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3 June 2011 Home

Tobacco far more addictive than nicotine – but why?

Murray Laugesen _________________________________________________________________________


Tobacco products

Risk of addiction to cigarettes very high

Of New Zealand 14-15 year olds who have smoked a packet of 20 cigarettes in their lifetime 85% are currently smokers when interviewed. After smoking 100 or more cigarettes, 95% become smokers.

Table 1. Number of cigarettes ever smoked in lifetime, and % still smoking (at age 14-15 years)1

Number of cigarettes ever smoked


1 cigarette


2 cigarettes


3-4 cigarettes


10-19 cigarettes


20-99 cigarettes


>100 cigarettes



Table 2. New Zealand smokers who view their own use of cigarettes as an addiction2



Age 15 and over










Smokes 1-10 cigarettes/day


Smokes 11-20 cigarettes/day


Smokes > 20 cigarettes /day


Nasal snuff

Nasal snuff which is ground tobacco powder, is at least as addictive as smoking tobacco, and acts within five minutes.3 It is much more addictive than nasal spray, its nearest nicotine equivalent. (Table 3)

Smokeless tobacco- Swedish snus

“The addiction is at least as powerful

as that associated with smoking”.4


1. Scragg R, Wellman RJ, Laugesen M, DiFranza JR.

Diminished autonomy over tobacco can begin with the first cigarettes. (based on ASH NZ surveys of year 10 students

2 National Research Bureau Ltd, Environmental Tobacco Smoke Study 1996. Wellington: Ministry of Health.

3. Nasal Snuff, a traditional less harmful way to use tobacco.


Nicotine products

Do they increase addiction?

(a) For recent smokers and ex-smokers, No. Nicotine replacement therapy (NRT or medicinal nicotine, and e-cigarettes) reduce cravings, making it easier to quit smoking. Fewer people smoking means decreasing addiction to smoking over a few weeks or months. The risk of prolonged addiction to NRT is under 10 percent. See below.

(b) For never smokers, rarely. See below.

Risk of addiction to nicotine in never smokers rare

Five never smokers and 429 ex-smokers used nicotine gum daily among 434 self-selected (addicted) respondents to an internet anti-smoking website.5

Never smokers rarely become addicted to nicotine gum despite its wide availability.5

Risk of prolonged risk is low for nicotine gum in ex-smokers (at 1 year, under 10%)

Table 3. Ex-smokers using nicotine replacement products (NRT) beyond the labeled period of use, as an indicator of continued dependence on nicotine.

% still using the product

After 15 weeks6

After one year7




Sublingual tablet









Chewing gum



Nasal Spray




Table 4. Nicotine inhaler in ex-smokers: Use, abuse, and dependency status 6 months after first use8



Still using it


Dependent, by definition (ICD10)


Dependent, on clinical expert interview


Harmful abuse (ICD10)


4. Boethius G, Bolinder G, Lambe M, Pershagen, G. Ryden L. Who benefits from increased use of snus? Dagens Nyheter. Sept 22, 2002. (5 scientists) Download.aspx?ID=4212

5. Etter JF. Addiction to the nicotine gum in never smokers. BMC Public Health. 2007; 7: 159.

6. West R, Hajek P, Foulds J, Nilsson F, May S, Meadows A. A comparison of the abuse liability and dependence potential of nicotine patch, gum, spray, and inhaler. Psychopharmacology (Berl) 2000; 149: 198-202.

7. Hajek P, McRobbie H, Gillison F. Dependence potential of nicotine replacement treatments: Effects of product type, patient characteristics, and cost to user. Prev Med 2007; 44(3):230-4.

8. Hughes JR, Adams EH, Franzon MA, Maguire MK, Guary J. A prospective study of off-label use of, abuse of, and dependence on nicotine inhaler. Tob Control 2005; 14: 49-54.

Why is tobacco more addictive than nicotine?


1) Tobacco, being a plant, contains a huge variety of substances besides nicotine.

2) Smoke is even more complex. Besides nicotine, tobacco smoke contains over 4000 different chemicals. This “cocktail” may be far more effective at causing addiction than is nicotine alone.

3) Tobacco, in whatever form, whether smoking tobacco, nasal tobacco snuff, or tobacco snus, is in each case more addictive than nicotine (see above). This superior addictiveness:

       Cannot be attributed to any common behaviour or product type, as behaviours differ by product and route of absorption. For example, while cigarettes and nasal snuff gives a rapid effect, snus does not.

       Cannot be attributed to any one manufacturing processes, or additive, as each type of tobacco is made in a different way.

       May be influenced by the social environment – whereas nicotine is sold as a medicine, in limited dose and for a limited period, tobacco is used as a lifestyle drug of pleasure.

       May be reinforced by the rituals of use.

       May be due to the chemical composition of the tobacco itself at the point of absorption, the smoke inhaled, the snuff or the snus consumed.

       Other substances in tobacco smoke, snuff, and snus, may work to enhance nicotine’s effect.


Monoamine oxidase, smoking, and tobacco addiction

A review by ESR and Victoria University of

Wellington scientists1 shows that nicotine can release dopamine, (the pleasure drug) but nicotine by itself does not have a strong effect. Mono-amine oxidase (MAO), an enzyme that mops up dopamine in the human and animal brain, is inhibited by substances in tobacco smoke. In rats sensitized with nicotine, MAO inhibitor substances greatly reinforce the addictive effects. With less MAO activity, the dopamine reward from the nicotine will be enhanced and this could enhance nicotine’s addictiveness. 



Smoking reduces MAO. Reduction of MAO-A by 28-38% in smokers’ brain scans, and of MAO-B in smokers’ blood platelets of MAO-B by 40% has been observed, compared with non-smokers and ex-smokers.

Recovery of MAO levels after stopping smoking does not occur overnight. Rather it takes days.2

The next step is to identify which substances in tobacco account for this difference. As the identity of these substances could possibly vary with the product, the focus naturally falls first on tobacco smoke, about which more is known.

ESR scientists found that the total particulate matter (TPM or “tar”) from cigarette smoke was more potent than nicotine alone in up-regulating nicotine receptors in human neural cells.3

Substances found in TPM in reasonable quantity, which can reach the brain, include Harman and Norharman (also found in coffee) which inhibit MAO A and MAO B enzymes respectively.


       Longer use of NRT (nicotine replacement therapy) or e-cigarettes to increase cessation success carries little risk of permanent dependency to nicotine.

       Nicotine electronic cigarettes are not a gateway drug trapping adolescents into nicotine addiction and tobacco smoking, as some fear. Reasons are: because

1) Few if any adolescents are using e-cigarettes despite adult smokers in UK and USA using them since 2007.

2) Never smokers rarely develop addiction to nicotine gum.

3) Addiction to nicotine in e-cigarettes is unlikely because the e-cigarette delivers much less nicotine than nicotine gum.

4) If e-cigarettes induce any weak nicotine dependency it will not be reinforced, as e-cigarettes lack any MAO-inhibitory effect.3


1 Lewis A, Miller JH, Lea RA. Monoamine oxidase and tobacco dependence. Neurotoxicology 2007 Jan;28(1):182-95. Epub 2006 Jul 21.

2 Gilbert DG, Zuo Y, Browning RA, Shaw TM, Rabinovich NE, Gilbert-Johnson AM et al. Platelet monoamine oxidase B activity changes across 31 days of smoking abstinence. Nicotine Tob Res 2003;53:136-43.

3. Ambrose V, Miller JH Dickson SJ, Hampton S, Truman P, Lea RA, Fowles J. Tobacco particulate matter is more potent than nicotine at upregulating nicotinic receptors on SH-SY5Y cells. Nicotine Tob Res. 2007; 9: 793-9.

Health New Zealand 2011