Everybody's High

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.

There's a naturally occuring molecule in your brain and body that is 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. Ongoing research conducted by Mechoulam, and his counterpart at the University of Buffalo, Herbert Schuel, 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 women feel sexier, but makes men 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.

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 says he never spent any time in jail and he got to keep his hash stash.

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 drugs 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.

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

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 America. 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, age 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."

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.

Everyone--parents, politicians, judges, police and jailers--is on a natural anandamide high every day, except perhaps hose 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, or who suffer any number of other maladies.


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