Post on 06-Aug-2020
transcript
nicm.edu.au
2
Tetrahydrocannabinol (THC)
Cannabichromene (CBC)
Cannabidiol (CBD)
(THCA)(THCV)
Beta-myrcene
Justin Sinclair
Research Fellow, NICM (Western Sydney University)
J.Sinclair@westernsydney.edu.au
www.tmconsultancy.com.au
What is Medicinal
Cannabis? The facts and the fiction.
Mental Health and Drug & Alcohol Nurses’ Forum
September 2017.
Alpha-pinene
Cannabinol (CBN)
nicm.edu.au
3
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)
• Lecturer – Endeavour
Disclosures
nicm.edu.au
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:
Seeds (i.e. oil, protein) and fibre (i.e.
Textiles, paper, building material)
Figure 1: Graphic representation of Cannabis
sativa (L), showing seeds, stamens, leaves,
ovaries and inflorescence. Photo from Kohler
(1887)
Cannabis Botany
nicm.edu.au
5
Figure 3: Graphic representation of present day ranges of various Cannabis biotypes. As seen in Clarke & Merlin 2013.
BLD – Broad Leaf Drug: Cannabis indica ssp.
afghanica
NLD – Narrow Leaf Drug: Cannabis indica ssp. indica
BLH – Broad Leaf Hemp: Cannabis indica ssp.
chinensis
NLH – Narrow Leaf Hemp: Cannabis sativa ssp.
sativa
Cannabis Origins
nicm.edu.au
6
Figure 2: The short, broad leaf exhibited
by Cannabis indica, or what is also
being described as a broad-leaf drug
variety.
Figure 3: The long, narrow leaf seen in
Cannabis sativa.
Acuminate apex
Cannabis Morphology
Serrated leaf margin
nicm.edu.au
7
Figure 4: The androecium, or “male place” of
the Cannabis plant comprised of filaments and
anthers, collectively known as stamens.
Figure 5: The female inflorescence made up of
many smaller florets and populated with
pistils/stigmas
Stamens
Pollen
Cannabis Morphology
nicm.edu.au
8
Figure 7: Magnified glandular trichomes on
Cannabis plant.
Pistils / Stigmas Glandular trichomes
Figure 6: The covering of glandular trichomes
on a female Cannabis plant.
Cannabis Morphology
nicm.edu.au
9
Figure 9: Hashish can be sifted or hand rubbed.
The hand rubbed product is known as charas.
Photo by Pierre Arnoud-Chouvy
Figure 8: The compressed glandular trichomes
of the Cannabis plant, known commonly as
hashish or hash.
Cannabis Morphology
nicm.edu.au
10
Figure 10: The covering of glandular trichomes
on a specific strain of Cannabis known as
“Bubba Kush”. This is crude herb that can be
smoked, vaporized or used to make edible
products (THC:@11-17% / CBD:
< @ 0.4%)
Figure 11: Another broad leaf drug variety
known as “Afghani Kush” obtained from a
licensed Medical Cannabis dispensary.
Cannabis Morphology
nicm.edu.au
11
Figure 12: Cannabis plant in vegetative growth stage...note the absence of flowers or buds forming
as yet.
Cannabis Morphology
nicm.edu.au
12
Figure 13: Cannabis plants under indoor lighting in vegetative growth stage.
Cannabis Morphology
nicm.edu.au
13
Figure 14: Outdoor Cannabis plants just starting the flowering stage...notice the Cola buds forming
at the end of the stems.
Cannabis Morphology
nicm.edu.au
14Cannabis Morphology
nicm.edu.au
15
Figure 15: The seeds of Cannabis, a
great nutritional source of oil and
protein.
Figure 16: The fibre obtained from Cannabis
stalks, used throughout human history for
millennia.
Cannabis Morphology
nicm.edu.au
16
Tetrahydrocannabinol (THC) Structure
Cannabidiol (CBD) StructureFigure 17: A large Cannabis
inflorescence nearing maturity and
harvest.
Cannabis Phytochemistry
nicm.edu.au
17
(Andre, Hausman & Guerriero 2016)
Cannabis Phytochemistry
nicm.edu.au
18
(Giacoppo et al. 2014; AHP 2014)
Cannabis Phytochemistry
(Giacoppo et al. 2014; AHP 2014)
nicm.edu.au
19
Psychoactive
Non Psychoactive
(Giacoppo et al. 2014; AHP 2014)
Cannabis Phytochemistry
Cannabigerolic acid (CBGA) Cannabidiolic acid (CBDA)Δ9-Tetrahydrocannabinolic acid (THCA)
Cannabichromic acid (CBCA) Cannabielsoinic acid
THCA THC
non-enzymatic
decarboxylation (heat)
nicm.edu.au
20
Tetrahydrocannabinol (THC) Structure Cannabidiol (CBD) Structure
Pharmacological actions attributed to CBD
Anticonvulsant (Jones et al. 2010)
Antagonizes effects of THC (Pertwee 2008)
Analgesic (Davis & Hartoum, 1983)
Anti-inflammatory (Booz, 2011)
Antiemetic / Antinausea (Rock et al. 2010)
Anxiolytic (Russo et al. 2005; Campos & Guimares, 2008)
Antioxidant (Hampson et al. 1998)
Neuroprotective (Hampson et al. 1998)
Pharmacological actions attributed to THC *
Analgesic (Rahn & Hohmann, 2009)
Antiemetic (Haney et al. 2007; Hollister 1971; Machado et al. 2008)
Anti-inflammatory (Hampson et al. 1998)
Antipruritic (Neff et al. 2002)
Bronchodilator (Williams et al. 1976)
Muscle relaxant (Kavia et al. 2010)
Antioxidant, Neuroprotective (Hampson et al. 1998)
symptoms of Alzheimer’s (Eubanks et al. 2006)
(Russo 2011; AHP 2014) * Denotes psychoactivity
Cannabis Phytochemistry
nicm.edu.au
21
Cannabichromene
Weak analgesic (Turner et al. 1980)
Anti-inflammatory (Davis & Hatoum, 1983)
Antimicrobial (Turner & ElSohly, 1981)
Cannabigerol
Analgesic (Cascio et al. 2010)
Anti-inflammatory
Antifungal (ElSohly et al. 1982)
Antipsoriatic (Wilkinson & Williamson 2007)
Cannabidivarin
Anticonvulsant (Hill et al. 2010)
Tetrahydocannabivarin
THC antagonist (Pertwee et al. 2007)
Anticonvulsant (Hill et al. 2010)
Improved glucose tolerance (Wargent et al.
2010)
Delta-8-Tetrahydrocannabinol *
Appetite stimulant (Avraham et al. 2004)
Less psychoactive then Delta-9-THC
Binds to CB1 receptors in the brain like
Delta-9
Antiemetic and analgesic
Cannabinol
Antipsoriatic (Wilkinson & Williamson 2007)
Sedative (Musty et al. 1976)
Antimicrobial against MRSA (Appendino et
al. 2008)
(Russo 2011; AHP 2014)
Cannabis Phytochemistry
nicm.edu.au
22
(Russo 2011; AHP 2014)
nicm.edu.au
23
Limonene
Anxiolytic (Carvahlo-Freitas & Costa, 2002)
Immunostimulant if inhaled (Komori et al.
1995)
Antioxidant
Apoptosis of breast cancer (Viguishin et al.
1998)
Beta-Myrcene
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)
Alpha-pinene
Anti-inflammatory (Gil et al. 1989)
Bronchodilatory (Falk et al. 1980)
(Russo 2011; AHP 2014)
CBD
CBD
THC
CBD
THC
Terpene Phytochemistry
nicm.edu.au
24
(Russo 2011; AHP 2014)
nicm.edu.au
25
(AHP 2014)
Flavonoids
Polysaccharides
Phenols
Coumarins
Glycosides
Alcohols
Steroids
Flavones
Flavonols
Cannabis Phytochemistry
nicm.edu.au
26
Dosage Form Pros Cons
Smoking Quick onset of effect; Cheap;
easy to adjust dosing
Smoke can irritate the lungs;
Pulmonary disease effect
Vaporising Quick onset of effect; better for
lung health than smoking
Vaporising units can be
expensive.
Edibles Long lasting effect; option for
those that do not smoke
Longer onset of action; can be
stronger effect.
Juicing Rich in THCA; non-
psychoactive
Not a great deal of evidence to
support this form.
Tinctures / Oils Easy to control dosage;
palatable; Good for children
Slower than smoking in onset.
Capsules Long lasting effect; option for
those that do not smoke
Longer onset of action;
Excipient ingestion.
Suppositories Absorbed quickly; Long lasting
effect
Difficult to administer; Needs
refrigeration
Topically Can be used for local skin
conditions; Not psychoactive
Not a great deal of evidence to
support this form.
Cannabis Dosage Forms
nicm.edu.au
27
Cannabis phytochemical Interaction
Cannabidiol (CBD) Can potently inhibit CYP3A4, CYP3A5
and CYP2D6 enzymes
Tetrahydrocannabinol
(THC)
In-vitro inhibition of CYP2C9 has been
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)
Cannabis specific drug interactions
nicm.edu.au
28How did we get here?
nicm.edu.au
29How did we get here?
nicm.edu.au
30How did we get here?
nicm.edu.au
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 (Ischaemicstroke)
Alzheimer’s Disease (Ramirez et al. 2005)
Figure 18: The female inflorescence (bud) of
“Super Silver Haze”, one of hundreds of
different Cannabis strains.
Cannabis lowers your IQ?
nicm.edu.au
32Cannabis lowers your IQ?
nicm.edu.au
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).
All Cannabis gets you “high”?
nicm.edu.au
34
(Anthony, Warner & Kessler 1994).
Cannabis is a drug of dependence?
nicm.edu.au
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).
Cannabis is a drug of dependence?
nicm.edu.au
36
We are
both legal
Cannabis is a drug of dependence?
nicm.edu.au
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)
Cannabis is a gateway drug?
nicm.edu.au
38
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%
Table 1: Percent of sample reporting using cannabis as a substitute.
0
50
100
150
200
250
Alcohol (EtOH)substitute
Illicit drug substitute Prescription drugsubstituteNumber of study participants
(Reiman 2009)
Cannabis is a gateway drug?
nicm.edu.au
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 socialacceptance (n=36)
Better symptommanagement (n=174)
(Reiman 2009)
Cannabis is a gateway drug?
nicm.edu.au
40Cannabis is a gateway drug?
nicm.edu.au
41Cannabis is a gateway drug?
nicm.edu.au
42Cannabis versus opioid medication
nicm.edu.au
43Cannabis is a gateway drug?
nicm.edu.au
44
Psychosis is an inability to distinguish what is real and can include delusions and hallucinations.
Psychosis can be a brief episode or longer term as seen in psychiatric conditions such as schizophrenia.
The exact cause of psychosis is unknown but likely involves a complex interplay of physical, genetic, psychological and environmental factors.
(Ksir & Hart 2016)
KEYWORDS:
How to join PubMed Commons
PubMed Commons home
Curr Psychiatry Rep. 2016 Feb;18(2):12. doi: 10.1007/s11920-015-0657-y.
Cannabis and Psychosis: a Critical Overview of the Relationship.
Ksir C , Hart CL .
Abstract
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
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-
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
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.
Evidence reviewed here suggests that cannabis does not in itself cause a psychosis disorder.
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
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
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.
Cognition; Marijuana; Mental illness; Psychotic disorder; Schizophrenia; THC
PMID: 26781550 [PubMed - in process]
PubMed Commons
0 comments
Abstract
1 2,3,4,5
Author information
LinkOut - more resources
Full text links
PubMed
Cannabis can cause psychosis?
nicm.edu.au
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.
Cannabis can cause psychosis?
nicm.edu.au
46
1%
25%
50%
75%
100%
1970 1980 1990 2010 Now200019601950
Years of Cannabis use (International)
Cannabis can cause psychosis?
nicm.edu.au
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.
Cannabis use is harmful?
nicm.edu.au
48Cannabis use is harmful?
nicm.edu.au
49
0
1000
2000
3000
4000
5000
6000
7000
80007060
1944
9801270
21.8
636192
LD50 mg/kg in rats (oral)
LD50 mg/kg in rats (oral)
Cannabis use is harmful?
nicm.edu.au
50Cannabis use is harmful?
nicm.edu.au
51How much Cannabis to cause death?
nicm.edu.au
52Cannabis hyperemesis syndrome
nicm.edu.au
53
“Truth is
always the
first casualty
of war”
- Aeschylus (523-456BCE)
To conclude.
Figure 21: Aeschylus (523-456 BCE)
nicm.edu.au
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.
Reference list
nicm.edu.au
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.
Reference list
nicm.edu.au
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.
Reference list
nicm.edu.au
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
Reference list
nicm.edu.au
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.
Reference list
nicm.edu.au
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.
Reference list
nicm.edu.au
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.
Reference list
nicm.edu.au
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.
Reference list
THANK YOU
© Copyright 2017 NICM Western Sydney University. All Rights Reserved.