*Lancet* (Volume 371, Number 9629, 14 June 2008)
includes a review article: “Tobacco addiction.”

The article is by Dorothy K Hatsukami, PhD, Lindsay F Stead, MSc b, &
Prakash C Gupta, PhD.

Here’s how the article starts: “Lung cancer was confirmed to be caused
by cigarette smoking over 50 years ago, and since then several other
diseases have been added to the list of diseases caused by smoking and
involuntary exposure to cigarette smoke.1,2 However, the worldwide
production and consumption of cigarettes has continued to increase
unabated during this period. There are about 1.2 billion smokers in the
world, half of whom will die from diseases caused by smoking.3 Smoking
causes 5 million deaths per year, and if present trends continue, 10
million smokers per year are projected to die by 2025. The prevalence
varies greatly, from less than 5% to more than 55% in different
countries. It also varies greatly between men and women, so prevalence
in both sexes needs to be examined separately.”

Here are some excerpts from the section on withdrawal symptoms:

[begin excerpts]

With chronic or even acute administration of nicotine, neural
adaptations occur to attain homoeostasis resulting from the increased
activity on the nicotinic acetylcholine receptor sites and increased
concentration of neurotransmitters. Although some subtypes of nicotinic
acetylcholine receptor are upregulated by chronic nicotine treatment
(ie, their numbers increase), receptors also become desensitised or
inactivated, which is one potential mechanism leading to the development
of tolerance.16,33,34 Because the body develops a homoeostatic response,
smokers have withdrawal symptoms on abstinence from the drug. These
withdrawal symptoms include negative affect such as irritability,
frustration or anger, anxiety, dysphoric or depressed mood,
restlessness, difficulty concentrating, insomnia, decreased heart rate,
and increased appetite.6 Other possible symptoms can include
constipation, cough, dizziness, increased dreaming, and mouth sores.35

Withdrawal symptoms, with the exception of weight, peak during the first
week of abstinence and then gradually drop to baseline levels by 2-4
weeks,35-37 although further studies have shown withdrawal to be
persistent and elevated for several months after quitting.38,39 However,
weight might increase over the course of 6 months, and then decrease or
become sustained.40 Studies have also shown individual variations in the
intensity, slope, and variability of symptoms.41 Symptoms of great
intensity, positive slope, and variability predict relapse to
smoking42,43 and those of craving and negative affect were the most
likely to be associated with relapse.44,45 Withdrawal symptoms can make
abstaining smokers more reactive to environmental events that engender
emotional reactions.46

In addition to the physiological basis for addiction, behavioural or
learning factors also sustain addiction. Stimuli in the environment
become associated with the positive reinforcing effects of nicotine and
withdrawal symptoms. With time and associative learning, these stimuli
begin to control behaviour, such that when a smoker is exposed to these
stimuli, they evoke craving for the drug or drug-seeking behaviour.
These stimuli could include smoking cues such as other smokers, an
ashtray, or a lighter; negative affect such as irritability, depressed
mood, or anxiety; situational cues such as a bar or after finishing a
meal; alcohol use; or sensory cues from smoking such as the harshness in
the throat and lungs and the taste.47-49 This associative learning has
been regarded by some to make an equally important contribution to
nicotine addiction as do the direct effects of the drug itself.23,50-53
Nicotine has also been noted to enhance the reinforcing effects of
stimuli or other reinforcers that are not associated with the
administration of nicotine, which is an effect that also contributes to
the addictive nature of nicotine.54-56

[end excerpts]

Here’s an excerpt from the section on treatment: “Treatments are
targeted towards dealing with the physical addiction to nicotine, the
psychological reliance on the effects of nicotine, and the behavioural
aspects of tobacco use. Several meta-analyses and public-health
guidelines have described evidence-based treatment approaches.69-71”

Here’s an excerpt from the section on pharmacotherapy:
“Pharmacotherapies for nicotine dependence can enhance quit rates by
about two-three-fold.69 Therefore, according to the UK and US Public
Health Service guidelines, all smokers should be considered for
pharmacotherapies, but with special consideration or exception given to
smokers with specific medical conditions, to those who smoke less than
ten cigarettes per day, to pregnant or breastfeeding women, and to
adolescents. Table 3 describes the various medicinal treatments that are
available to treat smoking addiction. The UK clinical practice
guidelines recommend nicotine replacement therapies (NRTs) and bupropion
as a first-line treatment,70 although bupropion is recommended as a
second-line therapy in New Zealand and Germany.87,88 In the USA, first-
line therapies are drugs that have been approved by the US Food and Drug
Administration (FDA) and include NRTs (except nicotine microtab),
bupropion, and varenicline.69 Second-line treatments–including clonidine
and nortriptyline–have shown efficacy but have not been approved by the FDA.”

The author note states that correspondence about the article may be sent
to Dorothy K Hatsukami, Tobacco Use Research Center, University of
Minnesota, 2701 University Avenue SE, #201, Minneapolis, MN 55414;
<h a t s u 0 0 1 @ u m n . e d u>.

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