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)
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Canada for MS Western world learns of bioactivity Religious use in India Archeological record of hemp cord Rimonabant withdrawn Hashish use in the Arab world Dronabinol Schedule III Medical use in China Marijuana Tax Act CSA 8000 BC 2000 BC 2700 BC 1850’s 1000 AD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
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