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BMED 443: Endocannabinoids and
Medical Marijuana
Instructor: Darrell A. Jackson, Ph.D.
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THC and Effects
When smoked THC is readily absorbed into blood Euphoria: 2 mg smoked; 5 mg oral
Changes in perceptual time and space: 7 mg smoked;17 mg oral
Changes in body image: 15 mg smoked; 25 mg oral
Pharmacokinetics
THC Half life 19 hours
11-hydroxy-THC half life 50 hours Complete elimination 2-3 weeks
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Behavioral Effects
Low - moderate doses
Loss of inhibition, relaxation, drowsiness
feeling of well being, exhilaration, euphoria
sensory - perceptual changes
recent memory impairment (confusion, memory
lapses and difficulties in concentration)
balance/stability impaired
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Behavioral Effects
High doses Pseudo-hallucinations
Synesthesia
impaired judgment, reaction time
pronounced motor impairment
increasingly disorganized thoughts, confusion,
paranoia, agitation
Not lethal even at very high doses
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Certain parts of the brain govern specific functions. Note the distribution of functions.
Movement is found in the Frontal Lobe.
FrontalLobebody
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When a person smokes marijuana, the active ingredient, cannabinoids or THC, travels quickly
to the brain. Note the areas where THC (magenta) concentrates. The VTA, nucleus accumbens,
caudate nucleus, hippocampus, and cerebellum are highlighted. THC binds to THC receptors
that are concentrated in areas within the reward system as well as these other areas. The action
of THC in the hippocampus explains its ability to interfere with memory and actions in the
cerebellum are responsible for its ability to cause loss of balance and coordination.
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Side Effects
Increased pulse rate
Caffeine, nicotine
Red eye
Decreased salivation No pupil change
cardiovascular (tachycardia)
respiratory (bronchodilation) musculoskeletal (muscle relaxation)
gastrointestinal (decreased motility)
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ENDOCANNABINOID SYSTEM
The firstendocannabinoiddiscovered was namedanandamide (AEA)
A second arachidonic-acid derivative 2-arachidonoylglycerol(2-AG) that binds to
cannabinoid receptorswas subsequentlydescribed
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ENDOCANNABINOID SYSTEM FUNCTION
Postsynaptic neurons synthesize membrane-boundendocannabinoid precursors and cleave them to release activeendocannabinoids following an increase of cytosolic freeCa2+concentrations
Endocannabinoids act as retrograde messengers by binding to
presynaptic CB1cannabinoid receptors, which are coupled tothe inhibition of voltage-sensitive Ca2+channels and theactivation of K+channels.
This blunts membrane depolarization and exocytosis, thereby
inhibiting the release of NTs such as glutamate, dopamineand GABA and affecting, in turn, processes such as learning,movement and memory.
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ENDOCANNABINOID SYSTEM
FUNCTION: Continued
Endocannabinoid neuromodulatory signaling isterminated by an unidentified membrane-transportsystem (T) and a family of intracellular degradativeenzymes, the best characterized of which is fatty acid
amide hydrolase (FAAH), which degrades AEA to AAand Et.
The endogenous cannabinoid system might also exertmodulatory functions outside the brain, both in the
peripheral nervous system and in extra-neural sites,controlling processes such as peripheral pain, vasculartone, intraocular pressure and immune function.
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Endocannabinoid System
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Cannabinoids Receptors
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Effect of THC on hippocampal function
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Medical Uses of Cannabis
1839 On the preparations of the Indian
Hemp, or Gunjah was published by a
British physician (OShaughnessy) working
in India
cannabis preparations were safe (nontoxic)
effective anticonvulsant
muscle relaxant
relieve the pain rheumatisms
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Medical Uses of Cannabis in the USA
1860 Ohio Medical Societyreported on the successfultreatment of stomach pain,chronic cough, and
gonorrhea using C.I ndica
1890s medical textincluded the statementCannabis is very valuablefor the relief of pain,
particularly thatdepending on nervedisturbances.
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Early 20th century
Psychologists usedpsychoactive agents to study
the workings of the mind
French physician, Moreau,
tried to treat a variety of
mental disorders with
hashish
Used to treat cholera,
tetanus, and rabies
Queen Victoria smokedmarijuana for painful
menstrual cramps
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Medical Uses of Cannabis
(1972) report found marijuana smoking tobe effective in reducing the intraocularpressure in a glaucoma patient
(1975) study showed THC was effective inreducing the severe nausea caused by cancerchemotherapeutic agents
Cachexia treatment Increase appetite
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THC FORMULATIONS
FDA has approved twodrugs, Marinol and
Cesamet, for therapeutic
uses in the U.S., which
contain active ingredientsthat are present in
botanical marijuana.
On December 22, 1992,
FDA approved Marinol
Capsules for the treatment
of anorexia associated with
weight loss in patients with
AIDS.
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THC FORMULATIONS
Bayers new cannabisproduct in Europemarijuana-extractspray called SativexIt provides immediate
symptomatic relief,similar to smokingcannabis, without the
health hazards associatedwith smoking.
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RimonabantRimonabant
CB1
Adipocyte
Brain
CB1
Adiponectin
FA oxidationFA oxidationBody weight
Central
effects
Metabolic
peripheral effects
Rimonabant (CB1 Blocker): A Multi-Impact Drug
Hyperinsulinemia
Insulin sensitivity restored
TG
HDL-C
Control of nicotine
dependence
Decrease in food intake
(palatable and non-
palatable food)
Van Gaal et al; Lancet (2005) 365: 1389-97
The Endocannabinoid System
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States where voter initiatives have allow for
medical use of marijuana
http://online.wsj.com/article/SB10001424052748703626604575011223512854284.html
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