Marijuana

Question 1

What is cannabis sativa?

Answer 1

hemp, used as a tough natural fibres
not psychoactive
illegal to grow as can be used to hide psychoactive plants

Question 2

What is marijuana?

Answer 2

dried preparation from flowering hemp

Question 3

What is the psychoactive ingredient in marijuana?

Answer 3

cannabinoids; ~70 different ones

- e.g. Δ9-tetrahydrocannabinol (THC)

Question 4

How can the potency of THC be increased?

Answer 4

preventing the flower from pollinating produces a sticky resin

Question 5

What are the other cannabis derivatives?

Answer 5

hashish-dried resin; from trichrome outgrowths of flower

hash-oil solvents; high in THC ~10-30%

Question 6

What are the routes of administration and their advantages/disadvantages?

Answer 6

smoking; only ~20-40% of THC is absorbed
vaporising; less irritating and more controlled
ingestion; slow but strong effect

Question 7

Medical uses for marijuana

Answer 7

glaucoma treatment
antiemetic; reduces nausea and vomiting
anticonvulsant
enhance appetite
analgesic

Question 8

What is the mechanism of action of cannabinoids?

Answer 8

metabotropic CB1 and CB2 receptors
CB1; found primarily in the brain (basal ganglia, hippocampus, cerebellum, not brainstem)
CB2; found in the immune system, glia

Question 9

Describe the pharmacokinetics of THC

Answer 9

highly lipid-soluble
reaches the brain very rapidly after inhalation
distributes to body fat stores hence rapid decrease in peak conc.
delay between peak plasma levels and subjective high

Question 10

What are the subjective effects of marijuana?

Answer 10

buzz
high
stoned

Question 11

What are the physiological effects of marijuana?

Answer 11

increased HR
blood flow to skin
appetite stimulation
red eyes; vessel dilation

Question 12

What are the undesirable acute effects of marijuana?

Answer 12

psychotic symptoms; depersonalisation, derealisation, agitation
anxiety
impaired judgement
motor impairment
impaired memory recall

Question 13

How are THC effects modelled in animals?

Answer 13

cannabinoids are readily discriminated from other drugs
low doses are reliably administered in monkeys
SA is highly unreliable in rats
dose-dependent effects
- Low; CPP
- High; CP aversion

Question 14

What has been found using synthetic cannabinoids?

Answer 14

animals will reliably self-administer synthetic THC

full agonist at cb1 and 2

Question 15

What is a partial agonist?

Answer 15

intermediate levels of intrinsic activity

becomes an antagonist in the presence of a full agonist

Question 16

What is an inverse agonist?

Answer 16

opposite pharmacological effect at a receptor to an agonist

Question 17

What is THC’s mechanism of action?

Answer 17

partial agonist at CB1

Question 18

What is the function of CB1 receptors?

Answer 18

reward sensitivity
CB1 K/O seem less responsive to rewards and less accumbal DA release
inverse agonist (rimonabant) blocks THC SA

Question 19

What is the mechanism of CB1R?

Answer 19

activation inhibits Ca2+ channels via g-protein

Question 20

What are the endogenous cannabinoids, their structure and mechanism of action?

Answer 20

structurally unrelated to THC
anandamide; partial CB1/2 agonist
2-AG; full CB1/2 agonist

Question 21

What is the functional mechanism of endogenous cannabinoids?

Answer 21

important regulators of synaptic transmission for glut and GABA synapses
retrograde messengers that alter the physiology of the presynaptic terminal

Question 22

What is the behavioural role of endocannabinoids?

Answer 22

hunger
feeding; rimonbant reduces feeding, anandamide increases feeding and pleasurable response to sucrose
social play; amygdala anandamide injections increase social playing juvenile rats

Question 23

What are the effects of repeated cannabinoid exposure?

Answer 23

mixed evidence

• many heavy users do not consume escalating doses
• tolerance can be induced in a few days in animal models
• reduced CB1R following repeated THC
• decision making and risk taking may become impaired
• withdrawal symptoms alleviated by THC

Question 24

What is the risk of THC dependence?

Answer 24

9-10%

Question 25

What is the link between marijuana and psychosis?

Answer 25

6-8% of schizophrenia cases could be prevented by removing cannabis consumption
exacerbates psychotic symptoms in patients
cannabis use has increased but not psychosis rates
common factor might increase cannabis use and schizophrenia risk