WEED

Question 1

What is marijuana made from?

Answer 1

flowering hemp (cannabis sativa)

Question 2

what was hemp used for?

Answer 2

fiber was used for rope, cloth, paper

medical reasons too!

Question 3

what are active ingredients in marijuana classified as?

Answer 3

hallucinogens

Question 4

what are the main compounds in marijiana

Answer 4

there are 70 unique compounds: cannabinoids, plus 400 identified ones
main ones:
psychoactive: THC
CBD: lower affinity for receptor, lacks intoxicating effects but maybe medicinal effects?

Question 5

what does marijuana act as an agonist on?

Answer 5

endogenous neurochemical system: endocannabinoids

Question 6

where is cannabinoid receptors expressed?

Answer 6

hippocampus, stritum, nac, pfc and amygdala

Question 7

what are the 2 types of receptors?

Answer 7

CB1: CNS (main effects)
- heteroreceptors to inhibit release of NTs
CB2: immune system, bone, fat cells, GI tract

Metabotropic (inhibitory)

Question 8

what are the effects of THC on CB1 receptors?

Answer 8

reduced locomotion, hypothermia, hypoalgesia, hyperphagia, cognitive deficits (CB1 recpetors)

if you block CB1 receptors with antagonist (rimonabant) you see reduction in these effects

Question 9

what is rimonabant?

Answer 9

CB1 receptor antagonist

Question 10

What are the two main endocannabinoids?

Answer 10

Anadamine (AEA): partial agonist -weight loss drug that caused depression
2-AG: full agonist
- on CB1

Question 11

describe metabolism of endocannabinoids?

Answer 11

anadamine: FAAH (fatty acid amide hydrolase)
2-AG: MAGL (monoacyl glycerol lipase)
- if you block these enzymes you increase endocannabinoid transmission

Question 12

Describe retrograde transmission.

Answer 12

• endocannabinoid synthesized on demand in response to depolarization and increased calcium influx on post syanptic cell.
• cross cleft (cause its lipid soluble) and activate CB1 receptors on nerve terminals (often GABA or glutamate terminals)
• net effect varies on cell type

Question 13

describe 2 other ways cannabinoids effect neural activity

Answer 13

non retrograde: anadamine activated a cannabinoid or TRPV1 (ion channel that causes depolarization) on postsynaptic cell

Activate receptors on nearby astrocytes resulting in extrasynatpic glutamate relase.

Question 14

what is TRPV1 responsible for?

Answer 14

depolarizing ion channel.

processing pain, mood, motor function, learning and memory

Question 15

what are the functions of endogenous cannabinoids?

Answer 15

• clarified through antagonist and KO mice
  Pain perception
  Nausea
• used as a cancer treatment for these 2 reasons
  Feeding/appetite
  learning/memory

Question 16

describe pain perception of cannabinoids? what type of pain is it most effective at treating?

Answer 16

• reducing CB1 transmission increases pain sensitivity
• stimulating cb1 receptors with agnoinsts reducies pain sensitivity
• work in brain and spinal cord
• effective at treating neuropathic pain (in cns not body) while opiods suck at this.

Question 17

describe nausea function onf canabioids

Answer 17

increasing cannabinoid activity reduces nausea and vomiting for a variety of conditions
- site of action in medulla (CNS)and gut (PNS)

Question 18

describe feeding behaviors of cannabinoids?

Answer 18

enhance motivational properties of food and stimulate appetite.
- CB1 receptors reduce food consumption in animals and humans
- Brain and GUt effects
AM6545 CB1 antagonist acts on periphery (doesn’t cross BBB) and reduces fod intake

Question 19

describe the learning and memory effects of endocannabinoids?

Answer 19

extinction of learned responses rather than acquisition.
- they don’t lose their fear conditioining (can’t overwrite the memory)

CB1 KO mice do not show normal extinction of freezing response (same with antagonists)
- maybe they have a role in overwriting previously established memories (or emotional associations)

Question 20

How is marijuana absorbed and metabolized? describe blood levels

Answer 20

inhaled or orally (oral is lower and more variable)
Vaporized: easy to absorb THC particles that enter lungs, rapid rise in blood levels

• dose, potency of plant, patterns of smoking (breathold) have an effect

concentrations decline because of liver metabolism and accumulation in fat stores (its very lipid soluble)
- rapid decline not just liver but cause its dispersing in the body and brain.

complete elimination is much slower cause its stored in fat tissues
- slowly leaks out ( weeks or months)

Question 21

what is marijuana’s half life?

Answer 21

+ 20 hours

Question 22

what is reverse tolerance?

Answer 22

• reverse tolerance (not feeling high the first time) may be related to becoming more experienced and holding breath better.

Question 23

what are the subjective effects of marijuana?

Answer 23

buzz, high, stoned, come down.

Question 24

what are physical responses to marijuana?

Answer 24

heart rate, bloow flow, eyes flushing increased hunger

transient psychotic symptoms (depersonalization, derealization, agitation, paranoia (its adverse for some people)

Placebo can produce these effects too

Question 25

when does maximum intoxification occur?

Answer 25

when plasma levels of THC are declining, after cigarette is finished. not yet equilibrated when plasma peaks, due to diffusions of THC between brain, plasma and fat stores.

Question 26

how does weed effect your behavior?

Answer 26

cognitive and psychomotor performance - impairs spatial verbal memory, time estimation, reaction time, intefere with all aspects of memory (encoding, consolidation, retrieval) - similarly induced in animals (systemically or in hippocampus)

Question 27

effects of weed with chronic use?

Answer 27

no overdose reports smoking can damage lungs reduce testosterone in men impair immune resistance and adverse effects on fetuses (animal studies) Impaired executive functioning for 2-3 weeks after stopping use. (some long term users show even more impairment PFC kinda stuff )

Question 28

how does chronic weed use effect youth

Answer 28

In youth: inversely related to academic performance, linked to amotivational syndrome (but we don't know if that's a preexisting trait or not)

Question 29

what brain abnormalilites is chronic weed use related to?

Answer 29

- Anterior cingulate (frontal lobes) regulating emotional and behavioral inhibition. - chronic users showed reduced activation here (in response to faces) meaning that they have maybe a deficit in appropriately judge emotional cues.

Question 30

What is weed's link to schizophrenia?

Answer 30

Smoking in youth with genetic predisposition can lead to schizophrenia (val/val + smoking = schizo) - Polymorphism in COMT (metabolizes dopamine faster in frontal lobes)

Question 31

What is weed's link to dopamine?

Answer 31

chronic cannabis is linked to impaired dopaminergic function in striatum, may play a role in long term mood disturbances, motivation, cognition, cannabis use disorders

Question 32

Are cannabinoids reinforcing?

Answer 32

Driven by CB1 receptors - regular users can tell THC from placebo and prefer it. - blocking CB1 receptors reduces effects Animals: story unclear. One monkey study did self administer, blocked by CB1 antagonist rimonabant. Rodents don't self administer THC tho - they have administered CB1 agonists, and show a place preference but only when exposed in home cage. other studies can't replicate this. THC less reinforcing compared to other drugs in animals. Implicated in reinforcement, dependence and relapse for ethano, nicotine and cocaine.

Question 33

How does weed effect PFC and striatum DA levels?

Answer 33

THC: increases PFC DA THC: mixed results for striatal DA (even tho other cannabinoid drugs increase DA in accumbens) - cannabinoids stimulate firing of DA neurons via inhibiting GABA release in VTA (cause there are no CB1 receptors on DA neurons) - in other drugs, they all activate mesolimbic DA pathway

Question 34

How do opiods work with cannabinoids?

Answer 34

reinforcing effects mediated by opiods possibly (in the monkey study, if opioid antagonist was give, it reduced self administration -unclear in humans

Question 35

Describe tolerance to marijuana.

Answer 35

repeated exposure causes tolerance. | - pharmodynamic tolerance (desensitization and down regulation)

Question 36

Describe withdrawal to marijuana

Answer 36

high doses of THC leads to withdrawal in animals udner certain conditions (tremors, shakes, increased grooming, hunched) - easier with precipitated withdrawal (not really spontaneously occuring) in humans: after chronic use is much less severe (102 weeks): irritability, increased anxiety and aggressiveness, depressed mood, sleep disturbances, decreased appetite - maybe its not so bad because it stays in body for so long?

Question 37

what is precipitated withdrawal?

Answer 37

give animal large amounts of drug,then give then an antagonist and see withdrawal symptoms

Question 38

what is dependence to marijuana?

Answer 38

manifested as a difficulty stopping use, craving for marijuana, unpleasant withdrwawl symptoms. - risk of dependence is related to USE patterns. people who use it daily have 50% probability of becoming dependent. - driven by withdrawal symptoms usually

Question 39

Describe the switch from recreational to chronic use?

Answer 39

5% people used it in some way. begins in adolescence and peaks in young adulthood - not tried it by mid twenties, less likely they will start it - don't show addictive profile of other drugs (alcohol, nicotine, cocaine) 10% of those who use it become dependent - overall risk is 20-25% - usually temporary and recovery rates are higher

Question 40

is weed a gateway drug?

Answer 40

no. risk factors that lead to heavy maijiana use are the same for hard drug use (family problems, drug use by family/peers, dislike school, early age) users with early postive responses to use have greater risk of becoming dependent harder drug use decreased after legalization but its best not to use in adolescence cause brain is developing and weed has effect in the brain.