Cannabis

Question 0

What are some alternative names for cannibas?

Answer 0

 weed, pot, bud, grass, green, reefer, Mary Jane, herb, skunk

Question 1

What are the general properties of cannabis?

Answer 1

 sometimes classified as a hallucinogen
 often given its own category
-primary effect is to inhibit neurotransmitter release by hijacking the body’s endocannabinoid system
 one of the most commonly used illicit psychoactive drugs
 2007 survey - between 143 and 190 million people had used cannabis at least once globally

Question 2

Where is cannibas derived from

Answer 2

 from the cannabis plant
 females produce sticky resin to trap pollen from males
 the active ingredient is concentrated in the resin
 found in different amounts in various plant parts - most in
flowering tops, less in the leaves, little in stalks
 trichomes are the glandular hair-like structures that contain the resin

Question 3

Want are cannabanoids

Answer 3

 66 chemicals unique to cannabis plants - cannabinoids
 all are extremely lipid soluble
 delta-9-tetrahydrocannabinol (THC) is the most ac&ve ingredient linked to “high”
 cannabidiol and cannabinol (not linked to high) may modify THC effects and along with THC make up the three most prevalent cannabinoids
 11-hydroxy-delta-9-THC is a metabolite which is psychoactive and contributes to effects

Question 4

What is the importance of the type of cannabis plant used

Answer 4

 genetics of cannabis plants and environment affects psychoactive potency
 changes in relative amounts of cannabinoids can affect the responses from using the drug

Question 5

What is the difference between cannabadiol vs THC effects

Answer 5

 cannabidiol proposed to protect against psychosis
 pure THC can cause temporary psychosis-like symptoms
and anxiety
 cannabidiol seems to antagonize these effects – seems to bind weakly to CB1 receptors as an antagonist but is an agonist at 5HT1A receptors and also binds to an “orphan receptor” GPR55 that also binds endocannabinoids

Question 6

Explain the properties of cannabis plant: canabis sativa

Answer 6

cannabis sativa
  20 ft tall in the wild
  shorter when cultivated (2 -3 ft) 
  medium [THC]
  cerebral(feel more creative, make more connections), energetic high (stimulates brain)

Question 7

Explain the properties of cannabis plant: canabis indica

Answer 7

cannabis indica
 3=tall
 high [THC]
 skunky smell
 body stone, mental clouding, couch-lock (lack motivation)
 can get hybrids between indica and sativa

Question 8

Explain the properties of cannabis plant: canabis ruderalis

Answer 8

cannabis ruderalis
 grows primarily in Russia, none in North Am.
 rarely if ever used recrea&onally
 1- 1.5 = tall, low [THC]

Question 9

Explain the preparation of marijuana

Answer 9

marijuana:

 dried leaves and flowers with basic cultivation methods,
 THC range of 2 - 8 %, can reach 20% with sophisticated growing techniques -hydroponics etc
 most commonly used preparation
 Canada is a net exporter
 Produced predominately in BC, Quebec and Ontario

Question 10

Explain the preparation of sinsemilla

Answer 10

sinsemilla:
 marijuana from seedless unpollinated plants
 more energy goes into resin/ cannabinoids
 [THC] ranges from 7 - 20% or higher
 may be referred to as “skunk” if the plants are hybrids
 high THC: cannabidiol ratio, linked to psychosis

Question 11

Explain the preparation of Hashish

Answer 11

Hashish
 concentrated resin from trichomes
 few if any leaves or other plant parts if high quality
 [THC] ranges from very low up to 70%
 packed into bricks of varying consistency

Question 12

Explain the preparation of hash oil

Answer 12

Hash oil
 boil hash in alcohol or other solvent
 filter out any plant residue, evaporate alcohol
 leaves a residue with 15 - 90 % THC

Question 13

Explain the absorption of THC if smoked

Answer 13

 if smoked, THC rapidly absorbed into blood
 enters brain under 10 seconds, peak effects felt within 5 - 10 minutes
 After 30 minutes, most has left the brain
 no difference between holding in smoke for 1, 10, or 20 seconds with respect to absorp&on - depth of inhalation more important than duration (deeper inhale=higher absorption)

Question 14

Explain absorption of oral THC

Answer 14

 if taken orally, absorption is poor
 very lipophilic and may not penetrate thin layer of liquid surrounding cells that line the GI
 baking it in foods with added oil helps
 need higher dose than if smoking to have same effects, but they last longer
 but delayed onset of effects ( up to 90 min.) may lead to overdosing

Question 15

Describe the metabolism of THC including half life’s

Answer 15

THC has a half life (t1/2) of 19 hours but metabolites have t1/2 of 50 hrs or more
 primary metabolite is 11-hydroxy-delta-9-THC
 metabolism mostly in liver and lungs
 high lipophilicity allows fatty &ssue to retain THC and metabolites (weeks, months?)
 if taken orally, significant first-pass metabolism

Question 16

What are some psychological effects of marijuana

Answer 16

 hilarity, euphoria, well-being and joyfulness, mellowness
 effects similar to alcohol but without aggression and recklessness (fewer accidents that are typical with alcohol even though motor performance is similarly impaired)
 mundane thoughts might take on great significance
 unconnected events suddenly seem to be connected to
one another
-rarely anxiety, panic and dysphoria - dose/experience related?

Question 17

What are sme of the effects on time and memory

Answer 17

 time distortion - time seems to pass at a different rate (slower)
 feelings of sharpened sensory awareness
 deficit in tasks requiring attention and vigilance - but could be a result of no longer caring about pleasing the researcher
 short-term memory effects - disruption of train of thought - thought to be from inhibition of acetylcholine release in the hippocampus
 Cognitive effects most pronounced in infrequent users

Question 18

What are some of the physiological effects

Answer 18

 increased heart rate as sympathetic tone increases, parasympathetic tone decreases -tolerance can lead to bradycardia
 blood pressure – most consistent effect
 reddening of eyes - dilation of small blood vessels
 sensation of intense hunger - CB1 receptors in nucleus accumbens and hypothalamus - chemotherapy for cancer, HIV treatment
 relaxation of muscles - mul&ple sclerosis treatment
 decrease in eye fluid pressure - glaucoma treatment
 analgesia - CB1 receptors in periaquaductal grey ma?er (brain region involved in pain pathways) – MS
 Also some evidence of enhanced remyelina&on in MS

Question 19

Explain the endocanabanoid systems

Answer 19

 endogenous cannabinoid (endocannabinoid) system modulates neurotransmitter release
 Involved in pain, hunger, learning, memory
 an example of retrograde neurotransmission (endocannabinoids travels from post synaptic cell to bind to receptors on presynaptic terminal)

Question 20

What are anandamide and 2- arachidoyl glycerol

Answer 20

 anandamide and 2- arachidoyl glycerol are endocannabinoids naturally produced in the brain
 they are integral parts of the cell membrane, and synthesized from membrane phospholipids

Question 21

Explain the cannabinoid receptors including the difference between CB1 and CB2

Answer 21

 coupled to G-proteins that decrease cAMP levels by inhibi&ng adenylate cyclase
 CB1 - primarily in CNS, presynaptic Activation inhibits influx of Ca2+, simulates K+ channels so that K+ flows outwards (efflux)
 net effect is inhibi&on of neurotransmitter release
 one of the most common receptors in the CNS
 Rimonabant CB1 receptor antagonist/inverse
agonist – tried as an&-obesity agent
 CB2 - outside CNS - immunomodulatory?

Question 22

What is Rimonabant

Answer 22

Rimonabant CB1 receptor antagonist/inverse agonist – tried as anti obesity agent
Caused depression therefore use decreased

Question 23

Explain the mechanism of endogenous cannabinoid

Answer 23

1. Presynaptic NT release
2. Post synaptic receptor activated
3. Depolarization triggers calcium influx into post synaptic
4. Calcium influx triggers endocanabanoid release from post synaptic
5. Binding of endocanabanoid on presynaptic CB1
6. CB1 receptor activated prevents further NT release by blocking calcium from entering presynaptic and increasing potassium Efflux

Question 24

What is the depolarization induced suppression of inhibition?

Answer 24

the mechanism of endogenous cannabinoid

Question 25

Explain the mechanism of exogenous cannabinoids

Answer 25

The same as endogenous except with THC, no need for depolarization or involvement of endocanabanoids

Question 26

What are the effects on dopamine levels

Answer 26

 proposed as link to schizophrenia as excess dopamine thought to underlie schizophrenia  dopamine release shown in humans only in 2009 subjects inhaled 8mg of THC (n = 9)  estimated a 136% increase in dopamine release in area of nucleus accumbens  measured 45 - 85 min. after inhalation  another study published in 2009 showed that a single 10 mg dose of THC induced no measurable dopamine release - but this was orally administered (n = 13)

Question 27

How does cannabinoids act if they inhibit NT release?

Answer 27

 in mesolimbic pathway, they inhibit neurons that release GABA - so they inhibit inhibition and cause disinhibition  mediated by CB1 receptor activation  net result is stimulation of dopaminergic neurons

Question 28

What are the tolerance and withdrawal effects

Answer 28

 with chronic THC exposure, CB1 receptors are internalized (removed from the neuronal membrane)  withdrawal symptoms:  hot flashes, sweating, runny nose, loose stools, irritability, anxiety, insomnia  usually not severe because of long half-life of drug and metabolites - results in very gradual decrease

Question 29

What are the links to cancer?

Answer 29

 Some sources claim marijuana smoke contains 50 to 70 percent more carcinogenic material than cigarette smoke  Other sources say basically similar levels in both  cannabis does not contain overtly toxic materials, but pyrolysis generates mutagenic polycyclic hydrocarbons, phenols, cresols  users exhibit more precancerous lesions and airway inflammation than non-users  however, largest study yet shows no correlation between smoking and lung, pharynx, larynx and mouth cancers  using a water-pipe (bong) in which smoke first passes through a water layer may remove cancer-causing components, but also tends to remove THC from the smoke and increase Tar:THC ratio

Question 30

What are the links to mental illness

Answer 30

 heavy users shown to have increased risk of schizophrenia  estimated to be related to 8% of all reported schizophrenia cases  increases risk 2 times the average in longitudinal studies over 15 years - 6 times the average in the subset of heavy users  linked with high [THC] varieties  increased risk the earlier first exposure occurs  linked with muta&ons in catechol-O-methyltransferase enzyme which metabolizes dopamine (mutation slows down metabolism)  also linked to depression, amotivational syndrome Use of cannabis prior to age 18 linked to a drop of 8 IQ points by age 30 (PNAS, 2012)

Question 31

Describe Synthetic/herbal marijuana

Answer 31

 Spice, K2 often labeled as incense, potpourri  Often actually legal and difficult to detect with screening  Contain synthetic cannabinoid agonists that were originally made in research laboratories  They are typically mixed with a selection of plants/herbs and it is unclear if they add anything to the experience  Some of the compounds are very potent at CB1 receptors and have not been tested in humans  Many cases of seizure, altered consciousness, extreme anxiety, a small number of suicides