Chapter 12: Psychomotor Stimulants

Question 1

How is cocaine consumed?

Answer 1

Cocaine HCl is water soluable and can be taken orally, intranasally, or by IV injection.

Cocaine base (including crack cocaine) is smoked.

Question 2

What methods of consumption have the fastest absorption and distribution of cocaine?

Answer 2

1. IV injection

2. smoking

Question 3

How is cocaine metabolized?

Answer 3

Cocaine is broken down by enzymes in the bloodstream and the liver. It has a short half-life of 0.5-1.5 hours, meaning it is quickly eliminated and the high produced may only last 30 minutes.

Question 4

What neurotransmitters does cocaine affect?

Answer 4

1. dopamine
2. norepinephrine
3. serotonin

Question 5

How does cocaine work?

Answer 5

Cocaine blocks the reuptake of DA, NE and 5-HT by binding to their respective transporters and inhibiting the functioning of the transporters. This increases the levels of these neurotransmitters in the synaptic cleft which increases transmission at the affected synapses.

Question 6

Which transporter is most important for cocaine’s effects?

Answer 6

Dopamine transporters

Question 7

How does cocaine affect dopamine transporters?

Answer 7

It inhibits dopamine uptake by:

1. binding to the dopamine transporter
2. increasing the frequency of transient dopamine release events
3. blocking the voltage gated sodium channel (at higher concentrations)

Question 8

What are the acute behavioural effects of cocaine?

Answer 8

1. feelings of euphoria, well-being, and exhilaration
2. heightened energy
3. heightened self-confidence
4. a “rush”

Question 9

What are the chronic behavioural effects of cocaine?

Answer 9

1. irritability
2. anxiety
3. exhaustion
4. total insomnia
5. psychotic symptomatology

Question 10

What are the physiological effects of cocaine?

Answer 10

1. increased heart rate
2. vasoconstriction
3. hypertension
4. hyperthermia
5. seizure (high doses)
6. heart failure (high doses)
7. stroke (high doses)
8. intracranial hemorrhage

Question 11

What is dopamine’s role in the behavioual effects of psychostimulant drugs?

Answer 11

Psychostimulant drugs increase locomotor behaviour through dopaminergic projections in the nucleus accumbens and increase stereotyped behaviours through projections in the striatum. The mesolimbic dopamine pathway is also important for the reinforcing effects of cocaine.

Question 12

What are the neurological effects of chronic cocaine use?

Answer 12

1. abnormal prefrontal cortical functioning
2. reduced dopamine release in the striatum
3. tolerance and/or sensitization
4. cognitive deficits

Question 13

What is incubation of cocaine craving

Answer 13

Increase in drug craving and drug seeking behaviour over time following withdrawal

Question 14

What treatment strategies have been explored for cocaine dependency?

Answer 14

1. cocaine vaccine
2. CBT
3. relapse prevention therapy
4. contingency management
5. pharmacotherapies have been developed but none are FDA approved

Question 15

How are methamphetamine and amphetamine metabolized?

Answer 15

Both drugs are metabolized slowly by the liver, thus causing a longer duration of action than cocaine. Metabolites are mainly excreted in the urine. The half-life ranges from 7-30 hours depending on the pH of the urine. This low rate of metabolism results in a longer-lasting high compared to cocaine.

Question 16

How do methamphetamine and amphetamine work?

Answer 16

They are indirect catecholamine agonists that stimulate release of DA and NE from nerve terminals and block the reuptake of these neurotransmitters. This increases synaptic dopamine levels. At high doses, they also inhibit the enzyme monoamine oxidase which breaks down catecholamines.

Question 17

What are the behavioural effects of amphetamines?

Answer 17

1. increased arousal
2. reduced fatigue
3. feelings of exhilaration
4. sleep delay
5. reduction in sleep time
6. improves performance of simple, repetitive tasks
7. enhances athletic performance

Question 18

How are amphetamines used therapeutically?

Answer 18

Amphetamine and methylphenidate are prescribed for children with ADHD. At relatively low doses, these stimulants produce calming and attention-enhancing effects.

It is also less commonly used to treat narcolepsy.

Question 19

What are the phases of psychostimulant sensitization?

Answer 19

Phase 1: Induction
When psychostimulant sensitization is established. This happens by activating glutamate NMDA receptors and, in some cases, D1 receptors.

Phase 2: Expression
When a sensitized response is manifested. It requires enhanced reactivity of dopamine nerve terminals in the nucleus accumbens.

Question 20

How does MDMA work?

Answer 20

MDMA is a recreational, psychostimulant drug that stimulates serotonin release and it is neurotoxic at high doses.

Question 21

How does methylphenidate work?

Answer 21

It is a prescription psychostimulant typically used to treat ADHD. It activates catecholamine transmission by blocking DAT and NET, thereby increasing extracellular levels of DA and NE.

Question 22

How does modafinil work?

Answer 22

Modafinil is an psychostimulant prescribed to treat daytime sleepiness associated with narcolepsy, obstructive sleep apnea, and being employed as a shift worker. It is a weak DA reuptake inhibitor.