Cannabis is More Than THC
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Cannabis is More Than THC

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  • Exploited for medicinal effects and recreational uses
  • De Long inactive doses of THC were enhanced by CBC, increasing brain levels. CBC is independent of CB1 and CB2. CBC .3% of Content in US.
  • What are you smelling?Nixon made MJ schedule 1…Schafer report he ordered disagreed with his politics…hmm wasn’t reminds me of England.

Cannabis is More Than THC Cannabis is More Than THC Presentation Transcript

  • Cannabis is More Than THC
    JahanMarcu
    4/22/2011
  • Where did Cannabis come from?
    Hillig KW. Genetic evidence for speciation in Cannabis (Cannabaceae).Genetic Resources and Crop Evolution. 2005;52:161-80.
  • A little more history…
    Shou-zhong, Y. 1997. The divine farmer's materiamedica: A translation of the ShenNong Ben Cao Jing. Boulder, CO: Blue Poppy Press.
    Perfumed Garden,  as translated by Sir Richard Burton, Park St. Press: Rochester, VT, 1992, p. 26.
  • Why do we care?
    GPCRs – target for pharmacological intervention - 1 and 2 adrenergic receptor; dopamine D2 antagonist
    Orphan receptors…
    Cannabinoid receptors -
    Amyotrophic Lateral Sclerosis (ALS)
    Cannabinoids↓ cell proliferation, induce apotosis in human GBM cell lines (J Neurooncol, 2005)
    CBD reduces breast cancer tumor aggressiveness (Mol Cancer Ther, 2007)
    Cannabinoids - neuroprotective role against NMDA excitotoxicity (Mol Pharmacol 2006)
    • Reduces progression of atherosclerosis (Nature 2005)
    • Schizophrenia
  • Timeline of Cannabis use and scientific advances
    Rimonabant
    in Europe and Canada
    for obesity
    Medical use
    legalized in
    CA and AZ
    Sativex licensed
    in Canada
    for MS
    Western world
    learns of bioactivity
    Religious use
    in India
    Archeological record of
    hemp cord
    Rimonabant
    withdrawn
    Hashish use
    in the Arab world
    Dronabinol
    Schedule III
    Medical use in China
    Marijuana
    Tax Act
    CSA
    8000 BC
    2000 BC
    2700 BC
    1850’s
    1000 AD
    1937
    2005
    2006
    2009
    1996
    1999
    1970
    Receptor
    knock-out
    mice
    Anandamide
    first endogenous
    ligand
    2-AG
    isolated
    ECS in bone
    CB1
    cloned
    SR141716A
    first antagonist
    D9-THC
    isolated
    Receptor
    binding
    GPR55
    Retrograde signaling
    Adenylyl cyclase
    inhibition
    Receptor
    mapped
    CB2
    cloned
    Precipitated
    withdrawal
    1994
    1984
    1988
    1964
    1992
    1993
    1995
    1990
    1998
    2005
    2001
    Updated from Childers and Breivogel, Drug Alcohol Depend, 1998
  • Terminology
    • Variety: can be grown from seed
    • Cultivar: clonal propagation
    • Strain: a variety that is propagated for an improved or unusual characteristic
    What do we have in the U.S.?
    • Confusion: cultivars that are mislabeled as strains
    • Genetic testing can distinguish between a strain and a cultivar
    • Example, Trainwreck, Bubakush, etc are cultivars from a THC variety or strain
    • THC tunnel vision; where are the CBC, CBG, THCV, etc varieties and strains?
  • Biosynthetic Pathways of Pentyl Phytocannabinoids
    (Russo, after de Meijer et al., 2003)
    +
    Geranylphosphate: olivetolategeranyltransferase
    Terpenoid synthases
    Essential oils
    CBCA synthase
    THCA synthase
    CBDA synthase
  • CBD plants; what about CBG,CBC,etc?
    • Specific genes for CBD and THC varieties and combos thereof (de Meijer et al.2003).
    • CBG plants found in Europe (de Meijer et al.2005).
    • Propyl Cannabis Strains (CBGV, THCV,CBDV)
    • CBC varieties (Meijer et al.2008)
  • Meijer et al.2008
  • Phytocannabinoids: The Future
    CBD: rheumatoid arthritis, inflammatory bowel disease (TNF-α inhibition)
    THCV: metabolic syndrome (CB1 antagonism), epilepsy (CB1-mediated)
    CBDV: epilepsy, bone formation/healing
    CBG: prostatic cancer (TRPM8 antagonism), anxiety (AEA reuptake inhibition?), antibiotic (MRSA et al.)
    β-Caryophyllene: selective CB2 agonist
    Courtesy of E. Russo.
  • Plant Wisdom: Synergy and Enhancement
    Anticancer THC & CBD (Marcu et al. 2010)
    Efficiency THC & CBC (De Long et al. 2010)
  • THC and Terpenoids
    May modulate activity in several ways:
    CB receptor interactions
    Increase THC affinity
    Remodel G proteins
    Changes to BBB; alters pharmokinetics
    “Generally, inhaled terpenoids cause sedation.”
    -McPartland
  • Major Components
    Beta-Caryophyllene
    Caryophyllene Oxide
    Limonene
    Linalool
    Myrcene
    Alpha-humulene
    Nerolidol
  • Conclusion
    A THC variety by any other name…
    The THC variety of Cannabis is NOT the only type of Cannabis
    Many new varieties of medicine await discovery
    Cannabis is not the only source of cannabinoids
    Different ingredients can enhance and inhibit different effects
    Freedomisgreen.com Cannabination.com