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Cannabis: A journey from college to bench to bedside

Cannabis: A journey from college to bench to bedside. Ken Mackie (IUB) Michael Vasko (IUSM). Pain therapies. Inadequately-treated chronic pain is a major clinical problem Current behavioral and pharmacological approaches: limited efficacy Need for better therapies

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Cannabis: A journey from college to bench to bedside

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  1. Cannabis: A journey from college to bench to bedside Ken Mackie (IUB) Michael Vasko (IUSM)

  2. 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)

  3. 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)

  4. 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

  5. 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?

  6. Bodor et al, 2005 (layer V) 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

  7. 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

  8. Acknowledgements • Funding: RR025761, DA021696, and DA011322 • LMIC • Brady Atwood

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