Stimulants and Alcohol

Cocaine - intake

• Snorted in powder form

• Smoked in its free-base form (crack)

Cocaine - Peak concentration

30-60 minutes

Cocaine - molecule type

Lipophillic

• Easily penetrates the blood-brain barrier

Cocaine - Half-life

30-90 minutes

• For those who use it regularly, it will clear body quicker – tolerance

Cocaine - Lethal dose

1 gram (pure)

Cocaine - short-term effects

Stimulant, increases:

• Euphoria

• Energy

• Confidence

• Talkativeness

• Activity

• Alertness

• Attention

Doesn’t give you more energy, just feels like it

Mono-amines

• Serotonin

• Dopamine

• Norepinephrin

• Epinephrin

Action of cocaine and mono-aminergic synapses

1.     Monoamines are made by enzymes

2.     Packaged into vesicles

3.     Neurotransmitters released from vesicles at synaptic cleft

4.     NTs bind to receptors on post-synapse

Reuptake channels

Clears NTs from synaptic cleft (reabsorption)

Reuse it, can pick it up, repackage it (in vesicle) and use it again.

Cocaine and reuptake channels

Blocks them

• NT does not get reabsorbed through reuptake pump

• Stays in synaptic cleft in a higher concentration

• Monoamines sit in synaptic cleft for longer

• Effect of NTs is stronger

However

• NTS are not being recycled

• Enzymes have to produce more, new monoamines

• Reduction in neurotransmitter production

Activity at noradrenergic synapses

Supresses arousal and plateau

• Sympathetic nervous system

• Noradrenalin – vasoconstriction

• Blood cannot flow into genitals

E.g. cocaine often causes erectile dysfunction

Cocaine Long-Term Effects - Comedown

• The lack of reuptake results in depletion of monoamines (serotonin, noradrenaline,…)

  • “crash” into depression after several hours

• This is usually remedied by taking more cocaine.

  • 2-3 day cocaine “binges”

• Binges – keep taking cocaine to keep low level of neurotransmitter in the synapse

  • Doesn’t keep working → leads to a crash

Cocaine Long-Term Effects - Health Consequences

• Destruction of the nasal septum

• Schizophrenia-like symptoms:

  • Hallucinations

  • Delusions of Persecution

  • Mood Disturbances

  • Repetitive Behaviours

Cocaine - Physiological effects

• Sexual dysfunction

• Tolerance

  • Need to take more to achiever the “desired” effects, such as euphoria, confidence

• Sensitisation

  • Only need to take a little for other effects, such as convulsiveness, stereotyped behaviour, addictiveness

Cocaine Addictiveness

Direct effect on Dopamine released in the N. Accumbens and Prefrontal Cortex

• Therefore, direct activation of the “seeking” or “reward” pathway

• Strong “psychological” addictiveness, much less physical addictiveness

Functions of monoamines with cocaine

Dopamine does not make you feel alert or on top the world – could be noradrenaline or serotonin

• Dopamine = addiction

• All monoamines = side effects

Cocaine Legal Status

CLASS A:

• Illegal to possess

• Illegal to sell

• Illegal to give away

• Possession: up to 7 years + unlimited fine

• Dealing: up to life + unlimited fine

 

Types of Amphetamines

• Speed (d-amphetamine): often taken orally

• Crystal Meth (methamphetamine): often smoked

• Ecstasy (MDMA): usually taken orally

• Mephedrone, Methadrone, Methylone (cathinone derivatives): snorted or orally

Amphetamines: Uptake speed and half-life

• It depends on the drug and the method of taking it

• Cross blood brain barrier with ease

Amphetamines and monoaminergic channels

Similar to cocaine

• Do not block reuptake channels

• Move NT in the wrong direction

• No action potential needed.

Ritalin (methylphenidate)

• Acts similar to cocaine by blocking monoamine reuptake transporter

• Release is more gradual

• Not the same immediate effects as cocaine

• Is an effective treatment for ADHD

Caffeine - intake

Coffee or soft drinks

Caffeine - Peak concentration

~40 minutes

Caffeine - molecule type

• Lipophillic

• Easily passes through blood-brain barrier

Caffeine - half-life

3.5-5 hours (longer in children)

Caffeine - Lethal dose

100 cups of coffee (10g of caffeine)

Caffeine’s Short-Term effects

• Increases alertness and wakefulness

• Induces clear thinking

• Induces restlessness

• Difficulty with fine movements

• Increases cardiac contractions

• Constricts blood vessels – increases blood pressure

Caffeine - Methodological issues

• Participants in study are instructed to not drink caffeine before study

• Therefore, they are going through withdrawal

• Drinking it would then make you more alert and clear thinking

Caffeine short-term side effects - Health consequences

• Anxiety

• Insomnia

• Change in mood

• Hypertension

Caffeine Physiological Action

Block adenosine receptors -> stop vasodilation -> higher blood pressure (vasoconstriction)

Associations of adenosine

• Inducing sleep

• Vasodilation

• Stimulates adrenaline release from adrenal medulla

Caffeine Long-term effects

Mostly sleep deprivation (especially slow wave sleep)

• Effects can be countered by using more caffeine to wake up in the morning

Caffeine - Physical dependence

Withdrawal symptoms include:

• Headaches (vasodilation)

• Sleepiness

• Irritability

• Difficulty concentrating

Caffeine - Psychological dependence

It increases dopamine release in the n. Accumbens.

• Evidenced by Adenosine receptors in the dopamine system

Caffeine legal status

Legal and available in drinks, over-the-counter headache medicine, etc.

• Headache medication – aspirin, paracetamol, and caffeine.

• Caffeine -> vasoconstrictors -> release pressure

Nicotine Short-Term effects - vomiting

• Effects brainstem area that affects nausea

• Develop tolerance to that effect very quickly

Nicotine Short-Term effects - Muscle tone

Reduces (relaxes)

• Reduction of withdrawal symptoms (craving makes you tense)

Nicotine Short-Term effects - Health consequences

• Reduces weight gain

• Increases heart rate and blood pressure

Nicotine Physiological Action

• Binds to nicotinic Acetylcholine receptors

• Nicotinic receptors are involved in the stimulation of the sympathetic nervous system, including the release of adrenaline from the adrenal gland

• Nicotinic receptors are also found in the brain

Nicotine Long-term effects

• The body easily develops tolerance

• Possibly wears out the heart more quickly

• Major problems are from other components of tobacco (and cigarette smoke), which can cause cancer, cardiovascular disease, etc

Nicotine Addictiveness

A large component of physical dependence: Withdrawal symptoms include:

• Craving

• Irritability

• Increased appetite

• Insomnia

Evidence for addictiveness of nicotine

• Injections of nicotine or saline

• Nicotine injection = increase dopamine in nucleus accumbens

• Saline = Small spike, significantly less than nicotine.

Nicotine Legal Status

• Legal to sell to most people

• Illegal to sell to people under 18 years old

Alcohol - intake

Usually ingested (mostly as drinks)

Alcohol - Peak concentration

30-90 minutes

Alcohol - Molecule type

Easily crosses the blood-brain barrier

• Both Lipophillic and Hydrophillic

Alcohol - Elimination

• Through the liver

• Breaks down at a steady rate

Alcohol Short-Term effects - low effect

• Mild euphoria

• Anxiolytic effect (lowers anxiety)

Alcohol Short-Term effects - high effect

• Slower reflexes

• Incoordination

• Sedation

• Memory problems

Alcohol Physiological Action - Agonist

GABA-A receptors (increases inhibitory processes)

Alcohol Physiological Action - Antagonist

NMDA receptors (suppresses excitatory processes)

Alcohol Long-term effects

• Cirrhosis of the liver: liver failure

• Brain damage (especially hippocampus: Korsakoff’s syndrome)

• Foetal alcohol syndrome

Alcohol Addictiveness - Physical dependence

• Tolerance is induced even from one night of drinking and results in mild withdrawal symptoms (hangover)

• After chronic use, there are very strong withdrawal symptoms (Delirium Tremens); this can be fatal

Alcohol Addictiveness - Psychological dependence

• It increases dopamine release in the n. Accumbens (as do other NMDA receptor antagonists)

• Strong heritable component to alcoholism

Alcohol Legal Status

Complex age laws:

·      Illegal to give to children under 5

·      5-18: specific rules about buying alcohol and entering pubs

·      Legal to buy and consume by anybody over 18

·      Driving under the influence can have heavy consequences