(alkamides) from Echinacea modulate tumor necrosis factor alpha mRNA expression
in human monocytes/macrophages via the CB2 receptor.
alkylamides dodeca-2E,4E,8Z,10Z-tetraenoic acid isobutylamide (A1) and
dodeca-2E,4E-dienoic acid isobutylamide (A2) bind to the CB2
receptor more strongly than the endogenous cannabinoids.
modeling suggests that alkylamides bind in the solvent-accessible cavity in
CB2, directed by H-bonding and pi-pi interactions.
screen with 49 other pharmacologically relevant receptors, it could be shown
that A1 and A2 specifically bind to CB2 and CB1.
A1 and A2 elevated total intracellular Ca2+ in CB2-positive
but not in CB2-negative promyelocytic HL60 cells, an effect that was
inhibited by the CB2 antagonist SR144528.
At 50 nM, A1, A2,
and the endogenous cannabinoid anandamide (CB2 Ki >200 nM)
up-regulated constitutive interleukin (IL)-6 expression in human whole blood in
a seemingly CB2-dependent manner.
A1, A2, anandamide, the
CB2 antagonist SR144528 (Ki <10 nM), and also the
non-CB2-binding alkylamide undeca-2E-ene,8,10-diynoic acid
isobutylamide all significantly inhibited lipopolysaccharide-induced tumor
necrosis factor alpha, IL-1beta, and IL-12p70 expression (5-500 nM) in a
Alkylamides and anandamide also
showed weak differential effects on anti-CD3-versus anti-CD28-stimulated
cytokine expression in human whole blood.
Overall, alkylamides, anandamide, and SR144528 potently inhibited
lipopolysaccharide-induced inflammation in human whole blood and exerted
modulatory effects on cytokine
expression, but these effects are not exclusively related to CB2
that botanical cannabinoids such as Δ9 tetrahydrocannabinol
exert some of their effect through binding specific cannabinoid receptor sites
has led to the discovery of an endocannabinoid signaling system.
CB1 receptor is heavily concentrated in the central nervous system,
but is found in other tissues as well, including liver, gut, uterus, prostate,
adrenals, and the cardiovascular system.
CB2 tends to be localized to
Anandamide and 2-arachidonoyl-glycerol
(2-AG), derivatives of arachidonic acid, were identified as endogenous ligands
to CB1 and CB2.
Of the botanically derived
cannabinoids, Δ9THC, which is the most potent psychoactively,
binds to both CB1 and
Δ8 THC also binds to
both, though somewhat less strongly.
Cannabidiol binds to none of the
receptors, is devoid of psychoactive effect, yet may have some
anti-inflammatory and smooth muscle
contraction inhibitory actions mediated either by a yet uncharacterized CB
receptor or another mechanism entirely.
"Up until the late
1980s, Cannabis research remained a rather esoteric feld involving a small
number of scientists in the United States and abroad.
were circumscribed by the politicized agenda of the
National Institute of Drug
Abuse, which subsidized studies designed to prove the deleterious effects
of cannabis while blocking inquiry into its potential benefts.
than discrediting cannabis, NIDA inadvertently facilitated a series of major
discoveries about the workings of the human brain.
the most exciting development in brain chemistry, spawned a revolution in
medical science and a profound understanding of health and healing." - Martin
A. Lee, The Discovery of the Endocannabinoid System
UNITED STATES DEPARTMENT OF JUSTICE
Drug Enforcement Administration
In The Matter Of )
) Docket No. 86-22
MARIJUANA RESCHEDULING PETITION )
OPINION AND RECOMMENDED RULING, FINDINGS OF
FACT, CONCLUSIONS OF LAW AND DECISION OF
Administrative LAW JUDGE.
FRANCIS L. YOUNG, Administrative Law Judge
DATED: SEP 6 1988
FRANCIS L. YOUNG, Administrative Law Judge
ACCEPTED SAFETY FOR USE UNDER MEDICAL SUPERVISION
With respect to whether or not there is "a lack of accepted safety
for use of [marijuana] under medical supervision", the record shows the
following facts to be uncontroverted.
Findings of Fact
Point 3. The most obvious concern when
dealing with drug safety is the possibility of lethal effects.
Can the drug cause death?
4. Nearly all medicines have toxic,
potentially lethal effects. But marijuana is not such a substance. There is no
record in the extensive medical literature describing a proven, documented
5. This is a remarkable statement. First,
the record on marijuana encompasses 5,000 years of human experience. Second,
marijuana is now used daily by enormous numbers of people throughout the world.
Estimates suggest that from twenty million to fifty million Americans
routinely, albeit illegally, smoke marijuana without the benefit of direct
medical supervision. Yet, despite this long history of use and the
extraordinarily high numbers of social smokers, there are simply no credible
medical reports to suggest that consuming marijuana has caused a single
6. By contrast
aspirin, a commonly used,
over-the-counter medicine, causes hundreds of deaths each year.
7. Drugs used in medicine are routinely
given what is called an LD-50. The LD-50 rating indicates at what dosage fifty
percent of test animals receiving a drug will die as a result of drug induced
toxicity. A number of observers have attempted to determine marijuana's LD-50
rating in test animals, without success. Simply stated, observers have been
unable to give animals enough marijuana to induce death.
8. At present it is estimated that
marijuana's LD-50 is around 1:20,000 or 1:40,000. In layman terms this means
that in order to induce death a marijuana smoker would have to consume 20,000
to 40,000 times as much marijuana as is contained in one marijuana cigarette.
NIDA-supplied marijuana cigarettes weigh approximately .9 grams.
A smoker would
theoretically have to consume nearly 1,500 pounds of marijuana within about
fifteen minutes to induce a lethal response.
9. In practical terms, marijuana cannot
induce a lethal response as a
result of drug-related toxicity.
Another common medical
way to determine drug safety is called the therapeutic ratio. This ratio
defines the difference between a therapeutically effective dose and a dose
which is capable of
inducing adverse reactions.
11. A commonly used over-the-counter product
like aspirin has a therapeutic ratio of around 1:20. Two aspirins are the
recommended dose for adult patients. Twenty times this dose, forty aspirins,
may cause a lethal reaction in some patients, and will almost certainly cause
gross injury to the digestive system, including extensive internal
12. The therapeutic ratio for prescribed
drugs is commonly around 1:10 or lower. Valium, a commonly used prescriptive
drug, may cause very serious biological damage if patients use ten times the
recommended (therapeutic) dose.
13. There are, of course, prescriptive drugs
which have much lower therapeutic ratios. Many of the drugs used to treat
patients with cancer, glaucoma and
multiple sclerosis are highly
toxic. The therapeutic ratio of some of the drugs used in antineoplastic
therapies, for example, are regarded as extremely toxic poisons with
therapeutic ratios that may fall below 1:1.5. These drugs also have very low
LD-50 ratios and can result in toxic, even lethal
reactions, while being properly employed.
14. By contrast, marijuana's therapeutic
ratio, like its LD-50, is impossible to quantify because it is so high.
15. In strict medical terms marijuana is far
safer than many foods we commonly consume. For example, eating ten raw potatoes
can result in a toxic response. By comparison, it is
physically impossible to
eat enough marijuana to induce death.
16. Marijuana, in its natural form, is one
of the safest therapeutically active substances known to man. By any measure of
rational analysis marijuana can be safely used within a supervised routine of
Cannabis poses a
threat to oil,
Utilizing marijuana for a vast array of commercial products would
create a green economic revolution which would deprive these industries of
Cannabis ruderalis originated in the mountainous regions
northwest of the Himalayas in central Asia.
Cannabis sativa grows wild
in Europe, central Asia, and Asia
Cannabis sativa introduced into American agriculture grows
wild in Kentucky, Iowa, Nebraska and Kansas as well as other many other
Cannabis indica grows wild in India, southeast Asia and the
Records of hemp farming date back 5000 years in China.
Hemp farming helped raise the
Pharaohs monuments in
When Nomadic "Aryan" tribes from
central Asia and Persia overran the
entire Mediterranean spreading out over the
Caucasus, west into Europe and
southeast into the Indian
subcontinent they brought cannabis.
estimates American cannabis cultivation was 10,000 metric tons or 22 million
2006 The cash value of the cannabis crop
is estimated at $35.8 billion which exceedes the cash value of corn,
In California 1.7 million plants are uprooted in 447 raids in 34
2007 In California 1.8 million plants
2008 California 1.9 million plants,
70% grown on public land uprooted.
California 4.4 million plants, mostly grown by Mexican cartels, are
|Cannabidiol was more
protective against glutamate
neurotoxicity than either ascorbate or a-tocopherol, indicating it to be a
The neuroprotection observed with cannabidiol and
THC was unaffected by cannabinoid receptor antagonist, indicating it to be
cannabinoid receptor independent.
Cannabinoids protected equally well
against neurotoxicity mediated by N-methyl-d-aspartate receptors,
2-amino-3-(4-butyl-3-hydroxyisoxazol-5-yl)propionic acid receptors, or
kainate receptors. N-methyl-d-aspartate receptor-induced toxicity has been
shown to be calcium dependent; this study demonstrates that
2-amino-3-(4-butyl-3-hydroxyisoxazol-5-yl)propionic acid/kainate receptor-type
neurotoxicity is also calcium-dependent, partly mediated by voltage sensitive
Cannabidiol, THC, and butylhydroxytoluene all
prevented dihydrorhodamine oxidation in a similar, concentration-dependent
manner, indicating cannabinoids to be comparable to butylhydroxytoluene in
Cannabidiol blocks glutamate neurotoxicity which
can be mediated by NMDAr, AMPA/kainate receptors.
cell death equally well (EC50 of 24 µM) in both NMDAr and
AMPA/kainate toxicity models
November 8, 2016
make recreational cannabis use legal.
Cannabinoids naturally occur
in every living animal on the planet above hydra and
the exception of insects.
Are you an
increase brain function and awareness.
actually good for you ?
Why is cannabis banned in
have been found to have antioxidant properties, unrelated to NMDA receptor
This makes cannabinoids useful in the treatment and
prophylaxis of wide variety of oxidation associated diseases, such as ischemic,
age-related, inflammatory and autoimmune diseases.
The cannabinoids are
found to have particular application as neuroprotectants, for example in
limiting neurological damage following ischemic insults, such as stroke and
trauma, or in the treatment of neurodegenerative diseases, such as
HIV dementia, Alzheimer' and Parkinson' disease.
A particular disclosed
class of cannabinoids useful as neuroprotective antioxidants is formula (I)
wherein the R group is independently selected from the group consisting of H,
CH3, and COCH3.
This application is a 371 of
PCT/US99/08769 filed Apr. 21, 1999, which claims benefit of No. 60/082,589
filed Apr. 21, 1998, which claims benefit of No. 60/095,993 filed Aug. 10,
Conclusion: Numerous diseases, such as anorexia,
emesis, pain, inflammation, multiple
sclerosis, neurodegenerative disorders (Parkinson'
disease, Huntington' disease,
Tourette's syndrome, Alzheimer' disease),
cardiovascular disorders, cancer,
disorders, to name just a few, are being treated or have the potential to
be treated by cannabinoid agonists/antagonists/cannabinoid-related compounds.
*** In view of the very low toxicity and the
generally benign side effects of this group of compounds, neglecting or denying
their clinical potential is unacceptable. ***
Conclusion: Properties of cannabis that might be of
therapeutic use include analgesia, muscle relaxation,
immunosuppression, sedation, improvement of mood, stimulation of appetite,
antiemesis, lowering of intraocular pressure, bronchodilation, neuroprotection
and induction of apoptosis in cancer
Conclusion: The experimental evidence reviewed in
this article argues in favor of the therapeutic potential of these compounds in
immune disorders and cancer.
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author feels that the faλsification of reaλity outside personal
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leader, no church buildings and in which each and every individual is
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c☣rp☣rate cartel already controls the w☸rld
ec☸n☸mic system, c☸rp☸rate media w☸rldwide, the
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