Drug Detox Explained

Forest Tennant, M.D., Dr. P.H.:

A national leader in the field of drug rehabilitation, Dr. Tennant is the author of more than 200 scientific papers, books, and videos on the sub­jects of neurochemistry and drug dependence. He is the Executive Director of the Research Center for Chronic Pain and Dependency Disorders and the Executive Director of the Community Health Projects Medical Group. He has served as a Public Health Fellow for the U.S. Public Health Service, as an Associate Professor at the UCLA School of Public Health, and is a member of the Drug Abuse Advisory Committee of the Food and Drug Administration. He is a Narcotics Training Consultant for the California Highway Patrol and the California Department of Justice. Dr. Tennant was the Keynote Speaker at the Conference on Human Detoxification, Los Angeles, 1995. “I am indeed delighted to be here this afternoon and to share with you what I hope will be somewhat of a historical per­spective, and to bring you up to where I believe we stand medically relative to what is known as detoxification. I first heard the word “detoxification” in the year 1968. I was an Army surgeon in Europe. Even at that time, the U.S. Army had to start doing something about its drug problems. Between the years 1966 and 1968, they established in New York City what they called “detoxifi­cation centers. I cannot tell you who coined that term. It referred primarily at that time to heroin addicts, who were put in hospitals and administered methadone to withdraw them from heroin. Shortly after that time, the term detox­ification came to mean “the substitution of a long-acting drug in the bloodstream for a short-acting drug that you are attempting to stop.” And that is a defini­tion that to some extent continues until this day. Needless to say, the terminology and activities of drug treatment have since taken quite an odyssey. What I would like to impress upon you is that, rather than getting caught up in semantics, it is critical today to understand that a huge amount of neurochemical and biochemi­cal research has gone on in the last 10 or 12 years. Above all, we now know about metabolite formation.

This work goes back to 1961, when a man who won the Nobel Prize, by the name of Axelrod, took a rat brain and put it in a test tube. On it, he put cocaine and amphetamine and he saw that dopamine and noradrenaline, or norepinephrine, were displaced from the brain. A few hundred studies from that time up until now have shown very clear­ly that one of the fundamental effects of drugs, once they hit the bloodstream, is to go to biochemical reservoirs in the body and displace from those reservoirs such things as the endorphins, acetyl­choline, cortisone, and some other bio­chemicals. This is true with every drug of abuse that we know about-nicotine, anabolic steroids, marijuana, and all other compounds. The drug comes in through the blood­stream to reservoirs and biochemicals are displaced. What reservoirs are we talking about? The major one in the body is the pituitary gland. The second most impor­tant are the adrenal glands, probably the hypothalamus in the brain is number three. You have also huge reservoirs in the spinal column, the sciatic nerve, and other big nerve endings in the body.

It is very critical for everyone who deals with drug dependence to understand that if, for example, you take heroin long enough your natural body levels of endor­phin will deplete-your body will make less of it because the drug provides it. If you take drugs like cocaine long enough at a high enough dose, your body’s stores of dopamine will deplete. Once you get this depletion, the body sets up what we call a “craving cycle,” desiring more of the drug to make up for the chemical that you have depleted.

The second basic science principle that you need to know about is that these chemicals that I have just talked about work in the body by attaching to some­thing that we call a “receptor site.” I’m sorry that we call it a receptor site because it’s something of a misnomer. I wish that we called these things “electrical trigger points.” The term “receptor site” comes from research on diabetes. Many years ago, endocrinologists knew that when the blood glucose went up after you ate a car­bohydrate meal, the rise in blood glucose acted like a drug of abuse. It calls forward out of the pancreas reservoir something called insulin. The insulin and glucose then travel together and they are received in muscles like your biceps and your quadriceps. The little spots on the mus­cles that receive the insulin and the glu­cose were called “receptors.” That wasn’t so bad, but then the cardi­ologists got into the act and they wanted to have cardiac “receptors.” And then the lung people wanted to have their recep­tors. And then disaster hit: The psychia­trists wanted their receptors.

Maybe they should have been called “trigger points.” It is body chemicals attaching to receptors in the brain, the spinal cord, the heart, the kidney, in the intestine, that make the bodywork. And we now know that drugs of abuse go to those receptors and trigger those receptors. That’s why we all like our caffeine and our nicotine. And our carbohydrates, and our marijuana, our cocaine, and all of these other compounds-because we can not only release certain chemicals, but we can also make those “trigger points” get triggered. The third thing that you need to be aware of is a fairly recent discovery. In my way of thinking, I don’t think this conference would be being held today if we hadn’t discovered this. That is this: once 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, and 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 differently. 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 of endor­phins, 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 pret­ty 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.

Let’s get back to detoxification. In its traditional sense, it was a substitution. You may be familiar, for example, with something called a drug’s “half-life.” Turns out that, in the field of depen­dence, we don’t care about a drug’s half-life, we care about the whole life.

The whole life of heroin is about six hours. In other words, if you go out here on the streets of Los Angeles and spend your twenty bucks for a fix of heroin, you’ll get six or eight milligrams of hero­in. You will intravenously inject it, and it will remain in the bloodstream above a level of five or ten nanograms for four to six hours-at which time, if you are truly addicted, you will have to re-use. That’s why a typical heroin addict will have to inject three, five up to eight times a day, depending on their
biology and how dependent they’ve become.

Methadone, on the other hand, after a single dose can stay 24 hours and a new compound known as levo-alpha-acetyl­methadol (LANM) will stay in the blood­stream 72 hours. So the original concept of detoxification back in the 60s and the 70s was to give a dose of methadone which would last 24 hours and the heroin therefore could be washed out since it didn’t last as long.

Do drugs really stay in fatty tissue? Yes, they do. Dr. Beckmann and I did a small study to actually prove that for the first time. You can take a simple urine speci­men, or a blood specimen today, and for a cost of about four dollars, you can deter­mine whether an individual is addicted. At least, you can get a good clinical idea that they are addicted simply by knowing the metabolite levels that you can expect to see for the addict, or for the heavy binge user, for the occasional user, or the person trying to withdraw.

Once we had low-cost technology to measure metabolite levels, we were able to plot “washout curves.

Consider the typical washout time for a cocaine addict. Over a period of around 15 or 16 days, the level of metabolites in body fluids goes down to zero. With a methamphetamine addict, on day one the patient may have 3,000 nanograms of amphetamine metabolites in the urine. At the end of 25 days, it is cleared out. Another example is PCP, which has metabolites that really like to store in the fat. The level may start at 500 nanograms and at the end of 43 days, there will still be some trace levels.

It was the determination of these washout curves some six or eight years ago which really gave us the real scientific information that those compounds are stored in the body somewhere, and that “detoxification” or withdrawal had to take on a new meaning. And that was, “How do we clear the body of all these metabolites?” What I would like to leave you with, indelibly in your mind, is this next case. This is a rou­tine, run-of-the-mill cocaine addict, of which America thinks we might have 300,000, half a million, a million-we don’t know.

This man starts out on day one, starts to detox down, and by the fifth sixth day of treatment, his metabolites have cleared out. But guess what? His craving comes back, and he relapses. What happened there on day six or seven? The receptor sites are no longer coated by either dopamine or the metabolites of cocaine. So he’s sitting there in withdrawal and in craving. And so he re-uses. He makes another run at cleaning up, and on the nineteenth day, he re-uses. He repeats this cycle over about a six or eight-week peri­od four or five times before successfully completing detoxification.

In summary. Fat-soluble metabolites or by-products store in the “tank.” You should also be aware that it’s not just the fatty tissue. These metabolites also store in brain tissue, in the adrenal glands, in nerve endings throughout the body. This stuff becomes a poor substitute for natural body chemicals. The number one job is to try to get all of these metabolites and by-products out of the body. And I must say that I have been a great fan of this particular treatment approach for quite some time because that has
been one of the fundamental tenets of their program.

In our field, nutritional supplements are a must. A certain drug treatment program in the US has for some time championed simple nutrients. They are great adjuncts to treatment. It is no secret that when we take someone into rehabilitation, they are pretty malnour­ished. We have done extensive studies on vitamin levels in serum and nutrient lev­els in serum, and addicts are terribly malnourished.

I would like to talk about some of the serious complications that we are seeing today, to raise the flag even higher for the need for proper detoxification, or if you prefer, “purification” or withdrawal. It is essential to get metabolites out of the. body. There are three basic effects on the immune system: cortisone depletion, leukocyte suppression, and abnormal pro­teins. Leukocytes are the white blood cells that wander around the body grabbing up viruses like the AIDS virus. The metabo­lites have a very deleterious effect on the immune system.

Another thing that metabolites may do, as well as the drug itself, is damage the receptors. This is the tragedy. Once the receptors get damaged enough, we know that the person may not return to a normal mental or physical state. I don’t have time to go into all the syndromes that result, but they cross a wide panora­ma, from diabetes to schizophrenia, to adrenal gland insufficiency, to poor memory, poor motivation-almost an Alzheimer’s state. They can be very mild or very severe. Another thing is not well appreciated at all, but it is serious. We know that the metabolites of cocaine and amphetamine, and maybe of PCP and marijuana, con­strict blood vessels. What that means is the blood vessels are shut down, to the point that you do not get enough blood in the brain or to the heart. Why do I point this out? The epidemic in recent years of crack babies, heart attacks, and strokes is due to the blood ves­sels being cut off. The blood cannot carry glucose or oxygen, and so tissue dies. The last complication I want to bring to your attention has to do with immune suppression and the infectious diseases that are plaguing the addict population. All of you are aware of AIDS.

Interestingly enough, in our intra­venous drug addicts in California, we find only about one percent with AIDS. We don’t know why. But 92 or 95 per­cent of them have hepatitis C. Hepatitis C has become the plague of the intra­venous drug addicts of California, and it appears that most of them are going to expire of complications of the disease.

Most of them are expiring somewhere between the ages of 48 and 55, usually after about 30 to 35 years of carrying the virus. If they have shared needles as little as two, three, or four times, they proba­bly carry the hepatitis C virus. There is no vaccine for it, there is no treatment for it.

Hepatitis C spreads like AIDS, pri­marily by blood exchange. It will spread to some extent by sex, it will spread to the babies. It apparently can also spread slowly by other “post-contact” routes- saliva, or air. We know that 20 to 25% of alcoholics carry hepatitis C, but we don’t know where they got it. Among non-addicts, forty percent of the hepatitis C cases in the state of California do not have a risk factor, such as a blood transfusion, intravenous drug use, or sexual contact with someone who carries the virus. We do know that the intravenous drug addict is the reservoir of hepatitis C. This is bringing in a dimen­sion that we have never had to deal with before. The bottom line is that through­out the state, there is great, great concern
about these infections, and we don’t know what they mean. We are very concerned about the infec­tious diseases, we are very concerned about what we now understand are the biochemical changes that occur in the addicts, and we are very concerned as to what all this means for the general popu­lation and what public policy should be.

Let me close by saying that it’s been an honor and a pleasure to be associated with this treatment center. The program that we have here is a first-class program. It’s a program that should be done by every­one before they get into the clutches of a physician. You don’t want to rely on us physicians. By the time we get the patient, it’s the end of the road. There’s no other referral. I can’t say that serious­ly enough.

We have three hundred and some thou­sand intravenous drug addicts in California that have been identified. They, in effect, are a dying population. They need all the care and humanity that we can give them. I salute you for being interested in this and I appreciate the opportunity to be here today.