Pharm 13 - Drugs of Abuse 1 - Cannabis

Question 1

Where in the brain is euphoria induced?

Answer 1

Nucleus accumbens (ventral striatum) - dopamine released here

Question 2

General pharmacodynamics of drugs of abuse, why is there euphoria?

Answer 2

Ventral tegmental area = area where there are dopaminergic cell bodies

These cell bodies project onto the nucleus accumbent (ventral striatum)

Known as mesolimbic dopamine system –> central reward pathway

Question 3

Rank the routes of administration from slowest to fastest

Answer 3

1. Eat - GI tract, very slow absorption
2. Snort - mucous membranes of nasal sinuses. Slow absorption
3. Inject - veins, rapid absorption
4. Smoke - small airways and alveoli, rapid absorption

Question 4

What is the classification of drugs of abuse

Answer 4

1. Narcotics/painkillers - opiate like drugs e.g. heroin
2. Depressants - alcohol, benzodiazepines, barbiturates
3. Stimulants - cocaine, amphetamines, caffeine, methamphetamine
4. Miscellaneous - e.g. cannabis, ecstasy

Question 5

Which is the most potent cannabinoid

Answer 5

Delta-9 tetrahydrocannabinoid

D9-THC

Question 6

Which cannabinoid may reduce some of the negative effects of THC?

Answer 6

Cannabidiol

Question 7

The negative symptoms of cannabis seem to be more dose related

Answer 7

Y

Question 8

Describe the bioavailability of cannabis when orally taken and when inhaled

Answer 8

Orally = 5-15%. Delayed onset, slow metabolism, first pass metabolism

Inhalation = 25-35%

Question 9

Cannabinoids are VERY lipid soluble substances. What does this mean

Answer 9

It slowly accumulates in fatty tissues (poorly perfused), and in long term smokers it can slowly leak back into the blood

Question 10

What is the metabolite of D9-THC which is even more potent than D9-THC

Answer 10

11-hydroxy-THC

This metabolite of cannabis (metabolised in the liver) is more potent than D9-THC

11-hydroxy-THC more likely to accumulate in fat

Question 11

What is the problem with enterohepatic cycling and cannabis

Answer 11

Cannabis is very lipid soluble, so if trying to eject cannabis out of the gut in bile, it will just keep getting reabsorbed by the SI

Question 12

There is a poor correlation between plasma cannabinoid concentration and degree of intoxication.

Answer 12

Y

Question 13

There is an endogenous cannabinoid system. What are the receptors involved and where are they?

Answer 13

CB1 receptor - hippocampus / cerebellum / basal ganglia / cerebral cortex

CB2 receptor - Immune cells

Question 14

What type of receptors are cannabinoid receptors and how are they linked to Adenylate cyclase

Answer 14

G-protein coupled receptors

Negatively linked to adenylate cyclase - They are depressants

Question 15

Name an endogenous cannabinoid-like substance produced

Answer 15

Anandamides - binds to CB receptors

Question 16

How does cannabis cause euphoria

Answer 16

Central reward pathway (VTA and Nucleus Accumbens) is inhibited by GABA.

Cannabis binds to CB1 receptors and causes disinhibition of GABA - causes dopaminergic neurones to start firing

Question 17

Which part of the brain does cannabis affect that is to do with performance monitoring and behavioural adjustment?

Answer 17

Anterior cingulate cortex - deals with error detection

Cannabis causes hypoactivity of this area

Question 18

Why does taking cannabis stimulate hunger?

Answer 18

Cannabis has positive effect on neurones in the lateral hypothalamus

Inhibits GABA (which inhibits Melanin Concentrating Hormone - MCH) - stimulating appetite

Cannabis directly stimulates orexin production (hormone/neurotransmitter which stimulates appetite)

Question 19

Cannabis is an immunosuppressant, how?

Answer 19

It has a negative effect on various immune cells.

Decreases B/T cell count, decreases cytolytic activity of NK cells, etc

Question 20

What other effects can cannabis have?

Answer 20

1. Memory loss - affects limbic regions and downregulates BDNF
2. Pyschomotor performance - cerebral cortex depression
3. Tachycardia / vasodilation (conjunctivae) - via TRPV1 receptor which stimulates Ca influx

Question 21

The medulla has very low CB1 receptor expression. Why

Answer 21

Low CB1 expression means cannabis cannot influence cardio-respiratory control, so you can’t OD on cannabis

Question 22

When can upregulation of CB receptors be regulatory?

Answer 22

in multiple sclerosis, pain, stroke (ischaemic vasoconstriction)

Question 23

When can up regulation of CB receptors be pathological?

Answer 23

Fertility / obesity (obesity when up regulation of CB receptors in adipocytes)

Question 24

When are agonists for CB receptors used?

Answer 24

To treat conditions where up regulation of CB receptors is regulatory

Question 25

Give examples of CB receptor agonists

Answer 25

1. Dronabinol - used to increase appetite in AIDS patients
2. Nabilone - antiemetic drug - prevents nausea and vomiting in chemo patients

Both dronabinol and nabilone are types of THC

3. Sativex - used to treat severe/moderate spasticity in multiple sclerosis patients

Question 26

Name a CB receptor antagonist and its purpose

Answer 26

Rimonabant - anti-obesity medication but also caused depression

Question 27

What percentage of cannabis elimination is gut and what is urine

Answer 27

Gut = 65%

Urine = 25%

Question 28

What is the Half life of cannabis

Answer 28

7 days in tissue