M in istry o f H ealth , W elfare an d S p o rt
The M ed ic inal U se o fC annab is
introduction
Willem K. Scholten, MSc, Pharm., MPA
Head, Office of Medicinal Cannabis (OMC)
Ministry of Health Welfare and Sport, The Netherlands
Conference on the Medicinal Use of CannabisLjubljana, 18 november 2002
M in istry o f H ealth , W elfare and S port
The Medicinal Use of Cannabis Introductory presentation
Overview
• About the plant• Some history• Renewed interest• Some key words for today and some science
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Part I
About the plant
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C annab is sativa L. or hemp,Konoplja• Cannabinaceae
• Formerly regarded as 3 species:– Cannabis sativa– Cannabis indica– Cannabis ruderalis
• Diecious: male plants and female plants• Strong fibers• Cellular hairs
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Related: H um ulus lupulus L., hopHmelj• Cannabinaceae
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Also related to the Urticaceae
• U rtica dioica, nettle Kopriva
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GW Pharmaceuticals plc. (United Kingdom): glasshouse
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Cannabis
• For medical use: flowering tops of female C annab is sativa L.
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Uses of hemp (1)• fibers
rope(cigarette) paperisolation material
• seedsbird foodlamp oilsoaplacquers and paints
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Uses of hemp (2)
• living plants:wind fences
• for its pharmacological activity:
- (narcotic) drug- medicine
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Part II
Some history
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Ancient medicine• China• 3000 BC
• malaria
• obstipation
• rheumatic pains
• absent-mindedness
• ‘women’s diseases’
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Ancient medicine
Also known in:
• Arabic traditional medicine
• Indian (Ayurvedic) traditionalmedicine
• Ancient Persian medicine
• Ancient Greece medicine
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Western medicine
• Introduced in 19th century• O’Shaugnessy (approx. 1830)• Frequently used by Queen Victoria• In many western pharmacopoeias:
– e.g.USP 1870:
– Cannabis indicae– Tinctura cannabis indicae
Ph. Ned Ed. V (1926)
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Ph. Ned. Ed. V (1926)
From: Dutch Pharmacopoeia Ed. V 1926
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Cannabis control• 19th century: legal
• 1909: Shanghai conference: pressure for Opium control byUS, resistance by UK – no treaty
• 1912: The Hague conference: Control Convention on opium,opiates and cocaïneUS pressure for inclusion of cannabis
• 1925 Geneva convention: includes cannabis upon pressureform multiple countries
Source: Fischer B et al., Control of cannabis use in western countries – a briefreview of history and present in: European City conference on cannabispolicy, The Hague 2001.
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Present treaties
Present treaties applicable on cannabis:
• Single Convention on narcotic drugs (1962)
• Vienna convention (1988) (United Nations’ convention against illicit traffic in
narcotic drugs and psychotropic substances)
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Discrepancy
• narcotics accepted asmedicine
morphinecocaineamphetamineopiumsynthetic THCmany others
•not accepted asmedicine
cannabismany other substancesisolated from cannabis
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Prohibition of cannabis
• Prohibition of cannabis in national legislationUSA: 1941The Netherlands: 1953
• Including prohibition of medicinal usesh ift in pharm acy p ractice from herba l d rugs tochem ica l substances in 20 th cen tu ry
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Part III
Renewed interest
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Renewed interest in cannabis.Why?
Public pressure
• From 1960ies: «recreational use» ofcannabis in many western countries
• cannabis users experienced alsobeneficious effects
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Renewed interest in cannabis.Why?
Public pressure in the Netherlands
• around 1994: law was not clear:was it allowed to prescribe cannabis?
• patients organisations• producer of medicinal cannabis
• Health Care Inspectorate enforced prohibition
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Renewed interest in cannabis.Why?Public pressure in CanadaGrowing numbers of Canadians are finding that only marijuana can treat theirpain and suffering, but using it makes them criminals.
T he Toronto S tar, M ay 2 , 1999
Patient’s bid to use marijuana legally in court today.N ationa l P ost, M ay 6 , 1999
AIDS patient sues Ottawa for a safe supply of marijuana; Right to smoke notenough
N ationa l P ost, January 21 , 2000
A puff eases pain of a life once ‘dead’.The E dm onton S un, A pril 12 , 2000
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Official reports• US Institute of Medicine (IOM), Marijuana and Medicine: Assessing the
Science Base, National Academy Press, Washington, DC, 1999 **• National Institutes of Health. Medical Marijuana. Workshop Proceedings:
February 19-20, 1997. Bethesda MD, USA.• World Health Organization. Cannabis: a health perspective and research
agenda. Publication no. who/msa/psa/97.4, 1997• Health Council of the Netherlands: Standing Committee on Medicine.
"Marijuana as medicine." December 3, 1996• British Medical Association. Therapeutic uses of cannabis. Amsterdam:
Harwood Academic Publishers, 1997.• The Report of the UK House of Lords, Select Committee on Science and
Technology, Session 1997-98, Cannabis: the scientific and medicalevidence. 9th Report, HL Paper 151, November 1998 **
** available on the internet
Renewed interest in cannabis.Why?
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Part IV
Some keywords,some science
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Constituents of cannabis (1)• Flowering tops of female plantshave glands that contain resin
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Constituents of cannabis (2)Main constituent:∆-9-tetrahydrocannabinol (THC or ∆-9-THC)0,5% - >20% (of plant dry weight)
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Constituents of cannabis (3)
• Cannabinoids
– THC (tetrahydrocannabinol)– CBD (cannabidiol)– CBC (cannabichromene)– CBG (cannabigerol)– CBN (cannabinol)– THC-V / CBC-V (propyl deriva tives)
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Constituents of cannabis (4)
Flavonoids
• terpenes
• many others, as in anyliving organism
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Pure substances:
one ou t o f m any substances
examples• dronabinol (= -9-THC)• cannabidiol (CBD)
Constituents of cannabis (5)
Dronabinol vs. full plant
Full plant (dried herb, extract,or processed extract indosage form):
contains m any substances
• about 70 cannabinoids(varying properties)
• terpenoids• flavonoids
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Constituents of cannabis (6)
Other constituent, other activity:
• THC (INN: dronabinol)
– Analgesic, Anti-spasmodic, Anti-tremor, Anti-inflammatory,Appetite stimulant, Anti-emetic
• CBD
– Anti-inflammatory, Anti-convulsant, Anti-psychotic, Anti-oxidant, Neuroprotective, Immunomodulator
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Constituents of cannabis (7)Consequences:
Pharmacological activity of cannabis is not necessary identical tothat of one single isolated cannabinoid
Pharmacological activity of one cannabinoid is not necessaryidentical to that of another cannabinoid
If not standardised: one batch of cannabis (the herb) is notnecessary identical to that of another cannabinoid
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Constituents of cannabis (8)
Requirements:
For re liab ility o f the resu lts : the cannabis used in anyclinical trial should be very well defined
For reproducib ility o f the resu lts : the productionmethod of cannabis used in any clinical trial shouldbe very well defined as well( no seized cannabis)
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Cultivationimportance of standardisation
Cannabis is like wine
• 70 cannabinoids with varioustherapeutic properties
• probably other chemical classeswhich contribute to therapeuticproperties
Cannabinoid content depends on• cannabis breed• soil• temperature• humidity• illumination• moment of harvesting
Wine
• many substancies (of which manyunknown) determine the taste
Wine quality depends on• grape breed• soil (calciferous or not)• good summer with much sun and
some, but not too much rain• wait with harvesting until the grapes
are sweet, but not until they are rotten
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The cannabinoid system (1)
Receptors
• CB1 receptors: central nervous system– THC strong agonist
• CB2 receptors: periphery (heart, intestine, spleen,immune system cells)
• CB3 receptors?
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Thecannabinoidsystem (2)Murine CB1 and CB2receptors, which bothshare the 7transmembrane-spanning structurecharacteristic of Gprotein-coupledreceptorsKlein TW et al., Thecannabinoid system andcytokine network, Proc SocExp Biol Med (2000)402:121-130
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The cannabinoid system (3)
• Endocannabinoids– anandamide
– 2-arachidonylglycerol (2-AG)
• Synthetic agonists and antagonists
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Several hundreds of indications mentioned in literature
There are a few promising indications:• controlling nausea and vomiting (cancer, HIV)• stimulating appetite (cancer, HIV)• slight spasticity with pain (multiple sclerosis)• (chronic) pain• Gilles de la Tourette’s syndrome• asthma• extra pyramidal symptoms• therapy resistant glaucoma
Indications
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Registered products
– synthetic dronabinol (Marinol®)• For severe nausea and vomiting associated
with cancer chemotherapy.• For the treatment of AIDS-related anorexia
and associated weight loss.
– nabilone (Cesamet®)• For severe nausea and vomiting associated
with cancer chemotherapy.
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Administration routes• oral
– herbal tea– capsules
• inhalation– cigarettes
not preferred – cancer risk!– vaporiser (180o Celcius)– metered dose aerosol– powder inhalation
• sublingual spray• eye drops• suppositories
vaporiser
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Administration routes (2)
Secure dispensing device
(dock + device + cartridge)
(GW Pharmaceuticals)
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Further reading
• Williamson E.M. et al, C annab ino ids in C lin ica lP ractice . Drugs 2000; 60(6):1303-1314
• British Medical Association, Therapeutic uses o fcannab is . Amsterdam: Harwood AcademicPublishers, 1997
• Journal of Cannabis Therapeutics
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http://home.planet.nl/~wk.scholten
M in istry o f H ealth , W elfare an d S p o rt
The M ed ic inal U se o f C annab isintroduction
Willem K. Scholten, MSc, Pharm., MPAHead, Office of Medicinal CannabisMinistry of Health, Welfare and Sport,P.O. Box 203502500 EJ Den HaagThe Netherlandsphone +31 70 340 5129 fax +31 70 340 7187e-mail: [email protected]
Conference on the Medicinal Use of CannabisLjubljana, 18 november 2002
