Cocaine and Stimulants

Question 1

What are the 2 determinants that drive drug epidemics?

Answer 1

Low perceived risk.

High supply.

Question 2

What’s different about crack cocaine?

Answer 2

Chloride removed, acts as weak base…

Can be vaporized at relatively low temperatures -> smoked.

Question 3

Does blocking dopamine receptors work for cocaine addiction / OD? Why / why not?

Answer 3

No. There’s no naltrexone/naloxone for cocaine.

Other neurotransmitters, such as glutamate, GABA, dynorphin/enkephalin are also involved.

Question 4

Why is cocaine + EtOH more common than what you would expect by chance?

Answer 4

Reduces anxiety from cocaine.

Cocaethylene metabolite formed is psychoactive.

Question 5

What is actually measured in the urine in drug tests for cocaine?

Answer 5

Benzoylecgonine - a metabolite.

Question 6

2 most severe CNS toxicities of cocaine?

Answer 6

Seizures, strokes.

Question 7

4 cardiac complications of cocaine use?

Answer 7

Angina
Myocardial infarction
Cardiomyopathy
Myocarditis

Question 8

Why can cocaine cause a perforated nasal symptom?

Answer 8

Chronic vasoconstriction -> necrosis.

Question 9

What happens in long-term sensitization to cocaine?

Answer 9

Same amount of drug produces greater craving afterward, correlated with increased dopamine in the brain. (though the euphoria experienced actually decreases).

Question 10

Mechanism of long-term sensitization?

Answer 10

Upregulation of NMDA and AMPA receptors in the dopaminergic neurons of the VTA.

Question 11

Part of brain most affected in chronic cocaine use?

Answer 11

Frontal lobes -> poor judgment / increased impulsivity.

Question 12

Is addiction more driven by need for high, withdrawal symptoms, or by craving?

Answer 12

By craving.

Question 13

Does short-term rehab work well?

Answer 13

Nope.

Question 14

What’s one effective short-term treatment for cocaine addiction?

Answer 14

“Contingency Management”: Reward abstinence with vouchers for stuff.
(gains don’t last, though)

Question 15

What treatment for cocaine addiction is longer-lasting?

Answer 15

CBT - but it’s still not great.

Question 16

3 possible medications that could be used for cocaine addiction?

Answer 16

Topiramate
Disulfiram
Cocaine vaccine.

Question 17

How would Topiramate help cocaine addiction?

Answer 17

Maybe by blocking AMPA/Kainate receptors in the VTA.
And increasing GABA signaling.
(it’s an anticonvulsant)

Question 18

What’s the MoA of disulfiram? What enzymes does it target?

Answer 18

Chelates copper, which targets…
Dopamine beta hydroxylase (DA -> NE)
Plasma esterases (cocaine breakdown)

Question 19

How might disulfiram help cocaine addiction?

Answer 19

Increased dopamine and decreased NE might cause cocaine not to have as much effect?
Might cause cocaine to cause more paranoia?

Question 20

Problem with disulfiram for cocaine addiction?

Answer 20

Because it inhibits plasma esterases, cocaine can reach dangerously high concentrations when taken.

Question 21

Idea behind a cocaine vaccine? Has it worked?

Answer 21

IgG neutralizing cocaine will keep in from crossing the BBB.

Proof-of-principle has been demonstrated, but the vaccine isn’t very immunogenic.