Project ECHO Neurobiology of Nicotine Dependence · Project ECHO Neurobiology of Nicotine...
Transcript of Project ECHO Neurobiology of Nicotine Dependence · Project ECHO Neurobiology of Nicotine...
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Project ECHONeurobiology of Nicotine
Dependence Maher Karam‐Hage, MD
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Disclosure
• Have been co‐investigator and study physician on two multi‐site smoking cessation studies 2007 & 2014 by Pfizer, maker of: Chantix®, Zoloft® & Geodon®
• Have received medication Chantix from Pfizer for: • 2 NIH funded 2006‐2014 and • 2 MD Anderson & CPRIT funded smoking cessation trials
2014‐2016
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Outline
• The basic neurobiology of reward
• Addictive nature of nicotine and interplay with neuro‐psych pathways
• The higher addiction potential of airway administration
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Outline
• The basic neurobiology of reward
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The Reward Pathway
and Addiction
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Natural Rewards
• Food
• Water
• Sex
• Nurturing
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Reward Pathway
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fMRI of Nicotine’s Effect on Blood Flow
Interplay of reward/appetitive system with behavioral control/executive system
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Nicotine: Primary Psychoactive Substance in Cigarette Smoke
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Nicotine & Nicotinic Receptors
Nicotine Molecule
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Nicotine & Nicotinic Receptors
Nicotine Receptor Structure
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Outline
• Addictive nature of nicotine and interplay with neuro‐psych pathways
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The Addictive Nature of Nicotine
• The addictive characteristics of nicotine are believed to be a result of its rapid, intense and short‐acting effects on dopamine release in the brain. More so when smoked.
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The Addictive Nature of Nicotine
Similar to addictions associated with cocaine, amphetamines and opiates, nicotine dependence (addiction) is a chronic, relapsing medical condition and warrants clinical intervention
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The Addictive Nature of Nicotine
Nicotine, cocaine, amphetamines and morphine act on different areas within the dopamine reward system that encompasses the mesolimbic portion of the brain.
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The Addictive Nature of Nicotine
Among users of tobacco, alcohol, cannabis, and cocaine: Tobacco users were more likely to be nicotine dependent (28%) than alcohol (5.2%), cannabis (8.2%) or cocaine (11.6%) users
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Nicotine stimulates dopamine, serotonin & norepinephrine release, which may help smokers modulate their mood.
GABAergic and glutamatergic activity are intimately involved in the process
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http://video.nationalgeographic.com/video/magazine/focal‐point/170822‐ngm‐focal‐
point‐addiction
National Geographic Video
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Outline
• The higher addiction potential of airway administration
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The Addictive Nature of Nicotine
When inhaled, nicotine reaches the brain within 7‐10 seconds
Via oral mucosa nicotine reaches brain around 5‐10 min, transdermal 10‐15 min
Nicotine’s half‐life is approximately 2 hours
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Nicotine Distribution in Blood After Smoking a Cigarette
Arterial Nicotine reaches the brain within 7‐10 seconds
Arterial
Venous
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Plasma Nicotine Concentrations for Nicotine-Containing Products
NRTs
Cigarette
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Bupropion and Varenicline
Bupropion:• A nicotine receptor antagonist within the first 1‐2 weeks of taking it
• Weak norepinephrine and dopamine re‐uptake inhibitor
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Bupropion and Varenicline
Varenicline:• A strong partial agonist on alpha4‐Beta2 nicotinic receptors, within days
• Very high affinity for the receptors that is not displaced by nicotine administration
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1. CDC. Surgeon General’s Report. The Health Consequences ofSmoking. 2004.
2. Foulds J. Int J Clin Pract. 2006;60:571‐576.
3. Fiore MC et al. U.S. DHHS, U.S. Public Health Service, 2000.
4. Changeux JP et al. Brain Research Reviews. 1998; 26:198‐216.
5. Kandel D et al. Drug Alcohol Depend. 1997;44:11‐29.
4. Henningfield et al. (1933). Drug Alcohol Depend 33:23‐29
References