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Cannabis
Prof. Suleiman Olimat
‫‪Cannabis‬‬
‫القنب الهندي‬
‫نبات الحشيش‬
Cannabis is a genus of flowering plant that includes
one or more species. The plant is believed to have
originated in the mountainous regions just north-west
of the Himalayas in India, though it could also have
come from Northern Africa. It is also known as hemp,
although this term usually refers to Cannabis cultivated
for non-drug use.
Cannabis spp.
There are three species known:
Cannabis sativa, C. indica and C. rudelaris
The leaves are the most recognisable and wellknown aspect of the cannabis plant. Despite
the great degree of variation found naturally in
local populations of cannabis, the leaves do not
alter greatly in appearance between varieties .
Hemp
What is Marijuana?
Marijuana is the dried mix
of flowers and leaves
form the female
Cannabis Sativa plant.
Hashish is the resin, or
sap, harvested from the
plant.
Hashish oil is the essential
oil of the female
Cannabis Sativa plant.
Marijuana – History of Use
• Cannabis – native to central Asia
• Chinese – first to use, employed for fabric, medicines
• India – country where first used for hallucinogenic properties
• Africa – introduced through Arab traders; used as medicine
• Europe – became popular in 1800s
• U.S.A. – 1900s -- use proscribed, outlawed
• End of 20th century – contentious debate regarding merits of
legalization
HempvsMarijuana-1
• The word "hemp"is English for a number
of varieties of the Cannabisplant,
particularly the varieties like "industrial
hemp" that were bred over time for
industrial uses such as fuel, fiber, paper,
seed, food, oil, etc
HempvsMarijuana-2
• The term "marijuana"is of Spanish
derivation, and was primarily used to
describe varieties of Cannabisthat were
more commonly bred over time for
medicinal and recreational purposes, like
Cannabisindica, and certain strains of
Cannabissativa.
HempvsMarijuana-3
• Two cannabinoids are preponderant in
Cannabis
• THC
CBD
• psychoactive ingredient antipsychoactive ingredient
Marijuana
Hemp
• (leaves and flowers of the female plant)
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•
High in THC
Low in CBD
High in CBD
Low in THC
Cannabis Biology
Major Drug Component – delta-trans-tetrahydrocannabinol (THC)
- binds to specific receptors in brain
THC- produced in glands on leaves and flowers
-- female plants produce more glands
-- gland production stimulated by heat, sunlight, drought
-- sinsemilla (sin = without semilla = seeds) – particularly strong
Hashish – product - relatively pure resin
Glands
THC
Chemical constituents of Cannabis
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Cannabinoids (66)
Nitrogenous compounds (27)
Amino acids(18)
Proteins/ enzymes (11)
Sugars (34)
Hydrocarbons (50)
Simple alcohols (7)
Simple aldehydes (12)
Simple ketones (13)
Simple acids (21)
Fatty acids (22)
Simple esters/lactones (13)
Steroids (11)
Terpenes (20)
Non-cannabinoid phenols (25)
Flavoroids (21)
Vitamins (1)
Pigments (2)
Elements (9)
Total known compounds (483)
What is a cannabinoid?
• Initially, compounds extracted by Cannabis spp
producing characteristic psychoactivity
• Later, compounds with a characteristic terpenoid
structure
• Currently, most any compound that produces
cannabinoid psychoactivity, natural or synthetic
• Occasionally, just compounds that will interact with
cannabinoid receptors
What are cannabinoids?
• Group of >60 dibenzopyran chemicals found in
leaves and flowering tops of female cannabis plant
(Cannabis sativa and Cannabis indica)
• Some common cannabinoids are:
In the plant:
In your body
(endogenous):
Synthetic
Δ9 – THC
2-arichidonyl glycerol
(2 – AG)
CP 55,940
Δ8 – THC
anandamide
HU – 210
cannabidiol and
cannabinol
Natural cannabinoids
Representative cannabinoids
Classical cannabinoids
Non-classical cannabinoid
Aminoalkylindole
CB1 antagonists
Endogenous cannabinoids
Receptors suggest endogenous ligands
Two main families identified
Both arachidonic acid derivatives
Precursors in membranes
“Made on demand”
Amides (anandamide)
Esters (2-AG)
• Significant differences
– Routes of synthesis
– Mode of degradation
(FAAH vs MAGL)
– Efficacy
Endocannabinoids
• Anandamide (Sanskrit ananda inner
bliss) is one endocannabinoid. It is found
in chocolate (though there is some
controversy over whether the small
quantity has any effect on the body). It is
about as potent as THC
Structure of THC and
synthetic analogs
Lipophilic side chain
Most potent
analog: 100s
times more
potent than THC
with
4 major cannabinoids in the plant:
• 2 isomers, a trans-delta-9-THC and a delta-8-THC
• A cannabidiol (the 2nd most abundant psychoactive
ingredient after THC)
• A cannabinol a decomposition product of THC that
accumulates as cannabis samples age.
After ingestion, delta-9 is converted in the liver to 11-Hydroxy
THC which is equally as potent and active.
THC
1,1’-di-methyl-pyrane ring (B ring)
• Variedly aromatic ring (C Ring)
Variedly unsaturated cyclohexyl ring (A
ring)
OH
O
Results of SAR
• Psychoactive properties are (-) transenatioselective
• Length, lipophilicity C3 alkyl chain
• Phenolic hydroxyl-group
• C9 substitute
OH
O
Modes of Absorption
• The most common method of absorption is smoking. Either in
a loosely rolled cigarette called a joint, or through a pipe or
water pipe.
Smoking and the Body
THC enters the body through the Lungs.
The smoke is inhaled and held in the lungs.
All affect how much THC will enter the
plasma
THC crosses the blood barrier through the
capillaries in the lungs
After inhalation THC can reach the brain in
about 14 seconds
After a 6 min smoking period, peak blood levels reached at
about 7 min (100 ng/ml plasma).
Most THC is absorbed from the blood within 30 min.
Moves rapidly into the brain and across the
blood/brain/placental barrier. Because fatty chains make it
very lipid soluble.
Half-life is about 19 hours. Can store in fat cells.
Established physiological effects are dose related.
Lethal dose for THC use has now been studied, and no
human deaths have been reported due to intoxication from
cannabis.
Metabolites
• Radioactively labeled delta-9-THC has
been found to persist in the body as an
active metabolite as long as 8 days after
use.
Primary metabolite has a half-life of 50 hours.
The complete elimination of the drug can take as
long as 6 weeks!
After ingestion, delta-9 is converted in the liver to
11-Hydroxy THC which is equally as potent and
active.
2/3 of metabolites are excreted in feces.
1/3 of metabolites are excreted in urine.
Cannabis
Pharmacology
Primary Cannabinoids from Cannabis are:
• Cannabinol (CBN), Cannabidiol (CBD) and
Tetrahydrocannabinol (THC)
• THC (D-9-THC ) is the only one with
significant psychoactive properties
• CBN - 1/10 th activity of THC; CBD - none
• 2 isomers, a trans-delta-9-THC and a delta-8-THC
• A cannabidiol (the 2nd most abundant psychoactive
ingredient after THC)
• A cannabinol a decomposition product of THC that
accumulates as cannabis samples age.
After ingestion, delta-9 is converted in the liver to 11-Hydroxy
THC which is equally as potent and active.
Therapeutic
• Antiemetic
• Reduction of intra-ocular tension
• Analgesic
• Muscle relaxant
• Anti-convulsant
• Anti-inflammatory
• appetite: “the munchies”.
It is one of the most well-known effects of marijuana: the
powerful surge in appetite many users feel after smoking
or ingesting the drug, colloquially known as "the
munchies.
Marinol
THC in a sesame oil suspension
Cannabinoid Receptors
Beforethe 1980s, it was often speculated that
cannabinoids produced their effects through non
specific interaction with cell membranes, instead
of interacting with specific receptors.
The discovery of the first cannabinoid receptors in
the 1980s helped to resolve this debate. These
receptors are common in animals, and have
been found in mammals, birds, fishes, and
reptiles.
There are currently two known types of
cannabinoid receptors, CB1 and CB2.
CB1 Receptors
Found primarily in the brain (specifically basal ganglia, limbic
system, including the hippocampus, and cerebellum)
􀂾Most dense in brain regions involved with thinking and memory,
attention and control of movement􀂾
Also present in both male and female reproductive systems as
well as in the lungs, liver and kidneys
􀂾Appear to be responsible for the euphoric and anticonvulsive
effects of Cannabis
􀂾Essentially absent in the medulla oblongata, the part of the brain
that is responsible for respiratory and cardiovascular
functions.
Thus, there is no risk of respiratory or cardiovascular failure as
there is with many other drugs.
CB2 Receptor
CB2 receptors are almost exclusively found in
the immune system (T cells, macrophages, B
cells), with the greatest density in the spleen
􀂾CB2 receptors appear to be responsible for
the anti-inflammatory and possible other
therapeutic effects of Cannabis
􀂾Also expressed on peripheral nerve terminals
Cannabis and Δ9- (THC) for weight loss?
• Obesity is one of the highest preventable causes of
morbidity and mortality in the developed world. It has
been well known for a long time that exposure to
cannabis produces an increase of appetite (a
phenomenon referred to as the 'munchies'). This
phenomenon led to an exploration of the role of the
endocannabinoid system in the regulation of obesity and
associated metabolic syndrome. This effort subsequently
led to the development of a successful therapeutic
approach for obesity that consisted of blocking the
cannabinoid CB1 receptors using ligands such as
Rimonabant in order to produce weight loss and improve
metabolic profile.
What is obesity ?
Obesity is characterized by an abnormal accumulation of
body fat, usually 20 percent or more over an individual's
ideal body weight. Obesity results when the size or number
of fat cells in a person's body increases. When a person
gains weight, these fat cells first increase in size and later in
number. When a person starts losing weight, the cells
decreas ein size, but their number generally stays the
same. This is part of the reason that once you gain a
significant amount of weight, it is more difficult to lose
it.
The clinical definition of
obesity is a body mass
index(BMI)of 30 or higher.
BMI = Weight (in kg) / Height
(in meters) Squared
Rimonabant
• Acomplia®(Sanofi-Aventis)
launched in Europe in 2006 for
oral treatment of obesity at 20 mg
once daily
Selective blocker of central
and peripheral CB1 receptors,
It reduces food intake and improves lipid and glucose
metabolism
Rimonabant
Despite being efficacious, Rimonabant
was associated with increased rates of
depression and anxiety and therefore
removed from the market.