2
Cannabichromene (CBC) Cannabinol (CBN)
Tetrahydrocannabinol (THC) What is Medicinal Cannabidiol (CBD) Cannabis? The facts and the fiction. Mental Health and Drug & Alcohol Nurses’ Forum September 2017.
(THCA) (THCV) Justin Sinclair Research Fellow, NICM (Western Sydney University)
Beta-myrcene Alpha-pinene [email protected] www.tmconsultancy.com.au nicm.edu.au 3 Disclosures
Justin Sinclair (Pharmacognosist)
MHerbMed (USyd) BHSc (UNE) ND DBM DNut FNHAA MICRS MSCC
• Research Fellow – NICM (Western Sydney University) • Scientific Advisory Board Member – Bioceuticals • Chief Scientist, Scientific Advisory Council – United in Compassion (Registered Charity) nicm.edu.au • Lecturer – Endeavour Cannabis Botany 4
Family: Cannabaceae (AHP 2014) Botanical nomenclature: (AHP 2014) . Cannabis sativa (L) . Cannabis indica (Lam) . Cannabis ruderalis (Janisch)
Common names: (AHP 2014) Pot, weed, cannabis, ganja, marijuana, hemp, reefer. Part used: Medicinally: Dried unfertilised female inflorescence, Resin glands (aka hashish), leaves
Industry: Figure 1: Graphic representation of Cannabis Seeds (i.e. oil, protein) and fibre (i.e. sativa (L), showing seeds, stamens, leaves, ovaries and inflorescence. Photo from Kohler Textiles, paper, building material) (1887)
nicm.edu.au 5
Cannabis Origins
BLD – Broad Leaf Drug: Cannabis indica ssp. NLD – Narrow Leaf Drug: Cannabis indica ssp. indica afghanica
BLH –FigureBroad 3: LeafGraphic Hemp: representation Cannabis of indicapresentssp. day ranges of variousNLH Cannabis– Narrow biotypes. Leaf Hemp: As seen Cannabis in Clarke & sativa Merlin ssp.2013 . chinensisnicm.edu.au sativa Cannabis Morphology 6
Acuminate apex
Serrated leaf margin
Figure 2: The short, broad leaf exhibited Figure 3: The long, narrow leaf seen in by Cannabis indica, or what is also Cannabis sativa. being described as a broad-leaf drug nicm.edu.au variety. Cannabis Morphology 7
Stamens Pollen
Figure 4: The androecium, or “male place” of Figure 5: The female inflorescence made up of the Cannabis plant comprised of filaments and many smaller florets and populated with anthers, collectively known as stamens. pistils/stigmas
nicm.edu.au Cannabis Morphology 8
Pistils / Stigmas Glandular trichomes
Figure 6: The covering of glandular trichomes Figure 7: Magnified glandular trichomes on on a female Cannabis plant. Cannabis plant.
nicm.edu.au Cannabis Morphology 9
Figure 8: The compressed glandular trichomes Figure 9: Hashish can be sifted or hand rubbed. of the Cannabis plant, known commonly as The hand rubbed product is known as charas. hashish or hash. Photo by Pierre Arnoud-Chouvy
nicm.edu.au Cannabis Morphology 10
Figure 10: The covering of glandular trichomes Figure 11: Another broad leaf drug variety on a specific strain of Cannabis known as known as “Afghani Kush” obtained from a “Bubba Kush”. This is crude herb that can be licensed Medical Cannabis dispensary. smoked, vaporized or used to make edible products (THC:@11-17% / CBD: nicm.edu.au < @ 0.4%) Cannabis Morphology 11
Figure 12: Cannabis plant in vegetative growth stage...note the absence of flowers or buds forming as yet.
nicm.edu.au Cannabis Morphology 12
Figure 13: Cannabis plants under indoor lighting in vegetative growth stage.
nicm.edu.au Cannabis Morphology 13
Figure 14: Outdoor Cannabis plants just starting the flowering stage...notice the Cola buds forming at the end of the stems.
nicm.edu.au Cannabis Morphology 14
nicm.edu.au Cannabis Morphology 15
Figure 15: The seeds of Cannabis, a Figure 16: The fibre obtained from Cannabis great nutritional source of oil and stalks, used throughout human history for protein. millennia.
nicm.edu.au Cannabis Phytochemistry 16
Tetrahydrocannabinol (THC) Structure
Figure 17: A large Cannabis Cannabidiol (CBD) Structure inflorescence nearing maturity and harvest. nicm.edu.au Cannabis Phytochemistry 17
(Andre, Hausman & Guerriero 2016) nicm.edu.au Cannabis Phytochemistry 18
(Giacoppo et al. 2014; AHP 2014)
(Giacoppo et al. 2014; AHP 2014) nicm.edu.au Cannabis Phytochemistry 19
Cannabigerolic acid (CBGA) Δ9-Tetrahydrocannabinolic acid (THCA) Cannabidiolic acid (CBDA)
Cannabichromic acid (CBCA) Cannabielsoinic acid
Psychoactive
Non Psychoactive non-enzymatic decarboxylation (heat)
THCA THC
(Giacoppo et al. 2014; AHP 2014) nicm.edu.au Cannabis Phytochemistry 20
Tetrahydrocannabinol (THC) Structure Cannabidiol (CBD) Structure
Pharmacological actions attributed to THC * Pharmacological actions attributed to CBD
Analgesic (Rahn & Hohmann, 2009) Anticonvulsant (Jones et al. 2010)
Antiemetic (Haney et al. 2007; Hollister 1971; Machado et al. 2008) Antagonizes effects of THC (Pertwee 2008)
Anti-inflammatory (Hampson et al. 1998) Analgesic (Davis & Hartoum, 1983)
Antipruritic (Neff et al. 2002) Anti-inflammatory (Booz, 2011)
Bronchodilator (Williams et al. 1976) Antiemetic / Antinausea (Rock et al. 2010)
Muscle relaxant (Kavia et al. 2010) Anxiolytic (Russo et al. 2005; Campos & Guimares, 2008)
Antioxidant, Neuroprotective (Hampson et al. 1998) Antioxidant (Hampson et al. 1998)
symptoms of Alzheimer’s (Eubanks et al. 2006) Neuroprotective (Hampson et al. 1998)
(Russo 2011; AHP 2014) * Denotes psychoactivity nicm.edu.au Cannabis Phytochemistry 21
Cannabichromene Tetrahydocannabivarin Delta-8-Tetrahydrocannabinol * Weak analgesic (Turner et al. 1980) THC antagonist (Pertwee et al. 2007) Appetite stimulant (Avraham et al. 2004) Anti-inflammatory (Davis & Hatoum, 1983) Anticonvulsant (Hill et al. 2010) Less psychoactive then Delta-9-THC Antimicrobial (Turner & ElSohly, 1981) Improved glucose tolerance (Wargent et al. Binds to CB1 receptors in the brain like 2010) Delta-9 Antiemetic and analgesic
Cannabigerol Cannabinol Analgesic (Cascio et al. 2010) Antipsoriatic (Wilkinson & Williamson 2007) Cannabidivarin Anti-inflammatory Sedative (Musty et al. 1976) Anticonvulsant (Hill et al. 2010) Antifungal (ElSohly et al. 1982) Antimicrobial against MRSA (Appendino et al. 2008) Antipsoriatic (Wilkinson & Williamson 2007) (Russo 2011; AHP 2014) nicm.edu.au 22
nicm.edu.au (Russo 2011; AHP 2014) Terpene Phytochemistry 23
Limonene CBD Anxiolytic (Carvahlo-Freitas & Costa, 2002) Immunostimulant if inhaled (Komori et al. 1995) Antioxidant Apoptosis of breast cancer (Viguishin et al. CBD 1998)
Beta-Myrcene THC Anti-inflammatory (Lorenzetti et al. 1991) Analgesic (Rao et al. 1990) Sedative & hypnotic (do Vale et al. 2002) Muscle relaxant (do Vale et al. 2002)
CBD
Alpha-pinene Anti-inflammatory (Gil et al. 1989)
Bronchodilatory (Falk et al. 1980) THC
(Russo 2011; AHP 2014) nicm.edu.au 24
nicm.edu.au (Russo 2011; AHP 2014) Cannabis Phytochemistry 25
Coumarins Flavonoids
Flavones Polysaccharides
Flavonols Alcohols
Glycosides Steroids Phenols
(AHP 2014) nicm.edu.au Cannabis Dosage Forms 26
Dosage Form Pros Cons Smoking Quick onset of effect; Cheap; Smoke can irritate the lungs; easy to adjust dosing Pulmonary disease effect
Vaporising Quick onset of effect; better for Vaporising units can be lung health than smoking expensive.
Edibles Long lasting effect; option for Longer onset of action; can be those that do not smoke stronger effect.
Juicing Rich in THCA; non- Not a great deal of evidence to psychoactive support this form.
Tinctures / Oils Easy to control dosage; Slower than smoking in onset. palatable; Good for children
Capsules Long lasting effect; option for Longer onset of action; those that do not smoke Excipient ingestion.
Suppositories Absorbed quickly; Long lasting Difficult to administer; Needs effect refrigeration
Topically Can be used for local skin Not a great deal of evidence to nicm.edu.au conditions; Not psychoactive support this form. Cannabis specific drug interactions 27
Cannabis phytochemical Interaction
Cannabidiol (CBD) Can potently inhibit CYP3A4, CYP3A5 and CYP2D6 enzymes
Tetrahydrocannabinol In-vitro inhibition of CYP2C9 has been (THC) observed (Cannabis smoke)
Cannabidiol (CBD) In-vitro inhibition of CYP2C9 has been observed (Cannabis smoke)
Cannabinol (CBN) In-vitro inhibition of CYP2C9 has been observed (Cannabis smoke)
nicm.edu.au How did we get here? 28
nicm.edu.au How did we get here? 29
nicm.edu.au How did we get here? 30
nicm.edu.au Cannabis lowers your IQ? 31
. Cannabis may cause short term memory impairment whilst under the influence. . This is considered reversible upon cessation...not permanent. . Certain Cannabis phytochemicals such as Cannabidiol (CBD) actually exhibit neuroprotective activity. . Animal studies are now showing the possibility of specific Cannabis phytochemistry assisting in:
. Foetal hypoxia (Alvarez et al. 2008) . Multiple sclerosis . Hypoxic brain injury (Ischaemic Figure 18: The female inflorescence (bud) of stroke) “Super Silver Haze”, one of hundreds of different Cannabis strains. . Alzheimer’s Disease (Ramirez et al. 2005)
nicm.edu.au Cannabis lowers your IQ? 32
nicm.edu.au All Cannabis gets you “high”? 33 . The psychoactivity of cannabis is largely dependent on the phytochemistry exhibited in the specific strain of the plant. . There exist numerous strains of Cannabis that have been selectively bred to be low in THC, but higher in other phytochemicals such as CBD. . Individual dosing (titration) and appropriate Cannabis strain selection is key to reducing psychoactive effects.
Figure 19: Harlequin, is rich in CBD and has much lower levels of THC (the main psychoactive cannabinoid) than most recreationally used varieties. Phytochemical profile produced with permission from Steep Hill (Halent) Laboratories (USA). nicm.edu.au Cannabis is a drug of dependence? 34
(Anthony, Warner & Kessler 1994). nicm.edu.au Cannabis is a drug of dependence? 35
. Cannabis dependency does exist but is also dependent on the individual. . Factors such as individual polymorphic expression, individual variability, the strain of Cannabis being utilised and the dosage taken are also important contributing factors.
(Anthony, Warner & Kessler 1994). nicm.edu.au Cannabis is a drug of dependence? 36
We are both legal
nicm.edu.au Cannabis is a gateway drug? 37
. A Gateway drug is defined as “one that apparently can lead to the use of harder, more addictive or dangerous drugs”. . Examples of hard drugs may include: . Heroine . Methamphetamine . Cocaine
(Reiman 2009) nicm.edu.au Cannabis is a gateway drug? 38 Table 1: Percent of sample reporting using cannabis as a substitute. Type of substitution # of Participants % of Participants EtOH substitute n = 134 40% Illicit drug substitute n= 87 26% Prescription drug substitute n= 219 65.8%
250
200
150
100
50
0 Alcohol (EtOH) Illicit drug substitute Prescription drug substitute Number of study participants substitute
nicm.edu.au (Reiman 2009) Cannabis is a gateway drug? 39
Reasons for using cannabis as a substitute
Less adverse side effects (n=197) Less withdrawal potential (n=103) Ability to obtain Cannabis (n=54) Greater social acceptance (n=36) Better symptom management (n=174)
(Reiman 2009)
nicm.edu.au Cannabis is a gateway drug? 40
nicm.edu.au Cannabis is a gateway drug? 41
nicm.edu.au Cannabis versus opioid medication 42
nicm.edu.au Cannabis is a gateway drug? 43
nicm.edu.au Cannabis can cause psychosis? 44 Psychosis is an inability PubMed . to distinguish what is Abstract Full text links real and can include Curr Psychiatry Rep. 2016 Feb;18(2):12. doi: 10.1007/s11920-015-0657-y. delusions and Cannabis and Psychosis: a Critical Overview of the Relationship. Ksir C1, Hart CL2,3,4,5. hallucinations. Author information . Psychosis can be a Abstract brief episode or longer Interest in the relationship between cannabis use and psychosis has increased dramatically in recent years, in part because of concerns related to the growing availability of cannabis and term as seen in potential risks to health and human functioning. There now exists a plethora of scientific articles addressing this issue, but few provide a clear verdict about the causal nature of the cannabis- psychiatric conditions psychosis association. Here, we review recent research reports on cannabis and psychosis, giving particular attention to how each report provides evidence relating to two hypotheses: (1) cannabis such as schizophrenia. as a contributing cause and (2) shared vulnerability. Two primary kinds of data are brought to bear on this issue: studies done with schizophrenic patients and studies of first-episode psychosis. . The exact cause of Evidence reviewed here suggests that cannabis does not in itself cause a psychosis disorder. psychosis is unknown Rather, the evidence leads us to conclude that both early use and heavy use of cannabis are more likely in individuals with a vulnerability to psychosis. The role of early and heavy cannabis use as a but likely involves a prodromal sign merits further examination, along with a variety of other problem behaviors (e.g., early or heavy use of cigarettes or alcohol and poor school performance). Future research studies complex interplay of that focus exclusively on the cannabis-psychosis association will therefore be of little value in our quest to better understand psychosis and how and why it occurs. physical, genetic, psychological and KEYWORDS: Cognition; Marijuana; Mental illness; Psychotic disorder; Schizophrenia; THC environmental factors. PMID: 26781550 [PubMed - in process]
(Ksir & Hart 2016) nicm.edu.au LinkOut - more resources
PubMed Commons PubMed Commons home
0 comments How to join PubMed Commons Cannabis can cause psychosis? 45
. In this UK study, it was estimated that to prevent one case of psychosis approximately 2000 young men would need to stop using Cannabis.
nicm.edu.au Cannabis can cause psychosis? 46
100%
75% 1%
50%
25%
1950 1960 1970 1980 1990 2000 2010 Now
Years of Cannabis use (International) nicm.edu.au Cannabis use is harmful? 47
. Statistics regarding Cannabis causing harm are skewed as they often involve multiple other drugs such as alcohol. . Data specifically relating to Cannabis overdose or toxicity is difficult to find. . Cannabis related harm is more likely, such as operating motor vehicles or predisposing to mental illness or accident.
Figure 20: An example of an old United States Pharmacopoeia Fluid extract of Cannabis. nicm.edu.au Cannabis use is harmful? 48
nicm.edu.au Cannabis use is harmful? 49
LD50 mg/kg in rats (oral)
8000 7060 7000 6000 5000 4000 3000 1944 LD50 mg/kg in rats (oral) 2000 1270 980 1000 636 21.8 192 0
nicm.edu.au Cannabis use is harmful? 50
nicm.edu.au How much Cannabis to cause death? 51
nicm.edu.au Cannabis hyperemesis syndrome 52
nicm.edu.au To conclude. 53
“Truth is always the first casualty of war”
- Aeschylus (523-456BCE) Figure 21: Aeschylus (523-456 BCE)
nicm.edu.au Reference list 54
Alvarez, FJ et al. 2008. Neuroprotective effects of the nonpsychoactive cannabinoid cannabidiol in hypoxic-ischemic newborn piglets. Pediatric Research. Vol. 64. pp. 653-658. American Herbal Pharmacopoeia (AHP) 2014. Upton, R, Craker, L, ElSohly, M, Romm, A, Russo, E & Sexton, M (eds). Cannabis Inflorescence. American Herbal Pharmacopoeia. Scotts Valley California USA. pp. 1-63. Anand P, Whiteside G, Fowler CJ, Hohmann AG. 2009. Targeting CB2 receptors and the endocannabinoid system for the treatment of pain. Brain Res Rev. 60(1). pp. 255-66. Andre, CM, Hausman, J-F, Guerriero, G. 2016. Cannabis sativa: The Plant of the Thousand and One Molecules. Frontiers in Plant Science. Vol. 7 Art. 19 pp. 1-19. Anthony, JC, Warner, LA, Kessler, RC. 1994. Comparative Epidemiology of Dependence on Tobacco, Alcohol, controlled substances and inhalants: Basic Findings from the National Comorbidity Survey. Experimental and Clinical Psychopharmacology. Vol. 2 No. 3. pp. 244-268. Bachhuber, MA, Saloner, B, Cunningham, CO & Barry, CL. 2014. Medical Cannabis Laws and Opioid Analgesic mortality in the United States, 1999-2010. JAMA Intern Med. Vol. 174. pp. 1668-1673. Baker D, Pryce G, Davies WL, Hiley CR. 2006. In silico patent searching reveals a new cannabinoid receptor. Trends Pharmacol Sci. 27(1). pp.1-4. Batkai S, Osei-Hyiaman D, Pan H, El-Assal O, Rajesh M, Mukhopadhyay P, et al. 2007. Cannabinoid-2 receptor mediates protection against hepatic ischemia/reperfusion injury. FASEB J. 21(8). pp. 1788-800. Ben Amar M. 2006. Cannabinoids in medicine: A review of their therapeutic potential. Journal of Ethnopharmacology. 105(1-2) pp. 1-25. Berdyshev EV, Boichot E, Germain N, Allain N, Anger JP, Lagente V. 1997. Influence of fatty acid ethanolamides and delta9-tetrahydrocannabinol on cytokine and arachidonate release by mononuclear cells. Eur J Pharmacol. 330(2-3). pp. 231-40.
nicm.edu.au Reference list 55
Bradford AC & Bradford WD. 2016.Medical marijuana laws reduce prescription medication use in Medicare Part D. Health Aff (Millwood). Jul 1; 35(7) pp. 1230-1236. Cao Q, Martinez M, Zhang J, Sanders AR, Badner JA, Cravchik A, et al. 1997. Suggestive evidence for a schizophrenia susceptibility locus on chromosome 6q and a confirmation in an independent series of pedigrees. Genomics. 43 (1). pp. 1-8. Cencioni MT, Chiurchiu V, Catanzaro G, Borsellino G, Bernardi G, Battistini L, et al. 2010. Anandamide suppresses proliferation and cytokine release from primary human T-lymphocytes mainly via CB2 receptors. PLoS One. 5(1):e8688. Clarke, RC & Merlin, MD. 2013. Cannabis evolution and ethnobotany. University of California Press. Berkeley USA. Currais et al. 2016 Amyloid proteotoxicity initiates an inflammatory response blocked by cannabinoids. Nature Aging and Mechanisms of Disease De Marchi N, De Petrocellis L, Orlando P, Daniele F, Fezza F, Di Marzo V. 2003. Endocannabinoid signalling in the blood of patients with schizophrenia. Lipids Health Dis.2. p. 5. Desfosses J, et.al. 2010. Endocannabinoids and Schizophrenia. Pharmaceuticals. 3. pp. 3103-26. Devane WA, Hanus L, Breuer A, Pertwee RG, Stevenson LA, Griffin G, et al. 1992. Isolation and structure of a brain constituent that binds to the cannabinoid receptor. Science. Vol. 258(5090) pp. 1946-9. Devane WA, Dysarz FA, 3rd, Johnson MR, Melvin LS, Howlett AC. 1999. Determination and characterization of a cannabinoid receptor in rat brain. Mol Pharmacol. 34(5). pp. 605-13. Di Marzo V, De Petrocellis, L. 2010. Endocannabinoids as regulators of transient receptor potential (TRP) channels: a further opportunity to develop new endocannabinoid-based therapeutic drugs. Curr Med Chem. 17. pp. 1430–49.
nicm.edu.au Reference list 56
Duncan M, Mouihate A, Mackie K, Keenan CM, Buckley NE, Davison JS, et al. 2008. Cannabinoid CB2 receptors in the enteric nervous system modulate gastrointestinal contractility in lipopolysaccharide-treated rats. Am J Physiol Gastrointest Liver Physiol. 295(1):G78-G87. Eubanks, LM, Rogers, CJ, Beuschner, AE, Koob, GF et al. 2006. A Molecular link between the active component of marijuana and Alzheimers disease pathology. Mol Pharmacol. Vol. 3. pp. 773-777. Fichna J, Bawa M, Thakur GA, Tichkule R, Makriyannis A, McCafferty DM, et al. 2014. Cannabinoids alleviate experimentally induced intestinal inflammation by acting at central and peripheral receptors. PLoS One. 9(10):e109115. Friedman D, Devinsky O. 2015. Cannabinoids in the Treatment of Epilepsy. N Engl J Med. 373(11). pp. 1048-58. Fuss, J, Steinle, J, Bindila, L, Auer, MK et al. 2015. A runner’s high depends on cannabinoid receptors in mice. Proceedings of the National Academy of Sciences. Vol. 112 No. 42 pp. 13105-13108. Gaoni Y, Mechoulam, R. 1964. Isolation, structure and partial synthesis of an active constituent of hashish. J Am Chem Soc. 86. pp. 1646-7. Galiegue S, Mary S, Marchand J, Dussossoy D, Carriere D, Carayon P, et al. 1995. Expression of central and peripheral cannabinoid receptors in human immune tissues and leukocyte subpopulations. Eur J Biochem. Vol. 232(1) pp. 54-61. Giacoppo, S, Mandolino, G, Galuppo, M, Bramanti, P & Mazon, E. 2014 Cannabinoids: New Promising Agents in the Treatment of Neurological Diseases. Molecules Vol. 19 No. 11 pp. 18781-18816. Grotenhermen F. 2006. Cannabinoids and the Endocannabinoid System. International Association for Cannabis as Medicine. Cannabinoids. Vol. 1(1):10-4. Guillot A, Hamdaoui N, Bizy A, Zoltani K, Souktani R, Zafrani ES, et al. 2014. Cannabinoid receptor 2 counteracts interleukin-17-induced immune and fibrogenic responses in mouse liver. Hepatology. 59(1). pp. 296-306. nicm.edu.au Reference list 57
Hashibe, M et al. 2006. Marijuana use and the risk of lung and upper aerodigestive tract cancers: Resulsts of a population-based case-control study. Cancer Epidemiol Biomarkers Prev Oct; 15 (10) pp. 1829-34. Herkenham M, Lynn AB, Little MD, Johnson MR, Melvin LS, de Costa BR, et al. 1990. Cannabinoid receptor localization in brain. Proc Natl Acad Sci U S A. Vol. 87(5) pp. 1932-1936. Hickman, M et al. 2009. If Cannabis caused schizophrenia – how many cannabis users may need to be prevented in order to prevent one case of Schizophrenia? England and Wales calculations. Addiction. Nov. 104 (11). Ishiguro H, Horiuchi Y, Ishikawa M, Koga M, Imai K, Suzuki Y, et al. 2010. Brain cannabinoid CB2 receptor in schizophrenia. Biol Psychiatry. 67(10). pp. 974-82. Izzo AA, Sharkey KA. 2010. Cannabinoids and the gut: new developments and emerging concepts. Pharmacol Ther. 126(1). pp. 21-38. Jackson, NJ, Isen, JD, Khoddam, R, Irons, DE et al. 2016. Impact of adolescent marijuana use on intelligence: Results from two longitudinal twin studies. Proceedings of the National Academy of Sciences. Vol. 113 No. 5 pp. E500-8. Juhasz G, Lazary J, Chase D, Pegg E, Downey D, Toth ZG, et al. 2009. Variations in the cannabinoid receptor 1 gene predispose to migraine. Neurosci Lett. 461(2). pp.116-20. Julien B, Grenard P, Teixeira-Clerc F, Van Nhieu JT, Li L, Karsak M, et al. 2005. Antifibrogenic role of the cannabinoid receptor CB2 in the liver. Gastroenterology. 128(3). pp. 742-55. Kano M. 2014. Control of synaptic function by endocannabinoid-mediated retrograde signaling. Proc Jpn Acad Ser B Phys Biol Sci. 90(7). pp.235-50. Ksir, C & Hart, CL. 2014 Cannabis and Psychosis: A critical overview of the relationship. Current Psychiatry Reports. Vol. 18 No. 2
nicm.edu.au Reference list 58
Li, H. 1974 An Archaelogical and Historical Account of Cannabis in China. Economic Botany. Vol 28 pp. 437-448. Ludanyi A, Eross L, Czirjak S, Vajda J, Halasz P, Watanabe M, et al. 2008. Downregulation of the CB1 cannabinoid receptor and related molecular elements of the endocannabinoid system in epileptic human hippocampus. J Neurosci. 28(12). pp. 2976-90. Maccarrone M, Bab I, Biro T, Cabral GA, Dey SK, Di Marzo V, et al. 2015. Endocannabinoid signaling at the periphery: 50 years after THC. Trends Pharmacol Sci. 36(5). pp.277-96. Mackie K, Lai Y, Westenbroek R, Mitchell R. 1995. Cannabinoids activate an inwardly rectifying potassium conductance and inhibit Q-type calcium currents in AtT20 cells transfected with rat brain cannabinoid receptor. J Neurosci. 15(10). pp.6552-61. Matsuda LA, Lolait SJ, Brownstein MJ, Young AC & Bonner TI. 1990. Structure of a cannabinoid receptor and functional expression of the cloned cDNA. Nature. Aug 9; 346 (6284) pp. 561-564. McGeeney, BE. 2013. Cannabinoids and hallucinogens for headache. Headache. Vol. 53(3) pp. 447-458. McKim, W. 2000. Drugs and Behavior. An Introduction to Behavioral Pharmacology. 4th ed. Sadle River: Prentice-Hall. Mechoulam R, Braun, P, Gaoni, Y. 1967. A stereospecific synthesis of (−)- 1 and (−)- 6- tetrahydrocannabinols. J Am Chem Soc. 89. pp.4552–4. Mechoulam R, Feigenbaum JJ, Lander N, Segal M, Jarbe TU, Hiltunen AJ, et al. 1988. Enantiomeric cannabinoids: stereospecificity of psychotropic activity. Experientia. 44(9). pp. 762-4. Merlin, MD. 2003. Archaeological evidence for the Tradition of Psychoactive plant use in the Old World. Economic Botany. New York Botanical Garden Press. Vol 57 No. 3 pp. 295-323.
nicm.edu.au Reference list 59
Muccioli GG, Naslain D, Backhed F, Reigstad CS, Lambert DM, Delzenne NM, et al. 2010. The endocannabinoid system links gut microbiota to adipogenesis. Mol Syst Biol. 6. p. 392. Munro, S, Thomas, KL & Abu-Shaar, M 1993. Molecular characterisation of a peripheral receptor for cannabinoids. Nature 365. pp. 61-65. Munsen AE, Harris LS, Friedman MA, Dewey WL & Carchman RA. 1975. Antineoplastic activity of cannabinoids. J Natl Cancer Inst. Sept; 55 (3) pp. 597-602. Nyholt DR, Morley KI, Ferreira MA, Medland SE, Boomsma DI, Heath AC, et al. 2005. Genomewide significant linkage to migrainous headache on chromosome 5q21. Am J Hum Genet. 77(3). pp.500-12. Pacher P, Mechoulam R. 2011. Is lipid signaling through cannabinoid 2 receptors part of a protective system? Prog Lipid Res. 50(2).pp. 193-211. Pacher P, Batkai S & Kunos G. 2006. The endocannabinoid system as an emerging target of pharmacotherapy. Pharmacol Rev Sep; 58(3) pp. 389-462. Pacher P & Kunos G. 2013. Modulating the endocannabinoid system in human health and disease – succusses and failures. FEBS May; 280 (9) pp. 1918-43. Pertwee RG. 1997. Pharmacology of cannabinoid CB1 and CB2 receptors. Pharmacol Ther. Vol. 74(2) pp.129-180. Piomelli D. 2013. A fatty gut feeling. Trends Endocrinol Metab. 24(7). pp. 332-41. Pistis M, Melis M. 2010. From surface to nuclear receptors: the endocannabinoid family extends its assets. Curr Med Chem.17(14). pp.1450-67.
nicm.edu.au Reference list 60
Raichlen DA, Foster AD, Gerdeman GL, Seillier A, Giuffrida A. 2012. Wired to run: exercise-induced endocannabinoid signaling in humans and cursorial mammals with implications for the 'runner's high'. J Exp Biol. 215(Pt 8). pp. 1331-6. Rajesh M, Batkai S, Kechrid Met al. 2012. Cannabinoid 1 receptor promotes cardiac dysfunction, oxidative stress, inflammation, and fibrosis in diabetic cardiomyopathy. Diabetes Mar; 61(3) pp. 716-727 Ramírez, BG et al. 2005. Prevention of Alzheimer’s disease pathology by cannabinoids: neuroprotection mediated by blockade of microglial activation. The Journal of Neuroscience Vol. 25. pp. 1904-1913. Romigi A, Bari M, Placidi F, Marciani MG, Malaponti M, Torelli F, et al. 2010. Cerebrospinal fluid levels of the endocannabinoid anandamide are reduced in patients with untreated newly diagnosed temporal lobe epilepsy. Epilepsia. 51(5):768-72. Reiman, A. 2009. Cannabis as a substitute for alcohol and other drugs. Harm Reduction Journal. Vol. 6. No. 35. pp. 1-5. Ross RA. 2009. The enigmatic pharmacology of GPR55. Trends Pharmacol Sci. 30(3). pp. 156-63. Russo EB. 2004. Clinical endocannabinoid deficiency (CECD): can this concept explain therapeutic benefits of cannabis in migraine, fibromyalgia, irritable bowel syndrome and other treatment-resistant conditions? Neuro Endocrinol Lett. 25(1-2):31-9. Russo EB. 2011. Taming THC: potential cannabis synergy and phytocannabinoid-terpenoid entourage effects. Br J Pharmacol. Vol. 163(7) pp. 1344-1364. Russo EB. 2016. Beyond Cannabis: Plants and the Endocannabinoid System. Trends in Pharmacological Sciences.37 (7). pp. 1-12. Sanchez AJ, Garcia-Merino A. 2012. Neuroprotective agents: cannabinoids. Clin Immunol. 2012;142(1). pp. 57-67.
nicm.edu.au Reference list 61
Sarchielli P, Pini LA, Coppola F, Rossi C, Baldi A, Mancini ML, et al. 2007. Endocannabinoids in chronic migraine: CSF findings suggest a system failure. Neuropsychopharmacology. 32(6). pp.1384-90. Sparling PB, Giuffrida A, Piomelli D, Rosskopf L, Dietrich A. 2003. Exercise activates the endocannabinoid system. Neuroreport.14(17). pp. 2209-11. Steffens S & Pacher P. 2012. Targeting cannabinoid receptor CB2 in cardiovascular disorders: promises and controversies. Br J Pharmacol. Sep;167 (2) pp. 313-23. Sugiura T, Kondo S, Sukagawa A, Nakane S, Shinoda A, Ioth K, Yamashita A & Waku K. 1995 2- Arachidonoylglycerol: A possible endogenous cannabinoid receptor ligand in brain. Biochem biophys Res Commun. Oct 4; 215 (1) pp. 89-97. Sykaras AG, Demenis C, Case RM, McLaughlin JT, Smith CP. 2012. Duodenal enteroendocrine I-cells contain mRNA transcripts encoding key endocannabinoid and fatty acid receptors. PLoS One. 7(8):e42373. Tashkin DP. 2013 Effects of marijuana smoking on the lung. Ann Am Thorac Soc. Jun 10(3) pp. 239-247. Wright KL, Duncan M, Sharkey KA. 2008. Cannabinoid CB2 receptors in the gastrointestinal tract: a regulatory system in states of inflammation. Br J Pharmacol. 153(2). pp. 263-70.
nicm.edu.au THANK YOU
© Copyright 2017 NICM Western Sydney University. All Rights Reserved.