Thank You For Pot Smoking

If Acomplia pans out, Sanofi-Aventis can thank the American stoner. In his own mellowed-out way, he hastened the dawning of the age of Acomplia.

More than 6 years ago, 62 pot smokers lucked into an awesome gig: Scientists at the National Institute on Drug Abuse (NIDA) offered to pay them to smoke dope.

The NIDA scientists wanted only seasoned pot smokers for their experiment - connoisseurs, if you will, who could make sophisticated judgments about the quality and intensity of a cannabis experience. Each applicant had to have an IQ higher than 85 (roughly that of Koko, the voluble gorilla) and prove his pot-smoking bona fides by failing a drug test. He also had to answer questions about his past, if he could remember it. Dudes were excluded if they suffered from major psychiatric illnesses, drank more than four beers a day, used hallucinogens, or had ever been knocked out for more than 3 minutes.

Those who made the cut (they were all males, between 21 and 45) reported to a NIDA laboratory and, after medical tests, received a pill a day later. That pill was either a placebo or a compound then known as SR141716. (It was also called rimonabant.)

Two hours later, each stoner took a seat before a computer screen and fired up a machine-rolled cannabis cigarette weighing 764 milligrams, precisely 2.64 percent of which was THC, marijuana's active ingredient. He was then instructed to commence puffing at a rate of 8 inhalations per minute. As the blunt disappeared, the stoner was asked at frequent intervals, "How stoned are you now? How high do you feel now? How strong is the drug effect you feel now?" The questions continued for more than an hour after the joint was gone.

The results were striking. Stoners who received SR141716 experienced major bummerage. They complained of being about 40 percent less stoned than those who took the placebo. Marilyn A. Huestis, Ph.D., chief of NIDA's Chemistry and Drug Metabolism Intramural Research Program, observed, "These findings confirm for the first time in humans the central role of CB1 receptors in mediating the effects of marijuana."

This was doubtless very interesting to Huestis, who hopes someday to use Acomplia, or something like it, to help habitual marijuana users wean themselves off dope. But what does the drug's effect on marijuana smokers have to do with its ability to promote weight loss, improve metabolism, and lower the risk of cardiac disease? Everything.

By showing that Acomplia impedes marijuana intoxication, Huestis gave Sanofi-Aventis every reason to hope that the drug could be effective against one of marijuana's loopiest side effects - a phenomenon scientists refer to as hyperphagia and stoners call "the munchies."

Manipulating the Munchies

It's estimated that about one in three Americans has tried marijuana at one time or another, and many of them have also subsequently inhaled a five-course breakfast at 4 o'clock in the morning. In college, I myself was once awakened by the screams of some moron who had burned his eyes with hot oil while trying to make popcorn in a frying pan - without a lid. The most irritating moment occurred when I realized that the moron was actually me.

But it was the antics of dope-smoking college morons that led scientists like Raphael Mechoulam, Ph.D., now of Israel's Hebrew University, to wonder how reefer smoke could have such wacky effects on the human brain. In 1964, Mechoulam discovered THC (short for delta-9-tetrahydrocannabinol), the single chemical responsible, and pharmaceutical researchers began wondering whether this discovery might yield a marketable drug. For instance, if they could figure out why and how marijuana gives people the munchies, maybe they could design an anti-munchie drug - an appetite suppressant.

So scientists set out to unravel exactly what happens in people's brains when THC makes them high. "We knew there had to be a receptor," says Allyn C. Howlett, Ph.D., of North Carolina Central University's Julius L. Chambers Biomedical/Biotechnical Research Institute. Every one of the body's trillions of cells, including those in the brain, is dotted with receptors - tiny proteins that lie in wait atop the cell's membrane like docking stations. Each receptor is constructed to bind with a particular type of ligand - a chemical that carries information from one cell to another, provoking particular behaviors.

The receptor she and others discovered came to be known as CB1 ("CB" for "cannabinoid"). Scientists were astonished to find out that not only is it one of the most plentiful receptors, but it is also found in nearly every major region of the brain.

"It's not very likely that this receptor exists just so people can experience the effects of marijuana," Howlett deadpans. "It had to have other purposes, and some of them were probably important."

In order to uncover these purposes, scientists still had to find the message-carrying chemicals (ligands) for which the receptor was actually meant. These substances, sometimes called "the body's inner dope," are more properly known as endogenous (that is, native to the body) cannabinoids, or endocannabinoids. It was Mechoulam who found the first one, and he named it "anandamide," from the Sanskrit word meaning "bliss."

Its exact role in the emotions is not yet known, but scientists strongly suspect that it is integral to that fine chunk of bliss you feel whenever you satisfy an oral craving - say, when you lick that first, sweet swirl of frosting off the top of your birthday cake. It is a crucial part of an internal reward system that, according to Daniele Piomelli, Ph.D., a professor of pharmacology at the University of California at Irvine, "seems to have been designed to make humans feel good about something they obtain after a long quest."

In other words, the ape-man who chowed down, and fattened up, whenever he tripped over a wildebeest carcass had a better chance of surviving an Ice Age winter than did a fellow who was content with a nosh. The endocannabinoid system that evolved accordingly is a masterpiece of natural selection. Its receptors are located by the millions, not just in the brain, but in the digestive tract, muscle tissue, bladder, liver, fat cells, and many other organs. It is a network of spectacular complexity, carrying intricate messages from one cell to another, from one organ to another, from one system to another. The fact that humans stumbled across so vital a part of themselves by way of a smoldering doobie is pretty hilarious, when you think about it.

Source: http://healthandfitness.sympatico.m...detect=&abc=abc

__________________
Was he robbed of the ashphalt that cushioned his face?