Nicotine and Caffeine

where is nicotine from?

originates from tobacco leaves

what are the two major species of tobacco plant?

• large-leaf Nicotiana tabacum (from South American

• small-leaf Nicotiana rustica (from North America

historically, what were the most common forms of tobacco use?

pipe smoking, cigar smoking, and chewing

How is nicotine used in e-cigarette form?

The device heats and vaporizes a solution of nicotine, resulting in an aerosol that is inhaled by the user

How much nicotine is within a single tobacco cigarette, and how much of it do we actually consume?

Each cigarette has 6-11 mg, but only 1-3 mg reaches the bloodstream

Tar

Fine particles present in cigarette smoke that are produced by combustion of the tobacco leaves. It contains a complex mixture of hydrocarbons, some of which are known to be carcinogenic

When tobacco is chewed or snorted, how is nicotine absorbed?

Membranes of the mouth and nostrils

Roughly how many puffs are in a single tobacco cigarette

10-15

What is the quickest and most efficient method of delivering nicotine to the brain

Smoking a cigarette

First generation cig-a-likes

Type of e-cigarette, designed to look and feel like tobacco cigarettes

Second generation clearomizers

type of e-cigarette that possess clear refillable reservoirs containing the e-liquid

Third generation mods

Large, higher voltage batteries with large tanks that yield a high Vapor delivery

Fourth generation pods

Small sleek devices with either disposable or refillable liquid containers

What is the half life of nicotine?

About 2 hours

Cotinine

Principal producteur of nicotine metabolism by the liver

How much of nicotine in the body is converted to cotinine?

70-80%

Cytochrome P450 2A6 (CYP2A6)

Specific type of cytochrome P450 that metabolizes nicotine into cotinine

Why is nicotine metabolism faster in women than in men?

CYP2A6 expression is increased by estrogens

How does menthol and Cyp2A6 interact

Menthol inhibits its activity causing a slower nicotine conversion to cotinine

What is the CYP2A6 genetic variation linked to?

Smoking behavior and nicotine addiction

Nicotinic acetylcholine receptors (nAChRs)

Family of ionotropic receptors that are activated by ACh and selectively stimulated by nicotine. They may also be called nicotinic receptors

Which neuronal receptor is more sensitive to nicotine?

Two a4 or a3 subunits with three beta subunits (typically b2)

Where are the high affinity nAChRS found in the brain?

Cerebral cortex, thalamus, striatum, hippocampus and monoamine containing nuclei

How does nicotine affect mood states

Increase calmness and relaxation, tension-reducing effect (but related partly to relief from nicotine withdrawal symptoms

What are side effects of nicotine to nonsmokers?

Heightened tension or arousal, lightheadness, dizziness and even nausea

What cortical area is strongly implicated in drug craving and addiction?

Insula

What parts of cognitive function does nicotine enhance?

Short-term episodic and working memory, attention, and fine motor performance

Dihydro-beta-erythroidine

Blocks high affinity nAChRs ( Receptors containing a4 andb2 subunits)

Methyllycaconitine

Blocks low affinity nAChRs consisting only of a7 subunits

Compared to men how does nicotine effect women differently?

More sensitive to nicotine reward/reinforcement, greater positive mood effects and have more difficult time hitting

Which pathway plays a key role in reinforcing nicotine’s effects?

The Mesolithic dopamine pathway from the VTA to the nucleus accumbens

What are some aversive effects of nicotine?

Nausea, dizziness, sweating , headache, palpitations, teacher ache and clammy hands

Nicotine aversion is dependent on nAChRS containing which unit?

A5 subunit

How does nicotine effect both the sympathetic and parasympathetic nervous system?

Stimulates the release of adrenaline and noradrenaline, increased heart rate and elevated blood pressure, increase of hydrochloric acid secretion in the stomach

Green tobacco illness

Cluster of symptoms produced by exposure to nicotine in workers harvesting tobacco plants

Symptoms of green tobacco illness

Nausea, vomiting, dizziness, weakness, abdominal pain, excessive sweating and salivation

Affective symptoms of abstinence syndrome

Anxiety, anger/irritability, depressed mood, anhedonia, insomnia, restlessness, hyprlagesia and powerful desire to smoke

Somatic symptoms of abstinence syndrome

Tremors, slowed heart rate, nausea, gastrointestinal distress and hunger and weight gain

Cognitive features of nicotine withdrawal

Difficulty concentrating, memory impairment

Mecamylamine

Antagonist at nicotinic ACh receptors, particularly at autonomic ganglia. It can be used clinically to treat hypertension

intermittent smokers

individuals who maintain a stable habit of non-daily cigarette smoking

flavour hypothesis

e-cigarettes are preferred because of the availability of many different flavours

health hypothesis

adolescents choose e-cigarettes because they are perceived to be a healthier option than tobacco cigarettes

price hypothesis

in some locales, e-cigarettes are less expensive than tobacco cigarettes

role model hypothesis

posits that adolescent e-cigarette use is prompted by peer users who are perceived as role models

nicotine resource model

theory that smoking is maintained due to positive effects of nicotine such as increased concentration and greater mood control

deprivation reversal model

theory that smoking is maintained by mood enhancement and increased concentration that occur when nicotine withdrawal symptoms are alleviated

why might MAO inhibition might contribute to the reinforcing effects of smoking?

it is important in the breakdown of DA

why does menthol result in reduced nicotine-mediated activation of these receptors?

it is found to be a negative allosteric modulator of both high and low affinity nAChRs

e-cigarette, or vaping, product-associated lung injery

syndrome that can be produced by vaping and that has the following features: dyspnea, nonproductive cough, chest pain, nausea and vomiting, abdominal pain, diarrhea, fever, and an unusual lung pathology shown by the appearance of ground-glass opacities in CT scans

bupropion (zyban)

drug that inhibits DA and NE uptake and is also a weak nAChR antagonist. it is used in the treatment of tobacco dependence

varenicline (chantix)

Partial agonist at high affinity α4β2 nAChRs. It is used for treating nicotine dependence.

caffeine

stimulant drug found naturally in coffee and tea. It is also consumed in tablet form and in various beverages such as drinks and energy drinks

major sources of caffeine?

• coffee beans (coffea arabica)

• tea leaves - theophylline

methylxanthines

class of naturally occurring chemicals that include caffeine and theophylline

how long does it take to completely absorb caffeine through the gastrointestinal tract?

within 30 to 60 minutes following consumption into the bloodstream.

paraxanthine

biologically active caffeine metabolite that exerts CNS stimulant activity like the parent compound

what are the biphasic effects of caffeine?

• low doses - stimulant effects

• high doses - reduced activity and anxiety-like symptoms.

what are common positive side effects of caffeine?

• stimulate arousal, increase concentration and reduce fatigue

at high doses, specifically exceeding 400mg, what are some side effects with caffeine that may occur?

tension, jitteriness, and anxiety

low or intermediate doses of caffeine have what sort of positive subjective effects?

• feelings of well-being, enhanced energy or vigor, increased alertness and ability to concentrate, self-confidence, increased work motivation, and enhanced sociability

what are some ergogenic (performance-enhancing_ effects of caffeine?

increased force of muscle contraction, enhance arousal and alertness, reduced perceived exertion and reduced feelings of muscle pain

what are the physiological responses to acute caffeine administration?

• increase blood pressure, respiration rate, enhanced water excretion, stimulation of catecholamine release from the adrenal medulla

caffeine intoxication

disorder produced by recent high-dose caffeine use and characterized by symptoms of restlessness, nervousness, insomnia, and physiological disturbances including increased heart rate, muscle twitching and gastrointestinal upset

caffeine dependence syndrome

disorder produced by chronic high-dose caffeine use and characterized by caffeine craving, difficulty controlling caffeine consumption, caffeine tolerance and withdrawal symptoms that occur following abstinence

what are the three criteria for caffeine use disorder?

• difficulty in reducing caffeine use

• continued use despite knowledge of adverse physical and psychological effects

• withdrawal symptoms upon abstinence from caffeine

adenosine

blockade of receptors for this substance is responsible for caffeine’s stimulant effects

which receptors are the most important for how adenosine affects the brain?

a1 AND a2a

A1 receptors

mostly found in areas like the cerebral cortex, hippocampus and cerebellum

A2A receptors

concentrated in the striatum and olfactory bulb, especially in brain cells that also have dopamine (DA) receptors

what happens when adenosine binds to A2A receptors?

reduces the ability of dopamine to activate D2 receptors, lowering arousal and activity levels

what happens when adenosine levels are low?

D2 receptors work freely, helping us feel more awake and alert

what happens when adenosine levels are high?

D2 activity is blocked making us feel more tired

how does caffeine affect adenosine receptors?

it blocks them, especially A2A, which stops adenosine from interfering with dopamine, which boosts alertness and energy