.1016/j.drugalcdep.2009.05.012.
197. NicotineReplacementTherapyforSmokingCessationorReduction:AReviewoftheClinicalEvidence.Ottawa(ON):CanadianAgencyforDrugsandTechnologiesinHealth;2014.http://www.ncbi.nlm.nih.gov/books/NBK195714/.
198. DouaihyAB,KellyTM,SullivanC.Medicationsforsubstanceusedisorders.SocWorkPublicHealth.2013;28(3-4):264-278.doi:10.1080/19371918.2013.759031.
199. HughesJR,SteadLF,Hartmann-BoyceJ,CahillK,LancasterT.Antidepressantsforsmokingcessation.CochraneDatabaseSystRev.2014;(1):CD000031.doi:10.1002/14651858.CD000031.pub4.
66
200. KaduriP,VociS,ZawertailoL,ChaitonM,McKenzieK,SelbyP.Real-worldeffectivenessofvareniclineversusnicotinereplacementtherapyinpatientswithandwithoutpsychiatricdisorders.JAddictMed.2015;9(3):169-176.doi:10.1097/ADM.0000000000000111.
201. MillsEJ,WuP,LockhartI,ThorlundK,PuhanM,EbbertJO.Comparisonsofhigh-doseandcombinationnicotinereplacementtherapy,varenicline,andbupropionforsmokingcessation:asystematicreviewandmultipletreatmentmeta-analysis.AnnMed.2012;44(6):588-597.doi:10.3109/07853890.2012.705016.
202. PascualFP,FontobaFerrándizJ,GilSanchezMC,PonceLorenzoF,BotellaEstrellaC.Two-YearTherapeuticEffectivenessofVareniclineforSmokingCessationinaRealWorldSetting.SubstUseMisuse.2016;51(2):131-140.doi:10.3109/10826084.2015.1018547.
203. ChangP-H,ChiangC-H,HoW-C,WuP-Z,TsaiJ-S,GuoF-R.Combinationtherapyofvareniclinewithnicotinereplacementtherapyisbetterthanvareniclinealone:asystematicreviewandmeta-analysisofrandomizedcontrolledtrials.BMCPublicHealth.2015;15:689.doi:10.1186/s12889-015-2055-0.
204. TannerJ-A,ChenowethMJ,TyndaleRF.Pharmacogeneticsofnicotineandassociatedsmokingbehaviors.CurrTopBehavNeurosci.2015;23:37-86.doi:10.1007/978-3-319-13665-3_3.
205. LermanC,SchnollRA,HawkLW,etal.Useofthenicotinemetaboliteratioasageneticallyinformedbiomarkerofresponsetonicotinepatchorvareniclineforsmokingcessation:arandomised,double-blindplacebo-controlledtrial.LancetRespirMed.2015;3(2):131-138.doi:10.1016/S2213-2600(14)70294-2.
206. LermanC,GuH,LougheadJ,RuparelK,YangY,SteinEA.Large-scalebrainnetworkcouplingpredictsacutenicotineabstinenceeffectsoncravingandcognitivefunction.JAMAPsychiatry.2014;71(5):523-530.doi:10.1001/jamapsychiatry.2013.4091.
207. HarmeyD,GriffinPR,KennyPJ.Developmentofnovelpharmacotherapeuticsfortobaccodependence:progressandfuturedirections.NicotineTobResOffJSocResNicotineTob.2012;14(11):1300-1318.doi:10.1093/ntr/nts201.
67
208. AlasmariF,Al-RejaieSS,AlSharariSD,SariY.Targetingglutamatehomeostasisforpotentialtreatmentofnicotinedependence.BrainResBull.2016;121:1-8.doi:10.1016/j.brainresbull.2015.11.010.
209. ElrashidiMY,EbbertJO.Emergingdrugsforthetreatmentoftobaccodependence:2014update.ExpertOpinEmergDrugs.2014;19(2):243-260.doi:10.1517/14728214.2014.899580.
210. TurnerJR,GoldA,SchnollR,BlendyJA.Translationalresearchinnicotinedependence.ColdSpringHarbPerspectMed.2013;3(3):a012153.doi:10.1101/cshperspect.a012153.
211. McClureEA,GipsonCD,MalcolmRJ,KalivasPW,GrayKM.PotentialroleofN-acetylcysteineinthemanagementofsubstanceusedisorders.CNSDrugs.2014;28(2):95-106.doi:10.1007/s40263-014-0142-x.
212. EsterlisI,HannestadJO,PerkinsE,etal.Effectofanicotinevaccineonnicotinebindingto2*-nicotinicacetylcholinereceptorsinvivoinhumantobaccosmokers.AmJPsychiatry.2013;170(4):399-407.doi:10.1176/appi.ajp.2012.12060793.
213. GoniewiczML,DelijewskiM.Nicotinevaccinestotreattobaccodependence.HumVaccinesImmunother.2013;9(1):13-25.doi:10.4161/hv.22060.
214. BellamoliE,ManganottiP,SchwartzRP,RimondoC,GommaM,SerpelloniG.rTMSinthetreatmentofdrugaddiction:anupdateabouthumanstudies.BehavNeurol.2014;2014:815215.doi:10.1155/2014/815215.
215. SousaAD.RepetitiveTranscranialMagneticStimulation(rTMS)intheManagementofAlcoholDependenceandotherSubstanceAbuseDisorders-EmergingDataandClinicalRelevance.BasicClinNeurosci.2013;4(3):271-275.
216. Dinur-KleinL,DannonP,HadarA,etal.Smokingcessationinducedbydeeprepetitivetranscranialmagneticstimulationoftheprefrontalandinsularcortices:aprospective,randomizedcontrolledtrial.BiolPsychiatry.2014;76(9):742-749.doi:10.1016/j.biopsych.2014.05.020.
217. ChaloupkaFJ,YurekliA,FongGT.Tobaccotaxesasatobaccocontrolstrategy.TobControl.2012;21(2):172-180.doi:10.1136/tobaccocontrol-2011-050417.
68
218. WarnerKE.Tobaccocontrolpoliciesandtheirimpacts.Past,present,andfuture.AnnAmThoracSoc.2014;11(2):227-230.doi:10.1513/AnnalsATS.201307-244PS.
219. Adachi-MejiaAM,CarlosHA,BerkeEM,TanskiSE,SargentJD.Acomparisonofindividualversuscommunityinfluencesonyouthsmokingbehaviours:across-sectionalobservationalstudy.BMJOpen.2012;2(5).doi:10.1136/bmjopen-2011-000767.
220. OesterleS,HawkinsJD,KuklinskiMR,etal.EffectsofCommunitiesThatCareonMales’andFemales’DrugUseandDelinquency9YearsAfterBaselineinaCommunity-RandomizedTrial.AmJCommunityPsychol.2015;56(3-4):217-228.doi:10.1007/s10464-015-9749-4.
221. BerrettiniWH,DoyleGA.TheCHRNA5-A3-B4geneclusterinnicotineaddiction.MolPsychiatry.2012;17(9):856-866.doi:10.1038/mp.2011.122.
222. AgrawalA,VerweijKJH,GillespieNA,etal.Thegeneticsofaddiction-atranslationalperspective.TranslPsychiatry.2012;2:e140.doi:10.1038/tp.2012.54.
223. WangJ-C,KapoorM,GoateAM.Thegeneticsofsubstancedependence.AnnuRevGenomicsHumGenet.2012;13:241-261.doi:10.1146/annurev-genom-090711-163844.
224. ChenL-S,BakerTB,JorenbyD,etal.Geneticvariation(CHRNA5),medication(combinationnicotinereplacementtherapyvs.varenicline),andsmokingcessation.DrugAlcoholDepend.2015;154:278-282.doi:10.1016/j.drugalcdep.2015.06.022.
225. BloomAJ,MurphySE,MartinezM,vonWeymarnLB,BierutLJ,GoateA.Effectsuponin-vivonicotinemetabolismrevealfunctionalvariationinFMO3associatedwithcigaretteconsumption.PharmacogenetGenomics.2013;23(2):62-68.doi:10.1097/FPC.0b013e32835c3b48.
226. UhlGR,WaltherD,MusciR,etal.Smokingquitsuccessgenotypescorepredictsquitsuccessanddistinctpatternsofdevelopmentalinvolvementwithcommonaddictivesubstances.MolPsychiatry.2014;19(1):50-54.doi:10.1038/mp.2012.155.
227. KingDP,PacigaS,PickeringE,etal.Smokingcessationpharmacogenetics:analysisofvareniclineandbupropioninplacebo-
69
controlledclinicaltrials.NeuropsychopharmacolOffPublAmCollNeuropsychopharmacol.2012;37(3):641-650.doi:10.1038/npp.2011.232.
228. TsaprouniLG,YangT-P,BellJ,etal.CigarettesmokingreducesDNAmethylationlevelsatmultiplegenomiclocibuttheeffectispartiallyreversibleuponcessation.Epigenetics.2014;9(10):1382-1396.doi:10.4161/15592294.2014.969637.
229. Ladd-AcostaC,ShuC,LeeBK,etal.Presenceofanepigeneticsignatureofprenatalcigarettesmokeexposureinchildhood.EnvironRes.2016;144(PtA):139-148.doi:10.1016/j.envres.2015.11.014.
230. JoubertBR,FelixJF,YousefiP,etal.DNAMethylationinNewbornsandMaternalSmokinginPregnancy:Genome-wideConsortiumMeta-analysis.AmJHumGenet.2016;98(4):680-696.doi:10.1016/j.ajhg.2016.02.019.
231. Moran-SantaMariaMM,HartwellKJ,HanlonCA,etal.Rightanteriorinsulaconnectivityisimportantforcue-inducedcravinginnicotine-dependentsmokers.AddictBiol.2015;20(2):407-414.doi:10.1111/adb.12124.
232. SutherlandMT,McHughMJ,PariyadathV,SteinEA.Restingstatefunctionalconnectivityinaddiction:Lessonslearnedandaroadahead.NeuroImage.2012;62(4):2281-2295.doi:10.1016/j.neuroimage.2012.01.117.
233. WeilandBJ,SabbineniA,CalhounVD,WelshRC,HutchisonKE.Reducedexecutiveanddefaultnetworkfunctionalconnectivityincigarettesmokers.HumBrainMapp.2015;36(3):872-882.doi:10.1002/hbm.22672.
234. MenossiHS,GoudriaanAE,deAzevedo-MarquesPéricoC,etal.Neuralbasesofpharmacologicaltreatmentofnicotinedependence-insightsfromfunctionalbrainimaging:asystematicreview.CNSDrugs.2013;27(11):921-941.doi:10.1007/s40263-013-0092-8.
235. NeesF,WittSH,LourdusamyA,etal.Geneticriskfornicotinedependenceinthecholinergicsystemandactivationofthebrainrewardsysteminhealthyadolescents.NeuropsychopharmacolOffPublAmCollNeuropsychopharmacol.2013;38(11):2081-2089.doi:10.1038/npp.2013.131.
236. SweitzerMM,DonnyEC,HaririAR.Imaginggeneticsandtheneurobiologicalbasisofindividualdifferencesinvulnerabilitytoaddiction.
70
DrugAlcoholDepend.2012;123Suppl1:S59-S71.doi:10.1016/j.drugalcdep.2012.01.017.
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WherecanIgetfurtherinformationabouttobacco/nicotine?
Tolearnmoreabouttobacco,nicotine,andotherdrugsofuseandmisuse,visittheNIDAwebsiteatwww.drugabuse.govorcontactDrugPubsat877-NIDA-NIH(877-643-2644;TTY/TDD:240-645-0228).
NIDA'swebsiteincludes:
Informationondrugsofuseandmisuseandrelatedhealthconsequences
NIDApublications,news,andevents
Resourcesforhealthcareprofessionals,educators,andpatientsandfamilies
InformationonNIDAresearchstudiesandclinicaltrials
Fundinginformation(includingprogramannouncementsanddeadlines)
Internationalactivities
Linkstorelatedwebsites(accesstowebsitesofmanyotherorganizationsinthefield)
InformationinSpanish(enespañol)
NIDAwebsitesandwebpages
drugabuse.gov/publications/drugfacts/cigarettes-other-tobacco-products
drugabuse.gov/publications/drugfacts/electronic-cigarettes-e-cigarettes
drugabuse.gov
teens.drugabuse.gov
easyread.drugabuse.gov
researchstudies.drugabuse.gov
72
irp.drugabuse.gov
Forphysicianinformation
NIDAMED:drugabuse.gov/nidamed
Otherwebsites
Informationonnicotine/tobaccoabuseisalsoavailablethroughthefollowingwebsites:
NationalCancerInstitute
CentersforDiseaseControlandPrevention
SubstanceAbuseandMentalHealthServicesAdministration
MonitoringtheFuture
ThePartnershipforDrug-FreeKids