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Scientists speculating that the cause of disease may be endocannabinoid deficiency
03-24-2010, 06:08 PM,
#1
Scientists speculating that the cause of disease may be endocannabinoid deficiency
Not Feeling Well? Perhaps You're 'Marijuana Deficient'
By Paul Armentano, AlterNet
Posted on March 24, 2010, Printed on March 24, 2010
http://www.alternet.org/story/146151/

For several years I have postulated that marijuana is not, in the strict sense of the word, an intoxicant.

As I wrote in the book Marijuana Is Safer: So Why Are We Driving People to Drink? (Chelsea Green, 2009), the word ‘intoxicant’ is derived from the Latin noun toxicum (poison). It’s an appropriate term for alcohol, as ethanol (the psychoactive ingredient in booze) in moderate to high doses is toxic (read: poisonous) to healthy cells and organs.

Of course, booze is hardly the only commonly ingested intoxicant. Take the over-the-counter painkiller acetaminophen (Tylenol). According to the Merck online medical library, acetaminophen poisoning and overdose is “common,” and can result in gastroenteritis (inflammation of the gastrointestinal tract) “within hours” and hepatotoxicity (liver damage) “within one to three days after ingestion.” In fact, less than one year ago the U.S. Food and Drug Administration called for tougher standards and warnings governing the drug’s use because “recent studies indicate that unintentional and intentional overdoses leading to severe hepatotoxicity continue to occur.”

By contrast, the therapeutically active components in marijuana — the cannabinoids — appear to be remarkably non-toxic to healthy cells and organs. This notable lack of toxicity is arguably because cannabinoids mimic compounds our bodies naturally produce — so-called endocannabinoids — that are pivotal for maintaining proper health and homeostasis.

In fact, in recent years scientists have discovered that the production of endocannabinoids (and their interaction with the cannabinoid receptors located throughout the body) play a key role in the regulation of proper appetite, anxiety control, blood pressure, bone mass, reproduction, and motor coordination, among other biological functions.

Just how important is this system in maintaining our health? Here’s a clue: In studies of mice genetically bred to lack a proper endocannabinoid system the most common result is premature death.

Armed with these findings, a handful of scientists have speculated that the root cause of certain disease conditions — including migraine, fibromyalgia, irritable bowel syndrome, and other functional conditions alleviated by clinical cannabis — may be an underlying endocannabinoid deficiency.

Now, much to my pleasant surprise, Fox News Health columnist Chris Kilham has weighed in on this important theory.

Are You Cannabis Deficient?
via Fox News

If the idea of having a marijuana deficiency sounds laughable to you, a growing body of science points at exactly such a possibility.

… [Endocannabinoids] also play a role in proper appetite, feelings of pleasure and well-being, and memory. Interestingly, cannabis also affects these same functions. Cannabis has been used successfully to treat migraine, fibromyalgia, irritable bowel syndrome and glaucoma. So here is the seventy-four thousand dollar question. Does cannabis simply relieve these diseases to varying degrees, or is cannabis actually a medical replacement in cases of deficient [endocannabinoids]?

… The idea of clinical cannabinoid deficiency opens the door to cannabis consumption as an effective medical approach to relief of various types of pain, restoration of appetite in cases in which appetite is compromised, improved visual health in cases of glaucoma, and improved sense of well being among patients suffering from a broad variety of mood disorders. As state and local laws mutate and change in favor of greater tolerance, perhaps cannabis will find it’s proper place in the home medicine chest.

Perhaps. Or maybe at the very least society will cease classifying cannabis as a ‘toxic’ substance when its more appropriate role would appear to more like that of a supplement.

Paul Armentano is the deputy director of NORML (the National Organization for the Reform of Marijuana Laws), and is the co-author of the book Marijuana Is Safer: So Why Are We Driving People to Drink (2009, Chelsea Green).
© 2010 Independent Media Institute. All rights reserved.
View this story online at: http://www.alternet.org/story/146151/
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03-24-2010, 08:03 PM, (This post was last modified: 03-24-2010, 08:04 PM by ---.)
#2
RE: Scientists speculating that the cause of disease may be endocannabinoid deficiency
God bless the coincidental environs of Kazhakstan.

\its the old adage of the straight getting high to realise the why pot is good maybe.


http://www.youtube.com/watch?v=MhMB_qXSCeE&NR=1
http://www.youtube.com/watch?v=MhMB_qXSCeE&NR=1
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03-24-2010, 08:07 PM,
#3
RE: Scientists speculating that the cause of disease may be endocannabinoid deficiency
Quote:Are You Cannabis Deficient?
Highly unlikely.
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03-24-2010, 10:45 PM,
#4
RE: Scientists speculating that the cause of disease may be endocannabinoid deficiency
I'm proficient... crinkled on hash.
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03-25-2010, 07:09 PM,
#5
RE: Scientists speculating that the cause of disease may be endocannabinoid deficiency
Is their any alternative or indirect way to increase endocannabinoids from some other source than cannabis?
There are no others, there is only us.
http://FastTadpole.com/
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03-25-2010, 07:52 PM,
#6
RE: Scientists speculating that the cause of disease may be endocannabinoid deficiency
(03-25-2010, 07:09 PM)FastTadpole Wrote: Is their any alternative or indirect way to increase endocannabinoids from some other source than cannabis?

I know that wormwood stimulates the same receptor sites as cannabis while killing off and fortifying against parasites, but I'm not sure if it's a source of endocannabinoids.
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03-25-2010, 08:00 PM,
#7
RE: Scientists speculating that the cause of disease may be endocannabinoid deficiency
(03-25-2010, 07:52 PM)h3rm35 Wrote:
(03-25-2010, 07:09 PM)FastTadpole Wrote: Is their any alternative or indirect way to increase endocannabinoids from some other source than cannabis?

I know that wormwood stimulates the same receptor sites as cannabis while killing off and fortifying against parasites, but I'm not sure if it's a source of endocannabinoids.

The only naturally occurring source of cannabinoids is cannabis.

I was not aware of the same receptor affinity for wormwood/absinthe. Do you have a source for that?
“Today’s scientists have substituted mathematics for experiments, and they wander off through equation after
equation, and eventually build a structure which has no relation to reality. ” -Nikola Tesla

"When the power of love overcomes the love of power the world will know peace." -Jimi Hendrix
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03-25-2010, 11:04 PM, (This post was last modified: 03-25-2010, 11:05 PM by h3rm35.)
#8
RE: Scientists speculating that the cause of disease may be endocannabinoid deficiency
http://www.nature.com/nature/journal/v253/n5490/abs/253365a0.html
Marijuana, absinthe and the central nervous system

J. DEL CASTILLO*, M. ANDERSON* & G. M. RUBOTTOM†

*Laboratory of Neurobiology School of Medicine, UPR, San Juan, Puerto Rico 00905
†Department of Chemistry, University of Idaho, Moscow, Idaho 83843

THERE are striking similarities between the psychological actions of the liqueur absinthe1 and the experiences frequently reported by users of marijuana2. We have therefore compared the properties of thujone and tetrahydrocannabinol (THC), which are believed to be the active principles of Artemisia absinthium and Cannabis sativa, respectively. Both substances are terpenoid, derived from the essential oils absinthol and cannabinol, and are formed by similar biosynthetic mechanisms3,4.

------------------

References
1. Zolotow, M., Playboy Magazine, 18, 169 (1971).
2. Marihuna, Chemistry, Pharmacology, Metabolism and Chemical Effects (edit. by Mechoulam, R.) (Academic, New York and London, 1973).
3. Geissman, T. A., and Crout, D. H. G., Organic Chemistry of Secondary Plant Metabolism, 246 (Freeman, San Francisco, 1969).
4. Mechoulam, R., in Progress in the Chemistry of Organic Natural Products (edit. by Zechmeister, L.), 25, 173–213 (Springer, Vienna, 1967).
5. Goodman, L. S., and Gilman, A., The Pharmacological Basis of Therapeutics, second ed., 335–337 (Macmillan, New York, 1958).
6. Wall, M. E., Brine, D. R., Brine, G. A., Pitt, C. G., Freudenthal, R. I., and Christensen, H. D., J. Am. chem. Soc., 92, 3466–3468 (1970).
7. Ben-Zvi, Z., Mechoulam, R., and Burstein, S., J. Am. chem. Soc., 92, 3468–3469 (1970).
8. Walling, C., Free Radicals in Solution, 375, 384 (Wiley, New York, 1953).
9. Stewart, R., in Oxidation in Organic Chemistry (edit. by Wiberg, K. B.), (Academic, New York and London, 1965).
10. Simonsen, J. L., The Terpenes, 2, 36 (Cambridge University Press, Cambridge, 1949).
11. Kosower, E. M., Molecular Biochemistry, 45, 91, 105 (McGraw-Hill, New York, 1962).
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http://serendip.brynmawr.edu/bb/neuro/neuro01/web1/Solano.html#4
Biology 202
2000 First Web Report
On Serendip

Absinthe: The Price of Creativity

Ingrid Solano

The practice of serious art, whether it be painting, music or literature, requires originalities of perception. At a level of neurobiology what this usually means is that the nervous system must respond in new ways to old inputs. How can in individual induce these responses that are needed for creativity? If creativity is a behavior, can it be influenced by things that occur in the brain?

Some artists seem to be naturally endowed with the gift of creativity and the creation of these new responses to old information. Some artists seek to place themselves in ambient conditions in order to induce these new responses of the nervous system. And other artists seek out the help of drugs. Drugs can have a wide variety of effects, from mild physical effects to huge effects on personality and behavior. At the end of the 19th century there was an era of great creativity in Europe. Particularly in France, the Belle Epoch era brought with it a generation of artists that produced an enormous output of creativity. These artists survived in artistic circles which brought with them the notorious alcoholic drink called "absinthe".

In 1910 to 1915 absinthe was recognized as a neurological poison throughout Europe, and it was also banned in the US. However, amongst the fans of absinthe we find some of the most creative minds of the era. These include; De Musset, Baudelaire, Verlaine, Zola, Oscar Wilde, Gaugin, Toulouse-Lautrec, Van Gough, Hemmingway and Picasso. (5) Oscar Wilde said of absinthe: "After the first glass, you see things as you wish they were. After the second, you see them as they are not. Finally, you see things as they really are, which is the most horrible thing in the world." Although absinthe had become the national drink of France by the end of the 19th century, absinthe had a reputation for inducing "insane and criminal acts" as well as convulsions and other effects of toxicity (1)

Though absinthe contains a high volume of alcohol (usually 70%), it is not the ethyl alcohol that is the important neuro-active ingredient, but the terpenoid alpha-thujone. Thujone is derived from the oil of the plants, Artemisia absinthium (common names: bitter wormwood, wormseed, Wermutkraut, Asscnizio, Losna, Pelin) and Artemisia pontica (Roman Wormwood), both of the daisy family. The plant is described as a fragrant perennial herb about 1-4 feet tall with silver-green leaves, silky hairs on both sides of the leaves, and small yellowish-green flowers present during July-September (4).

Like other terpenes, thujone can cause clonic/tonic seizures through its direct and rapid effects on neurons. There are descriptions of absinthe epilepsy with states of delirium between seizure attacks. These attacks have been related to absinthe's specific excitatory effects on the medulla and/or cortex. (4) Thujone-induced seizures were studied in animal models in the 1920's as a chemical model for epilepsy. Prior to electro convulsive therapy (ECT), terpenes such as camphor were used to treat depression and schizophrenia by the chemical induction of convulsions. Convulsions have been found to be caused by thujone in the recent experiment done by Hold. (3) Hold has also been able to prove that it is indeed Thujone and not the alcohol that causes these effects.

Thujone has a molecular structure similar to that of another terpenoid essential oil, tetrahydrocannabinol (THC). THC is the chemical in marijuana that induces its notorious 'high'. Its functional side groups, which resemble those of THC, are thought to act at the same specific receptor sites in the central nervous system as those occupied by THC. (4)

Thujone appears to effect chloride ion channels in the central nervous system. In neurobiology, ion channels are protein channels in cell membranes that allow ions to pass from extracellular solution to intracellular solution and vice versa. Most ion channels are selective and only allow certain ions to pass through. Each neuron has ion channels with various ion selectivities. Each nerve cell's parallel conductivity of "information" down its axon is contingent upon the opening and closing of ion channels along its cell membrane. At the end of a neuron, at its synapse, neurotransmitters are released based upon the "information" passed down by the changing concentration gradient and charge.

Neurotransmitters are chemical substances that cross the synapse between a presynaptic nerve ending and a post synaptic nerve ending. At the membrane of the post synaptic neuron the transmitter substances interacts with a receptor. Depending on the type of receptor, the result may be an excitatory or an inhibitory effect on the postsynaptic nerve cell.

GABA is the neurotransmitter substance gamma-aminobutyric acid. A GABA receptor is any of several membrane proteins that bind GABA and mediate its channels. GABA type A receptors produce an inhibitory effect on postsynaptic nerve cell membranes. Studies show that alpha-thujone in absinthe is a rapidly-acting and readily detoxified modulator of the gamma-amino butyric acid-gated chloride ion channel. Thujone also acts as a GABA-type A receptor antagonist. Thujone competitively inhibits the binding of the radioactive convulsant [(sub3)H] ethynylbicycloorthobenzoate to the known convulsant site linked to GABA-type A receptors in mammalian brain membranes. (4) Without access to GABA, a natural inhibitor of nerve impulses, neurons fire too easily and their signaling goes out of control. Perhaps this explains the state of psychosis and high sensitization described by the creative individuals who were addicted to the effects of absinthe. (2) Scientists had documented thujone's effects by 1916, but "nobody had ever figured out exactly where the toxin was working," says Hold. The original concentration of Old absinthe was about 260 parts per million of alpha-thujone. Though today the drink, which is still made in the Czech Republic, Spain, and most recently Great Briton, typically contains less than 10 parts per million. This is below the maximum concentration permitted by European beverage guidelines. Apparently, in today's absinthe the most toxic compound is the alcohol. However, the coveted bottle of Swiss La Bleu is said to contain 70 mg of thujone.

A look into the effects of the active ingredient of absinthe on the brains of its notoriously creative addicts may help to unlock the neurobiological explanations of creativity and creative behavior. Perhaps the pathways that this drink inhibits or excites may lead us to find the pathways of enlightenment, creativity and the phenomenon of art and our appreciation for it. Art (as well as our wish to create and understand it) is as profound a phenomenon as emotion and religious beliefs. Is the human phenomenon of feeling 'moved' or 'inspired' as simple as a rapid firing of an unusual amount of neurons? Might it be as specific as to be directly related to GABA-type A receptor antagonists?

The followers and influences of the absinthe phenomenon seem too specific to the artistically inclined (as well as a specific area of time and place noted for its artists and inspiration). Could this inclusion of a mere chemical substance be an unknown discovery in the neurobiological makeup of our minds? Would Picassos sell for hundreds of thousands of dollars were he not actively participating in the increase of synaptic firing in his cortex and medulla? Would the poetry of Baudelaire be renown the world over had he not been detracting from a natural inhibitor of nerve impulses, and thus causing the cells in his mind to send more signals than they normally would have been?

Perhaps these artists of the 19th century stumbled upon a key that may, in the future, allow us to genetically alter our children to be artistic prodigies. Artists mutilated themselves and committed suicide, all as a price for the drink they thought to be their inspiration. Perhaps their dedication should be further explored-they believed to have found something.

WWW Sources

1)Science Week, An article in Science Week

2)Science News: Toxin in absinthe makes neurons run wild.(alpha-thujone)(Brief Article), found in web search for 'absinthe neurobiology'

3)PNAS -- Höld et al. 97 (8): 3826 , Proceedings of the National Acadamey of Sciences

4) Clinical Toxicology Report, medical data

5) Absinthe FAQ , A source and aray of common knowledge, though the absinthe drinker should read with caution. Testament to modern absinthe use.
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03-25-2010, 11:21 PM,
#9
RE: Scientists speculating that the cause of disease may be endocannabinoid deficiency
Hmmm. Interesting. Thanks. Smile
“Today’s scientists have substituted mathematics for experiments, and they wander off through equation after
equation, and eventually build a structure which has no relation to reality. ” -Nikola Tesla

"When the power of love overcomes the love of power the world will know peace." -Jimi Hendrix
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