Psych 3822 Chapter 7: Nicotine and Caffeine

Where is nicotine found

Found in leaves of tobacco plants and tar particles.

What is the primary psychoactive ingredient in tobacco?

Nicotine

What is the most commonly used tobacco product?

Cigarettes.

Amount of nicotine in a cigarette

Contain about 10 mg nicotine, but only 1 to 2 mg gets absorbed when smoking

Amount of nicotine in a cigar

The amount of nicotine varies tremendously (5 mg to 350 mg!)

Tobacco products

Cigarettes, cigars, water pipes/hookahs, smokeless tobacco products (e.g. chewing tobacco, snuff, dipping tobacco), e-cigarettes (e.g. vaping)

Are water pipes safer than smoking cigarettes?

No, that is a misconception. You inhale more tar, smoke, nicotine, and carbon monoxide through a water pipe than you would from smoking a cigarette.

Smokeless tobacco products

e.g., chewing tobacco, snuff, dipping tobacco. No inhalation, but you're still at risk of developing various cancers

Vaping

Involves inhalation of vaporized nicotine (atomizer makes fine spray)

Vegetable glycerin

added to e-cigarettes to make "smoke" visible (may cause lipid related lung injury)

Amount of nicotine in a vape/e-cigarette

.3 to 4 mg of nicotine in 15 puffs

How have smoking rates changed among Americans?

The number of smokers is declining

Despite the decline in smoking cigarettes, there is a(n increase or decrease?) in vaping

Increase

Where are tobacco smoking rates the highest?

In parts of Europe, Asia, Central America, and South America. For example, more than 60% of males smoke in Russia and China.

In which Canadian province is smoking most prevalent?

Newfoundland

Which Canadian province has the highest average daily cigarette consumption

Nova Scotia

Secondhand smoke exposure associated risks

Cancer and heart disease. In kids: asthma, bronchitis, pneumonia, ear infections, SIDS

Thirdhand smoke

Remnants of tobacco smoking on material in the smoker's local environment (skin, hair, clothing, walls). Risk to young kids

What population is particularly vulnerable to thirdhand smoke exposure

Young children are at risk

How is nicotine absorbed when smoked

Mucous membranes (mouth, nose, throat) and lungs

How is nicotine absorbed when consuming tar

Tar from tobacco smoking sticks to the mouth, nose, throat, and lungs. Nicotine leaches from the tar.

Flue Curing

Treating leaves with vented heat (for cigarettes). Changes pH of tobacco smoke (making the smoke more acidic). Allows smoke to be inhaled (cigarettes). The large surface area of the lungs provides a very effective route for nicotine to be absorbed into the bloodstream.

How does flue curing alter how we absorb smoke?

Smoke is naturally basic. The harsh feeling of the basic smoke doesn't allow you to absorb the nicotine through your lungs, it is instead absorbed through the mouth. Flue curing makes the smoke more acidic, which gives it a smoother feeling when smoked, so it is more likely to be inhaled into the lungs. The lungs have a large surface area, which allows for absorption

*Peak absorption for cigarette smoke

Peak absorption varies, but on average 7 minutes

*Peak absorption for non-inhaled tobacco

About 20 minutes

*Peak absorption for e-cigarettes

About 20-30 minutes, which suggests nicotine is mostly absorbed through mucous membranes

How might smokers alter behaviours to adjust the amount of nicotine absorbed

They may adjust the number of cigarettes, duration, and depth of inhalation

How might vapers alter behaviours to adjust the amount of nicotine absorbed

They may adjust the level of heating used in the vaporizer

What injury may be caused by vegetable glycerin

Lipid related lung injuries caused by the fatty acids aerosolized by vapes

Where is nicotine primarily metabolised

Mostly in the liver by CYP-2A6 enzymes

*What enzyme breaks down nicotine

CYP-2A6 enzymes

*Nicotine is metabolized into

Cotinine, an active metabolite with a long 17 hour half-life

*Cotinine

Nicotine is broken down into this active metabolite. The amount of cotinine present in the bloodstream reflects how much nicotine they consumed. It binds to the same receptors as nicotine, but very weakly.

Cotinine half-life

It has a long half-life of 17 hours

Nicotine half-life

About 2 hours

Polymorphisms influence CYP-2A6 activity levels

Reduces metabolism of nicotine, prolongs nicotine effects (smoke less to achieve desired effect), common in Asians

What happens to your enzymes the more you smoke?

Enzymes build up and nicotine is metabolized more quickly.

Nicotinic ACH receptor: Ionotropic or metabotropic?

Ionotropic.

Is nicotine an agonist or antagonist for the nicotinic ACH receptor.

It is an agonist. When bound to the receptor site, positive ions flow into the neuron: Ca2+, Na+, K+, depolarizations

What happens when nicotine binds to a nicotinic ACH receptor?

Nicotine has biphasic effects: It first activates the receptor by opening the channel (agonist). Then, the receptor enters a desensitized state: the channels close and the receptor cannot be activated (functional antagonism). Desensitization occurs when nicotine is still bound to the receptor, In time, desensitized state ends and receptors can be activated again

Desensitization of nicotinic ACH receptors

Even though nicotine is still bound to the receptor, the receptor enters a desensitized state: the channels close and the receptor cannot be activated

Upregulation of ACH receptors

The brain compensates for the repeated closing of nicotinic receptor channels by upregulating the number of nicotinic receptors. You end up with more nicotinic ACH receptors expressed on post synaptic neurons.

How does the brain compensate for the desensitization of nicotinic ACH receptors?

By upregulating the number of nicotinic receptors

Distribution of Nicotinic Receptors: Peripheral Nervous System

In the ganglia of the ANS (sympathetic and parasympathetic). Overall activation increases sympathetic nervous system

Distribution of Nicotinic Receptors: Neuromuscular junctions

Postsynaptic side of neuromuscular junction in the somatic NS (critical for voluntary muscular contraction)

Distribution of Nicotinic Receptors: Central nervous system

Receptors are found in structures important for arousal and cognitive functioning (i.e., the hippocampus and cerebral cortex), motor functioning (i.e., the basal ganglia), and in the reward circuitry of the brain (i.e., VTA and the NA) where they increase dopamine...

What neurotransmitters does nicotine impact (he said we probably won't be tested on this)

Dopamine, glutamate, GABA, norepinephrine, serotonin, vasopressin

How does nicotine impact the nucleus accumbens?

Infusion of nicotine into the nucleus accumbens increases dopamine release in the nucleus accumbens

Two main physiological effects of nicotine

Main effects are on the cardiovascular system and appetite. Additionally, physiological effects are either acute or chronic

Effects of nicotine on the cardiovascular system

Heart rate and blood pressure. First cigarette of day increases heart rate and blood pressure, then, decreased responsiveness due desensitization state of receptors (acute tolerance)

Effects of nicotine on appetite

Reduces appetite

Effects of nicotine on movement

Depends on use (naïve or habitual users). Hand tremors increased in naïve users. Tolerance occurs over time. Increased purposeless behaviors in chronic users (e.g., finger tapping)

Does nicotine use increase purposeless or purposeful behaviours in chronic users?

Increases purposeless behaviours

Effects of nicotine on cognition

Improves attention, vigilance, information processing speeds (e.g. Stroop Test). Improved memory (word recall). Cognitive effects present in naïve users only (tolerance effect)

What subjective effects (negative or positive) do naïve nicotine users report

Naïve users report negative subjective effects. Nausea, disequilibrium, tension, jitteriness, confusion. Acute tolerance to these effects

What subjective effects (negative or positive) do habitual nicotine users report

Habitual users report positive subjective effects. Feelings of vigor, arousal, reduced fatigue. Habitual users likely to become addicted

How are researchers able to get rats addicted to nicotine

Rodents do not become addicted to nicotine unless a special paradigm is used due to the negative subjective effects for naïve users. Get them to press a lever for sucrose first, then start mixing bigger and bigger amounts of nicotine into the sucrose until tolerance to aversive effects develops and they're taking nicotine with no sucrose involved.

Nitrosamines

Chemicals in tobacco that promote cancerous tumor growth. Carcinogens make direct contact with the mouth, throat, esophagus and lungs. So you can see these types of cancer

Adverse effects of tobacco

Emphysema (COPD), Cardiovascular disease (Blood vessels to narrow and restrict. May lead to stroke, heart attack. Women who smoke have an increased risk of breast cancer. They may also begin menopause at an earlier age than women who don't smoke. During pregnancy: Tobacco causes slower gestational development, preterm births, low birth weight. This is due to the chemicals in smoked tobacco,but also the reduced oxygen to the fetus.

Adverse effects of tobacco during pregnancy

Tobacco causes slower gestational development, preterm births, low birth weight. This is due to the chemicals in smoked tobacco, but also the reduced oxygen to the fetus.

Adverse effects of tobacco: Cardiovascular disease

Blood vessels to narrow and restrict. May lead to stroke, heart attack.

Adverse effects of tobacco for women

Women who smoke have an increased risk of breast cancer. They may also begin menopause at an earlier age than women who don't smoke.

Substance use disorder criteria many nicotine users fit

Continue to use despite knowledge of adverse effects (disease) and desire to quit

Nicotine abstinence syndrome

Includes: craving, irritability, anxiety, hostility, concentration difficulties, impatience, insomnia

Chippers

Light smokers who fail to develop an addiction (~ 1/3 of all smokers). May smoke the same as non-chippers, but fail to show significant pharmacological effects, and fail to show withdrawal (can take it or leave it).

Smoking Cessation strategies: Cold Turkey

Abruptly and completely stopping the use of a habit-forming substance or behavior without gradual tapering

Smoking Cessation strategies: Nicotine replacement

e.g. nicotine patches, gum. Deliver small amounts of nicotine to help get rid of cravings

Smoking Cessation strategies: Varenicline (Chantix)

A partial agonist of nicotinic ACH receptors. Less activation of nicotinic receptors (reduces effectiveness of nicotine)

Smoking Cessation strategies: Bupropion (antidepressant)

Increases DA which may compensate for reduced DA in reward pathway with nicotine withdrawal

What is the best predictor of success in quitting smoking?

Research suggests that making it to two weeks of nicotine abstinence is the best predictor of success.

How many smokers relapse before 2 weeks of nicotine abstinence?

70-80% relapse before 2 weeks, so only 20-30% make it that far

How many smokers make it to 6 months of nicotine abstinence?

~50%

Without help, how many smokers make it to one year of nicotine abstinence?

3-5% without help

Caffeine

Mild psychostimulant of the xanthine family. Found in a number of plants: Kola nuts (colas) and coca tree nuts (chocolate), tea leaves and coffee beans. One of the most widely used drugs

How much caffeine does the average person consume per day?

227 mg per day

Mixing caffeine with alcohol

Caffeine has been introduced in alcoholic beverages. They have a mixture of alcohol and energy drinks. Some have been banned because they temporarily counter alcohol's effects which can lead to excessive drinking and alcohol poisoning.

How is caffeine administered?

Orally, mostly through beverages, but also food (e.g. chocolate) and pills (caffeine pills)

How is caffeine absorbed?

Across intestinal walls

Caffeine peak concentrations

At around 40 minutes

What barriers does caffeine cross?

Penetrates the blood-brain barrier and placental blood barrier

Where is caffeine metabolized?

In the liver

When caffeine is metabolized, what does it break down into?

Caffeine metabolism results in the two other naturally occurring xanthines: theobromine and theophylline. Also paraxanthine (all active metabolites).

How does nicotine impact the metabolism of caffeine?

Smoking increases CYP-1A2 enzymes leading to increased metabolism of caffeine (caffeine is metabolised more quickly).

How does taking antidepressants impact the metabolism of caffeine?

Antidepressants decrease CYP-1A2, which slows metabolism of caffeine

Caffeine half-life

Half-life varies tremendously (3-10 hours). Especially with use of nicotine (decreased) or antidepressants (increased)

Would caffeine half-life increase or decrease with the use of nicotine?

Decrease, metabolized more quickly

Would caffeine half-life increase or decrease with the use of antidepressants?

Increase, metabolism is slower

Adenosine (nucleoside)

primary role in the control of sleep

Where in the brain are adenosine receptors found and what are their functions?

ACh neurons in the cerebral cortex (produces drownsiness). DA neurons in the basal ganglia (slows movement)

How does caffeine affect adenosine receptors

Caffeine is an adenosine receptor antagonist. Caffeine reduces drowsiness and increases motor activity

Physiological, behavioural, and subjective effects of caffeine

Increases heart rate, blood vessel constriction, increases breathing rate, reduces appetite, increases attention and alertness, and produces positive mood

What is the daily caffeine limit for adults?

Recommended no more than 400mg per day

What is the daily caffeine limit for adolescents?

No more than 100mg per day

Caffeinism & symptoms

A clinical condition caused by the excessive consumption of caffeine. Agitation, anxiety, insomnia, negative mood, rapid heart rate and high blood pressure

What withdrawal symptoms were present in those who consumed 548 mg caffeine a day?

90% reported headaches, 85% experienced cravings, most reported difficulty concentrating, fatigue, irritability, anxious or depressed mood

Can caffeine use lead to tolerance?

Tolerance occurs with many subjective effects: Positive mood, improved alertness, anxiousness. Tolerance may not occur to physiological effects: Cardiovascular activity and blood vessel constriction.Chronic use leads to features of dependence.

Why is caffeine not considered a drug that can generate substance use disorder?

It doesn't pass the "common sense" test. We don't think about drinking coffee as something that is bad for you.

*Concerns about misuse of caffeine in adolescents

In one study (Bernstein et al, 2002), 22% of teenagers (average 244 mg per day, ranging from 49 mg to 767 mg) met criteria for substance abuse disorder. Other concerns include teenagers consuming energy drinks that have way more than the recommended daily limit of 100 mg per day.