3. Nicotine Flashcards
Sean Cole
Allen Carr (John Dicey)
Andrew Huberman
Anna Lembke
Sean cole had lung nodules from smoking 35 yrs
panicked if no smoke, withdrawl, cog slowing
Allen carr book on non-smoking to remove desire of smoking (john dicey successor) didnt believe in science though (studies show allen’s method and normal pharamco therapy have same success rate lowkey)
Andrew Huberman neuroscientist shows nicotine does have positives (improves att’n/memory/cognition) and withdrawl makes it harder to do those tasks
Anna Lembke wrote Dopamine Nation, withdrawl worsens if reintorduce stimuli, some people need nicotine replacement (patches) forever
what is vaping
designed to help smokers quit
cigs use combustion, vaping heats to aerosol instead
reduced release of carcinogens
still damages DNA though
FDA banned flavored vapes
what is nicotine
alkaloid made by tobacco plants
cigs contain 10 mg, 1-3mg makes it to blood
CNS stimulant felt within 10 seconds
JUUL matches cig in nicotine concentration
Nicotine metabolism
Metab’d to cotinine by CYP2A6 (used in urine tests, nicotine halflife 2hrs, cotinine 20hrs)
CYP2A6 more expression in women
Menthol inhibits CYP2A6
Low CYP2A6 activity = less likely to be smoker bc nicotine aversive
Nicotinic receptors
activatives cholinergic nAChRs
Alpha4Beta2 receptors, expressed DA in VTA
A4B2 KO = no self admin nicotine
PET studies radiotracer displacement show high affinity
Continuous depol = depol block
Biphasic effect - stim turns into block
Nicotine on smokers and non smokers
smokers - calm, relaxed, relieve withdrawl (restless/insomnia/no concentration)
Nonsmokers - tense/dizzy/nausea, tolerance due to rec. desensitzationN
Nicotine and Mmeory
enhances working memory animals studies
Improvement on 5CSRTT of attention
improved performance with acute or chronic, poorer performance during withdrawl
Non-smokers improve show enhanced performance
Nicotine and attention
MLA, an alpha7 subunit antagonist blocks nicotine effects of attention
A7 agonist to improve cog performance
if in low attention group, nicotine patches helped them
Mesolimbic pathway and nicotine
Lesions in NAcc block nicotine self admin
nAChR antagonists in VTA block self admin
DAr antagonists in NAcc block self admin
Nicotine and smoke on VTA
Nicotine doubles VTA DA firing rate, increases DA release in NAcc
Rats inhaling smoke stimulates DA neurons and nAChR antag blocks smoke effects
Tobacco smoke inhibits MAO-A/B = more DA/NE/5HT, reinforces
Nicotinic Receptors in ANS
Abundant in ANS ganglia para and sympa and adrenal medulla
Para activation = increase in HCL in stomach and increased bowel activity
Sympa = sympathomimetic, tachycardia/inc. BP
Adrenal Medulal = catecholamine secretion
Accidental Nicotine Posioning
swallow/farm tobacco/insecticides
symptoms - nausea/saliva/vomit/diarrhea, respiratory failure due to depol. block
Nicotine aversion
hard to do since aversive in animals
aversion mediated by Alpha5 subunit of nAChR expression in interpeduncular nucleus
Alpha5 KO = self admin more as dose increases, normal mice plateau due to aversion
Nicotine Tolerance
acute tolerance - cig smokers have acute in course of one day, desensitized receptors
24hr cycle, first cig of day is best, rest are to alleviate withdrawl, need resensitive over night
During withdrawl, increased ICSS threshold and withdrawl mediated by reduced DA NAcc and increased CRF amygdala
DSM5 Nicotine withdrawl
using nicotine >1 yr.
Using tobacco longer than planned, signs of tolerance, appearance of withdrawl
Nicotine 2ndary reinforcers
secondary stimuli associated with act of smoking can reinforce too
Denicotinized cigarettes were used more than actual nicotine IV
Nicotine replacement Therapy and Pharmaco Interventions
relieves withdrawl/harm reduction
Bupropion - OG was an antidepressant, dopamine/NE reuptake inhibitor NDRI, similar stimulant structure, reduces craving/withdrawl
Varenicline - partial A4B2 agonist, reduces craving, mroe effective than bupropion
What is caffeine and metabolism
from coffee beans
oral, completely absorbed in 1hr GI tract
metab’d to paraxanthine (CNS stimulant too) by CYP1A2, 95% elim’d in urine
Avg half life 4hrs
Biphasic effects of caffeine
in animals = low doses, stimulant, high doses reduce activity
in humans
low dose = positive subjective effects, alert/energy
high dose = anxiogenic, panic disorder
Cog/Autonomic effects caffeine
Cog effects alertness/att’n
Autonomic = increase BP/BPM, increase urine, increase respiration
Caffeine withdrawl and intoxication/use disorder
sleepy/irritable
craving, relief from withdrawl
Intoxication - restless/insomnia/tachycardia, like anxiety disorder toxcity/death
Use Disorder - difficult to reduce, continued use despite effects, withdrawl
Caffeine therapeutic uses
potentiates analgesia of aspirin
treat apnea in newborns (regularize breathing)
Epidemiological studies show range - reduce obesity, diabetes, cancer, parkisons (mostly bc of coffee beans antioxidants/antiinflaamoty
4 actions of caffeine
Dose dependent inhibition of cAMP, block GABAa receptors, stimulates Ca2+ release, blocks adenosine receptors
BUT only the blocking of A1/A2A adenosine receptors occurs at normal dsoes, rest at toxic levels
Adenosine and Caffeine
Adenosine - NT like, modulates sleep, caffeine antags A2A in striatum
A2A receptor co-expressed with D2r in striatum,
Adeosine allosterically negatively modules (inhibts) D2r signalling by agonzing A2A receptors = decrease DA affinity
Caffeine enhances DA bu antagonizing A2A
A2A KO = no caffeine increase in locomotor/att’n
Kratom
tree in coffee family
mitragynine, low level stimulant, high dose narcotic sedative
treat pain/diarrhea/anxiety/opioud withdrawl
binds MOR, but not opiodi chem structrue, not in controlled substance ac t
