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Plants and Pain Flashcards

1
Q

examples of a hallucinogen

A

Psilocibin= mushrooms - and is a serotonin agonist

Ayahuasca
-DMT
-monoamine oxidase inhibitor (increase synaptic serotonin levels)

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2
Q

examples of stimulants

A

coca leaves
-dopamine reuptake inhibitor ( increases synaptic dopamine levels)

tobacco
-stay awake, learn, remember
-cholinergic agonist at nicotinic receptors

coffee bean
-adenosine receptor antagonist

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3
Q

what properties of these plants are the most important?

A

analgesic properties

since the beginning of time we have sought this out, reduction of pain and we have derived these effects from botanical compounds

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4
Q

examples of analgesic drugs derived from plants:

A

salicylic acid (Aspirin) –> from the willow tree

opiates–> morphine, opium, thebaine

cannabis

capsaicin–> chemical ingredient in chilli pepper, topical cream for pain

menthol–> cooling properties

salvinorin–> compound, atypical opioid agonist with psychedelic effects

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5
Q

primary afferents

A

sensory neurons in the periphery (skin, organs)

ones that detect pain are called nociceptors –> there are also touch and temperature

there are two classes of primary afferents : A fibers and C fibers

from skin to spinal cord

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6
Q

A fibers

A

touch, warm temperature

myelinated (fast conducting)

end in specialized structures (Ruffini, pacininan, Meissner)

each structure detects specific NON painful stimuli (touch temp and vibration)

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7
Q

C fibers

A

-unmyelinated (slow coducting)

-end as free nerve endings in the superficial layers of the skin–> even up into the epidermis

-detect many types of painful stimuli (thermal, mechanical, chemical, electrical)

polymodal nociceptor

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8
Q

congenital insensitivity to pain

A

born without nociceptor’s

cannot detect pain

but pain is important for our survival

lifespan is shorter

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9
Q

painful stimuli are detected on __________?

A

free nerve endings of C fibers by specialized receptors

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10
Q

TRPV1

A

activated by heat and capsaicin (capsaicin plants, i.e chillis

causes burning pain

eating something hot opens those receptors

ion channel gated by temperature –> higher than about 40 degrees c

different ligands can also bind

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11
Q

TRPA1

A

-allyl isothionate (mustard oil)
-mustard, wasabi
-burning, inflammation
-different ligands from our immune system can bind

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12
Q

inflammatory receptors

A

neurokinin (NK)

bradykinin (BK)

cytokines

recruitment of immune cells to place of injury

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13
Q

what is Urishol?

A

-found in poison ivy, crosses the skin and initiates an inflammatory reaction that activates NK, BK, and cytokine receptors

causes itch and pain

Toxicodendron radicans = poison ivy

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14
Q

C fiber primary afferents synapse onto ______________ in the dorsal horn of the spinal cord

A

Secondary afferents

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15
Q

secondary afferents carry ___________ information up the spinal cord to the brain

A

nociceptive

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16
Q

pain happens in the ______

A

brain

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17
Q

T or F, “ pain is not processed in one singular part of the brain “

A

True

it emerges from coordinated regions across the brain

e.g. PFC, amygdala, primary sensory area

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18
Q

true or false, “ nociception does not equal pain”

A

true these terms are not necessarily interchangeable

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19
Q

nociception

A

-machine of the body

-relay of pain signal from periphery to the brain

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20
Q

pain

A

the integration of the pain signal with cognitive and emotional context (requires the brain, always a subjective experience)

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21
Q

is it possible to have nociception but not pain?

A

yes this is is possible, for example adrenaline rush

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22
Q

under nociception there are three branches what are they and how are they broken down?

A

sensory= how much it hurts and where

cognitive= context (where am i) memory (have i felt this before)

emotional= does the pain bother me?

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23
Q

can plants inhibit pain at many different levels of the nervous system?

A

yes they can

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24
Q

willowbark

A
  • salicylic acid (aspirin)

-decreases inflammation at the level of the primary afferent nociceptor

-interferes with the inflammatory binding and decreases inflammation and pain

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25
Opioid
any drug that binds to an opioid receptor includes opiates, as well as synthetic opioid agonists (fentanyl, heroin, oxycontin)--> those are not found in opium poppy but hits the same opioid receptor Salvinorin is an opioid
26
opium
is the dried latex obtained from the poppy how we orginally exploited the plant, semi refined substance directly from the poppy
27
opiates
any drug derived from opium
28
Mu opioid receptors
-widely spread out -peripheral neurons and spinal cord widely throughout brain--> opioids make you feel good in the absence of pain as well have analgesic and euphoria effects typical agonists would be : heroin, morphine, oxycodone, fentanyl
29
opioid overdose
inhibits part of brainstem fentanyl and car fentanyl fall asleep and stop breathing
30
opioid receptors are inhibitory _________
G protein coupled receptors 7 transmembrane receptor is very characteristic sets off cascade of signalling activation of opioid receptors--> inhibits neurons
31
morphine is an ______
agonist that activates opioid receptors, but that activation leads to decreased likelihood that the neuron will fire
32
what are the three classes of opioid receptors?
Mu delta kappa
33
Delta opioid receptor
decreases anxiety when activated typical agonists are: some drugs being developed to treat chronic pain conditions like migraine ( SNC80)--> NO botanical drugs that hit delta
34
every single analgesic on the market right now hits the _______ opioid receptor?
Mu opioid
35
kappa opioid receptor
activation leads to --> analgesia, dysphoria, hallucinations -widely expressed on the peripheral salvinorin--> short lasting but intense, limited use for pain
36
mu opioid receptor agonists are....
the gold standard pain killer they are excellent at treating severe, acute pain, but problems may arise with chronic use e.g. opioid addiction epidemic
37
opioid receptors inhibit _________?
nociceptors (C fibers) to block nociception in the spinal cord -blocks the ability of the nociceptor to send signal to the brain
38
dopamine
-involved in motivated behaviour -dopamine neurons are located primarily in the ventral tegmental area (VTA) (small nucleus in the brain)
39
the first time you take morphine there is a very large increase in what?
dopamine
40
opioid receptors in the VTA are located on inhibitory _____________?
GABAergic interneurons
41
opioids inhibit inhibition which is called ?
disinhibition which leads to a increase in dopamine release
42
which is a better analgesic drug, morphine or aspirin?
morphine
43
dopamine is very associated with ________?
addiction
44
we want drugs that alter the ________ and ________ components?
sensory and cognitive drugs that target the sensory as well as cognitive and emotional circuits will always be better analgesics
45
opioid receptors inhibit pain by:
1) decreasing nociception at the level of the C fiber, in the spinal cord and in the thalamus 2) decreasing the emotional and cognitive aspects of pain (makes the pain bother you less)
46
what is the catch 22 of trying to design a good non addictive analgesic?
opioids are good analgesics because they are rewarding (addictive)
47
cannabis
genus of flowering plant contains many bioactive compounds, but most studied are tetrahydrocannabinol (THC) and cannabidiol (CBD) THC is the primary psychoactive compound in cannabis
48
cannabinoids
more of a general name class of chemical compounds that act at the cannabinoid receptors
49
how do cannabinoids work?
cannabinoid receptors come in two flavors: CB1 and CB2 CB1 receptors are among the most abundant GPCR found in the brain, peripheral organs (heart liver fat stomach, testes), and peripheral nerves CB2 receptor distribution mostly on immune cells -inflammatory cells
50
how do cannabinoids work?
cannabinoid receptors are inhibitory G-protein coupled receptors (Gi coupled) cannabinoid receptors are located on the presynaptic membrane cannabinoid receptors leads to a decrease in cyclic adenosine monophosphate (cAMP) accumulation which inhibits the influx of calcium in the firing neuron and inhibits neurotransmitter release decrease synaptic transmission, inhibit neurotransmitter release
51
THC is a ________ agonist at CB1
partial
52
mechanism of action for cannabidiol (CBD)
Is poorly understood, but some evidence it can act act as negative allosteric modulator at CB1 (binds outside the binding pocket to block receptor activation) binds a lot of different targets poorly ( low affinity)
53
is it possible for CBD to blunt psychotropic effects of THC
maybe, we do not know for sure
54
THC general effects
euphoria relaxation disinhibition changes in perception vasodilation increases pulse rate
55
potential therapeutic effects of THC
attenuation of nausea increased appetite decreased intraocular pressure chronic pain relief
56
unwanted effects
-memory impairment -dysphoric state -visual hallucinations -depersonalization -psychotic episodes -anxiety
57
CBD effects
some suggest CBD has therapeutic potential for management of inflammation, anxiety, emesis, nausea, inflammatory pain, and epilepsy ( but usually doses many fold higher than what is biologically possible in vivo
58
pediatric epilepsy
is the only condition in which high-quality clinical data (randomized, placebo-controlled, control clinical trials) patients 2-18 years old with confirmed diagnosis of Dravet syndrome ( genetic disorder associated with severe seizures from birth) oral CBD significantly reduced frequency of seizures more than placebo
59
acute affect's
panic attacks, severe anxiety, psychosis, paranoia, convulsions, hyperemesis, these are rare and usually associated with high doses of THC
60
prenatal effects
cannabis use may lead to neuroanatomical and behavioral changes in offspring. fetal growth affected (particularly neurodevelopment), but dose-response relationship not identified
61
lung cancer
an adverse effect particularly through smoked cannabis
62
driving
driving while intoxicated seems to increase the risk of being in a motor vehicle accident THC impairs perception, psychomotor performance, cognitive functions, and affective functions decreased reaction time
63
is this statement true? " no documented evidence of a death that can be exclusively attributed to overdosing with cannabis, probably because sparsity of CB1 receptors in the brain stem region that controls respiratory and cardiovascular systems
true
64
psychosis does cannabis use in adolescence increase the risk of later developing psychotic disorders such as schizophrenia ?
Met/Met genotype there is no difference between marijuana use and not Val/Met genotype only increases risk if you use marijuana during adolescence Val/Val genotype is highly affected by drug use -correlative data suggesting are more likely to use cannabis use dose-dependently predicts the development of schizophrenia later
65
maybe a trigger in the development of schizophrenia in at-risk populations
66
physiological dependence
compulsive drug-seeking behavior in which the individual uses the drug receptively for personal satisfaction, often in the face of known risks to health
67
physiological dependence
revealed when withdrawal of the drug produces symptoms and signs that are frequently opposite of those sought by the user
68
cannabis withdrawal
is relatively mild and short lived symptoms of restlessness, irritability, mild agitation, insomnia, nausea, cramping, may be worse in chronic, long term users, and may contribute to continued drug use
69
dependence
addiction or substance abuse disorder is defined as the inability to control the use of legal or illegal substances despite negative consequences
70
smoked or vaped cannabis may be effective at treating conditions like:
chronic pain, chemotherapy, induced nausea, etc.
71
is this true or false? "A smoked plant is not ideal because hard to control dose ( different plants have different levels of active drug) "
true
72
have efforts to design synthetic cannabinoids (CB1 and CB2 agonists) been successful
some success but not nearly as effective as smoked cannabis
73
what is the optimal route of administration?
inhalation --> easy to titrate, quick onset
74

BOT 380 (3 decks)

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