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Cannabinoids
- Pharmacologically active compounds
- Over 60
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Hashish
- Dried resin from top of female plant
- THC usually 2-5%, but up to 15%
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Hash oil
- Organic extraction from hashish
- THC 10-20%, but up to 70%
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Absorption
- Very lipid soluble
- Good absorption if smoked
- Half life -> 1-10 days
- Rapid peak
- Slow absorption with oral
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Metabolism and clearance
- Rapid initial drop due to redistribution to fat
- Slower metabolism in liver
- Metabolites may persist for a week
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Effects of low-moderate dose
- Disinhibition, relaxation, drowsiness
- Feeling of well-being, exhilaration, euphoria
- Sensory-perceptual changes
- Recent memory impairment
- balance/stability impaired
- Decreased muscle strength
- Poor on complex motor tasks
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Effects with high doses
- Pseudohallucinations
- Synethesias
- Impaired judgement, poor reaction time
- Pronounced motor impairment
- Disorganized thoughts, confusion
- Not lethal
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Withdrawal
- irritability, anxiety, depression
- sleep disturbances, aggressiveness, decreased appetite
- Rodents- must give antagonist to get withdrawal
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Sensitization
- Stereotyped behaviors
- Locomotion
- Cross sensitive w/ amp and morphine
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Long term effects
- Amotiviational syndrome
- cancer and immune function
- memory problems
- mental illness
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Potential medical uses
- Glaucoma
- antiemetic
- anticonvulsant
- enhance appetite
- analgesic
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Development of synthetic cbs
- delta9-THC binds weakly and not full agonist
- 1986-1990s - CP and WIN series of compounds and agonists
- 1988 - first binding experiments
- 1990 - first localization
- 1990 - CB1 cloned
- 1993 - CB2 cloned
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Cb receptor localization
- Conserved across mamalian species
- Similar to cAMP
- Binding inhibited by cAMP analogues
- CB1 and 2 G-protein coupled
- Receptor density high
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Anandamide
- Endogenous Cb
- Similar actions to cb
- inhibit cAMP
- inhibit binding of cb
- only partial agonist at CB1
- decrease motor activity
- antinociceptive effects
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2-arachidonyl glycerol
- endogenous cb
- full agonist at CB1
- in brain in higher concentration than anandamide
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Locus of actions
- Memory effects - hippocampus
- Reward - mesostriatal DA system
- Motor activity - basal ganglia, cerebellum
- Analgesic effects - spinal cord and peripheral tissue
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