Download Cannabinoid receptors

Marijuana
Marijuana is a mixture of dried and crumbled leaves,
small stems, and flowering tops from cannabis sativa.
It can be consumed orally, as in cookies or brownies,
but is usually smoked in rolled cigarettes known as
“joints,” various kinds of pipes, or in hollowed-out
cigars called “blunts.”
The psychoactive compound Δ9tetrahydrocannabinol (THC), accounts for the use
of cannabis as a drug.
Marijuana potency (in terms of THC content) varies
widely, depending on the genetic strain of the plant
and growing conditions.
Potency can be increased by preventing pollination
and seed production by the female plants. This
marijuana is called sinsemilla (“without seeds”).
#1 most widely used illegal drug in US
It is classified as a mild hallucinogen
History of Marijuana
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Cannabis probably originated in China. Medical and religious use can be traced to
ancient China, India, and the Middle East, spreading to the Arab world.
Napoleon’s soldiers brought it to France from Egypt. It became popular with French
writers and artists.
Hemp was grown in colonial America, but marijuana smoking probably came to the
U.S. with Mexican and Caribbean immigrants in the early 1900s.
In 1937, the Marijuana Tax Act instituted a national registration and taxation system
aimed at discouraging all use of cannabis. It was overturned in 1969, but cannabis is
still tightly controlled
History of
Marijuana
In the 1930s, the US Bureau of
Narcotics launched a public
relations campaign to portray
marijuana as a social menace
that could destroy the youth of
America.
The propaganda included
magazine articles and antimarijuana films such as Reefer
Madness.
History of Marijuana
Marijuana remains a controversial
subject in our society—castigated
by many as a gateway to the socalled hard drugs, but praised by
others as an unappreciated medical
marvel.
Marijuana is produced from flowering
hemp (Cannabis sativa).
Hemp has been a major source of fiber
in many cultures for rope, cloth, and
paper.
Hemp seeds have been used for oil and
bird food.
Hemp also contains 70 unique
compounds known as
cannabinoids, plus more than 400
other identified compounds.
Hashish
Hashish is a cannabis derivative that
can be smoked or eaten.
It can refer to a relatively pure resin
preparation with very high
cannabinoid content, or a solvent
extract of leaves or resin.
Hash oil is an alcoholic extract. A
drop is placed on a tobacco or
marijuana cigarette.
9-tetrahydro-cannabinol (THC)
THC was identified as the major active
ingredient in 1964.
Burning marijuana causes the THC to
vaporize and enter the smoker’s lungs in
small particles.
Effective dose and latency to onset of effects
are influenced by the amount and potency
of the plant used, and patterns of smoking
(e.g., breathhold duration).
THC is easily absorbed by the lungs, and
blood plasma levels rise quickly.
Concentrations begin to decline as a result of
metabolism in the liver and accumulation
in the body’s fat stores.
In oral use, poor absorption results in low and
variable plasma levels, probably due to
degradation in the stomach and first-pass
metabolism.
9-tetrahydro-cannabinol (THC)
Blood THC levels decline
rapidly after smoking
marijuana, but complete
elimination from the body is
much slower because of
persistence in fat tissues.
The gradual movement of THC
metabolites back out of fat
stores means that urine
screening tests can detect
them more than 2 weeks after
a single marijuana use.
Cannabinoid Receptors
• A cannabinoid receptor in the CNS was
identified in 1988.
• Receptors occur in many brain areas.
• Cannabinoid receptors are metabotropic
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work via G proteins to inhibit cAMP formation
inhibit voltage-sensitive Ca2+ channels
open K+ channels.
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CB1 receptors
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CNS
Located on axon terminals
Inhibiting many neurotransmitters
CB2 receptors
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immune system
Bone
adipose (fat) cells
GI tract.
Cannabinoid Receptors in the Brain
Cannabinoid receptors (CB1)
•cerebral cortex
•hippocampus
•basal ganglia
•cerebellum
Receptor Autoradiography
Brighter areas show greater
receptor density
Figure A CB1 receptors are widely expressed in the neural
circuitry of the human brain that regulates mood
Cnr1 Expression
Endocannabinoids
• Arachidonoyl ethanolamide
(AEA), Anandamide
• 2-arachidonoylglycerol (2-AG)
• Oleamide
Endocannabinoids
Retrograde messengers:
carry information in the
opposite direction
Phytocannabinoids
Cannabigerol-type
CBG
Cannabielsoin-type
CBE
Cannabichromene-type
CBC
isoTetrahydrocannabinoltype
iso-THC
Cannabidiol-type
CBD
Cannabicyclol-type
CBL
Tetrahydrocannabinoland Cannabinol-type
THC, CBN
Cannabicitran-type
CBT
Probability of initiating marijuana
use as a function of age
Effects of Marijuana
Negative Effects:
lung damage
Impaired tracking ability
memory loss
reduced locomotor activity
hypothermia
hypoalgesia
adversely affect cognitive function
anxiety or paranoia
decreased sperm cell count
altering of mood
addiction like properties
tolerance formation
desensitization of receptors
Amotivational syndrome
Gateway drug?
Positive Effects:
reduced nausea
reduced pain
reduced MS spasticity
reduced symptoms of GI tract disorders
reduced cancer formation
reduced symptoms of neurodegenerative disorders
reduced symptoms of psychiatric disorders
CB1 antagonists can reduce obesity
fear alleviation
Hippocampal CB1 receptors are responsible for memory
impairment
Acquisition of THC selfadministration by squirrel monkeys
Time course of overall withdrawal discomfort in
heavy marijuana users undergoing abstinence
Desensitization of cannabinoid receptors produced
by chronic THC exposure
The New
Medicinal
Marijuana
• THC
• CBD
Cannabis and Multiple Sclerosis
Cannabidiol (CBD)
•Pain
•Shaking
•Spasms
•Spasticity
•Fatigue
•Sleep Quality
•Mobility
•Well Being
Cannabis and Cancer
MMP-2: enzyme that promotes spread of cancer