Chapter 13: Nicotine and Caffeine

Question 1

What is caffeine?

Answer 1

Caffeine is a stimulant drug found naturally in coffee and tea.

Question 2

What are the main behavioural effects of caffeine?

Answer 2

1. heightened attention and arousal
2. reduced fatigue
3. reduced sleep
4. enhanced mood
5. improved psychomotor performance
6. increased memory
7. improved sport performance
8. tension (doses +400mg)
9. anxiety (doses +400mg)

Question 3

What are the main physiological effects of caffeine?

Answer 3

1. increased blood pressure
2. increased respiration rate
3. diuresis
4. increased catecholamine release

Question 4

What is caffeine’s main mechanism of action?

Answer 4

It is not entirely understood yet. The psychological and behavioural stimulant effects are mediated by the ability of caffeine to block the A1 and A2A receptors for adenosine which enhanced dopaminergic transmission in the striatum.

Question 5

Describe caffeine tolerance.

Answer 5

Physical dependence and withdrawal symptoms can result from regular consumption of only 100mg daily. This tolerance is generally considered to be harmless. Daily consumption up to 400mg is considered safe, except for pregnant women. Withdrawal symptoms will last a few days and then dissipate.

Question 6

How is caffeine metabolized?

Answer 6

When consumed orally it is readily absorbed from the GI tract and is gradually metabolized and excreted with a typical half-life of approximately 4 hours.

Question 7

What are the clinical uses of caffeine?

Answer 7

1. pain relief

2. treatment of newborns with apnea

Question 8

What is nicotine?

Answer 8

Nicotine is the main psychoactive ingredient in tobacco, e-cigarettes, and electronic nicotine delivery systems like vape pens. It is an alkaloid found in tobacco leaves.

Question 9

How is nicotine consumed?

Answer 9

Nicotine in cigarettes is vapourized at 800 degrees celsius, enters the smoker’s lungs on tar particles in the smoke, passes through the lungs into the bloodstream and quickly reaches the brain. The amount that reaches the bloodstream is dependent on the number and length of puffs.

Small amounts can also pass through the membranes of the mouth and nostrils when tobacco is chewed or snorted.

Question 10

How is nicotine metabolized?

Answer 10

Nicotine is metabolized in the liver by the enzyme CYP2A6. The main metabolite is cotinine which is excreted mainly in the urine along with the other metabolites. The elimination half-life is about 2 hours.

Question 11

What is nicotine’s mechanism of action on postsynaptic cells?

Answer 11

Nicotine stimulates nicotinic acetylcholine receptors (nAChRs) in the brain and the autonomic nervous system. nAChR channels open and allow sodium ions to cross the cell membrane resulting in membrane depolarization and a rapid excitatory response by the postsynaptic cell.

Question 12

Describe the cellular effects of nicotine at high doses.

Answer 12

High-affinity nAChRs desensitize rapidly in the presence of nicotine leading to reduced transmission by ACh. Very high doses of nicotine can cause persistent activation of nAChRs, leading to a temporary depolarization block of the postsynaptic cell. When there is a depolarization block the cell cannot fire again until the nicotine is removed.

Question 13

How do nAChRs work on presynaptic cells?

Answer 13

They enhance the release of neurotransmitters such as glutamate.

Question 14

What are the behavioural effects of nicotine on smokers?

Answer 14

1. increases calmness
2. increases relaxation
3. relieves withdrawal symptoms
4. enhances performance on cognitive tasks

Question 15

What are the behavioural effects of nicotine on non-smokers?

Answer 15

1. tension
2. arousal
3. lightheadedness/dizziness
4. nausea
5. sweating
6. headache
7. palpitations
8. stomach ache
9. enhances performance on cognitive tasks

Question 16

What are the physiological effects of nicotine?

Answer 16

1. release of epinephrine and norepinephrine from the adrenal glands
2. tachychardia
3. elevated blood pressure
4. increased hydrochloric acid secretion in the stomach
5. increased muscle contraction in the bowel
6. increased metabolic rate
7. suppression of appetite
8. respiratory failure (high doses)

Question 17

What are the reinforcing properties of nicotine?

Answer 17

The reinforcing properties of nicotine involve activation of high-affinity receptors located in the VTA, which stimulates burst firing of the dopaminergic neurons and increases DA release in the NAcc.

Question 18

What happens with repeated exposure to nicotine?

Answer 18

1. tolerance
2. sensitization
3. dependence

Question 19

Describe acute nicotine tolerance.

Answer 19

Single doses of nicotine cause a rapid but transient form of acute tolerance that depends on desensitization of nicotinic receptors.

Question 20

Describe chronic nicotine tolerance.

Answer 20

Smokers do not have adverse reactions to high doses of nicotine. They have an up-regulation of nAChR levels in many brain areas, seemingly as a compensatory response to the chronic receptor desensitization associated with repeated nicotine exposure.

Question 21

Describe the mechanisms of nicotine withdrawal symptoms.

Answer 21

Individuals experience withdrawal symptoms upon abstinence. Withdrawal symptoms are mediated by:

1. resensitization of desensitized and up-regulated nAChRs
2. reduced activity of the mesolimbic dopaminergic pathway
3. increased CRF signaling in the central nucleus of the amygdala
4. activation of the nicotine aversion pathway

Question 22

What are pharmacological strategies for quitting smoking?

Answer 22

1. nicotine replacement therapy
2. non-nicotine drugs aimed at reducing craving and withdrawal symptoms
3. anti-nicotine vaccines

Question 23

Explain DiFranza and coworkers’s model of adolescent nicotine dependence.

Answer 23

Smokers pass through successive stages of “wanting,” “craving,” and finally “needing” a cigarette. Once nicotine dependence has developed, cigarettes become compulsory (i.e., smoked in order to alleviate withdrawal symptoms) instead of elective.