Drugs, Brain and Behaviour (16): Nicotine, Tobacco and Acetylcholine

Nicotine

The primary psychoactive and addictive compound in tobacco (Nicotiana tabacum).

Main Effect of Nicotine

Causes addiction and drives behavioural effects of smoking.

Forms of tobacco use

• Cigarettes (most common)

• Cigars

• Pipes

• Smokeless tobacco

• e-cigarettes.

Cigarette Smoke Composition

• Nicotine

• Carbon monoxide

• Tar

• Thousands of chemicals (many carcinogens)

Nicotine Absorption & Nicotine Distribution

Rapidly absorbed through the lungs. Nicotine reaches the brain in ~10–20 seconds.

Nicotine Metabolism

Occurs in the liver.

Main Nicotine Metabolite

Cotinine - Marker of Nicotine exposure.

Half-Lives Nicotine & Cotinine

• Nicotine: Approximately 2 hours

• Cotinine: Longer than nicotine

Smoking Behaviour and Dosing

Frequent dosing maintains Nicotine levels.

Nicotinic Acetylcholine receptors (nAChRs)

Ligand-Gated Ionotropic Receptors activated by both acetylcholine and nicotine.

Acetylcholine (ACh)

Neurotransmitter involved in:

• Attention

• Memory

• Muscle activation

Nicotine Mechanism

Mimics Acetylcholine and activates nAChRs→ Increases neuronal activity and neurotransmitter release.

Nicotine and Reward Pathway Activation

• Nicotine directly activates VTA dopamine neurons.

• Increases dopamine release in the nucleus accumbens (dependant on VTA activation)

Addiction Mechanism of Nicotine

Dopamine release reinforces nicotine use.

Other Neurotransmitters Affected by Nicotine

• Norepinephrine: Increased arousal and alertness.

• Serotonin: Mood regulation.

• Glutamate: Learning and memory enhancement.

• GABA: Inhibitory control.

Overall Effect of Nicotine

Combination of stimulation and relaxation.

Effects of Nicotine (depending on Dose)

Low–moderate dose Effects:

• Alertness

• Concentration

• Euphoria

• Reduced appetite

High dose Effects:

• Nausea

• Dizziness

• Vomiting

Cognitive Effects of Nicotine

Improved:

• Attention

• Working memory

• Reaction speed

Withdrawal Relief Effect

Cognitive benefits often reflect relief from withdrawal.

Nicotine & Rapid Delivery

Fast brain entry increases addiction potential.

Frequent Dosing Effect on Behaviour

Multiple puffs reinforce behaviour repeatedly.

Conditioned Cues

Smoking becomes associated with environments and behaviours.

Cue-induced Craving

Environmental triggers cause urges to smoke.

Nicotine Self-Administration

Animals will voluntarily take nicotine.

Tolerance

Reduced response after repeated nicotine use.

Mechanism of Tolerance

• Receptor Desensitisation

• Upregulation

Upregulation

Increase in receptor numbers with chronic exposure.

Nicotine Dependence

Compulsive use and difficulty quitting.

Withdrawal symptoms of Nicotine

• Irritability

• Anxiety

• Poor concentration

• Increased appetite

• Craving

Begins within hours, peaks in days, lasts weeks.

Relapse Cause

Smoking relieves withdrawal symptoms.

Smoking Health Risks

• Lung cancer

• Cardiovascular disease: Increased risk of heart disease and stroke

• Respiratory disease: Includes chronic bronchitis and emphysema.

Mechanism of Smoking Risks

Nicotine causes addiction; smoke causes most physical harm

Carbon monoxide (CO)

Gas in smoke that reduces oxygen delivery. Binds haemoglobin and strains the heart.

Tar

Sticky residue in cigarettes containing carcinogens → Damages lungs and increases cancer risk.

E-cigarettes

Devices delivering Nicotine via vapour without combustion. Fewer toxic combustion products than cigarettes.

Concerns about Vaping

• Still addictive and long-term effects unclear.

• “Gateway” to cigarette use: May increase Nicotine use in young people.

Smoking Cessation difficulty

Due to:

• Addiction

• Withdrawal

• Environmental cues.

Nicotine Replacement Therapy (NRT)

Provides controlled Nicotine doses to reduce withdrawal (e.g. Patches, gum, lozenges).

Smoking Cessation Medications

Varenicline and Bupropion.

Behavioural Support for Nicotine Addiction

• Counselling

• Habit-change strategies