efN,--V- a. (D;r
4 ;
DEPENDENCE ON CICARETTE SMOKING A REVIEW
U
15 .12.1977
AUT80R:. "A. Kay Comer
WNW
ISSUED Y7: R.E. Thor nton PROG. REP: 13.01.05
DISTR13L-,ION:
Dr. S.j. G:een Copy No. 1, 2, 3, 4
Dr. 1.W. 3ughes 5
Dr. R.A. 2anford 6, 7
R.N. Gi'~'-, Esq. 8
R.S. Wae--, Esq. 9, 10, 11
R.G. Nic~:clls, Esq. 12, 13
Herr E. Tittershaus, 14
Dr. F. Seehofer
Mr
A-J. Kruszynski
16
Dr. C.J.?- de Siqueira 17
Dr. D.G. --elton
Library is
19, 20
COPY N0.4~'-~;, -
v~
C:1
LO)
,1"A
011
Nj
BATCo document for Province of British Columbia 5
November 1999


CONTENTS
Page
S L;?,P.A R Y 1
IN--ODUCTION 2
1. DEF:NITIONS OF ADDICTION, HABITUATION AND
DEPENDENCE 3
2. E;:3F,4CE FOR THE ROLE OF NICOTINE AS A
DETERMINANT OF
Cl';A?,ETTE SMOKING 11
2.1 Historical 12
2.2 Evidence from Experiments Using Animals 14
2.1': Evidence from Experiments on Hwans: The
Effects
e .
.0 tiqe*#a
4-P t
a
Constituents on Smoking Be aVLour
17
2.4 Comparison of Cigarette, Pipe and
Cigar Smokin 37
,
. ~ . '-.% ..
3. 'EFFECTS OF SMOKING AND NICOTINE IN
TH: -. HUwdj SEYETS
3.1 Physiological Effects 41
3.2 Psychological Effects 47
3.3 Effects on Performance 53
4. DIF-F-PENCES BETWEEN SMOKERS AND NON-SMOKERS
AND BETWEEN
SMCFZRS OF DIFFERING CIGARETTE CONSUMPTION 56
4.1_jbyki?~ygical D~fferences_,*....; ~-A
4.2 Psychological Differences 63
4.3 Social Differences 71
5. S C
_11~ _PqTIVATION
.74
5.1 F-ha--acological Theories of Smoking
Motivation 74
5.2 3e,~avioural/Psychological Theories of Smoking
Motivation 75
5.3 Mixed Theories of Smoking Motivation 84
6. INITLA.TION OF SMOKING BFHAVIOUR 96
7. CESSArION OF SMOKING BEHAVIOUR IOL
8. TOLEFUICE TO NICOTINE AND WITHDRAWAL SYMPTOMS
126
9. THE M-NNECTION OF SMOKING WITH THE USE OF DRUGS
135
10. CO11PkRISON OF SMOKING WITH THE USE OF DRUGS
139
11. USE 2F THE TERMS "ADDICTION", "HABITUATION"
AND
"DEP:NDENCE" IN THE CONTEXT OF TOBACCO SMOKING 150
12. CONCLUSIONS 159
REFEIENCES 162
L7
L4
(_4
co
co
CZ)
Ln
BATCo document for Province of British Columbia 5
November 1999


Group Research & Development Centre,
British-American Tobacco Co. Ltd.,
SOUTIUMPTON.
AKC/CAL/46J 15th December 1977
DEPENDENCE ON CIGARETTE SMOKING - A REVIEW
(Report No. RD.1532 Restricted)
S UMMARY i.'
Dependence on cigarette smoking is reviewed with
reference to the
definitions of "addiction", "habituation" and
"dependence". Evidence
for the importance of nicotine in smoking
behaviour is discussed and a
number of the effects of smoking and nicotine are
considered. Differences
_,50-
between smokers and non-smokers are reviewed and a
variety
motivation theories are presented together with
information on the
phenomena of smoking
with the use of drugs is explored and comparisons
are made bet.een the
use of tobacco and drugs such as opiates and
marijuana.
It is concluded that the majority of smokers are
to some extent
depende-ic on smoking but that behavioural, social
and psychological
factors may be as important as those of a
pharmacological nature.
IL4 C::~
L4
0
CC)
Ui
\0 U.
C0 C__
U1
BATCo document for Province of British Columbia 5
November 1999


-2-
INTRODUCTION
Since interest was first' shown in the reasons for
smoking tobacco
there has been considerable confusion about the
use of the terms
"addiction", "habituation" and "dependence". The
purpose of this
report is to try and clarify the position with
regard to cigarette
smoking and also to discuss some of the theories
and experimental
a'
re lts,~ MAMN a t -.;e A I tt*s" o' pj c A en a na
t ng ;~IfIF"fAnKa" W'-"
5 u SMOK!,~g
motiv ation.
The report is divided into a number of sections;
each representin!"
a different aspect of factors involved in
cigarette smoking. An attempt
has been made to structure the sections in such a
way that they can be
read independently. This invclves a certain amount
of unavoidable
repetition and some publications are discussed in
more than one sec
it is hoped that a fairly representative selection
of the work on smoking
is presented here, although it is obviously not
possible to discuss all
--~ Tc- .. Na work of
pu S P.3- -d or~~
the a~iJlAli-'Slfflti6~r' 6m, -,;-h
Dr. M.A.H. Russell of the Addiction Research Unit,
Institute of Psychiatry,
at the Maudsley Hospital, London. He has published
a large number of
papers on a wide variety of aspects of smoking,
and his work is discussed
in relation to that of other authors.
iv V V11
BATCo document for Province of British Columbia 5
November 1999


-3-
1. DEFINITIONS OF ADDICTION, HABITUATION AND
DEPENDENCE
The intention in this section is to present some
of the definitions
that have been published, as this will form the
basis for discussion
of them and their relevance to smoking, in
subsequent sections.
The definitions of the terms addiction and
habituation which are
most often quoted were given by the World Health
Organi33tiOn in 1957 (224).
,o- V r ffrtltVrn ffitf
--Addiction74s said~,to_A "17
1
7%""
1
I
,
produced by repeated consumption of a drug". Its
characteristics include:
'
'
1. eed
;(C9m u1
An overpqwer~ing desi a br a
o.. continue tak.
drug and to obtain it by any means.
2. A tendency to increase the dose.
3. A psychic (psychological) and generally a
physical dependence on
the effects of the drug.
'
''
4.
Detrimental effects to he individual and to societ
t
j.
Habituation is a "condition" resulting from
repeated administration
---- of a d rut. - I ts-chargetErntl da-the lude
1- Uv 0 - i _0- 7. W'
(a) A desire (but not compulsion) to continue
taking the drug for
the sense of well-being it engenders.
M Little or no tendency to increase the dose.
(c) Some degree of psychlic dependence on the
effect of the drug
may be present but physical dependence and hence
an abstinence
syndrome are absent.
(d) Detrimental effects, if any, are primarily to
the individual.
The "official" definition of addiction given by
the Drug Addiction
Commi ttee of the National Research Council
(U.S.A.) (214) Is similar k,6~ -
that of the World Health Organisation but stresses
that the development
L4
L4
(JI
0 co
\0
CD
UM
(71
Cr\
BATCo document for Province of British Columbia 5
November 1999


-4-
of the means to continue administration of the
drug becomes an important
motive for the addict's existence.
Stungo (201) suggested in 1961, that the World
Health Organisation
definition did not sufficiently emphasise the
inevitability of abstinence
symptoms when an addictive drug is withdrawn. Ile
defined drug addiction
as: "a physical and psychic dependence on a drug
and the need to take
r
~sf ne i n ervals' t~~
ne n oses or,a or er c
of the development of tolerance and because,
otherwise severe abstinence
a- ar expeirleinced".':;
SYMPE~m e
As Larson and SilveLLe (124) have
indicated,,Lliere are at least.four
different ways of using the term "addiction". The
pharmacologist defines
it at a cellular level as involving an altered
physiological state, with
tolerance development. This state is produced by
repeated administration
of a drug and administration must be continued to
maintain the altered
state and prevent the development of the
abstinence syndro.e. Behavioural
scienfl"st. d ~YfEi-aj~ IMM-Ti-i" b-eEe-Vr.-.Tdr
-~a ,-d f-
use. There is an overwhelming involvement with
aspects of use and supply
of the drug and a high tendency to relapse after
withdrawal. Sociologists
delineate addiction on the basis of the harm that
the use of certain
drugs does to society in general. To the layman an
addiction is any
powerful habit that is difficult to break, whether
it applies to drugg
or activities. Any definition of addiction must,
thereiore, if it is to
be readily understandable, indicate in which sense
the word is being
used.
In 1964 the World Health Organisation suggested
that the word
"dependence" be substituted for both addiction and
habituation. The
03
(A
(A 4t*,
co
Ln \0
C)
CZ)
U-
011
BATCo document for Province of British Columbia 5
November 1999


-5-
definitions given here are taken from a report of
the Expert Committee
on Drug Dependence, which was published in 1974
(226).
"Drug: Any substance that, when taken into the
living organism, may
modify one or more of its functions."
"Drug dependence: A state, psychic or sometimes
also physical,
resulting from the interaction between a living
organism and a drug,
t!Lrjpe,4..*y haXp -1 and other.-kdsponses that'
always'indldd
V ..L
compulsion to take the drug on a continuous or
periodic basis in order
to avoid the discomfort of i6~-arse'n~e` T o 1 e
*rain*c It` t
present. A person may be dependent on more than
one drug."
,rsychic dependence: A condition in which a drug
produces a feeling
of satisfaction and a psychic drive that reqUires
a periodic or continuous
administration of the drug to produce pleasure or
avoid discomfort."
_wv
--caTIMpenaence: Awn"Z~d t e
a ive s a_~ t at manifesis itself
by intense physical disturbances when the
administration of the drug
is. susp wi chd rawal aor-abs t inence -.0ram..
-.rL-
_4 isturbances,ei
syndrome, are made up of specific arrays of
symptoms and signs Of a
psychic or physical nature that are characteristic
for each drug type."
"Dependence-producing drug: A drug having the
capacity to interact
with a living organism to produce a state of
psychic or physical dependence
or both. Such a drug may be used medicall-Y or
non-medically without
necessarily producing such a state. The
characteristics of the state
of drug dependence, once developed, will vary with
the type of drug
involved."
The American Psychiatric Association 1968 edition
of the Diagnostic
and Statistical Manual of Mental Disorders WSMII)
(4) substituted
0
Ln
A;WQ0.%*A, -0-
_r7
CY-)
Co
BATCo document for Province of British Columbia 5
November 1999


-6-
C.,
"drug dependence" for "drug addiction" with a
similar definition to that
used by the World Health Organisation. Drug
dependence was categorised
under "Personality disorders and certain other
non-psychiatric cntal
disorders". Freedman.(68), commenting on this,
points out that drugs
which are medically prescribed and the intake of
which conforms to
snedical need, are not included. For a psychiatric
diagnosis to be made,
i d 'A dendit of habittiW.M 60~a clear';;~~se.ol
geet in
$9 nee ~i Yi
P.4 0
the patient. The presence of an abstinence
syndrome is not the only
evidence'lor diagnosis. Fre'e~ma`n` also in'dic.a
t a d t h a t-W lal o u.
~- - 4A pl~ &h the term
"drug dependence" is an improvement over
"addiction", there are still
ambiguities. "Drug use is so inextricably a part
of modern society that
one is often referring to social definitions,
related to a particular
culture and situation".
Russell (168) has also commented on the
definitions of dependence
given by the World Health Organisation. He states
that physical dependence
generAllyJ%eJd...to -involve the-presence of
physiologii!31wada0tive
changes. These include: (i) tolerance to effects
of the drug primarily
due to changes at synapses and also in some cases
to increased capacity
U9
(A
U
UI
to metabolise and excrete the drug, as a result of
enzyme induction,
mainl- in the liver; (ii) withdrzm;al symptoms
resulting from re'--o---nd
overact,-viLy at synapses when the intake of t'Lie
drug is reducei or
discontinued. Fsychic dependence is believed to
have no such underlying
physiological mechanisms. Russell objects to the
distinction between
physical and psychological dependence since strong
dependence may occur
in the absence of a demonstrable withdrawal
syndrome and, as psychological
processes are mediated by physiological events in
the brain, then this
(J7
C*
1-0
Q>
(J1
BATCo document for Province of British Columbia 5
November 1999


is also, indirectly. a physical effect. According
to Russell it is
somewhat arbitrary how high a degree of dependence
is required before a
dependence disorder is termed an addiction.
Paton (157) suggested that "drug dependence arises
when as a result
of giving up a drug, forces - physiological,
biochemica'l, social or
environmental - are set up which predispose to
continued drug use".
..Rdssell (168Y-has crieInItif MOMInitidif and has
's*
ta
"dependence on a drug, object or activity requires
the crucial feature
e'at in th~W absence of Ihat dr
aff g, 0~ ect or ~c'
of negat ve u tivity. The T-
degree of dependence is equated with the amount of
negative affect which
may range from mild discomfort to extreme
distress, or may be equated
w-ith the amount of difficulty or effort required
to do without the drug,
object or activity". This is related to the theo
ry of Tomkins who
listed the phenomer~oT~jlcally oriented crite:-,a
for.psychological
addiction (206). lie said that the absence o--'
the addicting substance is
always noted-and awareU4dA"'dfI*Xb OHE6-17~ gul a
7! v` Mitf Fa f79-Vif ens e
negative affect for which there is also awareness
and this increases
(A
L4
with the t--'=e of deprivation. The addict ecFects
that only the addicting
substance ci-,i reduce this negative affect (cr
emotion) and produce
positive affacts, and these expectations are
invariably confirmed.
liorn (94) distinguished between "habit" vhich
reflects repetitive.
behaviour with no affective component, and
"6ependence" in which there
is an increasing desire or need for the effects
produced.
Hunt and Matara.zo (96) also discussed habit,
addiction and dependence.
Their definition of "habit" iii "learned behaviour
- a fixed'behaviour
pattern overlearned to the point of becoming
automatic and marked by
decreasing awareness and increasing dependence on
secondary rather than (ZD
BATCo document for Province of British Columbia 5
November 1999


-8-
primary reinforcement". They reserve "addiction"
for situations in
which tolerance occurs and dosage must be
increased to avoid withdrawal
symptoms. "Physical dependence" is said to be
related to addiction with
the body developing dependence on a drug, but
little tolerance is developed,
the dose is not increased and withdrawal symptoms
are minimal or missing.
Hunt and Matarazzo admit that the terminology is
somewhat confusing and
VM144% 02. "34
drtM7nRn%U'5'T6et.ee`n-1a'9V1
'-~e'~e'n5e*n-'c-e"'a7n*d*'add ction is diffic
They also define a term "awareness";
"consciousness of what Is going
law
.or the ability.'to make verbal report on the
pre~edfng or attendant
stimulus situation. It is minimal or missing with
the performance of
repetitive, stereotyped behaviour and present with
sc--e intensity in the
pbenomenon of craving and with the withdrawal
symptoms co=on to addictive
drugs." They also suggest that psychic and
physical di~peadence as
defined by the World Health Organisation can be
related to their on terms
"babit" and "a-areness", to avoid confusion
between purely physical
-ph`y.VM;L1`c.l basis (cf. Russlell (168)).
Finally in this section it may be useful to give
scme of the
de-finitions presented in various lay, and medical
dicticnarieg. The
Concise Oxford Dictionary (47) defines addict as:
De~ote, appily
C r habitually or compulsively; hence addiction
(noun) (esp. c-~ndition of
taking drug excessively and being unable to cease
doing so without
adverse effects; addictive (adjective), causing
addiction and dependence.
Addict (noun) Person addicted to a habit, esp. one
dependent on a
(specified) drug". Blakistons Could Medical
Dictionary (26) defines
"babit" as: "a behaviour pattern fixed by
repetition". reanings for
"habituation" include: "I. A condition of
tolerance to t~e effects of a
drug or a poison acquired by its continued use;
marked by a craving for
CU
L4 V7
U c0
1-0
0
CD
CD
LF1
--J
BATCo document for Province of BritiSh Columbia 5
November 1999


-9-
the drug when it is withdrawn. 2. Orug addIction,
especially a mild
form in which withdrawal does not result in severe
abstinence symptoms".
"Addiction is a marked psychologic and physiologic
dependence upon a
substance, such as alcohol or a drug, which has
gone beyond voluntary
control". The British Medical Dictionary (31),
however, records that
~-abituation is: "in drug addiction, the psychical
pa -rallel,,,to ac red,
hi h
,hysical tolerance". "Dependence :in this
dictionary, v ic was published
before the World Health Organisation switched from
the usi-of-I'addiction
to "dependence", is defined as: "In. a drug
addict, that state of body
and mind which is conditioned by ingestion of a
certain quantity of the
drug or an increasing quantity of it. Any decrease
in dose gives rise
Za abstinence symptoms".
One can see that there is little..agreement in the
area of,
~efinition,o
~uc cne of the sets of definitions which seems to
cover most points of
-'e-.; and which is fairly concise, is that in the
Merck Manual (143) The
f - '. 1 -.1. 11 - . -
:1'-o-..;lng paragraph is given under the heading
"Drug Dependence".
" Drug addiction is a state of periodic or chronic
intoxication,
eetrimental to the individual and to society. Drug
abuse is a behaviour
-zzer-
a characterised by the repetitive use of a drug or
drugs due to a
s--:~ng emot~Tnal or mental need to obtain
pleasure or to avoid disccmforrt.
i
P-z,ch.-c dependence or habituation is the
repeated use of drugs in order .
tz achieve a subjective "normal" state. Physical
dependence characterises
sc.e but not all types of drug dependence and is
defined as a state of
a,-zaptation to a drug as manifest by 1) the
withdrawal or abstinence...,
sTmdrome, the characteristic physiologic changes
that occur when the drug
is discontinued abruptly, when the effect of the
drug is counteracted
cry
(A U7
-ftvp". C)o -
CN
U-I
BATCo document for Province of British Columbia 5
November 1999


LO_
by a specific antagonist, or under certain
physiolo3ic stresses (e.&. severe
infections), and 2) tolerance, the need to
progressively increase the
dose in order to produce the effect originally
achieved by smaller
amounts. Addiction is a term with many social as
well as medical meanings,
but is usually applied to states where both
physical and psychic dependence
are present, characterised by marked involvement
with use of the drug
and the securing of ita supply, and i'
-high'tend'e"ricy to resume -use of
drug after its withdrawal". .4
In most cases an author tends t~ ~c-hoose the
definition which best
,'7?, suits his viewpoint. Most arguments
concerning the use of the terms
"addiction" and "habituation" in connection with
smoking tend tc centre
around the evidence for:
the pharmacological basis for the
u!k~,,q~_Xobacco--.-
(b) tolerance to cigarette smoking and/or
nicotine.
(c) tendency to increase the dose of nicotine.
syptcms and whether these can be considered
to constitute a "withdrawal syndrome".
In practice, the term "dependence" is now used by
many authors
but a diScussion of the issues involved in
distinguishing "addiction"
and is a useful way of revi"ewing some of the
effects of
nicat.,ne and smoking, some of the motivational
theories proposed for
smcking and the processes of smoking initiation
and cessation.
L4
_D
Uri
BATCo document for Province of British Columbia 5
November 1999


-11-
2. EVIDENCE FOR THE ROLE OF NICOTINE AS A
DETERMINANT OF CICAUTTF
SMOKING
Throughout these discussions it is assumed that
nicotine is the major
psychopharmacologically active principle in
tobacco smoke. It should be
remembered, however, that other smoke components
could also be of importance.
Most authors have disregarded this possibility but
it has been suggested
that d ch an tP
_fggnoids could be JmportM,to t -qFke;.1(7
ig 7g
"M ~MFWI
The two authors who appear to be most convinced
about the importance
of nicotine in7 cigarette smoking and have worked
ex tens &e1y' ;o`n' -ihe
subject, are Russell and Jarvik. They have,
however, different views
.1 r]X
about the exterLt to which the central role of
nicotine has been proved.
Russell states that: "There is little doubt that
if it weren't for
nicotine in tobacco smoke, people would be little
more inclined to smoke
than they are to blow bubbles or light
spiiVI~~r7sw'~~Mt)'.-*~-~'ariiik -however
seems to be less sure. Ile has said that he
believes that people have
stumbled on-the most efficient way
nicotine into the brai.n (104). He also thinks
(105) that it would be a
remarkable coincidence if the effects of this
powerful pharmacological
agent had nothing to do with the reasons for
smoking, but this does
CJ remain a possibility. It is also amazing that
the reinforcing properties
of nicc;tine have not yet been demonstrated
unequivocally.
Authors discussing smoking as an addiction usually
assume that
smoking has a strong pharmacological basis with
nicotine as the active
agent. Some of the evidence for, and against, this
is reviewed in this
section.
4 t*
L4
0
BATCo document for Province of British Columbia 5
November 1999


-12-
2.1 Historical
Tobacco seems to have been used first by American
Indians in the
form of c--'gars and in pipes. It is used in most
societies in the world
today. :a some primitive societies other oral
compulsive behaviour may
predominaze such as betel nut chewing or teeth
clicking (160). In fact
a number of societies seem to use the betel nut
for a similar purpose
~~
ct vit'.
to nicotl-=e, and it contains areco line, a
psychopharmacologically
alkaloid. Russell points out that some form of
elaborate non-nutritive
iA
hand-mouti: activity associated with taking t
i..lat!.ng all-loid has
been part of the human behaviour repertoire for
nearly 500 years (168).'
No population has been known- to give up tobacco
after being introduced
to it. The use of tobacco has survived various
forms of official disfavour
and penalties ranging from decapitation
to.e.-,comnunication.
Since it was brought to Europe in the 16th
Century, tobacco has
been used for chewing, snuffing and smoking. In
18th Century Britain
smuiring pr-2-3or-ainated (171). cigarettes appear
not to have been introduced
into this country until soldiers returned from the
Crimean War (1854-
56). At f--*:st cigarette snoking was a luxury
confined to the upper
classes but since that time it has spread to all
social classes (115).
Cigarette s=cking has also tended to displace all
other forms of tobacco
use. The possible reasons for this are mentioned
in section 2.4.
The fact that tobacco smoking has continued in the
face of so many
penalties and in recent years, health warnings and
high taxation, is
taken by Russell to indicate that it produces a
very strong dependence
(171). Jar-,ik also mentions the fact that in Eur
ope in World War II
people would go to incredible lengths to obtain
cigarettes, collecting
C.)
(A
Q-1
cz,
CD
CD
BATCo document for Province of British Columbia 5
November 1999


butte from the gutter, resorting to prostitution
and bartering meagre
food supplies (104).
The common factor in all forms of tobacco use is
nicotine. Tobacco
ingestion has never been widespread. Russell
believes that this is
because ingestion leads to metabolism of nicotine
in the liver to form
cotinine which is psychopharmaco logically inert.
Tobacco is only used NMI a,
- .. - -V - .? ,
. . sv.*. f,*Vt_._st1r *~_ *?.W
in ways allowing nicotine 'Eo bypass 'the liver
and enter the bi~in" TMt
active form. This means it must generally b e
absorbed through the . ~ j;.& :
_14
Waa. -
buccal or nasal mucosa or in the lungs (171).
According' to ~a"rvi .ra"
7
psychological theories of motivation fail to take
account of the use of
tobacco in non-smoked forms such as snuff or
chewing tobacco. This is
not entirely correct, however, since these
theories often seek only to
explain cigarette smoking as it is the most
widespr;V fo~Rof.A baccgAMM,
, ,1 1.11,11, -1 4 ~ -, -- ~e. . '~o
use at present, and they do not consider the
general case.
It should also be noted that herbal and other
ncn-tobacco cigarettes
--.& ..R ,- 11W -(VI
.d 'imo~fn`gmix-tu_r`e`s' for pipes, which contain
no nicotine, have never
become widely popular, although they have been
available for many years.
0.
These non-tobacco blends, however often seem to
have smoke which has a
very unpleasant taste and smell. Their lack of
success in terms of sales
y not be ent-;:ely accounted for by the a'--sence
cf nicot-_'ne but this
probably plays the dominant role since even
tobacc-~ smoke =ay be considered
to be unpleasant by the novice smoker.
On balance the historical evidence favours the
interpretation that
CO
(A
nicotine is of importance in tobacco use.
CO
C)
(_71
LTI
__4
ON
BATCo document for Province of British Columbia 5
November 1999


-14-
2.2 Evidence from Experiments Using -Animals
Russell often quotes the results of experiments in
which Monkeys
and rats learn to self-inject nicotine, as
evidence for the importance
of nicotine as a drug of dependence. He has said
that animals must be
either rewarded with something pleasant or
threatened with something
unpleasant, before they can be trained to do
anything. Monkeys self-
V~ Ti J e C ti c o E Ire' '16 r i t 'a =-.-a Ue
6"f "t.M.W. _1b ?? Vt rTn
in some way. The quality of acting as a primary,
"unnatural", reinforcer
-~,ir depend'ence'- p-rodulcl nig drugs'. 1). The
of behav*iour is hared with t T11
th: dependenceopotential
ways in which
of drugs may be determined by
animal experimentation are covered very thoroughly
in a recent World
Health Organisation publication (227).
Results of experiments on animals are, however,
not particularly
4 W. -
easy to interpret. The study on self-injection of
nicotine by monkeys
which is most widely referred to, is that of
Deneau and lioki (52).
-They used
connected to icJectors activated by a lever in
their cages. The Monkeys
would press the lever out of curiosity ard obtain
a dose of nicotine.
If they did not self-administer the drug at a
given dose level, nicotine
was automatically injected once an hour for
severall weeks or until self-
administration started. If this -as not sucessful
the dose was raised.
The authors mention that a raisin on the lever was
often needed to
induce pressing, so it appears that monkeys did
not always self-inject
nicotine readily.
At 25 Vg/kg two monkeys self-;~ministered
spontaneousl7 and the
others did after two to ten days automatic
injection. They averaged
CZ:
7
L4 (J7
Co
\0
BATCO doCUment for Province of British COIUMbia 5
Novernber 1999


from 0.7-1.7 mg/kg per day but the dosing patterns
w-e very variable
and sometimes changed by LOOZ on consecutive days.
Days on which a
large total dose wa3 taken were often followed by
reduced dosage the
CIO
L4
L4
next day.
Then, at one month intervals, the dose was raised
(to 50, 100, 200,
500, 1000 and 2000 jig/kg per dose). At each dose
the lever was pressed
f r e q u-101W 0n
le;s.: ~ 'ent' " a a z 166 ~.e Va"' er
'P"t ly an a a ven se'the m fuse, dminist'
nicotine. Of the six.monkeys in this part of the
experimenc,one
_,fefused
vg/kg, one at 100, one at 500, one at 006 ~fi n
at 50 still injected
2000 pg/kg averaging 9.6 mg/kg per day with a
maximum of 14 mg/kg. The
monkeys did not self-administer nicotine between
midnight and eight a.m.
(when the cages were in darkness).
Jarvik has done a number of-experiments usin egs
4, JAA 6
smoke (105). Ile says, however, that although they
will smoke they don't
inhale. Monkeys traiaed to smoke cigarettes also
show a high day to day
v~`r-TI-t'-on` in smoking and poor extin~tlon of
the behaviour (104). Glick,
Jarvik and Nakamura (76) persuaded monkeys to puff
smoke by making them
take 30 puffs to get one drink of water. They then
tested four rhesus
monkeys with drugs te see if their smoke/air
preference was altered.
Smoke %was usually preferzed under normal
circumstances. Mecamylammine,
which blocks peripheral and central actions of
nicotine, depressed the
smoke/air preference and produced a small decrease
in puffing. This may
indicate that smoke is aversive if not accompanied
by rewarding physiological
effects. RexamethoniL=, which blocks peripheral
actions of nicotine,
also reversed the smoke/air preference and
decreased puff rate. suggesting
BATCo document for Province of British Columbia 5
November 1999


-16-
that peripheral actions may act as an incentive.
Pentobarbital, a
general sedative hypnotic, merely decreased
puffing rate but did not
reverse smoke/air preference. Nicotine tartrate in
drinking water could
lower smoke/air preference if a suitable dose
level was chosen.
These experiments, have been covered in some
detail as they serve to
illustrate several points. Firstly monkeys do not
learn to smoke easily
A . ; AM -
"1 R- Wid'do IMET&6oka 4itv-vrorvm4 yq-eimiff.-
Sialng VeR -VOT7
'4'r
variable, as is self-injection when it is induced.
Jarvik has pointed
ind I c"a
out (104) -t
tei; th teqnkeys do not bave a fine degree of
control for nicotine. Animals will, however,
regulate the intake of
addicting drugs such as opiates, alcohol, cocaine
and amphetamine and
keep the dose more or less constant once
dependence is established.
Hutchinson and Emley (97) have stated that the
difficulty in inducing
fag;fn i tfi~n talroba c 4o or ~'C'otine usage in
animals may be due to incomplete
onsideration of cthe duall' nature of the
reinforcement process. There
:
jLre two
claasee-ofxroinforcersff*IM'gitllt*t~tL&inf6rcgrl'
whibh e fills
involve intake of, or contact with, substances
which are nutritive or
essential for life or health or mimic such agents;
the other class cause
reduction of noxiousness, aversiveness, pain,
irritation or stress.
C. Their results suggest that nicotine serves to
reduce reactions aad
affects caused by noxious agents and it is not
thereforre surprising that
anical experiments, in which stress is minimal, do
not lead to significant
tobacco usage.
There are several points which should be
considered in connection
vith the experiments on animals. ' A~ 'with a
human population it seems
likely that individual monkeys probably differ in
their reactions to
C)
U-1 - . - -~-
Q~)
41 ~1
On-
\C
(14 L_J
BATCo document for Province of British Columbia 5
November 1999


-17-
drugs and in their propensity for
self-administration. Thus experiments
on a small number of monkeys may not be
representative of larger samples.
In the Deneau and Inoki study, differences between
individuals are seen
in the maximum nicotine doses that were tolerated.
The monkey injecting
itself with 2000 jig/kg doses was taking very
large amounts of nicotine,
far more than the equivalent dosage taken during
smoking by human subjects.
~ Ms rd";' t To pp = i s' oW so w effects
It'lL 0orn ~ftN F
Me? ;F-t6t monk'y ra ne
due to nicotine in their drinking wat One would e*
I lual.. ni,otine
_~a`v'e little e ff
i.gesi'eta; in thiihiay would e~t since it 'would
be metabolised
in the liver.
Considerable caution must always be applied when
results on animals
are extrapolated to humans but there is an
indication that nicotine does
provide some sort of "reward" to monkeys. The pps
regard to comparisons with dependence producing
drugs is not, however,
as clear-cut as Russell suggests
_tiidencle f_-m -1 ' v '
----2.3 xperYmnef.its on Humans: The Effects of
Nicotine and
of Changed Delivery of Smoke Constituents on
Smoking Behaviour
As Jarvik has stated- "To prove that nicotine is
the essential
ingredient in cigarettes it is necessary to show
that cigarettes from
C_ which nicatine has been removed are not smoked
and, conversely, that
n1 cotine alone can substitute for cigarettes"
(105). This has been
extremely difficult to prove in practice.
The first study published an the effects of
nicotine on smoking
seems to be that of Johnston in 1942 (109). He
gave intravenous nicotine
to smokers and non-smokers. The smokers thought
that it was pleasant
and were disinclined to smoke for some time after
the injection if the
cc Q)
.6'r
w
U .
lr
0 \0
BATCo document for Province of British Columbia 5
November 1999


_18-
dose was adequate. Non-smokers termed the
sensation after injection
,, queer". This study lacked controls and no firm
conclusions can be drawn
from it, but it prompted Finnegan, Larson and
Haag, in 1945, to investigate
further (62). They obtained some low nicotine
tobacco and, by adding nicotine
to some of it, made up cigarettes delivering 0.34
mg and 1.96 mg nicotine
per cigarette. Their subjects were 24 smokers who
first kept records
o~ numberpjim4e .
forztheir owV-byand.- then.4the~,high
MicdeItMfcikAip C8511~1-1 7-
(about two weeks), then the low nicotine
cigirettes (about one month).
The differences in the numlvers smoke4 -were
'small and some subjectalwer-e
not concerned by the lack of nicotine in the low
delivery cigarettes.
at Nine subjects, however, missed the nicotine,
and did not adapt, but they
accepted the low nicotine cigarettes as better
than nothing. This
experiment showed thai nicotine may be of
importance for some smokers
but otn%rg.
Surprisingly the next study which is important in
this area was not
~967 3).,.J7hip_Ja_the, work of-Lucchesi, Schuster
-and-4NNO"--
until - -(IX
Emley, who realised the importance of doing an
experiment in which the
subjects were unaware of the purpose of the tests.
They carried out
six-hour psychological tests on subjects who were
fitted with an intravenous
drip delivering either saline or nicotine (in
doses which produced no
subjective effect in the subjects used). The
subjects were allowed to
awoke during the tests if they wished to, and the
number of cigarettes
smoked were recorded and the butts were collected.
Subjects were infused
with 4 mg nicotine per hour as this was equivalent
to the average smoking
dose at a rate of one to two cigarettes per hour.
Four subjects given
2 =g nicotine in the first hour, then 4 mg: per
hour for five hours
(A
L4
0
CD
U-1
BATCo document for Province of British Columbia 5
November 1999


_19-
(total 22 mg) showed a small decrease (average 2.7
cigarettes) in the
number smoked and a decrease in the amount of each
cigarette consumed.
when compared with the saline control. Nicotine
was also infused in a
way more closely resembling smoking. The
experimenters infused I mg
nicotine in 14 minutes at intervals of 32 minutes
(total 8 mg in six hours)
and found a significant decrease in number of
cigarettes smoked for
-4 bQft-e.-fthree:of f6dr-ONJIetts. One-406J i E t
-showed the
periodic administration and 12 mg continuous
administration (over six hours).
cqnc, ii`vle
-pla
The, lusi.o!l n -in this paper 8 &t nicotine'' y9
a small but
significant role in smoking and that part of the
craving for cigarettes
is satisfied by intravenous nicotine. In fact, if
the subjects had been
smoking for nicotine only and intravenous nicotine
had been a good
substitute, they could have reduced their
cigarette smoking to zero.
WNW-
Thfi is' an example of' what -ia*rvik calls "the
important role played by
secondary conditioning and functional autonomy in
the maintenance. of the
smoking babitg-(105) - He believes - that, - in
very~ much loiigo-t- term-'Rlddidef
the habit of smoking would be extinguished in the
presence of nicotine
from other sources or in the complete absence of
nicotine. Hutchinson
and Emley (97) agree with this and say that since
stimuli previously
associated with powerful reinforcers are known to
sustain response
sequences for long periods independent of primary
reinforcement, short-
term tests cannot be expected to show much effect.
The study by Lucchesi
et al. is very often quoted by Russell as
conclusive eviden ce that
nicotine is the prime reinforcer in cigarette
smoking, but as with the
other studies he mentions, the position is not
entirely clear-cut.
C>
BATCo document for Province of British Columbia 5
November 1999


-20-
In subsequent studies the technique of butt
analysii hag often
been employed to indicate the amount of nicotine
taken from a cigarette.
It should be remembered that results of this
technique can only give
estimates of the amount of nicotine which a
subject has obtained.
Inaccuracies will be greatest when small numbers
of butts are analysed,
unless subjects act as their own controls. The
amount of nicotine taken
M
from a cig .I _V ,a ut th~ am'o'unt whic remains
arette also glees no information b0
in the body to give a pharmacological effect,,ts
~~kkyarieg,~~ he',
depth of inhalation. This,"of course,.wi.11 apply
to all methods of
estimation of nicotine delivery, including puff
duplication.
A number of authors have tried to determine the
importance of
nicotine, by using cigarettes of different
deliveries. One very well-
known study is that of Ashton and Watson (13)., In
a driving simulator task was used, and 36 subjects
smoked either high
nicotine (2.1 mg) or low nicotine (1.0 mg)
cigarettes. It was found
_"' ~;_ - -._-..1-Q- ~. X, Y
-Tb7t' su e- more puffs on the lc-,;e,- nicotine
cigarette and
bj cts took I
obtained almost the same amount of nicotine (as
determined by butt
analysis), as did subjects smoking the high
nicotine cigarette. In
fact slightly more nicotine was taken from the low
delivery cigarette
by the sublects than by machine smoking, and
slightly less from the
high nicotine cigarette. The authors suggested
that the subjects were
unconsciously modifying their smoking pattern to
obtain an optimum dose
of nicotine for a given activity. This is shown by
the fact that more
nicotine was taken per unit time during rest than
during tasks and
slightly more nicotine was taken during the more
stressful task than the
tA
U
0
c0
A0
Co
BATCo document for Province of British Columbia 5
November 1999


less stressful one. The effects demonstrated are,
however, small, and
it seems possible that the results may have been
considerably different
if other types of cigarette had been chosen. The
high nicotine cigarette
was probably higher in nicotine than the subjects
were accustomed to,
and the low nicotine cigarette was not
particularly low in nicotine.
This seems to be, however, the first real
demonstration that subjects
y We'lhe m 1;f.Um avZr1.bI a _t
A-"Ic~Ii`n.MMV.A*r.
would no ecessaril a
n
. I
a high nicotine cigarette, but prefer to take
less. Frith (71) found
A! otine dei!v:e`rIes,:
that subjects' given ~Igarettes with three diffitn
took longer to smoke higher nicotine cigarettes,
and that they smoked
fewer of them in an eight-hour period. Agu4 (2)
did an experiment using
a lettuce cigarette control and three tobacco
cigarettes with different
nicotine deliveries. lie found that smokers whose
normal consumption was
... . . .. - ~ - . ... .1 ." 1. - pik
above ten cigarettes per day disliked the lettuce
cigarette most, but
light smokers disliked the high nicotine cigarette
most. Ile also found
that dIIff.'r6n6d_j -
ih'nico~tri^-ecFni-6iiE"o'f-cigarecces were
related cF-a"ifferences
in puff frequency and puff time.
Turner, Sillett and Ball (209) conducted an
experiment during which
subjects sooked a meditua delivery cigarette (1.4
mg nicotine) for a
week, then a low delivery cigarette (0.8 mg
nicotine) for a further
week, and a very low delivery cigarette (-cO.3 mg
nicotine) for the
last week. They found that there was a significant
increase in the
number of cigarettes smoked when subjects changed
from medium to low
delivery, but no difference in numbers of low and
very low nicotine
cigarettes smoked. They did find, however, that
the very low nicotine
cigarettes -ere smoked to a shorter butt length.
The ratio of observed
(A Q)
CO
CD
BATCo document for Province of BritiSh Columbia 5
November 1999


-22-
(butt) to expected (machine) filter nicotine
indicated chat subjects
took less nicotine from mediu.m and low delivery
cigarettes than expected,
but more from the very low nicotine cigarette. In
fact subjects took an
average of 0.89 mg nicotine from the medium
delivery 'cigarette. This
may be considered to be a rather surprisingly low
figure which may
suggest that these subjects were not typical of
the majority of U.K.
I -..- -
-
A; '-R-
*=
i
(6
k
~
th
f
iV
t
ll E
t A172)
ll
n
ers.
usse
ou
, one
ree.o
a
o
n
a
e
as po
g
smokers in Britain smoke Embassy Filter or Players
No 6 !Iiver74
-(dc
,p
.
,
about 1.3 mg nicotine), about 75Z of amokers smoke
medium nicotine
cigarettes and only about 12% smoke cigarettes
delivering less than 1.0 mg
nicotine (from figures published in 1975). There
is little evidence,
ho.ever, on the nicotine deliveries that the
majority of smokers obtain
from their cigarettes. Six of the 13 subjects used
b T
did, however, report that the medium cigarette was
too stron g . It was
shown, therefore, that the subjects made some
attempt to change their
1
d -
d
oking'pattern. 6 s3te for re uce nicotine
delivery, and that
the number smoked per day was also changed, to a
small extent.
One of the longest term experiments that has been
conducted is that
of Freedman and Fletcher (69). They used 200 male
subjects in two
groups. Group I smoked a cigarette containing 30X
NSM (i.01 mg
nicotine) for nine months and the control
cigarette (1.39 mg nicotine)
for 12 months. Group II smoked the control first.
There was no change,
on average, in numbers smoked per day for either
grotip when they switched
from one cigarette to another. Butt analysis was
conducted for 35
subjects for some months only, although it is not
clear from the paper
why all the results were not available for all
subjects who saved butts
U J.
(A
0
(
n \0-
.
Ln
co
(-n
BATCo document for Province of British Columbia 5
November 1999


-23-
(40 su~--Jects) and all months. The results quoted
from butt analysis
show that Croup I subjects took an average of 1.03
mg nicotine from the
NSM cigarette and 1.12 mg from the control. The
figure for the control
is an average for 11 subjects who took close to
the expected amount of
nicotine and six subjects who must have altered
the way in which they
smoked after nine months on the lower nicotine NSH
cigarette and averaged
-% -': -t- -"4" - IV
only'0.9 mg nicotine )"'trMe I +MW - .*- 4;`~' - ~
~ -, - --"" W-
contro . r'-
Group II took an average of 1.4 mg nicotine from
the control and
-4 1~4 Ov, 0.5
1.08 mg nicotine from the NSH cigaret~LV. These
figuiii are ver. y c 9e
to those obtained by standard machine smoking and
indicate that both
cigarettes were smoked in a si;-nilar way, with no
compensation for changed
delivery. Therefore it can be seen that most
subjects did not change
the num.-ers of cigarettes smoked or the way they
were smoked when
nicotine delivery as changed by 27%. A few
subjects however adapted
per-manenc,ly to the lower delivery cigarette and
maintained lower nicotine
Intakeli-75en
nijllne contr
Ha=ond and Carfinkel (88) conducted a survey on
98,632 male cigarette
smokers (aged 40-69 years) and compared the number
and type of cigarettes
they were smoking in 1959/60 with those in
1961/62. 832 of the men had
not: chanzed in terms of the nicotine deliveries
of the cigarettes they
smoked. l.' had changed from cigarettes delivering
1.9-2.7 mg nicotine
to those delivering 0.4-1.1 mg. Of the 994 men
showing this large
decrease, 65.1Z said there had been no change in
number of cigarettes
smoked, 16.31 had decreased consumption and 18.6X
had increased it. Of
the 9.5% who had changed to cigarettes of higher
delivery almost the
same number increased consumption as decreased.
These results, therefore,
for a large number of men, show no evidence for
compensation for changed
(A
(A
4-
0
Q;I
U'I
BATCo document for Province of BritISh Columbia 5
November 1999


_24-
delivery in teims of numbers smoked per day. It
must be remembered,
lio-.;cvcr, that self-report data are not always
occurate and that smoking
patZerns may ha*- changed. It is also probable
that only those who
could toLerate a reduced nicotine delivery without
greatly increasing
numbers of cigarettes smoked would switch to a
lower nicotine brand.
Cuillerm and his colleagues also have some
evidence that smokers
tend to take more smoke from,,
a. lower.4ijgo
IV.
T;..
'.V 4S
compared the effects of smoking Gaulaise (1.7 mg
nicotine) and Callia,
(0.7 mg nicotine) and found signififc~a~tly 6igher
blood carbo 'yNaLmoglobia
(CO11b) levels after sinoking the lower nicotine
cigarette. This was
~~--iurprising since this cigarette delivers less
carbon monoxide when
smoked by machine. The increase in number of lower
nicotine cigarettes
smoked (6%) was insufficient to explain the
increase in COllb and the
r v a-S
aut!:ora suggested that '~Ymi_subjects had-Ta'Ien
a;g~' P~ff ~11=e ` n
inhaled more deeply.
There are twq es cqnd.Wr
. _ . _4~_4ckL_ . .
be =entioned here. In a recent study in Group R. &
D. Centre (50) subjects
smol-ed a control cigarette exclusively for four
weeks (1.4 mg nicotine).
Half the subjects then switched to a higher
nicotine (1.8 mg) and half
r' j a lower nicotine (1.0 mg) cigarette for four
weeks. All subjects smoked
the control cigarette for the last four weeks of
the experiment. Results
for the numbers of cigarettes smoked are somewhat
difficult to interpret
due to the way in which the cigarettes were
issued. Results of butt
analysis and duplication of some of the smoking
patterns may be taken to
om th gh'
indicate that subjects obtained similar amounts of
nicotine r e
nicotine and control cigarettes, but rather less
from the lower nicotine cigarette.
cc
L4
00
\10
L
C)
C)
BATCo document for Province of British Columbia 5
November 1999


-25-
The average delivery achieved was 2 mg nicotine.
Deliveries taken
from each cigarette were higher than
machine-smoked deliveries. Subjects
also appeared to adjust to the changes in
cigarettes very soon after
they started to smoke them. Creighton (49) has
reviewed some of the
evidence for compensation for changed delivery
including work from
I.T.L. Montreal and Group R. & D. Centre,
Southampton. He concludes
TIM
that "mady?jpg~ablished-'96bkers do
com~eME?to&MTM-;M,)dry I
attempt to equalise nicotine delivery, when this
is possible."
Adams of Imperial Tobacco Limited (l5:'h..,qtud1
'd. 'three separate
e
panels of 16 heavy and 16 light smokers of each
sex and one panel of 15
males and 13 females. Only one panel was of
persons closely associated
with the tobacco industry. Eight cigarette types
were used giving a
range of tar and nicotine delivery and of pressure
drop. Eight groups
0 f subjects each smoked different types of
c--garettes in six, four-week
periods. As in the study by Creighton it is not
possible to interpret
results-for numbers 4 of:- C igare t ta 9 -smoked
~s into
of issuing cigarettes were observed. Results for
changes in nicotine
delivery indicated no changes for two panels and a
small increase in
total puff volume for an increase in nicotine
delivery for the other
p
auels. This is against the hypothesis that
compensation to constant
nicotine delivery occurs. U nicotine and tar
deliveries of a cigarette
were reduced simultaneously smokers increased the
volume of smoke taken.
Butt analysis results indicated that an average of
0.9 mg nicotine was
obtained from the range of cigarettes.
A study by Warburton and Wesnes (218) on the
effects of smoking (in
vigilance task performance has yielded some
results indicating that
L4
Q-1)
\0
C~:)
CD
U-1
(-n
co
c0
BATCo document for Province of British Columbia 5
November 1999


-26-
subjects in experiments smoke so as to increase
the nicotine delivery
of low nicotine cigarettes. Results of butt
analysis for a sample of
heavy and light smokers show that subjects given
cigarettes of 0.3 mg
and 0.7 mg nicotine delivery may obtain an average
of up to 0.68 mg
and 1.5 mg nicotine respectively. This way not,
however be applicable
to n-1 smoking conditions since subjects also
exceeded machine-smoked
nicotine diifv"e"r"1?t'f6!OA0tTg6
~Vffrne'llcfg"arett*e I.7 'mg) and werd~
smoking during a long test which may have caused
boredom in some subjects
and stress in others.
Schachter and his colleagues have also studied
smoking behaviour
using medium (1.3 mg) and low (0.3 g) nicotine
cigarettes (186). Seven
heavy smokers (over 20 cigarettes per day, smoking
the same number each
day and finding it difficult to stop smoking) and
five light smokers
VCA~
(under 15 cigarettes per day, numbers of
cigarettes smoked varying idely
according to circumstances and finding it easy to
stop smoking) were used.
Unfortunatelj~'EhWTM~Inidi~x or'smo~lng bJa`-o.'r
used was n'Lrnber 'o'f
cigarettes smoked per day. Results indicated that
heavy smokers smoked
more low than medium nicotine cigarettes even
though the low delivery
cigarettes ere disliked. The average increase was
257. Light smokers,
hcwever, did not alter the numbers smoked. Further
experiments in this
series (187, 188, 189, 196) concerned the effects
of changing urinary pH
on cigarette consumption. The proportion of
unchanged nicotine excreted
in the urine is said to be 35Z if urine is acid, U
if it is neutral and
less than 1% if it is alkaline. Schachter states
that the proportion of
nicotine remaining in the body, to give an effect
which the smoker may
desire, will therefore be lowest when the urine pH
is low. It was found
Cr,
(A
U
00
C~J
Qn
BATCo document for Province of British Columbia 5
November 1999


-27-
that urine pit could be manipulated by giving
vitamin C or Acidulin
tablets (which form hydrochloric acid in the
stomach) by mouth. This
caused small but significant decreases in urine pH
and increases in
number of cigarettes smoked. Cigarette consumption
was also increased
by stress and going to parties. Both of these
conditions caused a drop
in urine pit. If urine was maintained at neutral
or alkaline pit, however,
' 1thMe`x"pL_tAVM4e U_-Oc -Ur
*-TVR Mot , -Jft~ n., c
It was also found that all smokers smoked more in
the morning -.;hen blood
-
,`
tl 41"' f' W"
nicotine levels are low after the night's
abstinence. 1,oncl,~~e,
s:
Schachte
r
r7 l
: 699 that his results indicate that smokers smoke
for nicotine but that light
smokers have "tight cognitive control" of their
cigarette consumption.
He also suggests that the urinary pit mechanism is
the mediator for the
stress-smoking relation.
Unfortunately the conclustons of 'these studies by
Schachter must be
questioned, especially in relation to the use of
cigarette cons~ption
of-
urinary pH and cigarette consumption are
significant but tend to be
rather small. It seems that urinary pit may well
have an effect an
smo king behaviour but the relevance of this is
not clear if most smokers
are s,-king (as has been suggested by Russell.
(173) and by others) for
the i=ediate effects of nicotine which would be
unaffected by -he rate
of nicotine excretion.
Several authors have used yet another way of
changing the delivery
of cigarettes. This entails either marking
cigarettes or cutting them,
so that only a fixed proportion of'the cigarette
is smoked. Jarvik
was the first to use this approach and his work on
full- and half-length
0
Ok --M
C)
U,
,4 D
C)
BATCo document for Province of British Columbia 5
November 1999


_28-
cigarettes is considered towards the end of this
section. Stepney (198)
has studied 14 subjects smol ng their own brands
of cigarette to full
length or two-thirds length (as indicated by a
mark on the cigare:tes).
Cigarettes were smoked both inside and outaide the
laboratory. e n
observed La the laboratory, most subjects were
seen to take longer puffs
or more frequent puffs from the "shorter"
cigarette. Butt analysis
indicated that subjects smoked the cigarettes to
obtain more nicotine
M"'D
when they wer, n VT~=Oiory than during the res of
the day. Some
subject! s~Fted_th& a ~r r" cigarette so
asl.to.obtain more than the
expecte nicotine delivery (calculated an the basis
of the change -_'n
tobacco rod length). Deliveries from this
cigarette were bet-ween ~c and
95 Z of those obtained from the full-length
cigarette and blood
levels indicated that on average 71.7Z of the full
cigarette dose -.;as
obtain d CIS. cigarette.,,-There therefore s.eems
to be
so.e i-.dicaLion that subjects smoked to obtain
nicotine from a sh,-:--2r
cigarette but the effect is a fairly small one. It
is also interes-_-ag
R,_ - - ., _I .1. V , I - ,,- - W_ .- 1% %~
that In this study subjects took, on average, only
64-89Z of the n_:Z:~tine
deliveu obtained by standard machine smoking.
Finally in this section the work of Russell and of
Jarvik must ~e
mentiozed, Russell has done experiments using
cigarettes of diffe:-=:.t
delive---'es and using nicotine chewing-gum. In
one experiment Fussell
and his colleagues looked at plasma nicotine (181)
and carboxyhaencz*-obin
levels (180) after ten subjects smoked their own
brand, and high an--' low
nicotine c1garettes. On the same two days of two
weeks subjects s=kad
their om brand in the morning. For five hours in
the afternoon, on
days one and three they smoked their own brand and
on days two and -'cur,
high or low nicotine cigarettes (Capstan Full
Strength, 3.2 mg nicotine,
tA
(A
Un
U'l
(-n
BritiSh Columbia 6 November 1999
BATCO document for Province of


-29-
and Silk Cut Extra Mild, 0.14 mg nicotine). Each
smoker was consistent
from day to day in terms of mid-morning blood
nicotine level and this
was unrelated to n=ber of cigarettes smoked
preAously. When subjects
changed to the high nicotine cigarette there was a
significant decrease
of 38% in number smoked in five hours and plasma
nicotine levels were
similar to those for their usual brand. When they
smoked low nicotine
Or-.5~.!~jc
c garettes there was no signlli= increase in
number isimAed~n'~ pia-sma
nicotine levels were lower than under other
conditions. Carboxyhaemoglobia'.1 9-INE-4-
levels were'lower for both high and
- low nicotine crigarettes than for the
subjects' usual brand. This study shows that
subjects can regulate
their cigarette consumption and smoking patterns
to obtain their usual
blood levels of nicotine from a high nicotine
cigarette. Wben given the
low delivery cigarette, however, th ere unable to
obtain high blood--4-1-*--
nicotine levels and all subjects rated these
cigarettes very unfavourably.
It may be significant that they nevertheless
smoked more low nicotine
~~an hi"gh .:`c6ti-ne cigarettes although the
latter were rated only moderately
unfavourably. Russell suggests that the low
deliiery cigarette was too
low for the subjects to make any real effort at
compensation. At a recent
conference :--i Zurich (204), Russell reported
results Of an experiment
using XD4 filters. These are a series of
comm-erci.-Ily available cigirette
holders nubered from HI to H4, with progressively
larger holes which
dilute the sr-oke. Results for 18 subjects were
given. They smoked
normal cigarettes, then smoked cigarettes through
holders HI and H2
(reducing nicotine delivery by 35Z and 602
respectively). There was
some attempt by subjects to increase nicotine
delivery but little change
in number of cigarettes smoked. Blood nicotine
levels were higher than
those expected from machine-omaked deliveries but
differences were small
and compensation was less complete than was
expected by Russell.
L-4
CD
C)
~_n
LrI
BATCo document for Province of BritiSh Columbia 5
November T999


-30-
Russell and his colleagues have investigated the
effect of nicotine
chewing-gum as an aid to smoking withdrawal. They
fcund (176) that a 4
mg nicotine gum could give blood levels
approaching those of smoking,
but it had a number of undesirable side effects
and a 2 mg gum was used
for initial experiments (179) . This gum releases
nicotine over 20-30
minutes at a rate determined by the vigour of
chewing, and the nicotine
-93 -' '-OW .'- 1% 1. :
V I - *tl* -ec I ~o c W" ,
ih'A% -rbiMIM ibe-MMal--c~Ws su a .-I, b~d
tq-st-p,-.,.Tj
smoking were asked to smoke and chew gum (nicotine
gum or placebo for
'lift
two d ys each) for a week. They were then asked to
c~eq the gum an try
a
to stop smoking for two weeks. The gum was chewed
for 20 inutes at
the rate of one piece per hour for seven hours and
the-i one piece every two
bours for six hours. The contribution of nicotine
in the gum to the
outcome of treatment was said, in the conclusions
to the paperi to be
72 of the total reduction in cigarette consumption
and 151 of the
reduction in blood carboxyhaemoglobin. From the
resuics section of
the-PAMrfftlever
t%ie'ftiili~~s-"gp'pg'arr-a-be~'i~earer ' '-*-'---
likely that the decrease in number of cigarettes
smoked wy be due in
part to the length of time spent physically
chewing the gum. Russell
et al. say that their findings show a clear,
though =dest inhibitory
effect of nicotine on smoking (when subjects
smoked at -will during tile
first week). They suggest that the 2 mg gum may
not contain enough
nicotine to induce a larger effect, since it
produces blood nicotine
levels which are less than half those seen after
smoking. The results
for blood nicotine levels show that they are the
same for smoking only
or smoking + nicotine gum, so changes in Smoking
pattern WU3t have
occurred to keep a constant nicotine level.
However blood nicotine was
to
L4
C)
IVI
I
V.
BATCo document for Province of British Columbia 5
November 1999


-31-
higher for smoking only. than for smoking +
placebo gum, indicating
no regulation, and it is suggested that regulation
downwards may be
better than compensation upwards. This is a
conclusion which seems to
be fairly general frcrm the work on the role of
nicotine in cigarette
smoking. The reasons for the relatively small
effect of nicotine are
not adequately discussed in this paper. Brantmark,
Ohlin and Westling (29)
_s
1 :`~for InsI _e7t'd-porEed. n n IR It
Manc wer cigarette con u;ptIo`a when n cot ni
chewirig-gum was compared to a placebo. This was,
however, a 4 mg icotine
gum and subjects' were trying to stop smoking.
Johnston (110) has commented
that chewing-gum would not be expected to have
much effect as the effects
of nicotine obtained by buccal absorption may be
different from cigarette
smoking. This will be discussed in a later
section.
In a more recent study, Russell and his colleagues
have i d.-
"W*q
blood nicotine after chewing an improved version
of the 4 mg nicotine
g= (178). Subjects smoked normally on one day and
blood was taken two
9 In -, W tte"
minutes after b-m '~~tes ' fter a cigare---
(trough level). On another day subjects chewed one
pi:ce of 4 mg nicotine
g= every hour, chewing for 30 minutes. Blood was
taken before a gum
(trough level) and 25 minutes after starting a
giim (peak level).
Results showed that. on average, there was no
difference bet-;een chewing
g!= and smoking for either peak or trough plasma
nicotine levels. Some
subjects, however, achieved blood nicotine levels
which were two or
three times higher after the gum than after
smoking. In conclusion it
was stated that, although the chewing-gum produced
sufficient nicotine
to substitute for smoking, it was not clear
whether the nicotine contributes
to the capacity of the gum to satisfy a deprived
smoker or reduce his
sense of missing cigarettes. Few subjects did not
find the'gum unpleasant
L4
Lq
PC
4 1' a M,W Ww~
UI
X_`~.
BATCo document for Province of BritiSh Columbia 5
November 1999


but all but four obtained some satisfaction from
it. This was not,
hc-.;ever, related to the plasma nicotine
concentrations achieved and may
have been due to psychological factors.
Preliminary results have been given by Russell
(173, 40) for a.
experiment using intravenous nicotine. The
procedure used was very
similar to that of Lucchesi, Schuster and Emley
(133) but nicotine was
administeredjto mimic cigarette smoking
wIth.;~tJdWIdj--IWr-Dg MV6t 90.7
pulses delivered at the rate of one per minute.
The effect on smoking
was said to'be minimal and some sub ts even smok
~il nicot]i`
w e qe. ya
e4,
being administered. Russell has stated that the
analysis is incomplete
but the results seem to seriously challenge the
role of nicotine as the
nain reinforcer of smoking.
Another very recent study by Russell was designed
to investigate
t e ect. f ttl g ;ubjec~~ own ci~garettes ~o
three-~uar"Mes~
n and
half-length (175). Preliminary results of butt
analysis for this stud7
show, that,subi ec ts,.-on. average, smoked;.the
cigarettes in a similar way, taking slightly less
than the machine-
rmoked delivery of nicotine for each cigarette.
There was some attempt
increase the delivery of the half-length
cigarette, but the average
,.:res suggest that only 671 of the nicotine
delivery obtained from the
cigarette was taken. Thus subJects were either not
interested in
i=creasing their nicotine intake to maintain an
equal dose or were
0
L=2ble to do so when given a half-length
cigarette.
Jarvik has done a large number of experiments to
try and elucidate
tize role of nicotine in cigarette smokingg
working with & number of
different colleagues. Kozlowski, Jarvik and Gritz
(119) looked at the
effect of "preloading" subjects with nicotine, on
subsequent smoking.
%6 %-__
16 CD
CD
Ln
LF1
LTI
U~
BATCo document for Province of British Columbia 5
November 1999


-33-
Ine subjects who were unaware of the purpose of
the experiment were
deprived from smoking during a task, then given 0
mg, 1 mg or 4 mg
nicotine gum. They were then given high (1.3 mg)
nicotine, low (0.3 mg)
nicotine or zero nicotine (lettuce leaf)
cigarettes to smoke. After
this time they could smoke as they wished. High
nicotine preloads were
followed by less smoking than low nicotine
preloads. Nicotine In a
I-cigarbtte as tWpYlMd affeitg'dMe litency"To ~;t
c
not the number of puffs taken from this cigarette.
Nicotine preloads in
did not delay the next cigarette but decreased
ths~-Itim'e spiAlyp n.-
Ufff
a it. This.suggests that nicotine is playing an
important role but
that nicotine in cigarettes and in chewing-gum has
different effects on
s=oking behaviour. Jarvik, Click and Nakamura
(106) gave 17 smokers
f-:,ie capsules per day - each containing 10 mg
nicotine or a placebo.
nle oral nicotine induced a small (81) but
significant decrease in
nuzber of cigarettes smoked. It did not affect
subjective estimates of
"s t-zength" and "quality" -6f--e1&FdttV9-Th6
't6'bJirc?MTJbo;i
lazgesr changes due to oral nicotine were those
who habitually smoked to
the shortest butt lengths. Again nicotine is seen
to be having an
effect, but only a small one. Goldfarb, Jarvik and
Click (80) also
lccked at the effects of lettuce leaf cigarettes
with mid without added
nic~zine (0, 1,26, 2.251 mg nicotine). Fach type
of cigarette was smoked
for cne week by 13 subjects. All the cigarettes
were aVersive to the
subJects and, independent of nicotine content,
less of them were smoked
than the subjects' own brand. Despite this the
subjects continued to
smoke a fairly large number of the lettuce leaf
cigarettes even If they,
contained no added nicotine. This could mean that
nicotine in not
z
U
NOW-
CI-
CD
UM
Un
British Columbia 5 November 1999
BATCo document for Province of


-34-
_,rA7
C,
U3
(A
important, or that the subject continues to smoke
in the hope of obtaining
the nicot:-ne he desires. Goldfarb and Jarvik (79)
then looked at the
effect on 18 subjects of either cutting cigarettes
in half or only
allowing ~:moking down to a red line half way
along the length of the
cigarette. Subjects spent a week smoking their
usual brand (whole) then
a week of each of the cut and marked cigarettes
(also their usual brand),
Lr rma
followed *:7 4inal week an tphe* I A' tt JktTh"b
4 t- ,A
did not like the shorter cigarettes but there were
no significant differences
between we-aks, for number smoked or ratings of
"strZn&th"- ,6r - "qual i ty-'J'. L- r :,;: 41 i
-V, r.. . .: ~ -.!. ,' . ;:'i-Is , _. r-it 7.
Most subjests therefore reduced their tobacco
ccnsumption by almost
half. Th_,.5 result is difficult to reconcile with
the proposed Importance
of nicotine and requirement for opti..:um levels.
Although it is a possibility
that alte:Stions in smoking patterns were made,
these were unlikely to
lead to U-11 comped6ation--for tedu 6 ad "Bir3t
ilia intake. One*poinr.~-.,.t!,!~~--~-
however, ii thikt in the paper there is an
implication that at least some
of the su*:: -acts were pleased to have been able
to cut. their tobacco .
consu.pt.-~:: and the results may not be
applicable to another group of
smokers. --a a more recent experiment, Gritz,
Baer-Weiss and Jarvik (84)
have studied a further 12 smokers. The cigarettes
used were the subject's
0 `M brand Snd were standard, full-length
cigarettes; "proximal" cigarettes,
cut to onz-half length; or "distal" cigarettes,
irarked with a red line
half-way d:wn. The number of cigarettes given was
the same number the
subject us-.ially smoked. Subjects abstained from
smoking for the first
day and then on alternate days. On each "smoking"
day they were given a
different cigarette type. Subjective evaluations
of cigarette "strength",
and "satisfaction" were positively related to the
amount of nicotine
obtained from each cigarette type. A comparison of
"expected" nicotine
~j -I;i _- I -I.
".7
Jf-
C)
C-D
Qn
U1
(-n
BATCo document for Province of British Columbia 5
November 1999


-35-
(estimated nicotine presented to the smoker) and
"extracted" nicotine
(actual nicotine recovered in the urine) was made.
This showed that
subjects extracted proportionately more nicotine
from the half-length
cigarettes than from the whole cigarettes. Figures
for "extracted"
nicotine indicate, however, that subjects did not
take the same amount
of nicotine from the shorter cigarettes as from
the whole cigarettes.
Subjects ex4.1ctad,87X',of-'thiNhole
"proximal" cigarettes and 621 from the "distal"
cigarettes.
f -,Yink 46 Jarvi. (200) Jhayq! Jnyjikt1gaEedf
Stolerman, Gold gxkj
effect of two drugs on cigarette consumption.
Mecamylamine is a drug
which blocks the central actions of nicotine and
it caused an increase
in the number of cigarettes smoked and number of
puffs taken. The
increase in number was 301 but this is COY over a
period of two hours.
subject' ied to overcome the
IC19 thought that smokin increa ed as t9, t;
blocking effect. Pentolinium, a drug inhibiting
peripheral actions of
nicotine, had very.-lit tle - effec t.:on
leigarette cofflatiftiptibb -and- n11fhbWfONr
puffs taken. The authors conclude that this study
supports the hypothesis
that the desired effects of nicotine are on the
central nervous system.
They say that there is a small but clearly
demonstrable role for nicotine
47 ~ as a primary reinforcer of the smoking habit.
Goldfarb, Gritz-, Jarvik
and Stole-man (78) have also 3tudied the effects
of tar and nicotine
deliveries on subjective reactious and consumption
of cigarettes. In
their first experiment 20 subjects were asked to
smoke their own brand
(0.7-1.7 mg nicotine) for one week. Subjects then
smoked low nicotine
cigarettes (0.26 mg nicotine) and a control
cigarette (1.34 mg nicotine)
for a week each. These were commercially available
cigarettes. Low
U
0 0_1
Ln
C)
CD
cc
nt for Province of BritiSh COluMbia 5 NoveMber
1999
BATCo docuMO


-36-
delivery cigarettes were rated lower for
"strength" and "satisfaction"
than the control or usual brand. There was no
significant difference in
number smoked between control and low nicotine
cigarettes. in a second
experiment, on 15 subjects, six experimental
cigarettes -ere used. These
had three nicotine levels (0.39, 0.77 and 1.36 mg)
and two tar levels (8.8 and
15.9 mg). The first week the usual brand was
smoked. For the next
three 'weeks ~i arette A r e., k d,,one
nlcotin~,A,fa-
level each week. The mean number of cigarettes
smoked fell as the
nicotine delivery increased, independent of t~Lr
levels.' -"Strength" Aet5
xii; i
related only to nicotine level and "satisfaction"
ratings were not
related to tar or nicotine. Urinary nicotine
concentrations were determined,
and these were proportional to nicotine content of
the cigarettes.
Complete compensation was not, therefore,
demonstrated. Urinary nicotine
concentrations were not, however,-'as
'fi'1`gTrM16'%tjld'NivZ' 'bee`n~_e76pec"te_d :.
from machine-smoked deliveries. This gives some
evidence for the role
of nicotine but it is interestinkthat low
uicotiag,~;&,arpttp
rated as less "satisfying" in experiment 1, when
the brand was knob.
Brand image may therefore play a part in
determining subjective reaction.
Taken as a whole the results given in this
section, from a number
0 f authors, seem to indicate that nicotine does
play a part in detet,.ining
smoking behaviour, but it is by no means the only
factor involved. In
most of the experiments mentioned it seems
possible that the choice of
both subjects and cigarettes has influenced the
results to a large
extent. It seems reasonable to assume that some
people will be more
affected by manipulations involving nicotine than
others and this is
discussed further in the section on motivation. In
most cases the use
of cigarettes delivering less than 1.0 mg nicotine
(machine smoking)
L4
L4
Cb
\0
V1
CD
C)
(-"I
~Jrl
V1
11 C
1 Z
BATCO document for Province of BritiSh ColUMbia 5
Novernber 1999


i4 n_
LI!Z1
e-r,. 7PF
does not induce the "expected" reaction from
subjects in terms of
increase in number of cigarettes smoked. one
explanation is that, if
the nicotine available in a cigarette drops below
a certain critical
level, then subjects tend to "give up" and they
rate ~he cigarettes, in
many cases, as unpleasant or unsatiqfactory. As a
general rule subjects
are more sensitive to increases in nicotine
content of cigarettes than
r totdMdan1r1tA-tiT5 M-f adJustmAE*_a-'-bzfiokihg
EM opp -
"*%,d 6 U~.P~f
t-, 4- . N.
V, UE
of cigarettes. This may indicate that the
"nicotine adjustment mechanism"
is more suited to re~uc
~Dgpjcotine intake (.here the nicotine is taken
from a cigarette), than increasing it. Some of the
reasons why the
administration of nicotine by intravenous
injection or by capsules and
chewing-g,= is not "successful" in decreasing
smoking to any great
extent, are covered in the next section.
It can be said at this point that the available
evidence does not
support the conclusion that smoking is
specifically an addiction to
...nicotine and -thA"911-dt -Mvenl mbst-48mokers
will. regut,ste--;their--intake--rof--
the drug to provide constant amounts.
2.4 Comparison of Cigarette, Pipe and Cigar
Smoking
There seem to be a number of differences bet*,;een
cigarette, pipe
and cigar smoking in terms of physiological
effect, the people who smoke
one type of tobacco product or another, and the
motivatien fcr each type
of smoking. People who smoke cigars and pipes and
who have never smoked
cigarettes regularly, rarely inhale the smoke, yet
cigarette smokers who
change to cigars or a pipe often continue to
inhale (171). Cigarette
smokers are rarely as satisfied with non-inhaled
cigar smoking as with
inhaled cigarette smoking. Yet. as Jarvik has
pointed out (105),
L4
L4
0
CZ)
CD
U1
Ln
BATCo document for Province of British Columbia 6
November 1999


-38-
cigarette smokers who work for long periods of
time in an environment
where smoking is forbidden (like a lumber mill or
coal mine) may take to
chewing tobacco as a substitute. There are no data
given, howevert on
the extent to which this becomes a habit in its
own right or how much it
is used because it is thought to be better than
nothing at all.
Armitage (7) has said that, although a cigar
smoker does obtain a
dose of nicotine even if he does not inhale,.it is
open to ubt ._wh#_Wr.*WL- -*POW
Ico _~ 'a scr
enough n! Tin! M6. ""a 96 'bed into the
bloadstream quick y enough to give
the pharmacological effects which an inhaling
cijitretieM;Zker would
experience. Russell has said (171, 173) that lie
believes much of the
depend enc e -producing potency of nicotine in
cigarettes to be due to the
extremely rapid "intravenous-like" effect
following inhalation. The
slo.er effect after buccal absorption may be less
dependence-prcducing
and more like that,of alcohol or barbiturates
taken b~ mouth:" RUs-sell
believes that smoke from small cigars and
air-cured cigarettes (both
with alkaline smoke which enables buccal
absorption of nicotine to take,,
place) is inhaled more often than that from pipes
and large cigars.
This he explains by saying that small cigars
contain too little nicotine
to induce an appreciable effect by slow buccal
absorption. He believes
that inhalation of cigarette smoke produces a
bolus of blood containing
a nicotine ccricentration many times higher th2n
nicotine administered by
other routes, this reaches the brain quickly after
each puff (173).
This atay have special effects and once the
nicotine bolus has been
experienced the effects of nicotine in any other
form are not sufficient.
Multiple intermittent dosage probably leads to
higher nicotine concentrations
in the brain and bas a greater pharmacological
effect (at least in
animal experiments) than continuous administration
of the same dose over
the same period (9).
L4
L4
C) C__
110-
C)
Ln
C)
BATCo document for Province of BritiSh Columbia 5
November 1999


-38-
cigarette smokers ho work for long periods of time
in an environment
where smoking is forbidden (like a lumber mill or
coal mine) may take to
chewing tobacco as a substitute. There are no data
given, however, on
the extent to which this becomes a habit in its
own right or how =ch it
is used because it is thought to be better than
nothing at all.
Armitage (7) has said th.1t, although a cigar
smoker does obtain a
dose of nicotine even if he does not inhale it is
open,
e
u i a
no &h nicot ~ne bso~bed int-'. the bloodstream
quickly enough to give
~he pharmacological effects which sajnhaling
cigarette smoker. would.
experience. Russell has said (171, 173) that lie
believes much of the
dependence -producing potency of nicotine in
cigarettes to be due to the
Z -51
extremely rapid "in t ravenous- I ike" effect
following inhalation. The
slower effect after buccal absorption may be less
dependence- producing
__and more like that of alcohol or barbiturates
taken by mouth. Russell
believes that smoke from small cigars and
air-cured cigarettes (both
with alkaline smoke hich enables buccal absorption
of nicotine to take
NA .1 - I - - - . - .. - . . A-
place) is inhaled more often than that from pipes
and large cigars. .
This he explains by saying that small cigars
contain too little nicotine
to induce an appreciable effect by slow buccal
absorption. He believes
C
UO
L4
L4
0
that inhalation of cigarette smoke produces a
bolus of blood containing
a nicctine concentration many times hicher than
nicotine a&,.inistered by
other routes, this reaches the brain quickly after
each puff (173).
This may have special effects and once the
nicotine bolus has been
experienced the effects of nicotine in any other
form are not sufficient.
Multiple intermittent dosage probably leads to
higher nicotine concentrations
in the brain and has a greater pharmacological
effect (at least in
animal experiments) than continuous administration
of the same dose over
the same period (9).
Ln
CN
BATCo document for Province of British Columbia 5
November 1999


-39-
Certainly the amount of nicotine (and carbon
monoxide) absorbed
during cigarette smoking depends to a large extent
on inhalation.
Armitage et al. (8) studied smokers and
non-smokers who smoked cigarettes
spiked with 14 C nicotine. They found that smokers
who inhaled retained
82-92X of the nicotine in the mainstream smoke.
Non-smokers (who
pre-abLy were less likely to inhale deeply)
exhaled from 34 to 701 of
the mainstream nicotine. Ejrup suggested in 1965
(59) that the
concentratibna'of nicotine in the~relptratory
system may produce the
effects sought by smokers.
It has not yet, however, been proved that there
are clear cut
CV-1 differences in local nicotine concentration
in the brain from cigarettes
and cigars. It does seem logical to assume these
differences exist,
but, as yet, no experiments have been published in
which simultaneous
arterial and venous blood nicotine concentration
has been determined, at
sufficiently short inter-vals to detect any
nicotine "boli" which may
be present. It is also somewhat difficult to
explain the resultsof
k
experimenta designed to study the effects of
intravenous nicotine on
smoking. In the study by Lucchesi et al (133)
intermittent administration
of nicotine was slightly more efficient in
reducing cigarette consuL-Ption
than conti.~-_,ous administration. The effect
-.;as not large however.
Russell's e~~;eriment using intermittent
admirlstration sho.ed little
effect on sucking. Russell has said (40) that the
lack of effect on
s=king may have been due to dilution of the
"bolus". Blood from the
lungs goes direct to the brain (in about 7.5
seconds) whereas blood from
an injection in the arm would travel further and
take longer before
reaching the brain (13.5 seconds) (170).
Experiments in which nicotine
chewing-gum is used are probably more
representative of cigar or pipe
C;N
CD
V1
U1
CN
C:~
BATCo document for Province of British Columbia 5
November 1999


-40-
smoking than cigarette smoking, since the nicotine
is absorbed slowly
through the buccal mucosa.
It seems that inhaled tobacco smoke probably
produces different
effects from smoke held only in the mouth but
rzore work is necessary
before the exact differences are defined. Some of
the publications on
motivation are relevant to this point,
particularly that of Marcovitz
(135) in-MM ii'A'sEussed in a 'later 16eceiofi.
U
0
C)
(-n
Ln
C\
C)
BATCo document for Province of British Columbia 5
November 1999


-41-
3. THE EFFECTS OF SMOKING AND NICOTINE IN HUMAN
SUBJECTS
These effects can be divided into three general
categories:
1. Physiological effects e.g. on biochemistry,
heart rate,
electroencephalogram.
2. Psychological effects e.g. subjective reduction
of tension
under stress.
3.. Rffects,on performance e.g.
id-sitaulat6d-drivintIT441:
There are obvious overlaps in any system of
categorisation. Presumably
1. After-,*.;
ca
the basis for all effects mediated by nicotine is
phy;iol.g
a number of experiences with smoking, however, the
effects may appear to
be largely psychological. If the smoker learns
that smoking calms him
down in certain circumstances it may, therefore,
do so independently of
nicotine effects, by a conditioned response
reaction. Here factors such
jk'j~ .,S~
as merely ha~dliog a cigarette and watching the
smoke may be important.
Effects on pirformance are probably the result of
both physiological and
It is obviously not possible to consider all the
studies on the
effects of nicotine and smoking and a large number
of them have been
reviewed by Larson, Haag and Sil~ette (123, 124,
125, 126). Some are
covered here as an introduction to some of the
ideas -which will be
included in the section on smoking motivation.
3.1 Physiological Effects
Cigarette smoking and nicotine cause physiological
effects on both
central and peripheral structures in the body. For
the purposes of
simplification the effects are discussed here
under two headings:
(a) The effects on brain activity.
(b) Other effects, including peripheral effects.
U
U
0
V1
Cb CD
Lri
BATCo document for Province of British Columbia 5
November 1999


-42-
(a) Effect on brain activity
A number of studies have been Published in which
the acute effects
of s.oking on the human electroencephalogram (EEG)
have been investigated.
Many of these studies on the "resting" EEG have
been reviewed in a
previous report (44). A summary of much of the
work on the EEG and
smoking and nicotine is also given by Murphree
(148). The effects of
smoking on the background EEG and simple evoked
responses (to sounds a.nd
light flashes) are usually interpreted as being
atimu'lant"in nature.
The results of two studies, one on humans (61)
and.peoa a uirrel,
monkeys (38) suggest that smoking induces arousal
which is similar to
that seen under normal alerting conditions. It has
been suggested,
therefore, that nicotine may stimulate the normal
arousal pathways by
acting on the mid-brain reticular formation (38).
Two studies on the effects of.smoking after
deprivation have also -.W
shown stimulation of brain activity. Ulettt Itil
and their colleagues
(210, 102) found that the slowing of the EEG
activity after deprivation
I., - 17 '" A x _0 -
was reversed by smoking. The results of a recent
study by Knott and
Venables (117) also showed that deprived smokers
had slower alpha EEG
frequencies than non-smokers or non-deprived
smokers and that their
alpha frequency was increased by smoking. This
effect lasted at least
fifteen minutes. Non-deprived smokers, however,
shoved no change in
alpha activity after smoking and it was thoughc
that this way indicate a
degree of tolerance to the stimulant effects of
smoking.
Some experiments on smoking and the EEG have shown
that the effects
seen are not always those of stimulation. A small
study conducted in
Group R. D. Centre on the alpha rhythm (a
component of the normal EEG) (44),
(A
CD
~_n
Un
0%
BATCo document for Province of British Columbia 5
November 1999


-43-
did not show stimulant effects in all subjects.
The results could
be interpreted as indicating that cigarette
smoking enabled subjects who
are given information about their own alpha rhythm
prodLction, to alter
their brain activity in a way which they
considered to be desirable.
Friedman et al. (70) have also studied the alpha
rhyttim as an indication
of the ability to ignore distracting noises. (The
alpha rhythm disappears
V
when attention is~ paid to di 9 traction'
t~Mtl;IFTM ~~Kualtl!!M.
the stimulus has occurred.) They found that
nicotine-containing cigarettes
decreased the time taken by subjects to habituate
to (or ignoreY afetracting
stimuli.
OR Experiments on one particular aspect of the
EEG, the contingent
negative variation (CNV), have indicated that some
subjects appear to be
stimulated and some sedated by smoking. The
authors of one of the
stidief,' Ashto'~,' Tho~p;on and their colleagues
(10, 11) believe that
nicotine acts as a stimulant in small doses but
that it is a depressant
in ere is- evidence fthltlfill?`II~Tfie caser'
in'~~'Imals (9).
Ashton et al. related a depressant effect on the
CNV to a high rate of
nicotine intake per unit time in introverts and a
stiiriulant effect to
low rate of intake in extraverts. Several
aiithors, bo-,;ever, believe
C. that the doses of nicotine taken during smoking
would be in the sti=ulant
range (e.g. 207). The other study on smoking and
CNV was conducted at
Group R. & D. Centre (39, 45), and yielded results
similar to those
published by Ashton et al. The apparent effect on
the CNV (depressant
in some subjects and stimulant in others) was not
related in this study
to total smoke volume taken from the cigarettes.
However subjects
showing any significant changes in CNV (stimulant
or depressant) took
Q_J
C:)
C)
Un
0%
nt for Province of British Columbia 5 Novernber
1999
BATCo docurne


-44-
larger volumes of smoke than those showing no
change. This suggests
that the type of effect is independent of nicotine
dose. The hypothesis
which is favoured to explain both sets of results
is that nicotine
always acts as a stimulant but the effects seen
depend on the initial
arousal state of the subject. Other smoke
components could also have an
effect but nicotine is the most likely agent which
would cause a stimulant
effect on the brairr.- Carbon InonoXV19"hibb!
have a depressant effect on the CNV (85), but the
effect of levels found
after smoking cigarettes would be small.
Eysenck (60) has suggested that the effects of
nicotine depend on
the degree of cortical arousal which is a function
of (a) personality
(especlally extraversion-introvergion) and (b)
external conditions at
the time (for instance presence of stimulation).
The effects of nicotine
posit ve ';ati,e*and nicotine would therefore
be'uni4uely
could be i or ne
reinforcing as it would tend in all conditions (in
suitable doses) to
lead to a shift-in arousal -towards ~ the -optimum
-for-'a ~giVen -- activity,-
The evidence does indeed suggest that although
nicotine is predominantly
'a stimulant it may lead, under some
circumstances, to effects which are
apparently those of a sedative. This is borne out
by subjective impressions
of s-mckers (see psychological effects).
it is not known if the effects of nicotine on the
brain are direct
or indirect, but they may be a combination.
Nicotine readily passes the
blood-brain barrier and reaches the brain very
quickly if smoke is
inhaled. It is known that nicotine releases
acetylcholine in the brain
and this is a transmitter substance. Russell
believes (170) that this
may cause effects in the cerebral cortex for up to
two hours which may
L4
L4
03
\40
C)
Un
011
__1
CC
BATCo document for Province of British Columbia 5
November 1999


-45-
be impor:anc for light smokers. The short-lived
effecc due to acetycholirle
releas is, however, likely to be important to most
smokers and probably
affects t-'-e hypothalamus and reticular
activating syscem of the brain.
Nicotine also causes or facilitates release of
noradrenaline in the
brain and it is this which Jarvik (105) believes
is important to smokers.
W Other effects
The basis for t~a per ipherq4raffeatVof smokifig
41-M&T.Rr.
AW4,
T
primarily *3iochemical. Nicotine causes release of
adrenaline and
is predominantly
noradrenalLne from the aa~enal glan a. The effect
of this
stimulant. Blood sugar is increased as glucose is
released from glycogen
stores, blc-cd free fatty acid levels are raised,
and hydrocortisone is
released. Hickey and Harner (93) have suggested
that nicotine may be
used by some people to correct an inherent
bioenergetic deficiency, via
the release of glucose.
Smoking one to two cigarettes increases resting
heart rate by 15-25
beats per m.,ute, blood _Pres.s_ure..by-.tlO-20 ma
mercuryi's~i',51'lc ano'3-15 mat
mercury dias:clic, and cardiac output by about 0.5
litre/minute/square cm (185).
At the sa=e time as this stimulant reaction to
nicotine, stomach
contractions are inhibited and the patellar reflex
(knee-jerk reflex) and
electromyelcg:-aphic (muscle) activity are
depressed, a relaxation type of
response.
Franken'-zeuser, Myraten and Post have done a
number of experiments
relating catecholamine release and increase in
arousal to cigarette smoking.
rn one study (67) they investigated the effects of
smoking two, four
and six cigarettes in two hours. They found that
blood pressure, and
NA
C:)
VI
C)
BritiSh Columbia 6 November 1999
BATCO document for Province of


-46-
(A
skin temperature (which decreases due to
vasoconstriction), were most
affected by the first cigarette (after overnight
deprivation). The
second to sixth cigarettes caused progressively
smaller changes. Urinary
adrenaline rose continually as the number of
cigarettes increased but
noradrenaline increased only for the first two
cigarettes and was
unaffected by further smoking. Heart rate
increased until the fourth
Sm.
cigarette. In another experiment (66)-a control
~condltion (non-smoilnij
was compared with smoking,either two high nicotine
(2.3 mg) cigarettes
k
or two medium nicotine (I-i mg) cigarettes. The
higher doses of nicotine
which were presumed to have been taken from the
high nicotine cigarettes
produced larger and more persistent changes than
those from the lower
nicotine cigarettes, although these also had a
proaounced effect. In
later stud,es these cha ges were,related to
smoking under different
Pq_
conditions and to performance (see later). The
effects of smoking on
heart rate as related to the reactions of subjects
to stress are also
mentioned later.
The effects of smoking on patellar reflex have
been studied by
Isaac and Rand (100). They found the depression in
the reflex as more
pronounced in ncn-smokers (after smoking) and
light sr-.-kers than heavy
smokers. A high nicotine cigarette caused the
depression in more
subjects than a low nicotine cigarette. Domino and
voa Baumgarten (54)
also studied smokers (divided into three
categories depending on
cigarette consumption) and non-smokers. They used
a lettuce leaf
cigarette and two different tobacco cigarettes
(0.8 mg and 1.69 mg
nicotine). They found no differences between
smokers and non-smokers in
depression of patellar reflex after smoking. The
depression was not
CD
C)
V1
Ul
C__
BATCo document for Province of British Columbia 5
November 1999


-47-
seen with lettuce ci&arettei or sham smoking and
the higher nicotine
cigarette had more effect than the lower nicotine
cigarette (67% vs 457
depression of reflex). Nicotine in an aerosol also
caused depression of
the reflex. These results indicate that the
effects seen are almost
certainly due to the nicotine in cigarette smoke.
3.2 Psychological Effects
ftr dis-cu-sse?"in"th"is *"?000
section may be said to fall broadly into the
"psychological" category.
Much of this work concerns the reactions of
sG6kers and non-~6imok,;r-s~-'t.
stress and the way in which smoking behaviour can
be related to external
stress and internal arousal.
Eysenck has hypothesized (60) that since
extraverts are cortically
under-aroused they would smoke primarily for
stimulation, while introverts,
being cortically over-aroused would smoke mostly
for sedation. There
have been several studies in which this
hypothesis, and the more general
"feVIIi imolei more~le9s cigarettes under
one thif RffAent -f-eop or
different conditions, have been tested.
Frith (72) constructed a questionnaire in which
subjects are asked
to imagine themselves in various high- and
low-arousal situations. They
are then asked to indicate their desire to smoke
la these situations.
If nicotine is mostly a stimulant then people
should feel the need to
smoke in low-arousal situations. If nicotine can
act as a depressant
there should be a desire to smoke in high-arousal
situations. When the
questionnaire was administered it was found, on
average, that the low-
arousal situations induced more desire for
cigarettes than did high-
arousal conditions. This is consistent with
stimulant action of nicotine.
CO
C)
CD
Q1
BATCo document for Province of BritiSh Columbia 5
November 1999


-48-
Heavy smokers, however, showed a desire for
cigarettes on all occasions.
Men wanted to smoke more often in situations of
boredom and tiredness
(low arousal), whereas women indicated their
greatest desire to smoke
when under stress (high arousal). This is
difficult to explain in terms
of the original hypothesis that smoking behaviour
is determined by the
smokers characteristic level of arousal, since
women are not chronically
tt IMA 91 -7,,
*TbocrlM~~ ~,han men. Frit*h concluded that i?omen
may inhale less ana"
not be influenced by the pharmacological effects
of nicotine but they
may iAse the ritual of lighting and puffing on
cigarettes to calm themselves
stressful situations.
Myrsten and her colleagues (150) selected two
groups of male
smokers from a questionnaire based on Frith (72)
and McKennell (140) (see
later). The high- and low-arousal smoker groups
were chen.vtudi~j~.4poking
- -I- 4f
and not smoking in high- and low-arousal
experimental situations. The
results support the assumption that different
smoking habits are related
"specrfIc'difter ~es in the effects of smoking.
There were
no differences in performance of the high- and
low-arousal smokers, in
either arousal sit uation, when not smoking, but:
differences in performance
efficiency and subjective arousal were seen during
smoking. These
differences reflected the smokers' usual smoking
habits in terms of the
situations in which they would normally have
smoked.
Bartol (16) has also used the Frith questionnaire
when studying a
panel of 40 female subjects who were grouped as
neurotic extraverts,
neurotic introverts, stable extraverts and stable
introverts. There was
no significant difference in cigarette consumption
between groups and,
contrary to Eysenck's hypothesis, extraverts
showed a desire to smoke in
tA
LA
0
C:)
Ul
BATCo document for Province of British Columbia 5
November 1999


-49-
stressful situations and introverts in
non-stressful situaticns. Non-
prescription drug and coffee consumption were also
investigated. It
was found that extraverts often took coffee and
drugs together with
cigarettes. Introverts smoked or drank coffee in
non-stress situations
and tended to take tranquiLlizers when under
stress. The author concluded
that the situation with regard to smoking was very
complex and may be
confounded by the use of othei drugs.
Fuller and Forrest (73) hypothesised that it
should be possible to
manipulate amokini'by manipulating level of
arousal by exte'r'n'al means.
f1371-3; It was expected that nicotine would be
self-administered at a higher
rate by smoking in low-arousal conditions. 40 male
and 40 female smokers
smoked or simulated smoking in high- and
low-arousal conditions. In the
high-arousal situation heavy smokers (over 15
cigarette.~'Rerdayj._smoked
at a lower rate than in the low-arousal situation,
but obtained the same
dose of nicotine. There was no difference in
simulated smoking. All
subjects tended to smoke and simulace puffing less
during high arousal
(watching a stressful film) and may just therefore
tend to smoke more
-hen there is nothing to do (the low-arousal
condition involved relaxing
alone on a couch).
In a rather different type of experiment, Glad and
Adeqso (75)
attempted to determine the relative contributions
of tension reduction
and "behavioural contagion" to the instigation of
smoking behaviour.
The subjects were 72 males and 72 females divided
into heavy smoker
(over 15 cigarettes per day) and light smoker
(under ten cigarettes per
day) groups. They were placed In high- or
low-arousal conditions with
o3 other individuals who either all smoked or all
did not smoke. The
(A
L4
0
L-4
C)
C)
V1
Un
BATCo document for Province of BritiSh Columbia 5
November 1999


-50-
condi-.:-cns were different from those in other
studies in that they were
social in context and more relevant to real-life
situations. Tension
was i::d---ced by making subjects wait for
evaluation of their answers to a
diffic-.At questionnaire. The lo-arousal condition
was one with a
relaxed, friendly social atmosphere. The results
cast doubt on the
importance of cigarette smoking in tension
reduction. There was no
difference in the amount ofA~ng,_in high- and,
low-arousal situations,
or in self-reported anxiety in the tense situation
between those who
.did and did not smoke. The results do, however,
support the observation
that pe-.~ple tend to smoke mainly because those
around them do. This is
especial'.7 true for light smokers, but even heavy
smokers, who tend to
smoke in =ost situations anyway, increased their
number of cigarettes
and of puffs taken, when others ere smoking.
Anno-.!2er approach'has been to look for mood
changes after smoking~
Agug (3) gave 24 male subjects a mood adjective
check list (M.A.C.L.) (155)
and ac~_`.ation scale questionnaire. Different
nicotine content cigayettes
were the:t smoked. For all the M.A.C.L. factors
only "pleasantness"
was cor-ziated with nicotine delivery. For the
activation scale (an
which a subject estimated his position between the
extremes of deep
dreamless sleep and extreme fear) it was found
that a decrease in inrer
tensicm was related to nicotine content. This
supports the role of
nicotine as a tranquillizing agent. Heimstra (90)
administered the
H.A.C.L. to smokers who were allowed to smoke on
only sone occasions
during c---plex psychomotor or perceptual tasks or
a highly stressful
film. S=king tended to reduce mood fluctuations
during the experiments
and smokers who smoked showed less mood change
(including aggression)
LA
L4
C)
Ln
Ln
O\
BATCo document for Province of British Columbia 5
November 1999


during the task- than non-smoking smokers or
non-smokers. 7his was not,
however related to performance in the tasks.
Several workers have tried to relate smoking to
aggression.
Hutchinson and Emley (97) have studied biting
movements and jaw-muscle
contraction as an index of aggression. They
presented results for man
and for squ.:rrel monkeys indicating that intake
of small quantities of
7
~
'
`i
nxwd I
-
d
h
l
I
i
i
b
l
W ; z
uct
co t n
on
n
e
av
oura
.
oduc
f e r e
t
a
re
n
erns t
ps
associated -.rith aggressiveness, hostility and
irritability. These
same doses also el~v'ate ifii orienting and
anticipatory reactions. Titus
i~ the impact of aversive events can be reduced
and responses enabling
escape from or avoidance of aversive events are
also facilitated, thus
providing a ;owerful reinforcement due to
nicotine.
Dunn (204) has recently reported some work using a
machine which
~ , , "14- 1--*. --4,J"W"WWW*- ..
"cheats" the subjects of their rewards for
performing well in tasks. He
found that s=kers and non-smokers did not differ
in their displays of
aggression v~_en -but Oac 51. s'*howed less
decrement
in performance, due to agression, than deprived
smokers or non-smokers.
This suggests that smoking does not control
aggression as such but
minimizes its effect. Russell (173) has, however,
quoted the work of
Schechter and Rand (190) which indicates that
smokers deprived of
cigarettes are more aggresive in terms of
questionnaire answers and
behaviour in administering electric shocks to
other people. Smokers,
especially those with high cigarette consumption,
also tend to have high
chronic "anger" scores on questionnaires (203).
Nesbitt (152) has conducted a study with 30
smokers and 30 non-
swokers to measure their "emotional" responses to
electric shock.
L4
(A
C) (-n
CO
\0
CO
C)
C)
BATCo document for Province of British Columbia 5
November 1999


-52-
He recorded absolute threshold (when the shock is
first detected), pain
threshold (when the shock first becomes painful)
and endurance threshold
(when the shock is too painful to bear). The
measure of "emotion" was
the number of shocks of increasing magnitude that
a subject could receive
-before the endurance threshold. It was thought
that if smoking was
.stimulating then. as arousal increased, this
threshold may decrease, or
that if smoking was tranquilizing theii
smoking's.okers s~o`
1. - -It
take more shock than rion-smoking smokers. Both
smokers and non-smokerm
smoked a high (1.6 mg) nicotine or low (0.3 mg)
nicotine cigarette or
puffed on an unlit cigarette. It was found that
smokers who smoked
could take more shock than they could if they did
not smoke. This
effect was greatest if high nicotine cigarettes
were smoked. This was
not found for smoking and non-smoking non-smokers.
This indicates aa
intir'Mion ok-trabitual smoking and the acute
effects of nicotine. The
results are difficult to explain since smokers and
non-smokera differ in
_t,~j Lz~jit~~q tion ye t . nico t ine leve I -
appears' to - Ve' 1663 ~ tant for"'emoke rs.
One plausible explanation is that since smoking
increased arousal in a
similar way to the shock (as measured by heart
rate), the smoker attributes
his arousal to the cigarette alone and is not
alarmed by the shock. For
the non-smoker who smokes, however, the increase
in arousal due to
nicotine is unusual and way be attributed to the
shock, thus lowering
the threshold (there was a tendency for threshold
to decrease with
nicotine content for smoking non-smokers). Thus
the physiological
effects of smoking do appear to be important for
the "emotional" (psychological)
calming effects of smoking in experienced smokers
but in the opposite
direction to that expected on the basis of arousal
due to nicotine.
09
CA
L4
0
C)
C)
Lrl
O\
011
BATco document for Province Of British Columbia 5
November 1999


-53-
L4
cc
110
(_n
C)
CD
VI
LTI
ON
Finally in this section two studies can be
mentioned which indicate
that smoking is used to decrease stress. Pincherle
and Williamson (161)
found, that in a largle sample of medical
patients, heavy cigarette
smoking (over 20 cigarettes per day) was more
common in those patients
judged to be under excessive stress than in
non-stressed patients.
Lindenthal, Myers and Pepper (131) found a direct
relationship between
life stress and "psychological imp#irmgIttU,
The_7s-*o,.P
relationship between smoking and "psychological
impairment". increases
in smoking varied directly with psychological
status A~ir*t4 'the nature anil-
quantity of life stress. Thus smokers of a given
psychological status
have smoking rates associated with particular
numbers and kinds of life
crises. These data lend support to the role of
smoking as an aid to
coping with crisis.
3.3 Effects on Performance--
Some studies in which performance has been
measured have alread7
been mentioned bri~,.fy .. The studie S.Rq# ide
red J2k3;r,.9.pLy,,4W.Uwt&d&
small proportion of those in which some aspect of
performance in a task
has been recorded before and after smoking.
Heimstra and his colleagues (91) have found that
smoking can prevent
deterioration in a s=okers' performance in a
simulated driving task.
Ashton and her colle2gues (12) have also looked at
simulat.ed driving and
found that smokers had shorter reaction times in
some tests than non-
smokers, only if smoking was permitted
(non-smokers did not smoke). No
differences were seen when the effects of high
(2.1 mg) and low (1.0 mg)
nicotine cig arettes were compared. This would be
expected since the
average nicotine taken from each of these
cigarette types was nearly the
same (from results of butt analysis). Tarriere and
Hartemann (202)
BATCo document for Province of BritiSh Columbia 5
November `1999


-54-
investigated the performance of smokers, deprived
smokers and non-smokers
in a visual vigilance task. Smoking was found to
prevent performance
decre.enr. Smoking smokers performed better than
non-smokers and introverts
better than extraverts. Thus, introvert smokers
performed best, showing
little decrement in performance during the
two-hour test and extravert
non-smokers showed the largest decrement.
Frankenhaeuser and her
,,4olleagues (6fi).bave founO.that,j;,,Whsr level
oG-ip* Oc*cy~f#
be maintained in some parts of vigilance tasks if
smoking is allowed.
Some recent experiments conducted by Warburton and
Weisnes (218) have
also shovn that smoking and nicotine affect
performance in vigilance
les
tasks. Nicotine given on tablets which were
dissolved in the mouth
improved performance of both smokers and
non-smokers with a long vigilance
task and an intensive visual search task. Further
experiments showed
that"~'~if;'rmance was less efficient in
nori::smaker. folloZ M~ the' irorq"~~'
of three nicotine doses in the vigilance task.
Equal improvements in
---smoke -nicotias
Performance _werejs~en for _Iigh~.And qYy X,9_&4
mg
tablets. Heavy smokers also improved their
performance when given a
high nicotine (1.65 mg) cigarette, relative to
performance after a low
nicocine (0.3 mg) cigarette. There are some
indications that neurotic
C subJects show smaller performance decrements and
are more sensitive to
the effects of nicotine and smoking.
L4
Tong and his colleagues (207) have found that
reaction times in
tasks are decreased by noise distraction only if
smokers do not smoke.
This is in accord with the results of Friedman et
al. (70) on brain
activity and distraction which have been mentioned
earlier.
Andersson and Post (6) have tried to ascertain
whether smoking
affects learning in human subjects since it seems
to impair short-term
CO
U-4
CD
CD
Ln
Ln
C__
BATCo document for Province of BritiSh Columbia 5
November 1999


-55-
memory and facilitate long-term memory in rate.
First they looked
at 12 male subjects and found that smoking has an
initial detrimental
effect on learning of nonsense syllables. The
number of correct responses
decreased after the first nicotine containing
cigarette (compared with a
nicotine-free cigarette) but the second cigarette
reversed this trend.
Learning was then more improved by a nicotine than
non-nicotine cigarette.
'Ifffere in 11 ..,'b'*e"`re'late4 to the level of
arousal during
T
he nces reca
the experiment. The impairment of learning lasted
for about 30 minutes
during which arousal due to 'smoking
wi-as"h"ighest (as measured by heart
rate). The second cigarette produces a smaller
change in heart rate
than the first. In a further experiment on ten
subjects, similar results
were obtained by Andersson (5). There was a
temporary impairment of
learning after a cigarette. This was probably due
to inc:~jpased apusal
during learning since long-term recall (after 45
minutes) was improved
if smoking was allo,ed. At this later time the
increased arousal due to
smoking was no longer present. It is thought that
the cigarette affects
learning and recall only by altering arousal level
which has different
effects on the different aspects of information
processing.
L4
Lq
Q:)
CC
\C
Cr!
CD
Uri
Lrl
BATCo document for Province of British Columbia 5
November 1999


-56-
4. D77FERENCES BETWEEN SMOKERS AND NON-SMOKERS AND
BETWEEN SMOKERS
OFF DIFFERING CIGAfLETTE CONSUMPTION
As -ith other sections in this report this topic
cannot be considered
in isolacion and it may be related to both effects
of smoking a~d motivation.
The differences between smokers and non-smokerg
can be broadly divided
into three categories:
(a) Physiological differences
(b) Psychological differences
(c) Social differences
Once again the literature is extensive but an
attempt has been made
to refer to some of the most interesting studies
and those not adequately
covered in reviews of the subject. The papers will
mostly be considered
in chror.:Icgical order.
One -iroblem in discussing differences between
smokers and non-smokers
and smck=-:s with differing cigarette consumption
is to decide wbether-'
the diff2rences are intrinsic and present before
smoking started (the
"cons tit---: ional" hypothesis), or are "caused"
by smoking. Some physiological
differences between smokers and non-smokers are
included under the section
on tolera7ce to nicotine if they seem most likely
to be "caused" by
smoking. other differences which are less easy to
define are included
(A
LA
0
VI
in this section and some indications are givcn, if
these differences
are cons_:,_:ered to Support the "constitutional"
h~,pothesis. Where there
are indica:ions that one or other case may be true
the picture is often
considera'_-Ly confused by differences in the use
of other drugs by smokers
and non-s---ckers. This is discussed further in
the section comparing
smoking and other drug use but it may be noted
here that several studies
have shown that smokers and non-smokers often
differ in consumption of
tea, coffee and alcohol as well as other drugs
(108, 142, 203).
Q~-
C__
CD
CD
Ln
U11
CN
N)
BATCo document for Province of British Columbia 5
November 1999


-57-
4.1 7hysialogical Differences
In 1963 Seltzer (193) publi'ghed a paper giving
results obtained
from a study of college students which suggested
that there were differences
in a r=ber of descriptors of physique between
smokers and non-smokers
and also smokers with differing tobacco
consumption. Peters and Ferris
(159), however, found no relationship between
smoking and height and
weight4A a larger sample of4q to.. Russell.4168)
has stated-that.
the associations found between body-build and
smoking were probably due
to sa,mpling errors. There are, ~6'1'wey
~r. oFTe indications that adult
,
TAM_ ,w_
smokers tend to weigh less than non-smokers and
that ex-smokers are of
an intermediate weight between these two. Russell
(173) refers to che
work of Lincoln (130) who found that smokers are,
on average, 6.5 lb
lighter than non-smokers, although they take in
about 350 calories per
clay more than oon-smokers. The differences in
weight tend to increase
with age and men over 40 years of age who have
never smoked are, on
average, 13 lb heavier than. smokers (Russell
referring to Comstock and
Stone (46) and Kbosla and Lowe (114)). Russell
suggests that the gain
in weight commonly seen after giving up smoking
is, in one sense, a
return to normallry, rather than a manifestation
of oral substitution,
since non-smokers tend to expend calories less
efficiently than smokers.
Jenkins, Zyzanski and Rosenman (107) have also
noted that smDkers
studied at ages from 39 to 49 years had shown less
weight gain since the
age of 25 years although taking less voluntary
exercise than non-srookers.
These differences in weight may be due, at least
in part, to the effects
of smoking on glucose metabolism (93). Differences
in a variety of body
build parameters may be due to constitutional
differences but, for
weight, no firm conclusions can be drawn.
QD
(A
C-4 CO
O\
BATCo document for province of British Columbia 5
November 1999


-58-
A number of studies have been published rhich show
differences in
concentrations of various components of serum.
Among these studies is
that of Jenkins and colleagues (107). They fcund
that, when compared
with non-smokers, heavy smokers had higher serum
cholesterol levels,
-higher concentrations of triglycerides after
fasting and higher hematocrit
readings (percentage of blood volume occupied 5y
red cells after
c '4 1 I&M ~~! '.
e.trT M.Uf=5;~'Whe. fu"r'ther determina on r
obtained four years
after initial measurement., systematic se,rum
lipid differences were found
fA-
between non-smokers who remained non-smokers and
those who
smoking during the four years. These differences
were seen in the
readings taken initially and the overall patte-.
of differences did not
appear to be the result of elevated serum lipid;
influencing smoking
patterns. The data are consistent with the
hypc:~esis that common prior
factors Increase triglycerides and cause smokin;
or the hypothesis that
smoking raises triglycerides. Data for serum
chclesterol and lipalbumin
~6 _11`not't4 'readil -fn "' ."etF --r;T-f "'
31=-1 s,~6keris
:
u y terpr ed. Thomas 20
tended to have higher serum cholesterol levels
thea non-smokers. She
found, in addition, that smokers had higher
resti=g heart rates and
blood pressures. Russell (173), however, has
sta:-2d that smokers as a
group do not have higher heart rates or higher
blccd pressures than
noa-smoker3, although lie gives no references for
this.
As far as other differences of the "metabolic
type" are concerned
there is evidence that smokers metabolize some
types of compounds
differently from non-smokers (89, 126). Beckett,
Gcrrod and Jenner (19)
have investigated the metabolism of nicotine by
male and female smokers
and non-smokers. They gave an injection of
nicotine (equivalent to 1 mg
CO -
\0
Un
Un
nt for Province of British Columbia 5 November
1999
BATCo docume


-59-
nicotine base) and collected urine samples for 24
hours and analyqed
these for nicotine and cotinine. There were no
significant differences
between subjects for the time to eliminate half
the nicotine dose.
Female smokers excreted legs nicotine and more
cotinine than female non-
smokers and gave a higher combined recovery. This
suggests an increase
iu metabolism to cotinine which may be due to
enzyme induction. Male
smokers could bedivided ,into two groups. The~4.n"
E6~ery'!J
excreted less nicotine and cotinine than male
non-s=okers, suggesting
IUMt . b . 11 a m~*ft n' I 9~_t N" eis 6ccurring
an alternative pathway. I The
"high recovery" group excreted the same amount of
nicotine but more
cotinine than non-smokers. This suggests either
iihibition of further
cotinine metabolism or increased metabolism of
nicotine to cotinine due
to smoking. It can be concluded from this study
that there are sex
e I - - ____ _s
dlff~rence sM~ni co tine m'tab~~ ism an~ that
smokers and non D; iers
metabolise nicotine differently. The authors of
the paper believe that
___Gg~k#g.,al.te,r4.,nico tine metabolism~and this
is alao-t-be-view-which-r- %
Russell has expressed (173).
The possibility, however, still remains that t~e
differences seen
are constitutional and only those persons who are
ab*,e to metabolize
nicotine in a "desirable" way become smokers.
Lars~n 3nd Silvette (126)
refer to a study (208) which showed that regular
smc*.-ers metabolise
certain endogenous amines differently from
non-smokers. It was suggested
that these changes were due to chronic exposure to
nic:~tine but the7
were not reversed immediately on stopping smoking.
Russell (173) has
quoted reports which show that smokers tend to
have marginally more
tolerance to various psychoactive drugs. This
could be due to enzyme
tA
L4
0
(A
CD
LT1
Lrl
U4
SATCo document for Province of British Columbia 5
November 1999


-60-
:nduction caused by smoke constituents or to the
tendency for smckers to
-;se more alcohol and drugs in general, thus
acquiring some form of
tolerance to drug effects.
. Another aspect of smoke r/non- smoker
differences has been invesCigated
'Johns (108). He looked at the relationship
between sleep habits and
c'&arette smoking and also obtained information on
alcohol, tea and
c-offee consumption. The subjects were hospital
patients but the data
_*;`V.1rV1eepi-ng__Ih`abxts at home. Among the
males, the- i t.
ec er t
heavy smokers tended to go to bed on average 30
minutes later than non-
r=kers during the week and 40 minutes later at
weekends. This -.,a--
cL-sidered to be consistent with evidence from
personality data on
s=kers and non-sookers. Smoking -as not related to
"poor" sleep. The
a;;zhar suggests that there is a complex
interaction between a subject's
-lif'-style" and use of coffee and cigarettes. The
tendency to stay up
la:-=r at night may be enhanced by nicotine and
caffeine consumption, but
nights allow more time for, and may therefore
encourage, more
'iore'po
thfere -int to
-.,.dy e
spez~
ific differences in sleep habits between smokers
and non-s=kers
wh--'::Ii are directly related to smoking, as once
again there are ccnfounding
fac-_z)r9.
Me final approach to detecting differences between
smokers and
norA-z=okers which will be mentioned here is that
initiated by Brc-.-n (32).
She :ooked at the electroencephalograms (EEG) of a
number of subjects.
Sbe :ien analysed her results and showed
differences in brain activity
bet-.;een smokers and non-smokers and smokers with
differing cigarette
cons-=ption. Her first study indicated that heavy
smokers and non-
smokers differed in their responses to coloured
flickering and flashing
CC
C)
C)
O\
DATCo document for Province of BritiSh Columbia 5
November `1999


-61-
lights ',but noc in a colour-specific manner) and
Brown suggested thit
the differences could be related to fundamental
differences in the
mechanirms underlying brain activity. "Resting"
EEG was also recorded
and aga-:n differences were seen, which together
with the visual evoked
response results suggested that the brain activity
of heavy s.okers was
related ~_-o diffuse attention. The EEG's of heavy
smokers were of a
.P geperally higher frequenv.,,than those of`:p.
JEET i6quency
s~o
.
tends to rise and the EEG becomes more
desynchronized as "attention" is
AMICreasei). The frequency distribution of the EEG
for smokers of "average"
Cigarettri consumption and former heavy smokers
was intermediate betweea
that for non-smokers and heavy smokers. The visual
evoked response
results '-ever suggest t.~at former heavy smokers
resemble heavy smokers
and that "average" smokers are more like
non-sookers.
irol-IM (33) later published more results for a
larger sample of
subjects 'out considering only the "resting" EEC.
The results were
similar.. t~,those in the previous .s tudy-
Non-smokers -again ~shcwed -EEV.
patterns 'z-fpical" of rest but smokers allowed
patterns more indicative
of activa:41on, this being most marked in very
heavy smokers and intermediate
in average- smokers. Brown believes that her
results are consistent with
evidence z',-Iac smokers tend to be more extravert
than non-smokers. she states
that her findings suggest the following
hypotheses:
(a) T~iere is a characteristic family of brain
wave patterns
a constitutional characteristic of heightened
5 rain electrical excitability which may be
associated with a
-undamental physiologic predisposition to the
smoking habit or
some equivalent activity.
Q)
(A C-n
\0
CO
CD
VI
QTI
C71%
rI_I
U-1


-62-
(b) 1here is a positive relationship between
amount of smoking and
degree of brain excitability.
(c) Smoking rate is regulated to maintain
effective balance between
behavioural accompaniments of EF-C synchronization
and
desynchronization.
Some work done in Group R. & D. Centre (42) also
indicates that
there are, EEG differences between smokers and
non-smolCers?", In a lim 11
of 30 smokers and 30 non-smokers matched for age,
sex and personality,
'at
emkers were founVr6-~ave less power in the EEG
than non-smokeri
,
all frequencies considered. The differences seen
are independent of age
and tength of smoking history which either
suggests that the differences
may be constitutional or that changes due to
smoking occur soon after
smoking starts. Smoking does not appear to have a
cumulative effect.
Vhen smokers were subdivided according to
cigarette consumption it was
found that both medium and heavy smokers showed
less EEC power than non-
s~kera but ligh-t.smokers were jadistinguishable
-frozo noa:.!smokersii4W*PMO- ~-
These light smokers may therefore have a different
reason for smoking.
since reduced power of the higher EEG frequencies
in other smokers is
consistent with the effect of a stimulant
administered over a period of
time. This stimulant could obviousLy be nicotine
and its effect would
probably be to "normalise" the EEG's of smokers
and make them more
similar to those of non-smokers. Again it is
possible that the tendency
for smokers to drink more tea and coffee, which
both contain the stimulant
caffeine, may be a confounding factor. It was also
found that extraverts
showed reduced EEG power when compared with
introverts. Thus our results
are consiscenr with the idea that smokers may tend
to be wore extraverted
L4 Q-1
Q__
CD
Ln
Un


CDC7- -_
% -_
-63-
although the smokers and non-smokers In this study
could not be distinguish ed
on this dimension by questionnaire (156).
The results of this study are different from those
obtained by
Brown. Her methods of recording and analysis can
be criticised for a
number of reasons and her results were mainly
determined by subjective
assessment of the EEG. When her results are
recalculated so that they
are si.ilar~n form to chose obtaiaed..Ot Sjftbamp
ton - Lq"Puft
Brown found increased power in the EEG's of
smokers over non-smokers.
i
l'
,
"O
'
i
Ao
ct mat
ut
ure
e in
Comflict
the
ex
The studies juoted here are therefor
of the smoker/ncn-smoker differences in brain
activity. Brown suggests
that smokers have "activated" brain patterns
whilst we suggest that they
tend to be "less activated" than non-smokers. It
does, however, seem
fairly certain that differences in brain activity
do exist and that
tbese differences seem to be inherent and are,
therefor., likely to be
connected with the reasons for smoking. it is
hoped that future work
in the GrCup Dn C2 tra_oa_,%_~argqjamp1e
ot,subjecte.wilt"eriabl.
the nature of the differences to be elucidated.
4.2 Fsychological Differences
In 1970 Smith published a review of the empirical
studies of relations
between smoking and personality (197). He
considered a large nuober of
studies uhich used many different questionnaires
on widely varying
populations. He drew six conclusions about the
literature which are
summarised below:
1. Smokers are more extraverted than non-smokers.
In 22 out of
25 analyses. smokers were significantly more
extraverted than
non-smokers and no studies showed the opposite
finding.
CO
Un
(.-n
ON


-64-
2. Smokers have more anti-social tendencies than
nan-smokers.
27 of 32 analyses show smokers to be significantly
more anti-
social than non-smokers, none found the opposite.
As with the
extraversion studies a wide range of tests were
used and
populations studied.
3. More information is needed to support that
which is now
available on interrAl ternal orienthUbli tdt
smokef-f-a'p12-1
to be more externally oriented than non-smokers.
'
"
'_
.ilk
'
i'
-
iied show smokers are more'eiternajty
id
i~
6 al
.
.
.
.
a
s cons
e
Th
fl
& s
oriented and they think chance, fate and luck,
rather than
their skill and effort, account for what happens
to them.
Four of the results are significant, the fifth
nearly so.
4. It appears that smokers are more impulsive than
non-smokerip,
'
'
7'
Cut
needed to verify this. Seven
but again more info;;ation is
of ten studies show smokers to be significantly
wre impulsive
than.vori-smokers - none-are; significane~-In
n11e-bppU1tM1Mt1on.
5. There is support for the hypothegis that
smokers have stronger
oral needs than non-smokers, but more evidence is
needed.
Of four studies on smoking and "orality", three
show significant
positive associations. One of the three was,
however, based an
a very small sample and one achieved significance
only for the
comparison of heavy smokers and non-smokers.
6. Evidence suggests that smokers have poorer
mental health than
non-okers but more information is needed to
confirm this
and extra work is needed to define the opecific
aspects of
mental health referred to. A number of studies
have shorn
.03
4 :4
C:


-65-
poorer "mental health" in smokers but several
well-degigned
studies have not found a relationship. No studies
have found
:mokers to have significantly better mental health
than non-
..kers.
The author considers that only the first two
conclusions should be
regarded as positive.
.Wrt,
---flars 1969 studylohldh,
. . er~d?V.11 4*t-~
a=d Bown (215) studied university students. Among
the "psychological"
resul to which they ~reo~'ni. , imoycers were not
found to be more neurotic'
r7*, ttan non-smokers. Non-smokers were said to
respond more positively to
se:f-report attitude measures and they had more
pride in their own moral
c*aracter. The "stimulus hunger" theory for
smokers was supported as
was the concept of greater "oralitv" in smokers.
Russell, in 1971 (168),' suggested that although
significant personality
differences are found, they are small and there is
much overlap between
-kers azd arouoiai a0ekIfte,
danger-loving risk-takers who are belligerent
towards authority. They
dr:-k =are tea, coffee, alcohol: are more prone to
car accidents, divorce
and Job changing. Smokers also tend to be more
sexy* not only do the7
staz: at an earlier age, but they indulge with
greater frequency, variation
and enjoyment. All these characteristics cluster
with a degree of extraversion."
Clai=s that smokers are more tense, anxious,
emotional and neurotic are
usually not substantiated. Russell also says that
smoking is related
(especially after its withdrawal) with oral
activity like nail biting,
gum cl--eving, sweet eating and normal eating and
drinking. Eastwood and
Trevelyan, also in 1971 (56) investigated
suggestions that smokers tend
Q17
Q__
ON
C)


-66-
L4
to be nore restless, less dependable and more
neurotic than non-smoke-;.
In a r,-udy of 1471 subjects they compared the
smoking habits of IZ4
subjec:j with confirmed psychiatric disorders,
with matched controls.
No diff-arences were found in proportion of
smokers, amount smoked or
durati:= of smoking. The authors conclude that
there is no support f:r
the hy;.::thesis that smoking is related to
neurotic illness. They also
y!ah tyl .-the" , 141'64,6 okl?~F'11
"M, V
of psyci:iatric disorder (10-20Z of the
population). Also, middle-age-'
female have an excess of psychiatric disorders
over males but fewer of
a:M
them
smokers .
Fo!3 (65) in 1973 published results of a study in
which a qllestic---aire
was givE= to determine the degree of internal or
external orientation.
It was `~ othesised that smoking behaviour would
be related to perceive-
.P
salie-ice of the danger of smoking, Smokers would
be more fatalistic ar--'
believe less strongly than non-smokers that
smoking is dangerous. ThL:--2
was some. sripport-for--this,hypi6tbesib'but'-iia
seen. 7--e author concluded that psychological
factors may not underlie
much of --moking behaviour and that social
ps7chological or sociological
factors miy be more important in uriderstandiig
swoker/non-s.oker dLffreri-,:eg.
Nils_-on and Tibbling (153) conducted a st-,;dy
which may be consider=~_
to be at least partly physiological as well as
psychological. They
consider :chat the cigarette as a physical object
and smoking as a social
factor bo:h constitute "external world factors",
whilst cigarette smoke
as a cent--al stimulant constitutes an "internal
world factor". They
measured individual differences in after-effect
perception using an
oculogyra-l illusion and serial colour word test.
This is said to give
(Z)
C)
Cn
L.,4
CD


-67-
information on the individuals' relative degree of
investment in internal
and external world contents. The results showed
that, as predicted by
authors, subjects who showed a high dependence on
external world or
environmental factors tended to be heavy smokers
(over 20 cigarettes/day)
and very extraverted. It was suggested that these
subjects may need the
phar-maco logical effects of smoking to increase
their awareness of internal
world contents. For othe ps of.subjects the
recorded cigarette
.. 1r - -I ~~* ft
l-'r,orm" I -
'I'VO p1m "
consumpiio: V c"'ol'rrelated vi th~'extravers i
on/int rovers ion and after-
effect pe
as pre~.Lqt~e.d.
In 1972, in a study, on smoking and simulated
driving performance,
C2 -4 Ashton and her colleagues (12) used the
Cattell 16 Personality Factor
Questionnaire. They found that smokers were more
extravert and self-
reliant than non-9mokers but there were no other
significant differences.
Both smokers and~jqon-smokers scored similarly
for-anxiety and neuroticism.
In a paper by 83ttig (18) reference is made to a
study of 400
students. Cigarette smoking was found, by
questionnaire, to be_l,*:!,ked_
with reform/social/critical attitudes and, by the
Cattell Music Preference
Test, with sober/matter of fact/social make-up
behaviour. This is a
ratber different finding from others which tend to
indicate that smokers
are more rebellious and "fun-loving" than
non-smokers.
Fisher a~-.; Fisher, allso in 1975 (63), referred
to studies showing
that smokers describe themselves as using more
oral outlets than non-
smokers (e.g. nail biting). Smokers were said tp
be characterised by a
cluster of traits (e.g. danger-seeking,
compulsivity, concern with self-
stimulation) suggesting defence against oral
passive inclination.
Recently Mlott and Hlott (146) have investigated
smoking and fantasy.
They hypothesised that -individuals who smoke
fantasise more than those
L4
0 ~
\40
~_n
ON
SATCo document for Province of British Columbia 5
November 1999


who have stopped smoking or have never smoked.
They used the Lmaginal
Processes Inventory. This shows the extent to
which fantasy is used in
the areas of problem solving, fear of failure,
achievement, hostility,
sex, heroism and guilt. Using 90 subjects of each
se-x, the hypochesis
was supported for males only. They fantasised most
for all categories
considered, and specifically, male smokers used
achievement fantasy more
than non- swo~iors-br 7ex-~ smoke re h6wev e r,
f.ntaMAW~_.~"
least, especially with regard to achievement
fantasy, which female non-
;=e;r;s1 Iftost. The