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PYB260 > W7 - Cannabis > Flashcards

W7 - Cannabis Flashcards

1
Q

What is cannabis?

A
  • Cannabis sativa
  • Plants vary in size; male and female plants
  • Female plant must be fertilized by pollen from male plant to generate seeds
  • Female plant produces sticky resin at top to attract pollen and protect seeds
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2
Q

What are the active ingredients of cannabis?

A

Over 60 cannabinoids

active ingredient Delta-9-tetrahydrocannabinol (delta-9-THC),

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3
Q

What does the amount of active ingredient (THC) depend on?

A

o Preparation
o Route of administration
o Inactive ingredients altering potency or metabolism

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4
Q

What can create new cannabinoids?

A

• Burning cannabis, GI digestion & metabolism

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5
Q

What are the forms of cannabis?

A

• 3 forms of cannabis:
o Marijuana: dried leaves and flowers; usually smoked/baked
o Hashish: dried resin from female plant; usually smoked or baked
o Hash oil*: hashish boiled in alcohol, then residue is filtered & alcohol evaporated

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6
Q

What is the THC content of plants?

A
  • Changes over time:
    o 1960’s – 1.5%
    o 1990s – 3.5 - 4.5%
    o 2008 – 10%
    o Can be as high as 30% but typically contain 3-15% THC (see NSW study stats next slides; Swift et al., 2013).
    o Industrial hemp contains < 0.5 - 1% THC by Aus. & NZ laws & regulations.
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7
Q

What are the uses of Cannabis?

A

• Historically, hemp has been used for:
o Fibre (e.g. clothes/textiles, paper and rope)
o Oil (lamp oil & food) & as an ingredient in the manufacture of soap, paint and varnish (seeds)
o Medicinal purposes
o Psychoactive properties

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8
Q

What are the synthetic cannabinoids?What are they used for?

A 
o	Marinol (dronabinol –THC extracted from cannabis) &amp; Nabilone (Cesamet – entirely synthetic THC): to alleviate nausea &amp; vomiting in people w. cancer undergoing chemo &amp; radiation therapy; anorexia &amp; weight loss assoc. AIDS
o	Sativex (THC + CBD (+other cannabinoids + non-cannabinoids) extracted from cannabis): neuropathic pain assoc. multiple sclerosis
o	Epidiolex (CBD extracted from cannabis): “Investigational New Drug” for severe forms of epilepsy in children (incl. QLD govt study at Lady Cilento + NSW clinical trials)
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9
Q

What is the pKa of cannabis?

A

10.6

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10
Q

What is the absorption of cannabis orally?

A

Readily absorbed
o Not ionized: THC (weak acid) with a pKa = 10.6
o Lipid soluble: cannabinoids are extremely lipid soluble
o Peak effects: 1-3 hrs>ingestion; effects may last>5hrs

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11
Q

What is oral absorption effected by? What is the difference compared in inhalation?

A

o Absorption is slow and affected by considerable 1st pass metabolism
o Oral vs. inhalation: 1/3 potency; more likely assoc. vomiting & nausea

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12
Q

What is the absorption of cannabis when inhaled?

A
  • 10-25% of cannabinoids enter lungs
  • Peak blood levels < 15 mins; peak effects: 30-60 mins> ingestion
  • Holding smoke does not increase absorption
  • Depth (not duration) of inhalation may alter THC absorption
  • Vaporizers now popular method (< boiling point of THC decrease tars + other carcinogens entering lungs)
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13
Q

Where is cannabis distributed in the body?

A
  • Distributed to all areas of body (capable of altering all biological systems)
  • Concentrated in lungs, kidneys, liver
  • ~1% enters the brain but levels continue to increase after ingestion and peak blood levels
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14
Q

How is cannabis excreted ?

A
  • Initial metabolism in lungs or G.I. tract, dep. on admin

* Most metabolism in liver

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15
Q

What is the transformation of Delta-9-THC in liver?

A

• Delta-9-THC → 11-hydroxy-delta-9-THC → other metabolites (> 100)
o Other metabolites also have effects but most are less lipid solube and more easily excreted

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16
Q

What is the active metabolite of cannabis?

A

• 11-hydroxy-delta-9-THC (active metabolite)
o More active than delta-9-THC
o Penetrated BBB easier

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17
Q

What is the metabolism of other cannabinoids?

A

Cannabidiol (CBD) – (20 metabolites)
• Blocks enzyme that metabolizes THC (increased duration of action)
Cannabinol (CBN) – (20 metabolites)
• Increased metabolism of THC

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18
Q

What are the interactions between metabolites in the body?

A

Possible interaction effects btwn THC, CBN, & CBD to displace THC from blood binding sites (increased amount available for distribution)

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19
Q

How is THC excreted?

A

THC Phase 1 excretion:
- ½ life ~ 30 min; redistribution effect
Phase 2 excretions
- ½ life ~20-30 hrs; metabolism effect
- Slow metabolism due to lipid solubility and speed that THC is released from fatty tissues
- > Traces of THC can be detected 2-4 weeks> ingestion
- Excreted in faeces (55%) & urine (20%)
- Effects of frequent use on metabolism: unclear

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20
Q

What are the effects of cannabis on receptors?

A
  • 2 types of cannabinoid receptors

- Work on second messengers and neuromodulators

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21
Q

What is CB1 and what does cannabis do to effect it?

A
  • Located in CNS: cortex, hippocampus, cerebellum, basal ganglia, hypothalamus, & nucleus accumbens, brain stem, spinal cord
  • Uneven distribution of receptors in the CNS
  • Most in higher centres, therefore affect memory, emotional expression, mental process, but also movement
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22
Q

What is CB2 and what does it effect?

A
  • Located outside in the CNS in spleen and immune system; could account for effects on immune functioning
  • Affected by CBN
  • Recently found in brain too
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23
Q

What are endogenous ligands (endocannabinoids)?

A
  • Anandamide
  • Fat soluble, but simpler molecular structure
  • Exact function unknown
  • Discovery has lead to abundance of research
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24
Q

What is the function of endocannabinoids?

A

“relax, eat, sleep, forget & protect”

25
Q

What are the neuromodulating effects of endocannabinoids?

A
  • Alters functioning of: NE, DA, 5-HT, Ach, GABA, Histamines & Opoid peptides
  • Retrograde action – allow the postsynaptic neuron to shut down presynaptic neuron
  • Depolarization-induced suppression of inhibition
  • Depolarization-induced suppression of excitation
26
Q

What are the effects of cannabis on the body?

A 
Low-Moderate Dose: 
•	Dilation of small blood vessels in eyes 
•	Dry mouth, thirst 
•	Hunger 
•	Increase BP at low does/ Decreased BP at high doses or repeated use 
•	Increased HR 
•	Headaches 
•	Neusea/vomiting 
•	Talkativeness
27
Q

What are the effects of cannabis on sleep?

A
  • Increased drowsiness
  • Increased sleeping time
  • High doses cause insomnia
  • No withdrawal effects
28
Q

What are the effects of cannabis on perception?

A
  • Blurred vision
  • Usually no change in sensory thresholds (vs. subjective report)
  • Decreased pain sensitivity
  • Increase in time rate (time distortion effect)
29
Q

What are the effects of cannabis on attention?

A
  • Decreased performance on vigilance tasks/sustained attention
  • Decreased concentration
30
Q

What are the effects of cannabis on creativity?

A
  • No evidence
31
Q

What are the effects of cannabis on mood?

A
  • Gaiety – dreaminess
  • Anxiety/panic
  • Variability in subjective mood and arousal ratings
  • Depends on environment and mood of others
32
Q

What are the effects of cannabis on performance

A
  • Variable

* Depends on experience, instructions, motivation, setting, dose, performance task

33
Q

What are the effects of cannabis on driving?

A
  • Decreased performance for most people; potentiated by alcohol
  • Decreased ability to attend to peripheral stimuli
34
Q

What are the medically beneficial effects of cannabis?

A

• Decreased BP in eye – glaucoma
• Decreased nausea/vomiting – cancer treatments
o Nabilone and Marinol (synthetic cannabinoids)
• Anticonvulsant (epilepsy, CBD, e.g. Epidiolex) & spasticity (MS, e.g. Sativex/nabiximols)

35
Q

What are the acute effects of cannabis at high doses?

A

‘drug-induced psychosis’

  • Distorted perception, anxiety, panic, paranoia, psychotic-like experience
  • CBD may counteract such THC effects (Morrison et al., 2009)
36
Q

What are the longer-term effects of cannabis

A

: árisk of psychosis & schizophrenia (trigger 1st episode of psychotic illness; make pre-existing psychotic illness worse)

37
Q

What is a lethal dose of THC?

A

• Phylogenetically higher animals are less susceptible to acute toxicity of THC
➢ LD50 of THC administered intravenously is 40mg/kg in rats vs. 130mg/kg in dogs & monkeys (Rosencrantz, 1983; min. lethal dose in dogs is 3mg/kg – Fitzgerald et al., 2013).
—> No experimental evidence to determine lethal dose in humans

38
Q

What is unconditioned behaviour in animals?

A
  • Biphasic effect on SMA: ↑activity followed by ↓
  • High doses – ataxia
  • ↓ appetite & subsequent weight loss, but ↑ sweet preference
  • ↓ aggression
  • ↓ response to painful stimuli
39
Q

What is conditioned behaviour in animals?

A
  • Interferes with STM tasks (↓ neuronal firing in hippocampus)
  • Interferes with timing tasks
  • Performance on other tasks normal (except at high doses)
  • ↓ avoidance responding but not escape responding
  • Does not affect punished responding
40
Q

What is the discrimination in animals?

A
  • Reliable discrimination of THC from placebo
  • Delta-9-THC generalizes to:
  • Delta-8-THC
  • 11-hydroxy metabolite
  • CBN
41
Q

What is the generalisation in animals?

A
  • Partial generalization to sedatives
  • Does not generalize to:
  • CBD
  • Anandamide (unless at high doses of anandamide)
  • Or drugs from other classes
42
Q

What is the discrimination in humans?

A

• Humans can discriminate marijuana cigarettes which don’t contain THC <90 sec. inhalation; if THC content is > 0.09 %
Dissociation in animals & humans (state dependent learning)

43
Q

What is the self-administration tendencies?

A
  • Not typically self-administered by animals
  • In lab studies humans have fairly stable intake
  • Titration
  • Some studies show titration of dose
  • Others show inability to account for different potencies
  • May be more reinforcing if higher THC content (e.g., 1.95% vs. 0.63%)
44
Q

What happens to tolerance in animals?

A

Develops rapidly - 5-6 days

45
Q

What does tolerance develop to in animals?

A
  • Tolerance develops to:
  • ↑ SMA
  • ↓ SMA (slower to develop)
46
Q

What doesn’t tolerance develop to in animals?

A
  • Tolerance does not develop to:
  • Anorexic effects
  • Discrimination
47
Q

How long does tolerance last and what is the cross tolerance and assocations with this?

A
  • Tolerance lasts for > 1 month & there is cross-tolerance btwn delta-9 THC & its 11-hydroxy metabolite
  • Assoc. with ↓ cannabinoid receptors in some brain regions & down-regulation/desensitization of receptors
48
Q

What is the tolerance in humans?

A
  • Tolerance seen with high doses but not low doses
  • Tolerance develops to most psychological effects
  • No tolerance to increased food consumption
  • Most tolerance due to learning
  • (subjective) reverse tolerance?
  • Dose
  • Experience/situations/company etc.
49
Q

What is the withdrawal in animals?

A
  • In continuous admin. of high doses
  • Typically mild symptoms (e.g., ↑ SMA in rats)
  • Withdrawal symptoms may be masked by long ½ life
  • Injection that blocks cann. receptors →withdrawal: stress hormones
50
Q

What is the withdrawal in humans?

A
  • Onset 1-3 days post abstinence, peaks 2-6 days, lasts for 2 wks; typically mild:
  • Hot flashes, sweating, runny nose, diarrhea, hiccups, ↓ appetite
  • Irritability, restlessness, insomnia, anxiety
  • Cravings for cannabis
51
Q

What are the harmful effects on reproduction?

A
  • Males: ↓ testosterone, sex drive (dose-dependent), ↓ sperm motility
  • Interferes with fertility in females (anandamide & fertility)
  • Abnormal sleep patterns of newborns
  • Chromosomal damage
52
Q

What are the harmful effects on the immune system?

A

Complex but includes decreased immune functioning

53
Q

What are the effects on respiration?

A
  • Bronchodilation – helpful in asthma
  • ↓ size of lung passage – causes asthma
  • ↓ activity of macrophages
  • Increased risk of respiratory disease associated with smoking, including cancer
54
Q

What are the effects on cancer?

A
  • 50-70% more carcinogens than tobacco
  • Inhale more tar than tobacco
  • May accelerate carcinogenic effects of tobacco smoke
  • Antioxidant effects of THC & CBD?
55
Q

What are the effects on violence?

A
  • No empirical evidence; though widely held belief

* Usually show ↓ hostility

56
Q

What are the effects on mental disturbance?

A
  • Paranoia & anxiety
  • Acute psychotic episode
  • Can precipitate psychosis in people with psychotic tendencies
57
Q

What happens to the brain after LT use?

A
  • loss of mental functioning (mild), dose/recency effects
  • Animal research has found:
  • Altered brain structure (hippocampus)
  • ↓ neuronal plasticity & learning
58
Q

What happens to the reward response in nucleus accumbens?

A
  • ↓ Nacc response to monetary reward anticipation (Martz et al., August 2016)
  • ↑ mesolimbic response to cannabis cues vs. fruit rewards (Filbey et al., May 2016)
59
Q

What is the evidence of marijuana as a gateway drug?

A
  • High correlation but no causal evidence
  • Social not physical
  • Or personality variables (common factor model)

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