Substance Abuse and Drug Addiction

Question 1

What do drugs of abuse increase?

Answer 1

extracellular concentration of dopamine in the nucleus accumbens

Question 2

What acts on the ventral tegmental area (VTA)?

Answer 2

drugs and behaviours such as eating, sex and social interaction

Question 3

What does the VTA do?

Answer 3

produce dopamine and send it to the nucleus accumbens and the prefrontal cortex

Question 4

What is the nucleus accumbens?

Answer 4

the pleasure centre of the brain that leads to rewarding feelings

Question 5

What is the prefrontal cortex?

Answer 5

part of the brain responsible for emotions, learning and impulse control that helps the individual learn and repeat behaviours that lead to rewarding feelings

Question 6

What is experimental evidence for reward circuit involvement of dopamine?

Answer 6

• rats trained to press lever for electrical stimulation to certain brain regions
• when electrode placed in reward circuit (e.g. VTA or NAcc), rat keeps pressing lever because of pleasure elicited by dopamine release
• effect lost if electrode is placed outside reward circuit or if dopamine release is blocked

Question 7

What is a drug?

Answer 7

a substance which has a physiological effect when ingested or otherwise introduced into the body

Question 8

What is a drug of abuse?

Answer 8

a drug that has no medical function or is taken at doses higher than would be required for therapy or homeostasis

Question 9

What do all drugs of abuse result in?

Answer 9

significant toxicities both with short and long-term use

Question 10

What is drug addiction?

Answer 10

a state characterised by compulsive use of a substance resulting in physical, psychological or social harm to the user and continued use in spite of the harm

Question 11

What is tolerance?

Answer 11

to the diminished psychoactive effects after repeat use

Question 12

How does tolerance feed addiction?

Answer 12

users take increasing amounts of a drug to get the desired effect

Question 13

What is drug dependence?

Answer 13

an adaptive state that develops from repeated drug use and which results in withdrawal symptoms upon cessation of drug use

Question 14

What is physical dependence reflected in?

Answer 14

development of tolerance and presence of withdrawal symptoms upon cessation of drug use

Question 15

What does psychological dependence appear as?

Answer 15

a craving for the drug; may not cause physical harm but can lead to drug-seeking behaviour

Question 16

What is withdrawal?

Answer 16

when an individual becomes physically dependent on a drug and their bodies become less capable of functioning normal without it

Question 17

What are withdrawal effects often?

Answer 17

opposite to the effects of the drug itself

Question 18

Give examples of withdrawal symptoms

Answer 18

• feelings of fatigue and depression in cocaine withdrawal
• aches and pains with opioid withdrawal

Question 19

How do drugs increase the release of dopamine?

Answer 19

via the dopaminergic pathways

Question 20

What does artificial dopamine flooding do?

Answer 20

bypass normal controls which leads to a stronger and more prolonged activation of dopamine receptors

Question 21

What can excessive stimulation of dopamine receptors do?

Answer 21

alter the brain’s reward system, reducing sensitivity to natural rewards and increasing the desire for repeated exposure to the triggering substance or behaviour, which can contribute to addiction

Question 22

What are the 6 main types of drugs of abuse?

Answer 22

• stimulants e.g. cocaine, amphetamines
• depressants e.g. alcohol, barbiturates
• hallucinogens e.g. LSD, MDMA
• narcotics (opiates) e.g. opium, heroin
• cannabionols e.g. marijuana
• inhalants e.g. glue

Question 23

What are acute effects of cocaine?

Answer 23

• iIntense feelings of euphoria within 3-5 mins
• increased alertness, elation and energy
• increased sexuality

Question 24

How does cocaine act?

Answer 24

by blocking the reuptake of neurotransmitters like dopamine, noradrenaline, and serotonin in the brain

Question 25

What is the mechanism of action of cocaine?

Answer 25

1. inhibits transporters responsible for reabsorbing neurotransmitters back into nerve cells
2. neurotransmitters accumulate in the synaptic cleft which results in prolonged stimulation of the postsynaptic neurons
3. dopamine signalling is enhanced which causes euphoria, increased energy and reinforces the effects of the drug

Question 26

What are the local anaesthetic properties of cocaine?

Answer 26

it blocks sodium channels which prevents nerve conduction and causes a numbing sensation in the applied area

Question 27

What is the half life of cocaine and amphetamine respectively?

Answer 27

• cocaine - 50-90mins
• amphetamine - 5-10hrs

Question 28

What are acute effects of amphetamine?

Answer 28

diminished fatigue, increased alertness and reduced appetite

Question 29

What is the time of onset of amphetamine?

Answer 29

• injected - immediate
• inhaled - <5 mins
• ingested - >20 mins

Question 30

What is amphetamine made up of?

Answer 30

dextroamphetamine and levoamphetamine

Question 31

What are other forms of amphetamine?

Answer 31

• methamphetamine – can cause the feeling of euphoria and so has a high risk of dependence
• MDMA – can increase energy and sociability and alter perception of facilitated communication

Question 32

What can amphetamine be used to treat and how?

Answer 32

• asthma – bronchodilation
• ADHD – increases attention and focus
• narcolepsy – increases attention, focus and wakefulness
• obesity – dopamine and noradrenaline regulate appetite and food intake; adrenaline suppresses appetite

Question 33

What is the mechanism of action of amphetamine?

Answer 33

1. blocks dopamine uptake
2. inhibits breakdown of dopamine by monoamine oxidases (MAOs)
3. enhances release of dopamine from nerve terminals and vesicles

Question 34

What is amphetamine a substrate of?

Answer 34

dopamine transporter (chemical similar to the natural neurotransmitters dopamine and noradrenaline)

Question 35

What does amphetamine do once inside the cell?

Answer 35

it interferes with the vesicular monoamine transporter (VMAT) and impedes the filling of synaptic vesicles, so vesicles are depleted and cytoplasmic dopamine increases

Question 36

What are narcotics?

Answer 36

pain-relieving drugs with strong addictive properties

Question 37

What are the 3 types of narcotics?

Answer 37

• natural e.g. opium, morphine, codeine
• semi-synthetic e.g. herion
• synthetic e.g. methadone, fentanyl

Question 38

What are acute effects of opiates?

Answer 38

pain relief, euphoria, sedation, relief of anxiety and depression of cough reflex

Question 39

What are withdrawal effects of opiates?

Answer 39

dilated pupils, nausea, vomiting, diarrhoea and yawning

Question 40

What is the mechanism of action of opiates?

Answer 40

they bind to the opioid receptor on the GABA-producing interneurons resulting in the inhibition of GABA release and an increase in dopamine release

Question 41

What are medicinal therapeutics of marijuana?

Answer 41

increased appetite, attenuation of nausea, decreased intraocular pressure and relief of chronic pain

Question 42

What is the active ingredient in marijuana?

Answer 42

delta-9-tetrahydrocannabinol (THC)

Question 43

What is hashish/hash?

Answer 43

more potent than marijuana with similar effects also derived from the resin of the female plant

Question 44

What is the onset time of marijuana?

Answer 44

5-10 mins to last for 1-4hrs

Question 45

What are acute effects of marijuana?

Answer 45

• feeling high or pleasant sensation
• loss of coordination
• memory, judgment, and perception impairment

Question 46

How does THC act?

Answer 46

it mimics an endogenous cannabinol called anandamide which binds to cannabinoid CB1 receptor to inhibit the release of GABA which allows increased binding of neurotransmitters to their receptors

Question 47

What is the reward circuit comprised of?

Answer 47

VTA, nucleus accumbens and prefrontal cortex