Herbs: Promotional and Chemical Warfare

Weeds are plants the uses of which have yet to be determined. Herbs may be drugs that have yet to be discovered. Herbs contain alkaloids, chemicals not directly useful to the plants, but toxic to animals including insects. Animals who eat these substances and become ill will, thereafter, limit consumption of the offending plants. This is chemical warfare by plants against animals. Nearly half of all plants spend a major part of their chemical energy, derived from light, synthesizing these complex chemicals like curare, strychnine, atropine, digitalis, caffeine, nicotine, quinine, morphine, cocaine. A large percent of energy available to these plants goes into synthesizing alkaloids, but these chemicals are of considerable utility to the plants that produce them. If these chemicals had not been useful, the cousins of the plants that are without this drain on energy would have out-reproduced them, resulting in the extinction of those plants wasting energy producing useless chemicals. So far chemists have characterized 10,000 or so of these chemicals in various plants.

What is the animal contribution to this eons of chemical warfare? Humans and our mammal kin share many similar chemical mechanisms for disposing of these chemicals, and these mechanisms are active also against a great variety of unnatural substances including synthetic drugs, insecticides and herbicides. The power of the liver illustrates this counteracting ability. All the blood from the stomach and intestines passes through the liver before going back to the heart and everywhere else. The “first pass effect” means that some chemicals such as nicotine, when taken orally, are virtually eliminated from the blood in its first pass through the liver so that none enters the general circulation to get to the brain. To get a fix, a nicotine addict must absorb the drug through the lungs or the lining of the mouth. Inderal, also known as propranolol, is a synthetic chemical (it does not occur in nature) which is 98% destroyed in its first pass through the liver. This means that, for equal effect, an oral dose must be 50 times an injected dose because the injected dose bypasses the liver. When the liver is working on more than one chemical at a time, its action may be slowed or speeded up, and which it will be can scarcely be predicted.

Now back to the 10,000 or more natural chemicals produced by plants. All of these are by their contexts poisons, but many of them are useful medications especially if the dose can be carefully adjusted. Those in long usage by the medical profession have been purified, meaning the active substances have been separated from everything else in the raw product so that it can be weighed out in exact doses. This helps to avoid both toxic and ineffective doses. Here is a particularly interesting example: prior to the 1940s digitalis was available only in crude forms, either powdered leaves which could be made into pills or liquid extracts of leaves. These were dispensed as so many “cat units,” the dose which killed 50% of the cats to whom it was administered. This was obviously a rough estimate but the best available until digitalis was purified by the Eli Lilly Company culminating many unsuccessful attempts in the preceding centuries. Digitalis had proved to be very fragile during such processing. Since then digitalis has been much safer to use. Toxicity, which had been common, is now rare because exact doses are available. Remember that these substances are all capable of interacting in presently imponderable ways, with each other and with drugs, whether purified herbs, digitalis, quinine or, synthetic chemicals from the environment or medications from your pharmacist. The practical advice which flows from this is: get all of your medications from one pharmacy, even prescription eye drops because they go through the nasolacrimal duct and are swallowed. Modern pharmacies put your entire list of medications on a computer that is programmed to look for drug interactions like those we have been discussing. The pharmacist who discovers a potential adverse interaction will call your doctor. If the pharmacist asks you about herbal remedies, list those also, although the vast majority of interactions among herbs and interactions of herbs with medications are presently unknown and will remain so considering the enormous numbers of combinations that would have to be tested in animals or volunteers, one combination at a time. The bottom line: take herbal remedies for minor illnesses if you choose, but if you have a serious acute illness or a chronic one, stop your herbs until you talk to your doctor.

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Why doesn’t the FDA (Food & Drug Administration) take charge of these problems? Because of “promotional warfare” between promoters and the public---Congress removed “food additives” and herbal remedies from the FDA’s jurisdiction in the mid 1990s except for deaths and life threatening events. The recent deaths of several promising young athletes from Ephedra, a Chinese herb, illustrates this tragic point. Ephedra is the generic name of several species of plants that produce the alkaloid ephedrine (genus names are capitalized, species names lower case as in Homo sapiens).

Caffeine is a habit-forming drug but so low in toxicity it is hard to explain why plants bother to make it. It turns out that a very small concentration of caffeine kills slugs and snails, prevalent predators in the tropics. Theobromine, very similar to caffeine chemically, is the main alkaloid of chocolate. It was purified and used as a drug in medicine 50 years ago, and later abandoned because more effective remedies came along. So theobromine started as the active ingredient of an herb, became a drug and now has been cast out of both categories. In all probability it still kills slugs and snails. Incidentally rather small doses, a small handful of M&Ms, can be lethal to dogs. If such an alkaloid became useless in nature because all of the relevant predators became extinct, the plants making it would suffer a competitive disadvantage versus other plants. Only a random mutation could spare them this problem. Such a mutation, deleting the ability to make the alkaloid, would be harmful or helpful depending on the environment.

Not long ago, I was explaining to a young lady about caffeine: how it has a stereotyped withdrawal syndrome and users develop tolerance to toxic quantities. These characteristics are similar to other more seriously addicting drugs. (Tolerance permits animals to survive on an otherwise fatally toxic diet). She was interested and asked some intelligent questions, so I mentioned that chocolate contained theobromine, an alkaloid differing by only one methyl group from caffeine, and that if theobromine is addictive, it is even less so than caffeine. I also mentioned that, as far as I was aware, no one had demonstrated that theobromine addiction explained “chocoholics” or even demonstrated that theobromine is addicting at all. She brightened up a little more and became an instant research scientist.

Her response: “When I was three, I was given a puppy, who ate a little of everything that I ate including lots of chocolate. When I heard a few years ago that chocolate is poison to dogs, I figured that he had gradually acquired immunity to chocolate. Now from what we are saying it seems that theobromine is addicting and my puppy had acquired tolerance.” I really treasure such encounters with my public. My patient’s story is probably as good evidence as exists anywhere that theobromine is addicting. For more about addiction and tolerance see Biology’s Integrating Insights for Medical Science on < www.frantzmd.info > .

In general biology are found many examples of these interlocking relationships between plant toxins and other creatures. Here is an example. In Central America, there is a beautiful butterfly of the genus Parides. This genus always lays its eggs on vines of the genus Aristoloquia. The leaves contain aristoloquic acids in amounts that render them inedible except to Parides larvae. Somehow the poisons are separated from the useful food by the larva’s digestion and stored in the body of the larva in an inaccessible way that survives metamorphosis so the adult butterflies are also poisonous to predators as were the larvae. Meanwhile, other species of larvae have evolved to look like Parides larvae so they get a free ride--not being eaten because predators think they are the poisonous Parides larvae. Incidentally, our common monarch butterflies also become toxic by eating milkweed. Countless other such fascinating discoveries await us, especially in the tropics. And the weeds, dandelions and lambsquarters, are very good sources of vitamin A. So dandelions are actually useful weeds; dandelion seeds are beginning to appear in garden catalogues. All drugs were derived from herbs until aspirin was synthesized with the intent of creating the very first artificial (synthetic) drug a little more than 100 years ago.

Modern chemical drug manufacturing has now very nearly replaced the cultivation of herbs. However, drug manufacturers are beginning to clamor for permission to grow pharmaceuticals by genetically modifying plants including food crops grown outdoors where they could hybridize with our actual foods. Talk about predictable unintended consequences!

Already we are beginning to see the predicable unintended consequence of advertising prescription drugs directly to the public and creating felt needs in the public for drugs beyond the dictates of common sense and precautionary principles. This was well illuminated by The Bipolar Bamboozle by Flora and Bobby in the September/October, 2008, edition of The Skeptical Inquirer. Some more on that topic follows—socialism may be inefficient, but capitalism requires much regulation.

Early in my life some wordsmith defined tantrums as the normal psychosis of childhood. The diagnosis of adult psychiatric disorders in children became much more frequent after the publication in 1998 of a book The Bipolar Child, The Definitive and Reassuring Guide to Childhood’s Most Misunderstood Disorder by Demitri and Janice Papolos. This book caused an enormous increase in the diagnosis of bipolar disorder in children. This disease is also called manic-depressive psychosis. These events are similar to the fad of diagnosing attention deficit disorder (ADD) a few years earlier. (Severe cases of ADD do get worthwhile relief from treatment with brain stimulants).

In both instances the ability of the pharmaceutical industry to advertise prescription drugs to the general public, granted in the early 1990s, greatly contributed to these diagnostic and therapeutic fads. The problem is aggravated by the fact that brain stimulants improve personal efficiency in normal people and antipsychotic medications also reduce disruptive behavior in normal children with such behaviors. This ensures that the initial results of erroneous treatment are quite likely to seem favorable.

The problems from speed, the street name for amphetamine, and similar brain stimulant drugs are well known to the public. The various medications effective for bipolar disorder cause obesity consistently plus diabetes and disordered sexual development rather frequently. Expert consensus is that it is best to muddle along with ordinary disruptive behavior in childhood and postpone the diagnosis of bipolar disorder, or at least its treatment, until adolescence.

We have been talking about the hazards of misleading the public with too much hype in the media of some relatively rare conditions resulting in much meddlesome treatment. There are many examples over a long period of time of commercial interests intentionally misleading the public about medical matters. The tobacco companies’ efforts to sow doubt about the health problems of smoking were quite successful for forty years.

Did you ever hear of Librium? When its patent was about to expire, its manufacturer vigorously promoted Valium and successfully retained exclusive rights in Librium’s former niche for another patent cycle. Somewhat similarly, Nexium is replacing Prilosec for acid indigestion. A great many sleeping pills have appeared on the market for a slightly different reason: each one in turn was found to be habit-forming, and each new one at least partially overcame this expectation when first introduced, thus becoming widely used until the history was repeated. Ironically, the least habit-forming “sleeping pill” was promoted only as an antidepressant. It was not widely used but is still on the market as trazadone (generic name). If you really need a pill for sleep, it is one of the best. Please note that all sleeping pills reduce personal efficiency and aggravate symptoms of dementia for several days after use especially in the elderly. Again ironically, the longest acting drugs are the least habit-forming because their continued presence is like a gradual reduction in dose of a short-acting agent, but they accumulate after daily use with persistent addling of the mind for weeks after stopping them. Similarly, methadone is a long acting narcotic useful in treating narcotic addicts.

There are many more minor examples of creating mild confusion of the public about medications for commercial gain. Many of these examples are mixtures of two generic drugs, both of them useful for a particular condition. Combining them justifies a new brand name and a new patent with the same privileges as the patent holder of an innovative new medication with a novel and perhaps “breakthrough” mechanism of action. Ask your pharmacist whether your medication might be one of such combinations. If so, negotiate the two drugs as two separate generic prescriptions for a fraction of the cost. In our country manufacturers of generic drugs are inspected to be sure that they follow all “good manufacturing practices”—a truly meaningful requirement. Some generic manufacturers are also big name companies that make most of their profits from patented drugs.

Finally, write to Congress requesting that our country stop advertising prescription-only medications to the general public. It is a totally unnecessary and counterproductive expense. We are currently the only country that permits this type of advertising—New Zealand discontinued it a couple of years ago.

John A. Frantz, M.D.

August 18, 2008