truth initiative presentation template · rethinking nicotine ray niaura director of science and...

Rethinking Nicotine https://truthinitiative.org/news/re-thinking-nicotine-and-its-effects

RAY NIAURA

DIRECTOR OF SCIENCE AND TRAINING

• If nicotine cannot be totally banned and eradicated, then what kind of nicotine

use is society willing to accept?

• What is the potential for unintended consequences of reduced-harm nicotine

delivery products?

• What policies and regulations can ensure that harm from nicotine use are

minimized while simultaneously moving the entire population away from

deadly combustible tobacco products?

Tobacco control’s overarching goal is to save lives as rapidly and effectively as possible.

• Most of the physiological harm attributable to cigarette smoking

derives from the toxicants in tobacco and combustion products.

• Preventable morbidity and mortality has overwhelmingly been related

to combusted tobacco smoking, not to nicotine itself.

• Decoupled from combustion or other toxic modes of delivery, nicotine,

by itself, is much less harmful.

Central thesis of tobacco harm reduction

Nicotine Concerns: Cancer, Addiction, the Brain (Cardiovascular and respiratory effects – Neal Benowitz)

• There is no evidence that nicotine, by itself, is a carcinogen.

• Epidemiological evidence in human populations does not support the

basic science concern from laboratory studies that nicotine promotes

some cancer pathway activation.

• More research is required to demonstrate if, and to what degree, there

may be a concern about nicotine’s role as a cancer promoter.

Nicotine Concerns: Cancer

Nicotine Concerns: Swedish Snus Experience

Swedish snus delivers nicotine

systemically, at high doses, and

persistently throughout the day Evidence for cancer risk is nonexistent or weak

Nicotine Concerns: FDA PMTA product review and approvals FDA REVIEWED SWEDISH MATCH APPLICATIONS FOR 8 PRODUCTS

Comprehensive

review

Approved

Nicotine Concerns: Cancer PMTA EXECUTIVE SUMMARY

Actual

estimates of

potential harm

reduction

Reduced oral

cancer risk


Not risk free

Reduced risk

of other

cancers and

diseases


Appropriate for the protection of public health

Nicotine Concerns: Addiction

• Nicotine is addictive

• How addictive is it when it is de-coupled from tobacco?

• Little evidence for addiction to nicotine replacement products (NRTs)

USDHHS

recognizes

relative nicotine

safety and

reduced risk of

addiction for

certain

preparations

(NRT)


Dependence Cigarettes ENDS

Inability to quit/reduce X NE

Continued use

despite harms X NE

Compulsive use X NE

Craving/withdrawal X SE

NE – no evidence; SE – some evidence


• What does addiction mean if there is little to no harm?

• Cost, time, long-term neurophysiological effects?

Nicotine Concerns: The brain


Nicotinic acetylcholine receptors,

or nAChRs

Nicotine Concerns: The adolescent brain

Nicotine?


• Exposure in utero, during critical periods of fetal development,

may affect the function of certain neural systems in the long run.

• Some brain development continues through adolescence.

Findings in rodents that nicotine exposure during adolescence

affects these developmental processes have raised concerns

about adverse effects on adolescent neurodevelopment.

• The functional implications of the experimental rodent models for

humans are not currently clear.


• Some human studies suggest that nicotine can produce cognitive

and affective benefits.

• Certain subgroups of individuals that are experiencing cognitive

decrements (e.g., individuals diagnosed with ADHD, older adults

with mild cognitive impairment) might be most sensitive to

nicotine-related cognitive enhancement.

Nicotine selectively and simultaneously activates and de-activates brain activity

nAChR agonists decrease activity in default mode network (DMN) regions and increase activity in task-related regions.

These meta-analytic outcomes point toward a common neurobiological mechanism at the systems level by which nAChR agonists may enhance cognition and/or reduce tobacco craving.

Sutherland MT, Ray KL, Riedel MC, Yanes JA, Stein EA, Laird AR. Neurobiological impact of nicotinic

acetylcholine receptor agonists: An activation likelihood estimation meta-analysis of pharmacologic neuroimaging

studies. Biol Psychiatry. 2015 Nov 15;78(10):711-20.

(blue; baseline > drug) ; (red; drug > baseline)

Default mode network (purple transparency)

Executive control network (yellow transparency)

We need a reexamination of fundamental questions concerning nicotine:

• When nicotine is delivered to the body via means other than inhalation of combusted tobacco smoke, to what extent does it remain biologically harmful?

• When nicotine is decoupled from combustible tobacco, how worrisome is its degree of addiction liability, and what are its behavioral or social consequences to individuals and society?

• From a public health perspective, if nicotine can be used in substantially less harmful forms, would its widespread use have a positive or negative population impact on death and disease?

The evidence indicates that nicotine itself, while not completely benign, carries substantiallylower risks than smoking.

Nicotine: Concluding questions

Thank you

[email protected]

truth initiative presentation template · rethinking nicotine ray niaura director of science and...

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