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Drugs and Behavior > Exam 3: Cannabinoids > Flashcards

Exam 3: Cannabinoids Flashcards

1
Q

for the cannabinoid system was the receptor iscovered first or the endogenous ligand for the receptor

A

receptor first in 1988 - recent

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2
Q

psychoactive cannabinoids exert their effects by interacting with the ____

A

endocannabinoid neurotransmitter system

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3
Q

what are the 2 natural endocannabinoids

A

anandamide

2-AG (2-arachidonylglycerol)

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4
Q

on-demand synthesis and release of cannabinoids requires

A

increased calcium ions in postsynaptic neuron!!!

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5
Q

endocannabinoids are generated from

A

inositol phospholipids in the membrane that have fatty acid arachidonic acid

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6
Q

what converts NAPE into anandamide

A

phospholipase D

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7
Q

what is the precursor to 2-AG

A

DAG

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8
Q

2-AG and anandamide are taken up by

A

endocannabinoid membrane transporters on glial cells

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9
Q

COX-2

A

breaks down both 2-AG and anandamide

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10
Q

FAAH

A

breaks down anandamide into arachidonic acid and ethanolamine

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11
Q

MAGL

A

breaks down 2-AG into arachidonic acid and glycerol

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12
Q

2 cannabinoid receptors

A

CB1 and CB2

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13
Q

general description of cannabinoid receptors

A

inhibitory
metabotropic
- inhibit cAMP formation, voltage sensitive Ca channels, and they open K channels
presynaptic heteroreceptors - retrograde signaling

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14
Q

CB1 receptors

A

located on axon terminals
presynaptic - typically on glutamate or GABA neurons
concentrated in brain and spinal cord!!

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15
Q

CB2 receptors

A

most abundant outside CNS (for in CNS it is hippocampus and cerebellum)
immune system, bone, fat, GI tract
expressed by microglia

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16
Q

what is a partial agonist at CB1 receptors ONLY

A

anandamide

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17
Q

what is a full agonist at CB1 and CB2 receptors

A

2-AG

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18
Q

3 endocannabinoid signaling mechanisms discovered

A
  1. retrograde signaling
  2. anandamide remains in postsynaptic cell and activates a canabinoid receptor or TRPV1 receptor
  3. endocannabinoids activate receptors on nearby astrocytes, resulting in release of glutamate
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19
Q

endocannabinoid always synthesized in…

A

POSTSYNAPTIC element!!!

inc in intracellular Ca in postsynaptic triggers it

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20
Q

endocannabinoid retrograde signaling

A

CB1 receptors are activated by 2-AG and inhibit Ca mediated neurotransmitter release

CB1 receptors found on synapses with MGlu5 receptors in hippocampus and cerebellum

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21
Q

negative feedback mechanism for regulating glutamate

A
  • glutamate activates MGlu5 receptor
  • this inc intracellular Ca and triggers 2-AG synthesis and release
  • 2-AG diffuses across synapse and activates presynaptic CB1 receptors
  • inhibits voltage gates Ca channels and reduces glutamate release
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22
Q

TRPV 1 receptors in brain

A

regulate pain processing, mood, motor function, learning and memory
- spicy foods

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23
Q

cannabis

A

marijuana and hemp produced from the cannabis plant

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24
Q

2 most abundant cannabinoids

A

THC and CBD

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25
Q

what is marijuana potency dependent on

A

THC content

it varies deending on growing conditions and the genetic strain of the plant

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26
Q

cannabis indica

A

female plant, 3-7 ft tall, less than 5% THC - growing towards 10%
stringer/smellier “skunk weed”

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27
Q

cannabis sativa

A

most common
grows up to 18ft tall
produces 1-5lb of buds/smokable leaves
low level of THC (less than 3%)

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28
Q

what differs between cannabis indica and sativa

A

indica is more potent has more THC

both have same pharmacodynamics

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29
Q

sinsemilla

A

without seeds
no pollination
highest level of THC (5-11%) very potent THC

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30
Q

resin (hashish) thc content

A

15-20%

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31
Q

hash oil THC content

A

exceeds 60%!! - moe potent than smoking a bud from the actual plant

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32
Q

what has happened to the potency of thc cannabis overtime

A

it has dramatically increased

33
Q

what class is marijuana

A

schedule 1 drug
- recretional use legal in 18 states
medical use lgeal in 37 states
BUT federally it has no accepted medical use

34
Q

ROA for marijuana

A

inhalation: smoking (joints, pipes, bongs)
- typical joint has 0.5-0.8g cannabis with 8% THC
- vaporization: inhalation, ingesting water vapor

oral: edibles - pills, brownies, gummies
topical: oils/creams marketed for local activity, high CBD, low THC

Dabbing: cannabis extracted with butane to form waxy residue with high THC

35
Q

absorption of marijuana

A

smoking:
- THC easily absorbed by lungs
- 20-70% original THC in joint reaches lungs (only 30% enters circulation)

oral administration: GI tract, delayed onset of action, dec bioavailability

  • first pass metabolism - low and variable blood concentrations
  • 50% THC metabolized to 11-OH-THC before entering circulation
36
Q

distribution of marijuana

A

high lipid solubility - cannabinoids persist in body for long time - weeks to months if chronic user (crosses BBB and placental)

THC carried by blood and deposited in organs

Depot binding!!! - accumulates in fat stores over long period of time it is released into circulation - can detect on drug test for a while

smoked/vaped: rapid onset of action
oral: delayed onset but lasts longer

37
Q

metabolism of marijuana

A

oral: first pass metabolism

- 50% THC metabolized to 11-OH-THC

38
Q

excretion of marijuana

A

55% excreted as feces!!!
20% in urine

blood THC levels decline quick but complete elimination is much slower due to fat tissue

39
Q

psychoactive annabinoids exert their effects by interaction with the ____

A

endocannabinoid neurotransmitter system

40
Q

where are CB1 and CB2 receptors found?

A

CB1: cns, lungs, liver, kidneys
- presynaptic heteroreceptors regulate releas of other neurotransmitters

CB2: immune system, GI tract

41
Q

mechanisms of reinforcement

A
  • activation of mesolimbic DA system

- cannabinoids INDIRECTLY stimulate firing of DA neurons in VTA an enhance DA release in nucleus accumbens

42
Q

are CB1 receptors expressed by DA neurons?

A

NO
- cannabinoids activate CB1 receptors in GABAergic neurons of VTA reducing local GABA release
which releases DA neurons from inhibitory effects of GABA increasing cell firing

43
Q

THC effect on user: amygdala

A

panic/paranoia

44
Q

THC effect on user: basal ganglia

A

slower reaction time

45
Q

THC effect on user: brain stem

A

antinausea effects (medulla) and suppressed pain

46
Q

THC effect on user: cerebellum

A

impaired coordination

47
Q

THC effect on user: hippocampus

A

impaired memory, forgetful

48
Q

THC effect on user: neocortex

A

altered thinking, judgement, sensation, PFC changes

49
Q

THC effect on user: nucleus accumbens

A

euphoria - indirectly activate DA

50
Q

THC effect on user: spinal cord

A

altered pain sensitivity

51
Q

THC: learning and memory

A

cannabinoids suppress induction of long term potentiation (needed for learning) in the hippocampus by inhibiting glutamate neurons

long term potentiation aka learning requires glutamate!!

  • spect imaging shows reduced blood flow to hippocampus
52
Q

THC: pain

A

CB receptors in the PAG in brainstem on cells that process pain signals - lots of CB1 in PAG, lots of CB2 in spinal cord
activating CB1 will shut down the PAG and block pain signals from getting to brain

CB1 and CB2 receptors regulate both pain perception and the cognitive-affective responses to pain

53
Q

what receptors does CBD oil target vs THC

A

CBD oil targets CB2R

THC targets both CB1 and CB2

54
Q

effects of cannabinoid use depend on

A

dose
frequency of use
characteristics of user - male or female
setting

55
Q

what is the “high” associated with

A

euphoria, exhiliration, sense of disinhibition

56
Q

relaxation is the most common reported effect of being___

A

stoned

sensroy rxns: floating sensations, enhances visual and auditory perception, visual illusions, slowing of time

57
Q

how much to smoke and eat to get mild euphoria

A

2mg smoked

5mg eaten

58
Q

how much to smoke or eat to get perceptual and time distortions

A

7mg smoked

17mg eaten

59
Q

how much to smoke or eat to get hallucinations, delusions, disortions of body image

A

15mg smokes

25mg eaten

60
Q

is there a lethal dose?

A

NO
LD50 ~ 1:40,000
nearly 1,500 lbs of marijuana in about 15 min to kill onself - you wuld die of smkoe inhalation first

61
Q

acute effects

A

inc flushing of skin, blood flow o skin, inc HR, vasodilator (blood shot eyes), pupils dilate

inc hunger

reduced motor activity/drowsiness

62
Q

what brain regions involved in THC effects on hunger/feeding behavior

A

VTA and Nucleus Accumbens: enhanced pleasure from eating (why does this taste so good)

Limbic system: enhanced palatability (getting creative in kitchen)

Stomach and SI: regulates ghrelin, appetite stimulating hormone

Hypothalamus: inc craving/food intake

63
Q

effects of cannabinoids on psychomotor performance

A

acute exposure produces deficits in driving ability
- slow rxn time, poor coordination, drowsiness

bigger effects when marijuana combined with alcohol or other drugs

64
Q

smoking marijuana can sometimes produce transient psychotic symptoms

A

agitation, paranoia

  • expectation also plays role in what effects the drug will produce
65
Q

acute effects cannabinoid

A 
impaired verbal learning and memory 
impaired working memory 
impaired attention
impaired inhibitory control and other executive functions
impaired psychomotor function
66
Q

chronic effects cannabinoids

A

impaired verbal learning and memory
impaired attention; attentional bias
possibly impaired psychomotor function
possibly impaired executive function

67
Q

recovery of function with abstinence

A

likely persistent effects on attention and psychomotor function
possibly persistent effects on verbal learning and memory

68
Q

amotivational syndrome

A

chronic cannabis use associated with aimlessness, dec motivation, lack of planning, dc productivity

69
Q

cannabis and educational performance

A

inverse relationship
inc cannabis dec educational performance
poor academic performance can also inc canabis use

70
Q

tolerance

A

regular users report tolerance to behavioral and subjective effects
memory impairment, motor coordination, accelerated time passage

71
Q

PET imaging shows

A

widespread decreases in brain CB1 receptor binding in regular marijuana smokers

  • receptor binding recovered following abstinence from cannabis within a few days
72
Q

chronic cannabis exposure could change brain

A

unclear if brain abnormalities occurred prior to or after marijuana use

impaired striatal dopamine function: long term disturbances in mood, motivation, cognition

73
Q

physical health

A

smoking marijuana damages lungs
- smoke contains tar, carcinogens, carbon monoxide

regular marijuana smoking is associated with various respiratory symptoms

risk of heart attack significantly elevated during the hour after smoking marijuana, even ppl in 20s or 30s

74
Q

reproductive consequences

males and females

A

males: developing breast tissue due to inc release of breast-feeding hormone prolactin
- reduced sperm production and motility, erectile dysfunction

females: menstrual cycle irregularities
if used during pregnancy crosses placenta to fetus
- adverse effects may persist through adulthood

75
Q

medical uses of cannabis: cancer

A

reduces nausea and vomiting associated with chemo

limited evidence showing reduced tumor growth in patients

76
Q

medical uses of cannabis: weight

A

promotes weight gain in disorders that diminish appetite

77
Q

medical uses of cannabis: pain

A

reduces neuropathic pain from trauma or surgery

78
Q

medical uses of cannabis: glaucoma

A

relieves intraocular eye pressure

79
Q

medical uses of cannabis: autoimmune disease

A

inhibits immune system functioning

appears effective for multiple sclerosis

Drugs and Behavior (27 decks)

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