Chapter 8 - Nicotine

the principal source of tobacco

N tabacum L.

origin of tobacco

american, aboriginal peoples of north and south amreica

electronic nicotine delivery system

ENDS

the disease that tobacco was claimed to cure

the Plague

The U.S Surgeon General’s Report of 1964

linked smoking to cancer and other diseases

nicotine

the primary psychoactive substance found naturally in tabacco

Nicotinic Acetylcholine Receptors (nAChRs)

Ionotropic receptors in the central and peripheral nervous system that bind to acetylcholine (ACh) and nicotine. Their activation leads to an influx of sodium (Na+) and potassium (K+), resulting in an excitatory postsynaptic potential (EPSP)

absorption (nicotine)

nicotine → bloodstream through lungs (smoking/vaping), nasal mucous membrane (snuff/nasal sprays), skin (patch), and mouth (chewing tobacco, dip, dissolvables, gum)

distribution (nicotine)

absorption → crossing the blood-brain barrier, placenta, and entering breast milk

metabolism (nicotine)

breakdown of nicotine, primarily by cytochrome (P450) enzymes in the liver. genetic polymorphisms can affect the rate of metabolism

CNS effects of nicotine

arousal, increased breathing rate, potential vomiting (with tolerance), feelings of a “rush” or “buzz” and improvements in attention, fine motor skills and short-term episodic memory

PNS effects of nicotine

increased heart rate and blood pressure, vasoconstriction, laxative effects (with tolerance)

nicotine toxicity

the poisonous effects of excessive nicotine exposure, with an LD50 of approx. 60 mg in adult humans. acute poisoning can lead to nausea, vomiting, seizures, hypotension, coma and death

harms of chronic tobacco use

increased risk of various cancers, heart and lung diseases (including COPD), reduced reproductive capacity, and the dangers of second-hand smoke exposure

nicotine addiction

driven by nicotine’s effects on the brain’s reward pathways, particularly the release of dopamine in the nucleus accumbens (NAcc)

withdrawal symptoms

a range of unpleasant physical and psychological effects that occur upon cessation or reduction of nicotine use, including cravings, insomnia, low mood, anxiety, irritability, tremor, headaches, and nausea

smoking cessation

the process of quitting smoking, which can involve various methods including going cold turkey, using nicotine replacement therapies (NRT), and prescription medications like bupropion and varenicline

Nicotine replacement therapy (NRT)

pharmaceutical products (e.g., patches, gum, lozenges, nasal sprays) that deliver nicotine w/o the harmful components of tobacco smoke, helping to reduce withdrawal symptoms during cessation

bupropion

a prescription medication that acts as a norepinephrine and dopamine reuptake inhibitor and a nicotinic acetylcholine receptor antagonist, aiding in smoking cessation by recusing cravings and withdrawal symptoms

varenicline

a prescription medication that acts as a partial agonist of nAChRs and a competitive antagonist, helping with smoking cessation by reducing withdrawal symptoms and blocking the rewarding effects of nicotine smoking

smoking was reduced throughout the 1990s because of

increase in cigarette prices and taxation, antismoking campaigns, halted ads

the older you get the

less likely you are to smoke, peaks at 18-25 and then decreases after

countries to reduce greater than 50% reduction in smoking

canada, and mexico

of the more than one billion smokers worldwide,

80% live in low, or middle, income countries

according to the FDA, a drug is defined as a substance intended by its makes:

a) to affect the structure or functions of the body
b) for use in the diagnosis, cure, mitigation, treatment or prevention of disease

what act put tobacco products under FDA control

the Family Smoking Prevention and Tobacco Control Act

peak nicotine levels occur in _____ mins of vaping

5

absorption from the mouth and digestive system

buccal membranes in the cheeks and under the tongue or swallowed by saliva, peak levels between 20-35 mins

smokeless tobacco users who “dip” 8 to 10 times a day might be exposed to the same amount of nicotine as if they smoked:

30 to 40 cigs

nicotinic receptors are

pentameric - made up of five subunits, organized as a ring around a central pore

neuropharmacology of nicotine

nicotinic receptors → activated by nicotine, all subunits are changed and pore opens → positively charged ions (Na+ and K+) pass through = excitatory postsynaptic potential

what happens when nARChS are located presynaptically?

function as neuromodulators, stimulating the release of other neurotransmitters

what nAChRs are believed to be the ones that mediate nicotine’s reinforcing effects?

a2, a4, B2

nicotine and rats (speed)

nicotine enhanced speed of performance but had no effect on accuracy

nicotine and rats (learning tasks)

no effect on learning tasks but interfered with timing tasks and the ability to withhold responding

nicotine and rats (radial arm maze)

nicotine facilitated working memory, have to remember which arm they have already been to, nicotine improves performance on this task and increases the number of arms the rat enters before making an error

rats and conditioned reinforcement (nicotine and light)

saline + no cues = response dropped fewer than 5 infusions per session
nicotine + no cues, saline + cues = response dropped to around 10 infusions per session but climbed back up after nicotine was added back in

a₅ subunit

mediate the aversive effects of nicotine experienced at higher concentrations, people who carry a particular form of the gene that makes a₅ subunits with diminished function are at a much greater risk of being smokers and of suffering from respiratory disease