Lecture Notes on Cocaine, Amphetamines, Caffeine, and Nicotine

Methods of Cocaine Intake

• Snorting: Powder is placed on mucous membranes inside the nose for absorption via blood vessels.

• Smoking: Crack cocaine is smoked, allowing rapid entry into the bloodstream.

  •  leads to quicker peak effects compared to snorting.

Pharmacokinetics of Cocaine

• Reaches peak in blood at 30-60 min

• Cocaine is lipophilic, easily crossing the blood-brain barrier.

• Half-life = 30-90 mins

  • Regular users clear the drug more quickly due to tolerance.

  • Clearance rate depends on body fat percentage, frequency of use, and body size.

Cocaine's Effects

• Users report feeling good, confident, euphoric, and full of energy.

  •  increased talking, activity, alertness, and focus (though sometimes scattered).

  • Cocaine doesn't add glucose but creates the feeling of increased energy.

Mechanism of Action

• Cocaine affects monoaminergic synapses (those using monoamines as neurotransmitters).

• Monoamines include serotonin, dopamine, and noradrenaline (norepinephrine).

Synaptic Transmission

• Neurotransmitters (e.g., dopamine, serotonin) are synthesized and packaged into vesicles.

• Action potentials trigger the release of neurotransmitters into the synaptic cleft.

• Neurotransmitters bind to receptors on the postsynaptic side.

• Autoreceptors provide negative feedback, regulating neurotransmitter release.

• Reuptake channels recycle neurotransmitters from the synaptic cleft back into the presynaptic terminal.

Long term effects:

• Lack of reuptake results in depletion of monoamines

  • "crash" into depression after several hours

• Usually remedied by taking more cocaine

  • 2-3 day cocaine binges

• Destruction of nasal septum

• Schizophrenia like symptoms

  • Hallucinations

  • Delusions

  • Mood disturbances

  • Repetitive behaviours

• Sexual dysfunction

• Tolerance for desired effects goes up

Reuptake Channels-  reduce neurotransmitter concentration in the synaptic cleft, terminating neurotransmission.

• Enable recycling and reuse of neurotransmitters.

• Cocaine blocks reuptake channels, causing neurotransmitters to remain in the synaptic cleft longer and at higher concentrations.

• Cocaine prolongs the effect of released dopamine, serotonin, and noradrenaline.

Autoreceptors vs. Reuptake Channels

• Both are in the presynaptic membrane but have different functions.

• Autoreceptors bind neurotransmitters and trigger internal signaling to stop further release.

• Reuptake channels actively transport neurotransmitters back into the presynaptic terminal.

Interactions with SSRIs

• SSRIs (Selective Serotonin Reuptake Inhibitors) act similarly to cocaine but specifically on serotonin synapses.

  • Combining cocaine and SSRIs may lead to additive effects at serotonergic synapses, potentially causing serotonin syndrome.

  • Cocaine also affects dopaminergic and noradrenergic synapses, unlike SSRIs.

Neurotransmitter Clearance

• Neurotransmitters in the synaptic cleft will eventually disappear through leakage or enzymatic breakdown.

  • Blocking reuptake slows down clearance.

  • The block by cocaine is not perfect; some channels remain open, and cocaine itself is eventually cleared.

Addiction

• Cocaine triggers the compulsion system, leading to repeated drug-seeking behavior.

• Users may dislike the drug's effects but feel unable to stop.

• Cocaine is a textbook example of psychological addiction due to its effect on dopaminergic synapses.

Dopamine's Role

• Dopamine is responsible for addictiveness, but other effects are due to noradrenaline and serotonin.

• Dopamine is not responsible for alertness or feeling "on top of the world".

Legal Status

• Cocaine is a Class A drug, illegal to possess, sell, or give away in the UK.

  • Research requires strict controls and accounting for every milligram.

  • Possession can lead to up to seven years in jail; dealing can lead to life imprisonment.

Amphetamines

• Amphetamines work on the same synapses and reuptake channels as cocaine.

  • diverse group of drugs, including ecstasy.

• Different amphetamines vary in their effects on monoamines, uptake speed, and clearing time.

• Most amphetamines reverse reuptake channels, pushing neurotransmitters out without needing action potentials.

• Some amphetamines, like Ritalin, block reuptake channels like cocaine.

  • Release is more gradual

  • The general effect is increased monoaminergic neurotransmitters in the synaptic cleft.

ADHD Treatment

• The effectiveness of some amphetamines for ADHD may relate to their slow uptake, providing a steady drug level.

• Monoamines are involved in attention, so increasing activity at these synapses helps with attention problems.

  • Amphetamines are also stimulants so they can cause hyperactivity.

  • The mechanism by which amphetamines calm people with ADHD is not fully understood.

Legal Status

• Class B:

  • Illegal to possess, sell and give away

Caffeine

• A commonly consumed stimulant found in drinks like coffee, tea, energy drinks, and soft drinks.

Pharmacokinetics

• Taken through the digestive system, with a delay before entering the bloodstream.

• Concentration in the bloodstream peaks about 40

• Easily crosses the blood-brain barrier.

• Biological half-life = 3.5 to 5 hours but can be longer for children.

Effects

• Increases alertness and wakefulness.

• May improve clear thinking but can also cause restlessness and shakiness.

• Increases cardiac contractions and constricts blood vessels, raising blood pressure.

• Some argue that the cognitive benefits are due to countering withdrawal symptoms in regular users.

Negatives

• Can cause anxiety and insomnia.

• May worsen mood symptoms.

• Contraindicated for individuals with high blood pressure.

Mechanism of Action

• Caffeine blocks adenosine receptors.

• Adenosine is a neurotransmitter involved in sleep induction and vasodilation.

• By blocking adenosine, caffeine promotes alertness and wakefulness.

• It also counters adenosine-induced vasodilation, leading to higher blood pressure and vasoconstriction.

• Caffeine also triggers adrenaline release.

Long-Term Effects

• Insomnia and difficulty concentrating without caffeine are common withdrawal symptoms.

• Withdrawal symptoms occur in the morning as caffeine is cleared from the body overnight.

Addictiveness

• Caffeine is addictive, causing physical dependence.

• Regular users may experience headaches and sleepiness upon withdrawal.

• May also cause irritability and difficulty concentrating.

• Evidence suggests it releases dopamine in the nucleus accumbens, indicating potential psychological addictiveness.

Nicotine

• Comes from tobacco, including nicotine in vapes.

Methods of Intake

• Smoked or vaped, allowing rapid absorption through the lungs.

• Quickly enters the bloodstream and crosses the blood-brain barrier.

• Some studies suggest that a quarter of the nicotine gets to the brain in 7 seconds.

Pharmacokinetics

• Chronic smokers have a biological half-life of about two hours, requiring regular use.

Short-Term Effects

• Induces vomiting (initially, but tolerance develops).

• Regular smokers report relaxation, likely due to reducing withdrawal symptoms rather than a direct relaxing effect.

• Reduces weight gain.

• Increases heart rate and blood pressure.