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Pmcol 200 > L17 > Flashcards

L17 Flashcards

1
Q

cannabis

A

genus of flowering plant.

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2
Q

bioactive compounds in cannabis

which one is man psychoactive compound

A

tetrahydrocannabinol (THC) and cannabidiol (CBD).

THC is the primary psychoactive compound in cannabis.

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3
Q

cannabinoids=

A 
class of chemical compounds that act at the cannabinoid
receptors.
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4
Q

terpenoids

A

non-cannabinoid constituents,

give plant characteristic smell.

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5
Q

In vitro and in vivo studies found some terpenoids to have anti-____, anti-___ and anti ___ effects

do clinical trials support this?

A

In vitro and in vivo studies found some terpenoids to have anti-inflammatory, anti-bacterial and anti anxiety effects, but no clinical trials
to support this

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6
Q

Possibility of____ between
compounds.

May explain ____ in experience based on
strains, makes harnessing clinical utility very____

A

synergy

differences
difficult

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7
Q

absorption, aka____ =

A

bioavailability

fraction of an administered drug that
reaches effectors (plasma, central nervous system)
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8
Q

most pharmacokinetic information relates to____, only

A

THC

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9
Q

• smoking provides rapid and efficient delivery from ___ to the___.
Bioavailability of smoked THC is___%, reaching peak plasma concentration in ____ minutes.
•when ingested, bioavailability around ___%, time to peak plasma
concentration is ____ hours

A

• smoking provides rapid and efficient delivery from lungs to the brain.
Bioavailability of smoked THC is 25%, reaching peak plasma concentration in 6-10 minutes.
•when ingested, bioavailability around 6%, time to peak plasma
concentration is 2-6 hours

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10
Q

THC is highly ___ so rapidly taken up by tissues with high

____ flow, including heart, lungs, brain and liver.

A

THC is highly lipophilic so rapidly
taken up by tissues with high
blood flow, including heart, lungs,
brain and liver.

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11
Q

• Tissues with less blood flow accumulate THC more ____ and
release it over a ____ period of
time (i.e. adipose tissue)

A

• Tissues with less blood flow
accumulate THC more slowly and
release it over a longer period of
time (i.e. adipose tissue)

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12
Q

THC stored in __ in chronic, frequent cannabis smokers can be released into the blood for
____

A

Fat

days

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13
Q

THC metabolism mostly done where by what

what metabolites produced

A

liver
cytochrome P450 2C9
OH-THC and THC-COOH

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14
Q

•Within 5 days, ___-___% of a THC dose
is excreted, primarily as __,
65% in __ and 25% in __

A

•Within 5 days, 80-90% of a THC dose
is excreted, primarily as metabolites,
65% in feces and 25% in urine

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15
Q

detect THC in urine ___ days for low dose THC,

can extend to
___ in chronic daily cannabis
smokers (because THC is ___
can accumulate in adipose tissue)

A

detect THC in urine 2-5 days for low dose THC,

can extend to
weeks in chronic daily cannabis
smokers (because THC is lipophilic
can accumulate in adipose tissue)

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16
Q

What type of protein receptors are cannabinoid receptors

A

inhibitory
G-protein coupled receptors (Gi
coupled)

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17
Q

cannabinoid receptors come in two

flavors:

A

CB1 and CB2

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18
Q

CB receptors leads to decrease in
____ accumulation which inhibits
the influx of ____ in the firing neuron
and inhibits neurotransmitter release.

A

cAMP

Ca2+

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19
Q

decrease synaptic transmission,

____ neurotransmitter release

A

decrease synaptic transmission,

inhibit neurotransmitter release

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20
Q

THC is a ____ agonist at

___

A

THC is a partial agonist at

CB1

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21
Q

cannabidiol (CBD)

mechanism of action

A

negative allosteric
modulator at CB1 (binds
outside the binding pocket to
block receptor activation)

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22
Q

CBD can blunt ____

effects of ___

A

CBD can blunt psychotropic

effects of THC

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23
Q

•CB1 receptors are among the most abundant ____.

A

•CB1 receptors are among the most abundant GPCRs.

24
Q

•CB1 receptors found in __,__,___
•CB2 receptor distribution mostly on __ ___
Pharmacodynamics

A

•CB1 receptors found in brain, peripheral organs (heart liver fat
stomach, testes) and peripheral nerves.
•CB2 receptor distribution mostly on immune cells.
Pharmacodynamics

25
Q

• Preclinical research suggests CBD has ___ ___ for
management of inflammation, anxiety, emesis, nausea, inflammatory pain,
and epilepsy. May influence effects of ___. Clinical data ___ for these
claims.

A

• Preclinical research suggests CBD has therapeutic potential for
management of inflammation, anxiety, emesis, nausea, inflammatory pain,
and epilepsy. May influence effects of THC. Clinical data lacking for these
claims.

26
Q

• no documented evidence of a death that can be exclusively attributed to overdosing with
cannabis, probably because ___ of ___ receptors in the brain stem region that
controls ___ and ___ systems.

A

• 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.

27
Q

-a lot of correlative data suggesting _____
are more likely to use cannabis, and early cannabis
use dose-dependently predicts the development
of _____ later on.

A

-a lot of correlative data suggesting schizophrenics
are more likely to use cannabis, and early cannabis
use dose-dependently predicts the development
of schizophrenia later on.

28
Q

schizo studies do not indicate causation.
Does not take into account reverse causality
(people with __ __)are more likely to use cannabis), bias, and confounding variables
(i.e.: some other unknown factor increase risk of
both cannabis use and psychosis leading to
spurious associations).

A

existing psychosis

29
Q

Majority of people who use
cannabis do/do not develop schizophrenia.
However,
cannabis can/can’t elicit acute psychosis, can worsen
course of _____schizophrenia, and may be a trigger in the development of schizophrenia in
at-risk populations. (ie __ ___)

A

do not
can
pre-existing
genetic predisposition

30
Q

Psychological dependence =

A

compulsive drug-seeking behavior uses the drug receptively for personal
satisfaction, often in the face of known risks to health

31
Q

Physiological dependence =

A

Physiological dependence = revealed when
withdrawal of the drug produces symptoms
and signs that are frequently opposite of those
sought by the user

32
Q

Cannabis withdrawal is hard/mild, short/long lasting

symptoms

long term users and other effects

A

relatively mild and
short-lived. Symptoms of restlessness,
irritability, mild agitation, insomnia, nausea, and
cramping. May be worse in chronic, long-term
users, and may contribute to continued drug
use

33
Q

Addiction

Diagnosed by __ diagnostic criteria.

A

the inability to control the use of legal or illegal substances despite negative consequences
11

34
Q

severity of the substance use disorder is
determined by the ____ of criteria the
person meets (2/11 = mild; 4/11 = moderate,
6+/11 = severe)

A

severity of the substance use disorder is
determined by the number of criteria the
person meets (2/11 = mild; 4/11 = moderate,
6+/11 = severe)

35
Q

Approximately _% of those who use cannabis

develop a substance use disorder **

A

9

36
Q

Synthetic cannabinoids:

A

a manufactured compound whose
properties imitate those of the active constituents of
cannabis

37
Q 
why synthetic cannabinoids?
•increased \_\_
•\_\_\_ off target effects
• \_\_\_ dosing
•better \_\_\_ studies
A 
why synthetic cannabinoids?
•increased specificity
•decreased off target effects
• easier dosing
•better controlled studies
38
Q

Nabilone:

A

synthetic analog of THC

39
Q

Dronabinol:

A 
(-) trans isomer of △9-
THC, approved for nausea and
vomiting in patients who undergo
chemotherapy and anorexia in AIDS
wasting syndrome.
40
Q

Nabilone and Dronabinol

how are they taken and why

A

partial agonists at the CB1
receptor
orally. Oral THC analogs have less psychotropic effects than cannabis.

41
Q

Nabiximols (Sativex): ____ drug (cannabis ___)
• 1:1 mixture of ___ and ___,
sublingual spray
• first licensed in Canada for relief of pain in adult patients suffering from __ or ___.
• Less ___ effects than smoked cannabinoids.

A 
Nabiximols (Sativex): Botanical drug
(cannabis extract)
• 1:1 mixture of THC and cannabinol,
sublingual spray
• first licensed in Canada for relief of pain
in adult patients suffering from multiple
sclerosis or cancer.
• Less psychotropic effects than smoked
cannabinoids.
42
Q

• Rimonabant is an ____ agonist at the ___ receptor
• originally approved for the
treatment for ___, but later
withdrawn due to serious adverse effects (__ and __ __)

A 
• Rimonabant is an inverse agonist
at the CB1 receptor
• originally approved for the
treatment for obesity, but later
withdrawn due to serious adverse
effects (depression and suicide
ideation)
43
Q

• Cannabinoid receptors exist because

A

we have endogenous cannabinoids
(“endocannabinoids”) that mediate mood,
feeding, motor function

44
Q

2 flavours of endocannabinoids

A

anandamide (AEA) and

2-arachinoyl glycerol (2-AG)

45
Q

Endocannabinoid synthesis

A

AEA and 2-AG are made from the phospholipid bilayer of the cell membrane

46
Q

AEA and 2-AG are ___

neurotransmitters

A

retrograde

47
Q

In contrast to most neurotransmitters
(i.e. glutamate, GABA), AEA and 2AG are/are not stored in vesicles, but rather
synthesized __ ___ when and where they are needed.

A

On demand

48
Q

Endocannabinoids increase/decrease nueronal release of other nt

A

decrease

49
Q

synthesis of AEA and 2-AG stimulated by

produced only in __ regions of brain

A

increase in conc of intracellular ca when postsynaptic neuron gets depolarized

active

50
Q

AEA and 2AG are rapidly cleared from the synapse and inactivated by ___ or ___.
____ of these enzymes prolongs the activity of endocannabinoids

A

AEA and 2AG are rapidly cleared from the synapse and inactivated by fatty-acid amide
hydrolase (FAAH) or monoacylclycerol lipase (MAGL). Suppression of these enzymes
prolongs the activity of endocannabinoids

51
Q

Because AEA and 2AG are synthesized and
released on demand at the site of action,
___ of AEA or 2AG metabolism would
enhance CB1 activation where AEA and 2AG
levels are ___, not globally throughout the
brain

A

Because AEA and 2AG are synthesized and
released on demand at the site of action,
inhibition of AEA or 2AG metabolism would
enhance CB1 activation where AEA and 2AG
levels are highest, not globally throughout the
brain

52
Q

FAAH/MAGL inhibitors do not produce typical
____ effects of THC, sedation, catalepsy,
or hypothermia, but do have ____ effects.
• several compounds under development for the
treatment of __ ___

A

FAAH/MAGL inhibitors do not produce typical
psychoactive effects of THC, sedation, catalepsy,
or hypothermia, but do have analgesic effects.
• several compounds under development for the
treatment of chronic pain

53
Q

BUT, recent clinical trial of FAAH inhibitor

____ halted, because of several ___ ___ ___

A

BUT, recent clinical trial of FAAH inhibitor
(BIA-2474) halted, because of several severe
adverse events

54
Q

Acute effects are ____ and usually associated with ____ doses of THC
Eg. panic attacks, severe anxiety, psychosis, paranoia, convulsions,hyperemesis

A

Rare, high

55
Q

prenatal effects: cannabis use may lead to ___ and ____ changes in
offspring. Fetal growth affected (particularly ____), but dose-response
relationship is/not identified.

A

• prenatal effects: cannabis use may lead to neuroanatomical and behavioural changes in
offspring. Fetal growth affected (particularly neurodevelopment), but dose-response
relationship not identified.

56
Q

• lung cancer: particularly through ____ cannabis
• driving: driving while intoxicated seems to increase/decrease the risk fo being in a motor vehicle
accident. THC impairs perception, psychomotor performance,

A

• lung cancer: particularly through smoked cannabis
• driving: driving while intoxicated seems to increase the risk fo being in a motor vehicle
accident. THC impairs perception, psychomotor performance,

Pmcol 200 (12 decks)

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