Lecture 5 - Cannabis 1 Flashcards
1
Q
Background
A
- Produced from the weedlike plant: Cannabis Sativa (Hemp)
- Uses: rope, cloth, paper, seeds used for oil, birdfeed (not used as a psychoactive early in history)
- Psychoactive agent = ∆9Tetrahydocannabinol (THC)
- Found in all parts of the plant, but concentrated in the sticky resin secreted the flowering tops of female plants
- Over 70 other non-psychoactive agents including Cannabidiol (CBD)
- Cannabidiol can be used a food supplement because its not a psychoactive substance (THC is)
2
Q
Marijuana
A
- Dried and crumbled leaves, small stems, flowering tops of the plant
- Primary form
- Usually smoked in joints, pipes, bongs (inhale vapourised THC)
- THC content varies
3
Q
Sinsemilla
A
- Pollination of female plant prevented (segregate plants)
- ↑ potency of THC
4
Q
Hashish (solid)
A
- Prepared from resin
- Potency varies with concentration
- Can be added to joint to increase potency
5
Q
Hash oil
A
- Reduced alcoholic extract
- Single drop placed in a joint
6
Q
History of marijuana
A
- 8000 B.C. = archaeological record of hemp cord
- 2700 B.C. = medical use in China
- 2000 B.C = religious use in India
- 1000 A.D = Hashish (synthesised form of cannabis plant) use in Arab world
- 1850s = Western world learns of bioactivity
- 1937 = Marijuana Tax Act
- 1996 = first state laws legalizing medical use
7
Q
THC content
A
- Typical joint contains approximately 0.5 – 1g of cannabis
- A joint with 1g of cannabis, 4% THC content, contains 40 mg of THC
- THC content in of samples analysed in 1995 contain 4% THC, raising to average of 15% in 2015 (ElSohly et al,. 2016)
- Behaviours associated with consuming THC increase drastically over this time period
8
Q
Smoking
A
- Burning marijuana results in vaporisation of THC
- THC readily absorbed through the lungs into blood plasma
- Only about 20% of original THC is absorbed into lungs
- Absorption can be increased by breath holding (Black et al., 1998)
Increased high with 15 s breath hold vs. 7 s (could be a placebo effect) - After peak levels reached, concentration falls
- Half-life of about 20-30 hours – once metabolised in liver, some is stored in fat storage
- May detect marijuana up to 2 weeks after initial consumption
- Metabolism in liver and fat storage
- Although THC levels in blood plasma decline very rapidly, smokers do not report peak until after the joint has been finished (needs time to travel into system and target site matters - journey to travel into the brain)
9
Q
Administration effects
A
- Route of administration has a substantial effect on how long the effect lasts (Agurell et al., 1986)
- Blood plasma levels of THC following smoking vs. oral consumption
10
Q
Oral consumption
A
- Ingestion -> metabolism in liver -> absorbed into blood plasma
- Slower/delayed effects relative to smoking (smoking bypasses liver metabolism, goes straight from lungs to blood plasma)
- Effect is more sustained, due to slower metabolism and adsorption into blood plasma (lasting 4-8 hours)
11
Q
Cannabinoid receptor
A
- Devane et al. (1988)
- Cannabis receptor = CB1
- Agonist = THC
- Antagonist = SR141716
- Cannabis receptors active in areas consistent with behavioural effects
- E.g. hippocampus which is associated with spatial memory
- Also found in high densities in globus pallidus, substantia nigra, cerebellum and cingulate gyrus
12
Q
Effects of cannabis antagonists
A
- Effects of Marijuana attenuated by treatment of CB1 antagonist (SR141716) – works against it
- If you administer THC and SR141716, should decrease effects of THC
- Two groups: placebo control and SR141716 group
- Responses recorded over next hour:
- Rating of drug effect (feeling high/stoned) – lower in SR141716 group
- Increase in heart rate – lower in SR141716 group
- However, antagonist effects are not completely abolished (effects of marijuana not completely abolished by presence of antagonistic material/placebo effects)
13
Q
Endocannabinoid system
A
- Endo = natural/internal
- Given the presence of natural (endo)cannabinoids – Is there a normal regulatory function of the system?
- Neurotransmitter = N-arachidonoylethanolamine (AEA) aka anandamide (ANA)
- This is the natural neurotransmitter which cannabis hijacks
- Effects of CB1 antagonist (Richardson et al. 1988)
- SR 141716 induces hyperalgesia (↑ pain sensitivity)
- Endocannabinoids ↓ responsiveness to pain
- Endocannabinoid system regulates pain sensitivity in the body
14
Q
Effects of CB1 knockout
A
- Varvel & Lichtman (2002)
- Two groups: rats who express CB1 receptor naturally and rats who don’t
- Normal acquisition of spatial learning in a maze (both groups)
- Impaired reversal learning (if you switch where end spot of maze is, rats who don’t express CB1 receptors take longer)
- Marsicano et al (2002)
- CB1 mice show normal fear conditioning
- Impaired extinction (when conditioned fear removed, rats don’t learn again very well)
- CB1 results in a deficit in new learning
- A deficit in unlearning/new learning
15
Q
Behavioural and physiological effects
A
Depends on dose and time for effects to take place
16
Q
The buzz
A
- Brief perception of light-headedness, dizziness
- Tingling sensations in the extremities
17
Q
The high
A
- Feelings of euphoria, exhilaration
- Disinhibition (the “giggles”)
18
Q
Being stoned
A
- Reached with a sufficiently large amount of marijuana
- Feelings of being calm, relaxed & dreamlike
- Sensations of floating, enhanced visual and auditory perception
- Slowing of the perception of time
- Changes in sociability (increases or decreases)
19
Q
Psychopathology
A
paranoia, anxiety, panic (more likely in 1st time users, or after high doses)
20
Q
Physiological effects
A
- Increased blood flow to skin (sensation of warmth)
- Increase in heart rate (sensation of a pounding pulse)
- Increase in hunger (the “munchies”)
- Demonstrated in humans (Foltin et al., 1988) & rats (Williams et al., 1998)
- Hyperphagia (increased appetite and consumption) (Williams & Kirkham, 2002) induced by THC and abolished by CB1 antagonist
- Palatability (animals approach tannins more) increases in rats following Δ9THC administration (Williams & Kirkham 2002; Jarrett et al., 2005)
21
Q
Cognitive deficits
A
- Oral THC administration impairs verbal memory (Curran et al., 2002)
- Psychomotor functions affected (makes driving dangerous)
- Cognitive tolerance in heavy users (Hart et al., 2001)
- Dose dependant – low doses have relatively few effects (especially in heavy users)
- Task dependent – if task demands are high → impaired performance
22
Q
Rewarding effects of cannabinoids
A
- Tanda et al. (2000)
- Phase 0: intravenous cocaine → lever press
- Phase 1: extinguished with saline
- Phase 2: intravenous THC → lever press
- Phase 3: effect abolished with CB1 antagonist
- Phase 4: intravenous THC → lever press
- Rats press levers to get administrations of THC
23
Q
Conditioned place preference
A
- Valjent and Maldonado (2000)
- Conditioned place preference with THC in mice (prefer certain area in maze)
- Only works if mice pre-exposed to THC in home cages (before being introduced to experimental apparatus) because initial effects of THC may not be enjoyable e.g. anxiety, paranoia
- First experience = aversive, then rewarding
- (Type of maze is aversive)
