EVERYBODY'S HIGH

Getting Stoned Is Just A Matter Of Degree. Our Brains Give Us All A
Marijuana-Like High Every Day, Like It Or Not

You've heard of a "natural high?" Well, it turns out we're all a little bit
high all the time-whether or not we smoke dope. In fact, the pleasures
derived from marijuana, sex and chocolate are all tied together. by similar
chemical reactions in our brains.

Right now, there's a naturally occurring molecule in your brain and body
that's chemically similar to THC, or delta-9 tetrahydrocannabinol, the
stuff in marijuana that gets users high. The scientists who discovered this
natural THC-like body chemical in 1992, most notably Raphael Mechoulam of
the Hebrew University of Jerusalem, named it "anandamide" after the
Sanskrit word for ecstasy, "ananda." THC molecules can plug into the
brain's receptors for anandamides quite easily, he found, but THC lasts
longer than anandamides, overwhelming the brain's pleasure sites and
causing-at least in novice users-feelings of giddiness and ecstasy.

For almost 30 years, Jewish researchers have dominated the world's research
into marijuana and why it produces a "high" when smoked. Recently, Dr.
Mechoulam and his counterpart at the University of Buffalo, Herbert Schuel,
explained to Boulder Weekly how and why most people are high most of the time.

Mechoulam's and Schuel's ongoing research shows that anandamides appear to
be involved in regulating and balancing the body's biochemical systems,
influencing or controlling the reproductive, sleep, fight-or-flight and
appetite cycles.

"It's a quirk of nature that THC works on our receptors," Mechoulam
remarked. "We were lucky to be the only group in the world working on this
chemical."

All mammals, fish, birds and reptiles seem to have anandamide-based
regulatory systems; it's even found in cacao nuts, from which chocolate is
made.

"It is found in substantial quantities in chocolate, and may account for
the feelings of pleasure that come from chocolate," Schuel said. Other
researchers have found that chocolate seems to prolong the marijuana
high-as pot users have long claimed.

Street mythology about marijuana has always held that the drug makes girls
easier to seduce, that it makes guys impotent or sterile, that it induces
drowsiness, and that it prolongs life by easing cumulative stress. Turns
out that these two specialized geniuses, Mechoulam and Schuel, no longer
view the above as mythology.

Experiments with rats, Schuel explains, show that marijuana causes some
"enhancement of sexual activities," at least for the female rats "who
appear much more eager than the males." Tests of heavy pot-smoking human
males show lowered sperm counts to the point that marijuana could be
considered an effective contraceptive, Schuel said, although "it's not a
cut-and-dried thing. Sometimes when both smoke, they have babies."

One of Schuel's studies with sea urchins reveals that anandamides inhibit
the process of sperm penetrating and entering the egg cell. When
anandamides or THC are present, the sea urchin sperm-which actually has
anandamide receptor sites on its surface-cannot break through the egg's
tough protein coat.

Many people consider marijuana to be a virtual panacea, good for the
prevention and treatment of glaucoma and as a digestive aid, or as a
treatment for asthma, nausea, insomnia, constipation, menstrual pain,
headaches, hangovers, hiccups, eating disorders and lack of appetite.

Schuel agrees that, with the discovery of anandamides, "there's an enormous
potential for new medicines and home remedies. There are medicinal aspects
plus the psychogenic effects." Cannabis-based medicines were common in the
19th century and may become so again in the 21st century, the two
scientists speculate.

Already, European researchers are testing an anandamide-based stroke
treatment that, if used quickly enough, seems to protect and cushion the
brain from the worst effects of stroke, Mechoulam said.

History of THC Research

In the early 1960s, Dr. Mechoulam was fresh from post-doctoral studies at
the Rockefeller Institute in New York and working at the Weizmann Institute
in Rehovot, Israel. He was looking for a unique field of research in which
to work and make his scientific name.

"I decided to initiate... a re-examination of the chemistry of hashish,"
Mechoulam wrote in a 1998 edition of the International Cannabinoid Research
Society newsletter. Mechoulam's preliminary research showed that ancient
Assyrians used cannabis for mind-expanding and medicinal purposes 4,500
years ago. "Apparently nobody was working on this plant resin, although
from a careful perusal of the literature it was quite obvious that, in
spite of several claims to the contrary, the active constituent had not
been isolated in a pure form and its structure was unknown," he wrote.

Mechoulam persuaded an administrator at the Weizmann Institute to contact
Israel's top law enforcement commander "and ask for a few kilograms of
hashish," he wrote.

"Within a week I went to police headquarters and signed a receipt, 'free of
charge,' for five kilograms of hashish... still packed in their original
cotton bags, with the trademarks of the Lebanese suppliers."

Mechoulam thought he had fulfilled all procedural requirements to legally
obtain the illicit substance, but later he found out that only the Israeli
Ministry of Health could legally dispense "narcotics" and that he had
technically broken the law. But he never spent any time in jail and he got
to keep his hash stash, Mechoulam explains.

In 1964, Mechoulam and a fellow researcher, Prof. Yehiel Gaoni, isolated
THC for the first time. Mechoulam applied to the U.S. National Institute of
Health (NIH) for a research grant, and was turned down flatly. "The drug
was only used by South American natives and was unknown in the United
States, I was told."

But mid-'60s pot politics turned things around. "A U.S. senator had asked
NIH whether they knew anything about marijuana, as his son had been caught
smoking it," Mechoulam wrote. "The senator wanted to know whether his son
had permanently damaged his brain."

Dr. Dani Efron, at that time the head of pharmacology for NIH, contacted
Mechoulam immediately. "In order to not look out of touch, they asked for
my help. We supplied them with 10 grams of pure delta-9 THC-the entire
world supply-and we got a grant," Mechoulam wrote. "Much of the early
research on THC in the U.S. was done on our material, although Dr. Efron
kept his source of supply a secret."

Dr. Mechoulam has held an NIH grant ever since. In the late 1960s, he went
on to synthesize most of the other cannabinoids in marijuana, finding that
delta-9 THC is the only one that showed measurable laboratory effects on
rhesus monkeys.

In a 1970 article in Science magazine, Mechoulam speculated that the human
body metabolized THC into another chemical that acted on the molecular
level to produce the drug's high. Later he found this metabolized substance
in mammalian urine, leading to today's urinalysis industry... "and we had
neglected to patent it!" he added.

In 1988, an American research group that included Bill Devane announced
they had found evidence of a cannabinoid receptor in the mammalian brain.
Devane joined Mechoulam in Israel to further research this question: Did
our brains evolve to receive marijuana?

"We assumed that such a receptor does not exist for the sake of a plant
compound," they concluded.

Other drugs, like opium, had been found to bind at the molecular level to
brain receptor sites intended for endorphins, the body's natural pain
reliever. Mechoulam and Devane decided to look for the natural version of
THC, and in 1992 they announced finding a fatty molecule that bound
naturally to the cannabinoid receptor site.

"Now, there have been about 12,000 papers published on it," Mechoulam adds
proudly.

How Anandamides Work

Anandamides are produced by our brains and bodies to achieve a sort of
yin-yang biochemical balance, and do not produce the extreme "high" of
marijuana, Mechoulam says.

"They're completely different, from a chemical point of view, from THC," he
said. "But they combine in the receptor sites the same way." Anandamides
are quickly broken down by the body after they have served their intended
purpose, and do not last as long as THC metabolites, which remain in the
body for weeks.

"The body, the way I see it, is made of compounds which enhance
(biochemical) reactions and compounds which reduce reactions," Mechoulam
says. "Anandamide is basically a compound that reduces activity; for
example, it reduces the formation of many neurotransmitters that are
stimulatory."

Anandamides play a survival role for young mammals-their instinctive
suckling behavior seems integrally tied to the presence of anandamides. "If
we block the system (from receiving anandamides), there is no suckling,"
Mechoulam explains.

Scientists today use genetic engineering to create special strains of mice
that have no anandamide receptors. "These mice are called 'knock-out'
mice... and they survive pretty well," Mechoulam said, but he explained
that knock-out mice die at a younger age than their anandamide-receiving
counterparts and don't reproduce as well.

What would happen if a human were born without the ability to produce or
receive anandamides? "I don't think he or she would be born. I don't think
they could survive. It would probably be a very difficult life," Mechoulam
remarked.

But it fits the logic of earlier research into the brain chemical dopamine
to assume that there are humans who produce too much or too little
anandamide, Mechoulam explained. "There are people with lots of dopamine
that are schizophrenics and others who don't have enough dopamine.

"Lack of anandamide levels can cause spontaneous abortions" in mammals,
Mechoulam said. "And it makes sense that disease would shut down the
anandamide system."

But testing a human to see if their anandamide levels are correct would
require a painful spinal tap to find the specific enzyme produced by the
body's breakdown of anandamides, which is why today's research remains
confined to rats, mice and sea urchins.

"We can't do that painful procedure (to humans) just for research,"
Mechoulam said.

Across the world, in differing cultures with wildly varying socioeconomic
structures, a consistent 10 percent of the population smokes marijuana,
studies have shown. Could these be people born with low levels of natural
anandamides?

Schuel thinks questions like this will be answered soon, now that countries
like Canada and Holland are allowing recreational use of marijuana while
anandamides research continues in Israel and Ameica. Here, though, "there's
a big disconnect between the public policy world and the science of
biochemistry," he said, which will prevent America from legalizing
marijuana any time soon.

But there are already websites selling anandamides and a legal snythetic
analog of THC that, Schuel estimates, is 100 to 1,000 times stronger than
marijuana.

The Israeli Connection

Schuel says that the major reason that research into THC and anandamides is
based primarily in Israel-rather than some drug Mecca like Holland or
Canada-is that Dr. Mechoulam chooses to live and work there. "Raphael is
the big mover-I'm just a little fish in the pond," he said, complimenting
the elder Mechoulam, who's 72.

"There are quite a few people and hundreds of groups working on
cannabinoids all over the world now," Mechoulam says, diverting all
reverence away from himself. "The world is not just made of small countries
anymore. It doesn't matter if my fellow researchers are in Canada, France,
Spain, NIH or California, we have these frequent contacts. I am currently
refereeing several papers that are up for publication."

Schuel thinks the reason it was Jews who broke ground in marijuana research
dates back to World War II and has nothing to do with drugs. "Hitler drove
all the Jewish physicists out and they came to America and built the bomb,"
he said, pointing out the tradition of Jewish intellectual inquiry.

"Studying for study's sake is a glorious endeavor," Schuel said, noting
that today people from an infinite variety of ethnicities work in the
cannabinoids research field all over the world. Compared to their
percentages in the general population, Jews are more often drawn to careers
in science, academic research or writing than other demographic groups, he
noted, so it was only natural that Jewish researchers were first drawn to
the esoteric field of marijuana research.

In the January 2003 issue of High Times magazine, writer Chris Bennett
claims that ancient Hebrew royalty and religious leaders used anointing oil
containing a large amount of marijuana extracts. Bennett, who referenced
his article heavily with scriptural and historical citations, goes on to
claim that Jesus might have been called Christ because he was anointed with
this oil, called "kaneh-bosem," which was reserved for kings.

"Anointing was common among the kings of Israel. It was the sign and symbol
of royalty. These kings led their people with the benefits of insights
achieved through using the holy anointing oil to become 'possessed with the
spirit of the Lord,'" wrote Bennett.

"The ministry of Jesus marked the return of the Jewish Messiah-kings, and
thus the re-emergence of the holy oil. Jesus was called the Christ because
he violated the Old Testament taboo on the cannabis oil and distributed it
freely for initiation rites and to heal the sick and wounded," Bennett's
article continues.

Maybe the claims of Rastafarians-who say that marijuana is a sacrament,
that it allows them to be closer to God and that they are one of the lost
tribes of Israel-are not too far from the literal truth.

Even Judges Are High

Everyone alive-including parents, politicians, judges, police and
jailers-is on a natural anandamide high every day. . . except perhaps for
those who lack certain genes to produce or receive the natural THC-like
chemical. Thanks to Mechoulam and Schuel, someday soon there will be
cannabinoid-based or anandamide-based medical treatments for those who
can't sleep, who have no appetite, who develop strokes or heart conditions,
who suffer asthma or glaucoma, who are too restless or anxious, or who
suffer any number of other maladies.

When that day comes, perhaps a memorial will go up for every person who
suffered or died in prison for smoking or selling an innocent, medicinal
herb and to those who devoted their lifetimes to expand the human race's
knowledge of marijuana, cannabinoids and anandamides.