Cannabis

Question 1

Cannabis

Answer 1

• sometimes classified as a hallucinogen (often given own category)
• inhibit NT release by hijacking body’s endocannabinoid system
• one of most commonly used illicit psychoactive drugs
• from cannabis plant (females produce sticky resin at end of tiny hairs (trichomes) to trap pollen from males, active ingredient in resin)
• > where buds are have most resin

Question 2

Cannabinoids

Answer 2

• 66 chemicals
• all extremely lipid soluble
• delta-9-THC (most active), cannabidiol and cannabinol
• changes in relative amounts of cannabinoids can affect responses from using drug
• Cannabidiol (protect again psychosis), bind weakly to CB1 receptors as antagonist ans agonist at 5HT1A and binds to orphan receptor GPR55
• pure THC (temporary psychosis and anxiety)
• structures on flashcards

Question 3

Cannabis sativa

Answer 3

• 20 ft tall in wild (shorter when cultivated 2-3 ft)
• medium [THC]
• cerebral, energetic high
• narrow blades in the leaves

Question 4

Cannabis indica

Answer 4

-3 ft
-high [THC]
-skunky smell
-body stone, mental clouding, couch-lock
(can get hybrids between indica and sativa)

Question 5

Cannabis ruderalis

Answer 5

• weed like shrubby
• 1-1.5 ft
• rarely used recreationally
• grows in russia
• low [THC]

Question 6

Marijuana

Answer 6

• dried leaves and flowers
• THC 2-8% (can reach 20% with sophisticated growing techniques eg hydroponics)
• canada net exporter

Question 7

Sinsemilla

Answer 7

• marijuana from seedless unpollinated plants (female)
• more energy goes into resin/cannabinoids
• THC 7-20% or higher

Question 8

Skunk

Answer 8

• hybrid with high [THC] in same range as sinsemilla
• string smell
• high THC low cannabidiol ratio (linked to pychosis)

Question 9

Hashish

Answer 9

• concentrated resin from trichomes
• few leaves or other plant parts
• THC ranges from low to 70%
• packed into bricks of varying consistency

Question 10

Hash oil

Answer 10

• boil hash in alcohol or other solvent
• filter out any plant residue, evaporate alcohol
• residue with 15-90% THC

Question 11

Absorption

Answer 11

• if smokes THC rapidly absorbed into blood (brain under 10 secs, peak effects 5-10 minutes, left brain after 30 min)
• orally absorption poor, very lipophilic (tough to get out of stomach into blood), baked in foods with added oil helps, need higher dose, effects last longer but delayed effcts (up to 90 minutes)

Question 12

Metabolism

Answer 12

• THC half life of 19 hrs
• metabolites half life of 50+ hrs
• primary metabolite is 11-hydroxy-delta-9-THC
• metabolism mostly in liver and lungs
• high lipophilicity allows fatty tissue to retain THC and metabolites
• if taken orally significant 1st past metabolism

Question 13

Psychological effects

Answer 13

• hilarity, euphoria, well-being, mellowness
• similar to alcohol but not aggression and recklessness
• thoughts become profound, time distortion, sharpened sensory awareness, maybe attention deficit?, STM effects (inhibition of acetylcholine release in hippocampus), cog effects
• rarely: anxiety, panic and dysphoria

Question 14

Physiological effects

Answer 14

• increased heart rate (tolerance can lead to bradycardia, decreased hr and bp in frequent users) and bp (SNS increase)
• redden of eyes (dilation of blood vessels)
• hunger (CB1 receptors in NAcs and hypothalamus)
• relaxation of muscles
• decreased fluid eye pressure
• analgesia (CB1 receptors in periaquaductal grey matter)
• some evidence enhanced remyelination in MS

Question 15

Endocannabinoid system

Answer 15

• modulates NT release (retrograde neurotransmission, post to pre)
• involved in pain, hunger, learning, memory
• Anandamide (AEA) and 2-arachidoyl glycerol (2-AG) are endocannabinoids naturally produced in brain (synthesized from membrane phospholipids) both very lipophilic

Question 16

Endocannabinoid system process in brain

Answer 16

• post to pre
• NAPE->(ca2+enters)->PLD cleaves NAPE->releases Anadamide->passes through cleft -> presynaptic CB1 ->G-proteins->inhibits AC (decreased NT, increase K+, decreased CA2+)
• ECT transports back to post and hydrolyzed by FAAH
• look in notes

Question 17

CB1 and CB2 receptors

Answer 17

• coupled to g-proteins that decrease cAMP by inhibiting adenylate cyclase
• CB1: CNS, pre, inhibits influx of Ca2+, stimulates K+ channels so flows outwards, inhibition of NT release
• CB2: outside CNS, immunomodulatory

Question 18

Effects of dopamine levels

Answer 18

• thought to be linked to schizo b/c excess DA but other drugs more DA
• evidence not there is human studies but is in animal
• > need more research

Question 19

How does dopamine increase if cannabinoids inhibit NT release?

Answer 19

• inhibition of inhibition causing disinhibition
• inhibit neurons that release GABA
• mediated by CB1 activation
• net result is stimulation of dopaminergic neurons
• get Ca influx to trigger cascade of events, DGL inhibits GABA (*more in notes)

Question 20

CB1 antagonist

Answer 20

• Rimonabant
• prevents rewarding effects of other drugs
• decreased DA release

Question 21

Tolerance and withdrawal

Answer 21

• chronic THC exposure, CB1 receptors internalized
• withdrawal symptoms: hot flashes, sweating, runny nose, loose stools, irritability, anxiety, insomnia (not severe b/c long half life of drug and metabolites)

Question 22

Cannabis and Cancer

Answer 22

• does not contain overtly toxic materials but pyrolysis generated metagenic polycyclic hydrocarbons, phenols, cresols
• users more precancerous lesions and airway inflammation than non-users but one study shows no link
• water-pipe may remove chemicals but also removes THC

Question 23

Mental illness

Answer 23

• heavy users have increased risk for schizophrenia (linked with high THC ow cannabidiol)
• increased risk earlier 1st exposure occurs
• linked to mutations in COMT gene which metabolizes DA and AKT a protein that controls gene transcription and cell death in neurons
• but could people be self medicating?
• lots evidence for?? (more in notes)

Question 24

Synthetic/herbal marijuana (spice, K2)

Answer 24

• chemical are being synthesized on the black market and added to plant matter and being sold as alternative to THC (eg napthoylindole)
• bp elevated, seizure, agitated
• full agonists to CB1 and CB2, metabolites also agonists and magnify effects (THC only partial agonist)
• may stimulate pathways not stimulated by THC
• may promote rapid desensitization & internalization of receptors

Question 25

Vaporizers and marijuana

Answer 25

• heat without burning
• THc vaporizes at 180 to 200 degrees
• same amounts of THC delivered
• fewer combustion products (less CO)

Question 26

Munchies mechanisms

Answer 26

• increases olfaction (presynaptic CB1 receptors on glutamate releasing neurons that normally stimulate inhibitory neurons in the main olfactory bulb, THC mimicks endocannabinoids of the hunger circuits stimulating receptors to trigger feeding), more sensitive to smell of food *notes
• increased pleasure when eating (increase in DA itself then more DA with food)
• increased activity of hunger signalling pathways (CB1 and GHS-R1a (grhelin) receptors pair up as part of hunger signal pathway, increase AMPK (signals to increase energy in body) in hypothalamus and triggers hunger *more in notes!!

Question 27

Cannabinoids treatment of nausea/vomiting

Answer 27

• primary signal for vomiting seems to be 5HT
• THC prevent 5HT release (by CB1 receptors) and binds to 5HT3 receptors and decreases activity
• cannabidiol agoinst at 5HT1A autoreceptors and prevents 5HT release
• BUT cannabinoid hyperemesis syndrome (in longer term users, constant vomitting and stomach pains, compulsive hot showers, symptoms vanish when stop use)

Question 28

Cannabis and driving

Answer 28

• most studies show increased risk except 2
• 2x risk getting in fatal collision
• effects of automated tasks