Cannabinoids

Question 1

% of THC in leaves/flowers/stems can be dried and then smoked, like tobacco

Answer 1

(0.3 – 30% THC)

Question 2

% of THC hashish

Answer 2

(up to 60% THC)

Question 3

% of THC hash oil

Answer 3

(up to 90% THC)

Question 4

THC effects

Answer 4

analgesic; euphoriant or sedative; anxiolytic or anxiogenic; appetite stimulant; hallucinogen

Question 5

possible clinical use in treatments

Answer 5

glaucoma; anorexia; and to reduce nausea associated with chemotherapy

Question 6

most pharmacologically active of the 61 cannabinoids

Answer 6

Δ-9 THC

Question 7

Pharmacokinetics

usually inhaled or taken orally; oral administration leads

Answer 7

“first-pass” metabolism

Question 8

smoking is 3-5 times more potent even though only about

Answer 8

20%-30% of drug present is actually absorbed

Question 9

oral bioavailability ~

Answer 9

4-12%

Question 10

liver metabolism converts THC to a more potent metabolite

Answer 10

11-hydroxyl-THC

can lead to perception of a slower but more intense high

Question 11

THC and many metabolites are very

Answer 11

lipid soluble;

Question 12

behaviorally significant levels of THC within

Answer 12

5 minutes when smoked;

Question 13

peak effects w/in

Answer 13

30 min that last around 3 hr; oral administration peaks

~ 30 min – 2 hr

Question 14

metabolized by liver enzyems ….

Answer 14

several CYP-450 enzymes

Question 15

main metabolite

Answer 15

11-hydroxy-Δ9 THC

Question 16

½ life

Answer 16

20-96 hr for THC; about 50 hr for some of its metabolites.

Question 17

Depot binding

Answer 17

means that there are measurable THC levels for up to 2 weeks after a single dose.

Question 18

ED50

Answer 18

5 mg dose;

Question 19

no known LD50 so TI very

Answer 19

high….lol

Question 20

most THC stored in….

Answer 20

fat, then released like a time capsule.

Question 21

unusual elimination; excretion in

Answer 21

urine (1/3) and feces (2/3)

Question 22

acts in brain at

Answer 22

CB-1 receptors;

Question 23

presynaptic; reduces…..

Answer 23

Ca2+ influx to reduce neurotransmitter release.

Question 24

receptor is linked to…..

Answer 24

G-proteins

Question 25

G-proteins can

Answer 25

directly decrease Ca2+ influx increase K+ currents (K+ shunt) via change in cAMP (2nd messenger)

Question 26

Why should there be cannabinoid receptors in the brain?

Answer 26

To bind endocannabinoids

Question 27

endocannabinoids

Answer 27

2-AG more common; more potent at CB-1 receptors; synthesized when Ca2+ enters via VG-Ca2+ channels. best known is anadamide (Sanskrit for “internal bliss”); implicated in brain control of stress, pain and nausea, and learning (LTP); synthesized when Ca2+ enters via GLU receptor activation.

Question 28

Where are cannabinoid receptors?

Answer 28

very high concentrations in cortex (alterations in perception, cognition, affect), hippocampus (alterations in cognition and affect) and basal ganglia and cerebellum (alterations in movement and cognition).

Question 29

Low Dose Effects:

Answer 29

increased sensory processing; slowing of time; decreased anxiety; mild euphoria; increased sense of well-being more open to suggestions and seeing associations between events motor skills often compromised by inability to concentrate completion of complex cognitive tasks reduced due to inability to pay attention; short-term memory decreased ``` appetite stimulated (CB-1 receptors in hypothalamus increase ghrelin release; CB-1 receptors in olfactory bulbs make foods taste better) leading to “munchies” ```

Question 30

A Endocannabinoids 'fine-tune' neurotransmission by

Answer 30

reducing inhibitory transmitter release. Inhibitory GABA terminals in the hippocampus express more CB1 receptors than do excitatory terminals, and consequently they are more sensitive to cannabinoids. This facilitates LTP at adjacent glutamate synapses.

Question 31

THC disrupts the

Answer 31

endocannabinoid system in the hippocampus. THC inhibits the long-term-potentiation of CA3–CA1 synapses by activating CB1 receptors on glutamatergic terminals, inhibiting Ca2+ influx and suppressing glutamate release. This mechanism appears to underlie the detrimental effect of THC on hippocampus-dependent learning and memory.

Question 32

SR 141716A - Rimonabant:

Answer 32

(Acomplia) CB1 inverse agonist

Question 33

WIN 55,212-2:

Answer 33

CB1 agonist

Question 34

Ibipinabant (SLV319, BMS-646,256):

Answer 34

CB1 antagonist

Question 35

High Doses

Answer 35

produce hallucinations, distorted thought, anxiety no known LD50 and no confirmed instances of brain pathology associated with lung irritation and possible concern about cancer chronic use can lead to tolerance and dependence; contributes to abuse potential of THC; endocannabinoids may be at root of “addiction”…for other drugs; food; sex; etc.