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Friday, May 19, 2006

Pharmaceuticals and Fats - Interesting Combinations 

Now I didn't know this:

Today is the 31st anniversary of me arriving in Camp Cornwallis on Basic Training....

[The physical exertion in Basic Training] results in a generally slimmer waistlines , and lowered body fat levels. This lower body fat levels....this can lead to problems.

Trouble was....I was SUCH a bad boy when I was in school. Early '70s, lots of drug use....

The loss of body fat was unexpected, and it had really unexpected side effects. All those chemicals in my body fat started coming out, and so not only was I sick, miserable, tired, but I was also stoned out of my feakin' skull the whole time I was in Basic Training....

Drugs retained in body fat? Yup:

Regular users, upon stopping marijuana use, may experience withdrawal effects. These may include agitation, insomnia, irritability, and anxiety. Because the metabolite (the substance formed when the body breaks down the drug) of marijuana may be stored in the body's fat tissue, evidence of marijuana may be demonstrated in heavy users through urine testing up to 1 month after discontinuing the drug.


PCP is fat soluble and thus can remain in the body for prolonged periods.


The marijuana "high" is much like a depressant drug, except marijuana abuse creates a reverse tolerance....[L]ess and less marijuana needs to be ingested to create a "high" sensation. This is caused by the inability of marijuana's active ingredient, delta-9-tetrahydrocannabinol (THC) to dissolve in water. Rather than being flushed from the body, THC attaches to fat cells. THC will remain in the body for up to ninety (90) days. Hence, the more marijuana smoked, the less is needed to achieve a "high".

Some interesting ramifications of the whole metabolite thing, from the Toronto Rehab Center:

[O]nce a Drug of abuse hits the bloodstream and makes its first pass through the liver, the Drug is altered and soMething called a "by-product," or a "metabolite," is formed. We now know that the component of a Drug of abuse that we get addicted to is the metabolite of the Drug, not the Drug itself. This is a terribly important concept. In other words, Heroin is converted to morphine in less than 120 seconds after it hits the bloodstream. We don't really have Heroin addicts, we have morphine addicts. We don't really have Cocaine addicts, we have benzoylecgonine addicts. Even Alcohol has a metabolite. Nicotine has a metabolite called cotinine. Marijuana has two primary metabolites.

It is the metabolite that supports the Addiction. It is the metabolite that gets stored in the body fat, and to some extent it is the metabolite that gives you some of the signs of Drug influence. Certainly the long-term effects of the Drugs derive from the metabolites.

Apparently, once a Drug hits the bloodstream, the body says, "Gee, the body's taken in a toxic substance. I've got to get rid of it." It tries to rid itself of the Drug of abuse by excreting it- through the breath, through the bile, through the urine. (It also has the mechanism to change the toxin to a metabolite.)

Here's where the rub comes in. We don't know much about these metabolites yet, We used to say they were inactive, they were inert. We now know different. We do know the body makes the metabolite and it will store it in the reservoirs, and in some cases it uses the metabolite. In other words, if you have a shortage ofendorphins, fine. It will use the metabolites of Heroin or morphine as a substitute.

If you're short of your dopamine, it will use the metabolites of Methamphetamine and Cocaine as a substitute. If your nicotine, after several years, has driven out some of your serotonin, the cotinine and other metabolites of nicotine will be happy to substitute, at least for a while.What we don't know is how destructive those metabolites are. We really don't have a good feel for that. We don't like them when we find them in the body and, of course, we try to get them out of the body.

Three things occur when you take Drugs: one is, the metabolites get formed; secondly, the Drugs will attach to these trigger points known as receptors; and thirdly, Drugs of abuse will deplete natural body chemicals, and in fact substitute for them. What we call Drug dependence is really a substitution phenomenon.

When you want to get yourself recovered, you've got to stop your chemical. Your body has got to not only wash out residues, but your natural body substrates have got to come back up to pret- ty normal levels. And your receptor sites have got to re-function for you to recover and to stay clean and dry, If your receptor sites and your neurochemical substrates do not come back up to a pretty normal level, you will probably remain a lifelong addict.

Something to explore later (I know an addict who died a couple of years ago). But let's get back to marijuana and body fat:

A marijuana joint might seem an odd starting point in the search for weight-loss secrets.

Yet a compound switching off the same brain circuits that make people hungry when they smoke cannabis looks set to become the world’s first blockbuster anti-obesity medicine, with sales tipped by analysts to top $3 billion a year.

Sanofi-Aventis SA’s Acomplia, or rimonabant, which could be approved by US regulators as early as next month, is the first of a new wave of treatments that may spell fat profits for some pharmaceutical companies....

Business Week looked at Acomplia in December 2004:

Ever wonder why marijuana smokers get the munchies? So did a team of scientists at Sanofi Recherche lab in Montpelier, France. Fifteen years ago they began investigating marijuana's effects on the brain, including the well-known fact that cannabis makes users hungry. "We set out to try and create an anti-marijuana," a drug that could suppress appetite by blocking the same switch in the brain activated by cannabis, says Gérard Le Fur, senior executive vice-president and board member at newly merged French pharmaceutical giant Sanofi-Aventis (SNY).

They succeeded beyond their wildest dreams, discovering a medicine that not only helps people lose weight but also shrinks abdominal fat, helps people stop smoking, improves cholesterol levels, and helps patients better regulate blood sugar.

Talk about a potential blockbuster. Initially, though, Sanofi will take it slow. It will seek approval of the drug, Acomplia, in Europe and the U.S. by the second quarter of 2005 as a treatment for just two of the conditions: obesity and tobacco addiction. Because patients in Acomplia trials regained weight after stopping treatment, the company hopes regulators will approve it for long-term use....

as the first in an entirely new class of drugs that affect a pleasure center in the brain, even the slightest hint of psychiatric side effects may lead regulators to demand more long-term safety data, potentially delaying Acomplia's launch beyond 2006 as planned....

Acomplia is the first in a new class of compounds under development to block receptors found in the brain and in fat tissue known as cannabinoid type 1 (CB1). These receptors control hunger and tobacco addiction. Chronic overeating and smoking sends them into overdrive. Blocking the CB1 receptors dramatically reduces such cravings. Results of a two-year clinical trial in the U.S. showed patients given Acomplia lost an average of 19 pounds, compared with five pounds for patients given a placebo. Those on Acomplia also reported higher levels of HDL, the good cholesterol, lower levels of triglycerides, and improved sensitivity to insulin. All are important in keeping heart disease at bay.

And this article ran just yesterday:

Sanofi-Aventis' (SNY) Acomplia may have received EU recommendation, but concerns over safety look set to continue until the drug is firmly established on the market, says Morgan Stanley. Says some scientists have pointed out that data presented at a recent symposium had shown that treated patients experienced less "joy" than patients on placebo.

And what kinds of things will happen if you take Acomplia and marijuana simultaneously? You smoke de joint in the morning, the THC makes it to your body fat, then you take the Acomplia, you lose the body fat, the THC kicks into your system...that's bound to warp a mind.

From the Ontario Empoblog (Latest OVVA news here)

Thanks for the education!
Does this mean that I now have a degree in cannibiology?

You may groan now.
The medics told me it was a fairly common phenomonon. Makes more sense that it was "old stuff" stored in my body fat than the alternative theory...that the military was feeding me PCPs just to watch me twitch!

As for stopping it dead....well, I continued to use alcohol rather heavily and smoked for another 10 years. I have totally stopped the smoking, and only drink a beer once or twice a month now, even though I always have a case of beer in the fridge, and I make a lovely wine. I sort of got out of the habit....

Nice to see my story got you thinking!
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