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Cannabis: A journey from college to bench to bedside
Ken Mackie (IUB)
Michael Vasko (IUSM)
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Pain therapies
• Inadequately-treated chronic pain is a major clinical problem
• Current behavioral and pharmacological approaches: limited efficacy
• Need for better therapies• Cannabinoids as novel pain therapeutics:
– Cannabinoids = active components of cannabis (e.g., THC)
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Cannabinoids
• Analgesic efficacy similar to codeine• Actions fundamentally different from opiates• Cellular site of action > 2 receptors
– CB1 > well studied, analgesia, but psychoactivity
– CB2 > little studied, analgesia, no psychoactivity
• Therapeutic approaches:– Ligands to activate cannabinoid receptors– Enzyme inhibitors to increase endogenous ligands
(endocannabinoids)
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Goals of our study (1)
• What does CB2 do in neurons?
– CB1 inhibits neurotransmitter release
– Will CB2 receptors do the same?
• CB2 is highly inducible– Therapeutically beneficial(?)– How to study function?
• Introduce into cultured neurons– Deliverable 1: Will CB2 inhibit
neurotransmission in vivo?
Maresz et al. J. Neurochem. 95 (2005) 437-45
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Goals of our study (2)
• What is the in vivo role of CB2? – Deliverable 2: Develop lentiviral tools to over express
and knock down CB2 expression in sensory neurons
– Deliverable 3: Will over expression of CB2 decrease pain?
– Deliverable 4: Will knockdown of CB2 increase pain?
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Will CB2 inhibit neurotransmission in vivo?
• Background:– CB1 receptors inhibit
neurotransmission
• Approach– Culture neurons from CB1 KO mice
– Express CB2 receptors in these neurons
– Examine neurotransmission• Exogenous cannabinoids• Endogenous cannabinoids
Bodor et al, 2005 (layer V)
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Summary
• CB2 receptors in neurons can inhibit neurotransmission– Presynaptic site of action
• Tools have been made to over express and knockdown CB2 expression in vivo
• Next – test and demonstrate efficacy with in vivo models
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Acknowledgements
• Funding: RR025761, DA021696, and DA011322
• LMIC• Brady Atwood