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PHARM 2 > Cannabis I > Flashcards

Cannabis I Flashcards

1
Q

What is cannabis and what is classified as in the drug classifications?

A

cannabis is one of the most commonly used illicit psychoactive drugs (143-190million globally have tried it)

  • it sometimes is classified as a hallucinogen but it has its own category
  • it works by inhibiting NT release by hijacking the body’s endocannabinoid system
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2
Q

Where does Cannabis come from?

A

comes from the cannabis plant

the female cannabis plant produces a sticky resin to trap pollen from males and the active ingredient (THC) is concentration in the resin (mostly located in the flowering tops of the plant)

trichomes are the glandular hair-like structures that contain the resin

THC is contained in resin within the trichomes of the female cannabis plant

hair like structures (trichomes) contain sticky substance called resin –> resin has THC

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3
Q

What are cannabinoids and what are their properties?

A

66 chemicals unique to cannabis plants called cannabinoids

three most abundant ones in cannabis are: THC, cannabidiol and cannabinol

  • ALL extremely lipid soluble
  • detail-9-tetrahydrocannabinol (THC) is the most active ingredient linked to ‘high’ and is a PARTIAL AGONIST at the cannabinoid receptors (activates them to an extent)
  • Cannabidiol and cannabinol may modify THC effects and along with THC make up the three most prevalent cannabinoids found in cannabis plants
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4
Q

What affects the psychoactive potency of cannbis?

A

genetics of the cannabis plants and environment… manipulating the life cycle of the plant can affect THC concentration AND changes in relative amounts of cannabinoids (ratios between them) can affect the responses from using the drug i.e PURE THC can cause temporary psychosis-like symptoms and anxiety

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5
Q

What is the relationship between cannabidiol and psychosis and THC?

A

Cannabidiol is proposed to protect against psychosis

  • seems to bind weakly to CB1 receptors as an antagonist (sits on receptor and prevents other things from binding to it like THC)
  • cannabidiol is an agonist at the 5HT1A receptors (serotonin) which are implanted in mediating the effects of some antidepressants

the higher the cannabinol in cannabis the lower the THC content and vice versa

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6
Q

What is the Cannabis Sativa plant properties? (4)

A
  1. 20ft tall in the wild but 2-3ft when cultivated
  2. medium [THC]
  3. tends to have higher cannabidiol levels than indica plant
  4. cerebral, energetic high
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7
Q

What are the properties of Cannabis indica? (4)

A
  1. 3ft tall
  2. high [THC]
  3. skunk smell
  4. body stone, mental clouding, cough-lock (won’t stop coughing)
  • can get hybrids between sativa and indica though
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8
Q

What are the properties of Cannabis ruderalis? (4)

A
  1. grows primarily in Russia, none in North America
  2. rarely used recreationally
  3. 1-1.5ft tall
  4. low [THC]
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9
Q

How is marijuana prepared?

A
  • dried leaves and flowers
  • use basic cultivation methods (THC weight range of 2-8% of the dried stuff)
  • can reach 20% THC with sophisticated growing techniques like hydroponics (soilless way of growing marijuana that yields very high [THC])
  • Mostly in BC and Quebec
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10
Q

What is sinsemilla?

A

marijuana that comes from seedless unpollinated plants

most energy goes into the resin/cannabinoids

[THC] ranges from 7-20% or higher

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11
Q

what is ‘skunk’?

A

typically a hybrid with high [THC] in same range as sinsemilla (7-20%)

distinctive strong smell

bred for high THC: cannabidiol ratio

linked to psychosis

pretty common

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12
Q

What is Hashish and its properties?

A

Hashish is a concentrated form of resin from trichomes

does not include leaves and has mostly resin for good quality

[THC] ranges from very low to up to 70% depending on how good the resin concentration is to the leaves

packed into bricks varying consistency (depends on how old it is and how much oxygen its been exposed to)

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13
Q

What is Hash Oil?

A

boil hash in alcohol or other solvent

filter out any plant residue, evaporate alcohol

whats left is a residue with 15-90% THC

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14
Q

What is the absorption of cannabis when smoked?

A

THC is rapidly absorbed into blood

enters the brain in under 10 seconds, and has its peak at 5-10 minutes

after 30 minutes, MOST OF THC HAS LEFT THE BRAIN

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15
Q

what happens to absorption if you hold the smoke in for longer?

A

there is NO SIGNIFICANT DIFFERENCE IN HOW LONG YOU HOLD THE SMOKE IN WITH RESPECT TO ABSORPTION

DEPTH OF INHALATION MORE IMPORTANT THAN DURATION… you can have a quick deep inhale than a slow shallow one

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16
Q

what is the absorption of cannabis when taken orally?

A

absorption is poor

cannabis is very lipophilic and may not penetrate thin layer of liquid surrounding cells that line the GI

baking it in foods with added oil helps increase absorption in GI

need higher dose than if smoking to have same effects, oral lasts longer

delayed onset of effects are up to 0-minutes and may lead to overdosing

17
Q

What is the metabolism of THC? whats its half life and what is the metabolite that is formed

A

THC has a half life (t1/2) of 19 hours

but its metabolites have t1/2 of 50hours or more

the primary metabolite is 11-hydroxy-delta-9-THC which is a psychoactive and contributes to overall effects of cannabis (stick around in the body for a long time)

  • metabolism mainly occurs in liver and lungs
  • the high lipophilicity allows fatty tissue to retain THC and metabolites for weeks or even months

if taken orally, a lot of it will be metabolized via first-pass metabolism

18
Q

What are some of the psychological effects of cannabis? (6)

A
  • hilarity, euphoria, well-being, joyfulness and mellowness
  • mundane thoughts might be significant, unconnected events suddenly seem to be connected to one another
  • deficit in tasks requiring attention and vigilance –> but could be a result of no longer caring about pleasing the researcher
  • amotivational syndrome –> due to decrease dopamine levels in chronic heavy users especially if they start young
  • short-term memory loss –> disruption of train of thought –> thought to be from inhibition of aCH release in the hippocampus
  • cognitive effects are most pronounced in infrequent users
19
Q

what are some of the physiological effects of cannabis? (8)

A
  • increased HR and sympathetic tone increases (NE and NORE)
  • parasympathetic tone decreases and tolerance can lead to bradycardia (super decreased heart rate to accommodate for the increase HR while high)
  • blood pressure might be lower in chronic users as well to accomodate for increase Bp while on marijuana
  • Redding of eyes because of dilation of small blood vessels
  • sensation of intense hunger
  • relaxation of muscles
  • decrease eye fluid pressure
  • analgesia –> CB1 receptors found in PAQ grey matter (brain region that is involved in pain pathways)
20
Q

what are three disorders that marijuana could potentially help with the symptoms? (4)

A
  1. chemotherapy and decrease hunger/anorexia -> heightens olfactory cues and increases pleasure from eating certain things
  2. M.S. –> relaxation of mm. from cannabis helps with muscle spasm in people with M.S. and also evidence of enhanced demyelination in M.S. so cannabis can be neuroprotective
  3. Glaucoma -> cannabis decreases pressure of fluid in eyes and that can help people with glaucoma who have increase eye pressure fluid
  4. analgesia –> used as a painkiller because binds to CB1 receptors of PAQ
21
Q

what is the endocannabinoid system?

A

endogenous cannabinoid system modulates neurotransmitter release and it is involved in pain,, hunger, learning and memory

Endocannabinoids are retrograde neurotransmission because instead of having NT go from presynaptic neuron to post synaptic neuron it goes from post synaptic neuron to presynaptic neuron

22
Q

what are the 2 common endocannabinoids naturally produced in the brain?

A
  1. anandamide (AEA)
  2. 2-arachidoyl glycerol (2-AG_

they are synthesized when phospholipids are cleaved out precursors (found in lipid bilayers)

23
Q

How to cannabinoid receptors function? how are they activated?

A

cannabinoid receptors are coupled to g-proteins that decrease cAMP levels by inhibiting adenylate cyclase

it is normally activated by endocannabinoids

24
Q

what is CB1 receptor? how is it activated and what are the results of its activation?

A

CB1 receptor is primarily in the CNs and it is presynaptic

its activation inhibits the influx of Ca2+, stimulates K+ channels so that K+ flows outwards (efflux)

the net effect is inhibition of NT release

one. of the most common receptors in the CNS

25
Q

What is Rimonabant?

A

it is a CB1 receptor antagonist/inverse agonist –> and tried as an anti obesity agent

helps people stop feeling hungry, chronic use developed severe depression (mood involvement with CB1)

26
Q

what is the CB2 receptor?

A

primarily outside the CNS and it is thought to be immunomodulatory

low levels in brain tissue of CB2 mostly in immunity cells and stimulates the immune system

27
Q

What are some of the receptors and transporters that the endocannabinoid system works on? (5)

A

PLD: phosphilpase D

mR: metabropic receptor that increase calcium influx when activated

iR: ionotropic receptor –> one which allows calcium to enter when activated

T: endocannabinoid transporter

FAAH: fatty acid amide hydrolase breaks down anandemide to arachidonic acid (AA) and ethanolamine (Et)

28
Q

what is the 4 steps of endocannabinoid activation?

A
  1. calcium entrance (via NT receptor activation or calcium channel opening) into post-synaptic cell triggers enzymes to synthesize AEA or 2-AG from membrane lipid precursors
  2. they are released into the synaptic cleft where they bind to CB1 receptors
  3. this initiates processes that inhibit NT release
  4. They can be removed from the cleft by a transporter and recycled

picture in the notes

29
Q

what effect does THC have on dopamine levels (how rewarding is it)? what is the link to schizophrenics?

A
  • THC is proposed as a link to schizo as excess dopamine is thought to underlie schizophrenia
  • dopamine release shown in humans only in 2009 subjects inhaled 8mg of THC (n=9)
  • estimated 136% increase in dopamine release in the nucleus accumbens
  • measured 45-85 minutes after inhalation

another study in 2009 showed that a single 10mg dose of THC induced no measurable dopamine release but it was orally administered so that could be confounding bc the peak is lower

dopamine and THC is dose related…

30
Q

How does dopamine increase if cannabinoids inhibit NT release?

A

in the VTA, cannabinoids inhibit the release of GABA (CB1 inhibits GABA release), so they inhibit inhibition and cause disinhibition

in the VTA, there does not seem to be inhibition of glutamate release by cannabinoids

net result is stimulation of dopaminergic neurons

31
Q

What does the experiment show about how cannabinoid antagonist can affect dopamine release by other drugs?

A

Using Rimonabant which is a CB1 release antagonist so it causes GABA to not be disinhibited and have dopamine levels modulated

This can be used to treat drug addiction bc you can prevent THC from blocking GABA release when taking cannabinoids with other drugs like ethanol or cocaine

PHARM 2 (14 decks)

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