Compensatory Behaviour by Smokers

cigarettes฀ are฀ used฀ or฀ two฀ or฀ more฀ cigarettes฀ are฀ smoked฀ in฀ rapid฀ succession฀ [56] .฀ Observations฀of฀this฀kind฀were฀made฀with฀the฀Marlboro฀Light฀brand฀ [57] .฀In฀fact,฀observa- tions฀and฀indings฀obtained฀with฀light฀cigarettes฀have฀often฀been฀the฀subject฀of฀publications฀ [25,฀54,฀58,฀59] .฀The฀health-related฀consequences฀of฀long-term฀use฀of฀these฀cigarettes฀can- not฀ yet฀ be฀ foreseen,฀ especially฀ because฀ they฀ are฀ smoked฀ with฀ greater฀ intensity,฀ deeper฀ inhalation฀and฀larger฀inhaled฀and฀exhaled฀volumes฀ [60] .฀Many฀smokers฀were฀previously฀ unaware฀that฀light฀cigarettes฀have฀or฀had฀vents฀in฀the฀ilter฀to฀improve฀ventilation฀e.g.฀the฀ Winston฀“Reds”฀brand฀ [61–64] .฀The฀tobacco฀industry฀argued฀unoficially฀that฀as฀the฀ciga- rette฀increasingly฀burns฀down,฀the฀holes฀become฀blocked฀and฀hence,฀the฀release฀of฀nicotine฀ is฀increased฀ [65] . Cigarettes฀with฀selective฀reductions฀in฀nicotine฀delivery฀have฀been฀considered฀as฀poten- tial฀tools฀to฀prevent฀or฀treat฀nicotine฀dependence฀or฀reduce฀harm฀by฀virtue฀of฀reduced฀nico- tine฀and฀nitrosamine฀delivery.฀An฀important฀question฀is฀whether฀individuals฀smoke฀these฀ products฀more฀intensively,฀as฀has฀been฀shown฀to฀occur฀with฀ventilated-ilter฀cigarettes.฀To฀ investigate฀this฀issue,฀we฀compared฀conventional฀highly฀ventilated฀ilter฀cigarettes,฀having฀ very฀low฀tar฀and฀nicotine฀yields฀when฀smoked฀by฀Federal฀Trade฀Commission฀method฀1฀mg฀ tar,฀2฀mg฀carbon฀monoxide฀[CO],฀2฀mg฀nicotine,฀with฀low฀nicotine฀content฀cigarettes,฀ manufactured฀from฀a฀genetically฀modiied฀strain฀of฀tobacco,฀which฀had฀higher฀tar฀but฀lower฀ nicotine฀yield฀14฀mg฀tar,฀13฀mg฀CO,฀02฀mg฀nicotine.฀A฀total฀of฀16฀cigarette฀smokers฀par- ticipated฀in฀two฀8-h฀sessions฀order฀counterbalanced฀during฀which฀they฀smoked฀each฀type฀ of฀cigarette฀ad฀libitum.฀Expired-air฀CO,฀plasma฀nicotine฀and฀smoking฀topography฀measures฀ were฀collected.฀Subjects฀showed฀signiicant฀increases฀in฀smoking฀when฀using฀the฀highly฀ ventilated฀ilter฀cigarettes฀and฀puff฀volume฀was฀signiicantly฀greater฀than฀with฀the฀low฀nico- tine฀content฀cigarettes.฀Subjects฀achieved฀an฀expired-air฀CO฀level฀of฀as฀high฀as฀74฀with฀ the฀low฀nicotine฀content฀cigarettes;฀the฀latter฀produced฀CO฀levels฀similar฀to฀those฀measured฀ at฀baseline฀when฀subjects฀smoked฀their฀habitual฀brands฀of฀cigarettes.฀Plasma฀nicotine฀levels฀ obtained฀ when฀ subjects฀ smoked฀ the฀ highly฀ ventilated฀ ilter฀ cigarettes฀ also฀ were฀ signii- cantly฀higher฀than฀when฀they฀smoked฀the฀low฀nicotine฀content฀cigarettes.฀These฀results฀ indicate฀that฀the฀delivery฀of฀substantial฀amount฀of฀smoke,฀with฀selective฀reductions฀in฀nico- tine฀yield,฀appears฀to฀prevent฀compensatory฀smoking฀behaviour.฀Further฀studies฀should฀ determine฀whether฀similar฀results฀are฀obtained฀in฀naturalistic฀environments฀ [66] .

3.3.6 Optimising Nicotine Release

According฀to฀the฀tobacco฀industry,฀one฀of฀its฀crucial฀research฀objectives฀was฀to฀increase฀the฀ availability฀of฀nicotine฀released฀from฀tobacco฀to฀smokers฀as฀the฀free฀base:฀the฀pH฀of฀tobacco฀ has฀an฀important฀function฀in฀this฀context.฀Depending฀on฀pH,฀nicotine฀is฀present฀in฀the฀form฀ of฀a฀diprotonated฀or฀monoprotonated฀salt฀and฀as฀the฀free฀base฀ [67] .฀The฀former฀is฀the฀bound฀ form฀pK 1 ฀=฀3.02฀and฀the฀latter฀is฀the฀freely฀available฀form฀pK 1 ฀=฀8.02.฀The฀free฀form฀ penetrates฀biological฀membranes฀very฀rapidly฀and฀extensively,฀whereas฀the฀penetration฀of฀ the฀ bound฀ form฀ is฀ very฀ much฀ slower฀ and฀ less฀ quantitative.฀ Because฀ the฀ nicotine฀ base฀ reaches฀the฀brain฀far฀more฀rapidly,฀the฀tobacco฀industry฀became฀aware฀of฀this฀property฀of฀ free฀ nicotine฀ at฀ a฀ very฀ early฀ stage฀ [68] .฀ The฀ higher฀ the฀ pH,฀ the฀ greater฀ the฀ amount฀ of฀ extractable฀nicotine฀ [69] .฀The฀pH฀of฀cigarette฀smoke฀is฀between฀6.5฀and฀7.0,฀a฀range฀in฀ which฀nicotine฀is฀absorbed฀primarily฀in฀the฀lungs,฀whereas฀the฀nicotine฀from฀alkaline฀cigar฀ smoke฀is฀absorbed฀primarily฀in฀the฀mouth,฀not฀least฀because฀of฀the฀larger฀doses฀of฀nicotine฀ involved฀ [70] .

3.3.7 Importance of Absorption Rate

Since฀physiological฀effects฀are฀to฀be฀anticipated฀very฀much฀more฀rapidly฀from฀non-bound฀ free฀nicotine฀as฀the฀ammonium฀ion฀than฀from฀bound฀nicotine฀as฀ammonium฀chloride,฀ smoke฀with฀a฀high฀pH฀is฀richer฀in฀nicotine.฀Consequently,฀the฀nicotine฀yield฀of฀cigarette฀ smoke฀may฀be฀considered฀as฀a฀measure฀of฀the฀strength฀of฀the฀cigarette฀ [71] ฀because฀more฀ rapid฀absorption฀is฀then฀to฀be฀expected฀ [72] .฀Nevertheless,฀nicotine฀is฀absorbed฀in฀the฀fol- lowing฀three฀forms: • ฀ As฀salt฀from฀the฀particulate฀phase฀1 • ฀ As฀free฀base฀in฀the฀particulate฀phase฀2 • ฀ As฀free฀base฀in฀the฀gas฀phase฀3 The฀ratio฀23฀has฀long฀been฀considered฀to฀be฀important฀for฀the฀nicotine฀effect฀ [73] .฀ Altering฀the฀pH฀of฀cigarette฀tobacco฀was฀intended฀to฀provide฀an฀extra฀“kick”฀ [74,฀75] .฀ Moreover,฀this฀objective฀was฀to฀be฀achieved฀by฀a฀increasing฀the฀Burley฀content฀in฀the฀ tobacco฀blend,฀b฀reducing฀the฀sugar฀casing฀used฀for฀the฀tobacco,฀c฀using฀alkalis฀–฀espe- cially฀ammonium฀compounds฀–฀for฀the฀tobacco฀blend,฀d฀adding฀nicotine฀to฀the฀tobacco฀ blend,฀e฀removing฀acid฀constituents฀from฀the฀tobacco,฀f฀using฀special฀ilter฀systems฀ which฀permit฀removal฀of฀acids฀and฀addition฀of฀alkalis฀to฀mainstream฀smoke฀and฀g฀using฀ ilter฀systems฀that฀dilute฀the฀inhaled฀air฀to฀a฀major฀extent.฀Some฀of฀these฀considerations฀ have฀already฀been฀tested฀at฀Philip฀Morris฀ [76] .

3.3.8 Ammonium and pH Manipulation

During฀cigarette฀smoking,฀the฀free฀nicotine฀base฀is฀absorbed฀in฀the฀pulmonary฀alveoli.฀In฀ many฀cases,฀nicotine฀is฀found฀only฀in฀trace฀amounts฀in฀the฀particles฀of฀exhaled฀mainstream฀ smoke.฀The฀intensity฀of฀nicotine฀delivery฀was฀further฀increased฀by฀the฀addition฀of฀ammo- nium฀salts฀cf.฀the฀practices฀of฀Philip฀Morris฀ [9] .฀At฀the฀same฀time,฀the฀measurements฀of฀ tar฀and฀nicotine฀in฀the฀FTC฀smoking฀machines฀were฀no฀longer฀representative฀Tables฀ 3.5 ฀ and฀ 3.6 ฀because฀the฀ratio฀of฀free฀to฀bound฀nicotine฀could฀not฀be฀determined;฀also฀the฀tar฀ yields฀measured฀were฀lower฀than฀in฀reality฀Tables฀ 3.5 ฀and฀ 3.6 ฀ [77] .฀The฀use฀of฀ammo- nium฀technology฀permitted฀the฀downward฀manipulation฀of฀nicotine฀yields฀measured฀in฀the฀ smoking฀machines,฀but฀the฀smoker฀still฀got฀the฀expected฀“kick”฀ [78] .฀This฀was฀the฀decisive฀ inding:฀the฀greater฀the฀alkalinity฀of฀mainstream฀smoke,฀the฀faster฀the฀build-up฀of฀nicotine฀ in฀the฀blood฀and฀hence฀the฀“kick”.฀The฀tobacco฀industry฀declared฀the฀added฀ammonium฀ salts฀as฀“lavour฀correction฀agents”฀and฀not฀as฀additives฀to฀enhance฀the฀nicotine฀effect.฀ Seen฀in฀these฀terms,฀no฀objection฀to฀these฀pH฀manipulations฀can฀be฀serious฀enough.