Drugs of Abuse: Cannabis

Question 1

Which areas of the brain does cannabis act on

Answer 1

Nucleus Accumbens

Ventral tegmental area

Question 2

Identify the ‘reward’ pathways in the brain activated by drugs of abuse

Answer 2

A rewarding stimulus
Ventral tegmental area -> nucleus accumbens
Nucleus accumbens release dopamine (reward)

Question 3

What are the routes of drugs of abuse administration

Answer 3

Intra-nasal - snort
Oral - eat
Inhalational - smoke
Intra-venous - inject

Question 4

What is the rate of absorption for snorting and eating drugs of abuse and why

Answer 4

Snort - slow absorption - mucus membrane of nasal sinuses

eat - very slow absorption - GI tract

Question 5

What is the rate of absorption for smoking and injecting drugs of abuse and why

Answer 5

Smoke - Rapid absorption as it can return to the left atria/ventricle rapidly to be projected to the brain

Inject - rapid absorption - Must return to the heart and be projected to the pulmonary system first before then being returned to the heart and subsequently brain

Question 6

What are the types of drugs of abuse and give examples of each

Answer 6

Narcotics/painkillers - heroin
Depressants - alcohol, benzodiazepines, barbiturates
Stimulants - cocaine, amphetamine, caffeine, metamphetamine
Miscellaneous - cannabis, ecstasy

Question 7

What is the dosing of cannabis

Answer 7

150mg THC
300mg THC (hashish oil)

Question 8

Describe the oral route of administration for cannabis

Answer 8

5-15%
Delayed onset/slow absorption
First pass metabolism

Question 9

Describe the inhalation route of administration for cannabis

Answer 9

25-35%

50% of a drug will be exhaled out while the remainder of the drug must travel deep into the lungs

Question 10

Describe the pharmacokinetics of cannabis in fat

Answer 10

Slowly accumulates in poorly perfused/less vascularised fatty tissues
Fatty acid conjugates therefore build up in fatty tissue, resulting in concentration ratios between fat and plasma of up to 104 : 1. THC and its hydroxy metabolites (fatty acid conjugates of 11-OH-THC)

Question 11

Describe the relationship between plasma cannabinoid concentration and degree of intoxication

Answer 11

Poor correlation between plasma cannabinoid concentration and degree
of intoxication
Plasma cannabinoid concentration does not give any indication of THC in fat, in the bile or in the gut

Question 12

Describe the elimination of cannabis

Answer 12

In the liver, GIT and urine
Liver - 11-hydroxy-THC - more potent
GIT - 65%, bile + enterohepatic recycling
Urine - 25%

Question 13

How long after smoking a cannabis cigarette will the effects persist in the body?

Answer 13

Can persist in the blood for 30 days

Half life of 7 days in tissue

Question 14

Which receptors are involved in cannabis action

Answer 14

CB1 -hippocampus/cerebellum/cerebral cortex/basal ganglia

CB2 - immune cells

Question 15

Describe the CB1 and CB2 receptors

Answer 15

G-protein (i/o) coupled receptors that are negatively coupled to adenylate cyclase

Question 16

Identify the ‘reward’ pathways in the brain activated by cannabis

Answer 16

1. CB1 stimulated by cannabis
2. Slowing of activity of the GABA interneurone to VTA
3. VTA -> NAcc at a higher rate
4. Dopamine release

Question 17

What are the pharmacodynamic effects of cannabis and the areas which are involved in these

Answer 17

Psychosis, schizophrenia
Food intake (hypothalamus)
Memory loss (limbic)
Psychomotor performance (cerebral cortex)

Question 18

What are the peripheral effects of cannabis

Answer 18

Immunosuppressant

Tachycardia/vasodilation -> conjunctivae

Question 19

What are the effects of cannabis on food intake

Answer 19

Positive effect on orexigenic neurones in the lateral hypothalamus

1. Presynaptic inhibition of GABA increases MCH neuronal activity
2. Increased orexin
   production

Question 20

What are the immunosuppressant effects of cannabis

Answer 20

CB2 receptors are found on immune cells so cannabis causes depressing of activity 
	B cells
	T cells
	NK cells
	M cells 
	Macrophages

Question 21

Explain why cannabis causes psychosis and schizophrenia

Answer 21

Hypoactivity of the anterior cingulate cortex (ACC)

Question 22

What is the function of the anterior cingulate cortex (ACC)

Answer 22

Involved with performance monitoring with behavioural adjustment in order to avoid losses
Error Detection

Question 23

When are CB1 receptors unregulated and where

Answer 23

Liver and adipose tissue

Multiple sclerosis/pain/stroke – regulatory (good)

Fertility/obesity - pathology (contributes to development)

Question 24

What is the onset of cannabis -

Answer 24

Seconds to minutes

Question 25

What is cannabis Sativex and what is it used for

Answer 25

Δ9-THC + CBD
Analgesic
Symptom improvement
MS

Question 26

What is Donabinol and nabilone and what is it used for

Answer 26

-Δ9-THC
Stimulates appetite in AIDS patients and those who have undergone chemo
Prevents feelings of nausea

Question 27

What is anandamide

Answer 27

endogenous cannabinoid with binds to the receptors

Question 28

Describe the expression of CB1 receptors in the medulla and explain its relevance

Answer 28

Low CB1 receptor expression in the medulla.
The medulla is where the cardiorespiratory control resides. Cannabis is not capable of suppressing cardiorespiratory control

Question 29

What is rimonabant used for

Answer 29

Blocks the effects of the cannabinoid

Anti-obesity