Herbal, Pharmaceutical and Real Medicine

If doctors who practice integrative medicine are still a scarce commodity, how much more so medical specialists who still maintain an integrative orientation? Sidney Kurn, a respected California neurologist, is one of that especially rare breed. In this article he gives us a little education in both the science and the business of pharmacological medicine, and its herbal alternatives.

by Sidney Kurn, M.D.image

Therapeutics is the noblest pearl and the supreme treasure, and it holds first place in medicine; and there is nothing on earth that can be valued more highly than the curing of the sick.  The nature and force of a disease must be discovered by their cause and not by their symptoms…for we must not merely extinguish the smoke of the fire but the fire itself.  If we want the earth to produce better grass, we must plow it, and not merely tear out the bad grass.  Similarly, the physician…should direct his thought to the origin of the disease, and not only to that which the eye sees.  For in this he would see but the symptoms and not the origin; similarly smoke is only the symptom of the fire, not the fire itself.

Nature Of Disease
Philippus Aureolus Theophrastus Bombastus von Hohenheim (Paracelsus)
(1493-1541)

Introduction

As the saying goes, “A fish does not know he is in water until he is removed from it.”  As physicians, we tend not to know our cognitive paradigm unless forced by circumstances to explore outside its boundaries.  The cognitive paradigm is formed through consensus and evolves slowly over time.  We are initiated into the established medical consensus in the early years of medical school and this worldview is consolidated in residency and then in continuing medical education after we complete our training.  Without knowing it, we tend to reject our own individual experience that falls outside the boundaries of our medical worldview.  Numerous articles in mainstream media and our general and specialty journals make clear the role of the pharmaceutical industry in the current medical therapeutic paradigm.  The following appeared in the New York Times, March 2, 2009:

In a first-year pharmacology class at Harvard Medical School, Matt Zerden grew wary as the professor promoted the benefits of cholesterol drugs and seemed to belittle a student who asked about side effects.  Mr. Zerden later discovered something by searching online that he began sharing with his classmates.  The professor was not only a full-time member of the Harvard Medical faculty, but a paid consultant to 10 drug companies, including five makers of cholesterol treatments.
“I felt really violated,” Mr. Zerden, now a fourth-year student, recently recalled.  “Here we have 160 open minds trying to learn the basics in a protected space, and the information he was giving wasn’t as pure as I think it should be.”

Mr. Zerden’s minor stir four years ago has lately grown into a full-blown movement by more than 200 Harvard Medical School students and sympathetic faculty, intent on exposing and curtailing the industry influence in their classrooms and laboratories, as well as in Harvard’s 17 affiliated teaching hospitals and institutes.

They say they are concerned that the same money that helped build the school’s world-class status may in fact be hurting its reputation and affecting its teaching.
The students argue, for example, that Harvard should be embarrassed by the F grade it recently received from the American Medical Student Association, a national group that rates how well medical schools monitor and control drug industry money.

Harvard Medical School’s peers received much higher grades, ranging from the A for the University of Pennsylvania, to B’s received by Stanford, Columbia and New York University, to the C for Yale.  Harvard has fallen behind, some faculty and administrators say, because its teaching hospitals are not owned by the university, complicating reform; because the dean is fairly new and his predecessor was such an industry booster that he served on a pharmaceutical company board; and because a crackdown, simply put, could cost it money or faculty.

The following appeared in a publication of ProPublica, an independent non-profit newsroom that produces investigative journalism in the public interest:

Stanford Faculty Still Taking Drug Firms’ Money

December 20, 2010 | Tracy Weber and Charles Ornstein, ProPublica

As medical schools wrestle with how to keep drug companies from corrupting their faculties, Stanford University is often lauded for its tough stance.

The school was one of the first to stop sales representatives from roaming its halls in 2006.  It cut off the flow of free lunches and trinkets emblazoned with drug names.  And last year, Stanford banned its physicians from giving paid promotional talks for pharmaceutical companies.

One thing it didn’t do was making sure its faculty followed that rule.

A ProPublica investigation found that more than a dozen of the school’s doctors were paid speakers in apparent violation of Stanford policy — two of them were paid six figures since last year.

Dr. Philip Pizzo, the dean of Stanford’s medical school, sent e-mail to medical school staff last week calling the conduct “unacceptable.”  Some doctors’ excuses, he wrote, were “difficult if not impossible to reconcile with our policy.”

My goal is not to discount the potential life-saving role of pharmaceuticals, but simply to show the often hidden role that money; in this case pharmaceutical money, plays in our epistemology, the boundaries of our perceptual world.  As the saying goes, “When all you possess is a hammer, every piece of hardware tends to look like a nail.”  When our education, grant money, and educational forums derive a significant income from the pharmaceutical industry, the biomedical world takes on a mechanistic shape that can be modified by drugs.  As Thomas Kuhn points out in The Structure of Scientific Revolutions, anomalous results in experiments are attributed to errors on the part of the experimenter, since they fall outside the epistemology, the consensual way of knowing, rather than a sign of the limits of the paradigm.  This occurred in classical physics until the anomalous results reached a crisis, shifting the paradigm with the emergence of relativity and quantum mechanics.  This is slowly happening in medicine, with the inadequacy of our therapeutics in dealing with chronic disease, the emergence of multi-antibiotic resistant organisms, and the rise in deaths caused by prescription medication.  In case the latter surprises us, the press is filled with articles such as the recent one in the Los Angeles Times:

Drug Deaths Now Outnumber Traffic Fatalities In U.S.
September 17, 2011 | By Lisa Girion, Scott Glover and Doug Smith

Fueling the surge are prescription pain and anxiety drugs that are potent, highly addictive and especially dangerous when combined with one another or with other drugs or alcohol.

Propelled by an increase in prescription narcotic overdoses, drug deaths now outnumber traffic fatalities in the United States, a Times analysis of government data has found.

Drugs exceeded motor vehicle accidents as a cause of death in 2009, killing at least 37,485 people nationwide, according to preliminary data from the U.S. Centers for Disease Control and Prevention.

While most major causes of preventable death are declining, drugs are an exception. The death toll has doubled in the last decade, now claiming a life every 14 minutes. By contrast, traffic accidents have been dropping for decades because of huge investments in auto safety.

Public health experts have used the comparison to draw attention to the nation’s growing prescription drug problem, which they characterize as an epidemic.  This is the first time that drugs have accounted for more fatalities than traffic accidents since the government started tracking drug-induced deaths in 1979.

Perhaps the foregoing serves as enough introduction to our real topic, appearing in the title, “herbal, pharmaceutical and real medicine”.

Plant Medicine

Physicians are quite familiar with drugs, single molecular compounds, of which many have known mechanisms of action.  In simple terms, herbs consist of numerous constituents, which can be divided into primary and secondary metabolites.  Primary metabolites are essential for the growth, development and reproduction of a plant whereas secondary metabolites are less important in these functions.  In some cases, phytochemistry, the study of plant chemistry, cannot always assign a function for a secondary metabolite, although some appear to play a role in plant defense against animals and pathogens, including other types of plants.

Despite the occasional study reporting on lack of efficacy of an herb, PubMed has many thousands of studies on the efficacy of plants in both the laboratory and clinical setting. Many clinical studies fulfill the cardinal principles of a well-constructed clinical trial.  This efficacy presents a dilemma for the standard medical paradigm, alluded to above.  This is well summarized in Principles and Practice of Phytotherapy by Simon Mills and Kerry Bone:

While many conventional drugs or their precursors are derived from plants, there is a fundamental difference between administering a pure chemical and the same chemical in a plant matrix.  It is this issue of the advantage of chemical complexity, which is both rejected by orthodoxy as having no basis in fact and avoided by most researchers as introducing too many variables for comfortable research.  Herein lies the fundamental difference between the phytotherapist, who prefers not just to prescribe chemically complex remedies but often to administer them in complex formulations, and the conventional physician who would rather prescribe a single agent.” 

The authors go on to state,

“Is there any advantage in chemically complex medicines?  Life is indeed chemically complex, so much so that science is only beginning to grasp the subtle and varied mechanisms involved in processes such as inflammation and immunity.  It does seem logical that, just as our foods are chemically complex, so should our medicines be.  But hard proof of this advantage has been difficult to establish…” (2)

Classification of plant secondary metabolites is a field onto itself, and a full discussion is outside the scope of this short article.  A brief classification, focusing on the salient features of each class includes the following:

Alkaloids:  These contain a ring with nitrogen and can have dramatic effects of the central nervous system.  Examples include caffeine, atropine, nicotine, morphine, ergotamine, mescaline, adrenaline and ephedrine.
Polyphenols:  These are also known as phenolics and contain phenol rings.  This class includes anthocyanins that give grapes their purple color, isoflavones such as the phytoestrogens from soy and the tannins that give tea its astringency.  Other examples include resveratrol in red wine, capsaicin in chili and paprika, thymol in thyme, cinnamic acid in cinnamon, rosmarinic acid found in rosemary, thyme, oregano, sage and peppermint.

Terpenoids:  These are built up from terpene building blocks, terpenes consisting of two paired isoprenes (isoprene are short 5 carbon molecules with two double bonds).  The names monoterpenes, diterpenes, triterpenes and sesquiterpenes are based on the number of isoprene units.  Terpenes are the most structurally diverse and numerous among plant natural products.  While often associated with conifers, they also are produced by flowering plants and even various insects.  The resin produced by most plants is a viscous liquid composed mainly of volatile fluid terpenes.  They are quite potent, and a tiny amount provides fragrance.  The fragrance of rose and lavender is due to monoterpenes.  Recent work on Cannabis sativa notes that the aroma is due to terpenes, and some of the terpenes appear to modulate the physiological and psychoactive effects of cannabis.  For the reader interested in a full discussion of cannabinoids, terpenes and the “entourage” effect of the complexity of these components, I recommend the Autumn 2011 edition of O’Shaughnessy’s, a newspaper Journal of the latest science and news related to Cannabinoid Medicine (3) (http://cannabisclinicians.org/wp-content/uploads/2011/12/OS-2011-Terpenes+Minor-CBs.pdf).

Another class of terpenes, the carotenoids (tetraterpenoids), produce the reds, yellows and oranges of fruits and vegetables such as pumpkin, corn and tomatoes.

Glycosides:  These consist of a glucose moiety attached to an aglycone, a molecule that is only bioactive in its free form but inert until the glycoside bond is broken by water or enzymes.  This molecular mechanism defers the availability of the active molecule until it is needed.  Important examples include the anti-oxidant glycosides hesperidin, naringin, rutin and quercetin.  Other well-known glycosides include the cardiac glycosides (digitalis), salicin (converted in the body to salicylic acid) and the anthraquinone glycosides in senna, rhubarb and aloe.

Just as pharmaceutical drugs require “receptors” in the body to initiate their effects, secondary plant constituents also have receptors in the human body.  Although not fully understood, it is clear that agonism and antagonism at these receptor sites account for much of the therapeutic and occasional toxic effects of plant constituents.  This is well summarized in this abstract from an article in QJM: An International Journal of Medicine:

Individuals who regularly eat fruit and vegetables gain protection against a number of diseases. These advantages are usually ascribed to the rich vitamin, antioxidant and dietary fiber content of fruit and vegetables.  However, clinical trials testing whether these nutrients are protective against specific diseases have been less consistent.  The secondary metabolites of plant metabolism, particularly those from the terpenoid and phenolic families, could provide some of this health protection, through regulatory effects on the functional domains of ancient conserved proteins and DNA regions common to both plants and mammals.  Small‐molecular‐mass molecules can regulate gene expression in a variety of ways, e.g. targeting DNA sequences, inducing gene expression and binding to protein‐regulating sites.  Secondary plant metabolites may also modulate the function of transmembrane channel receptors and enzymes. (4)

“Functional domains of ancient conserved proteins and DNA regions common to both plants and mammals” refers to ancient, from an evolutionary standpoint, demarcated sites in proteins and DNA identical in structure in both plants and humans.

Numerous examples of these phytochemical effects exist in the scientific literature. Again, detailed discussion of this lies beyond the scope of this article.  One example would be the binding of numerous flavonoids to the GABA receptor.  Since the GABA receptor, the binding site for benzodiazepines, is probably the second most prevalent receptor in the central nervous system, second only to the glutamate receptor, this established property of flavonoids begins to assume some significance in understanding the role of food and herbs in the physiological states of the CNS.  In contrast, the monoterpenoid thujone, found in wormwood (absinthe), sage, oregano and mint is a GABAa receptor antagonist.  This may explain the mild activating effect of the alcoholic beverage absinthe as well as the aforementioned herbs.

This is a very brief look at receptors for herbal constituents in humans.  In addition, since herbs contain many different classes of compounds, a few of which are itemized above, their effect on human metabolism and the CNS is complex.  It is unlikely that the full metabolic effects of a single herb are known.  Even a common herb such as valerian has multiple alkaloids, terpenes and flavonoids, not to mention other multiple secondary metabolites.  A mathematical theory such as graph theory is appealing to approach this complexity.  Unfortunately, it is not clear that enough information is available on enough herbs to use a mathematical approach to clarify the “topography” of the herb-metabolic interactions.

In terms of the human metabolic system, herbal constituents act mildly at numerous receptor sites while a pharmaceutical agent acts strongly at one or at most several receptor sites.  There are advantages and disadvantages of both from a system theoretic standpoint.  A gentle action at numerous sites reduces the risk of side effects and tends to have an alterative effect.  By alterative effect, I am referring to the tendency of herbs to restore metabolic processes to normal from a deviation of either over activity or under activity.  The disadvantage is the lack of strong efficacy when the patient is quite ill.  Herbs tend to interact with metabolic systems globally, with both agonist and antagonist effects at numerous receptor sites.  This probably explains the alterative effect.  Drugs have strong, focused effects on the metabolic system.  This may be life saving when the pharmaceutical chemical restores a singular deficit or reduces excess at a focal point in the system.  The risk is an excessive effect of the drug at the desired site or a strong action at a site that does not require any modulation.  Acting alone, a drug does not have the benefit of other chemicals to modulate the effect of the “active principle” or drug.

Plant Medicine, Pharmaceutical Medicine And Real Medicine

These ruminations bring us to the focal point of the article, that is, an objective comparison of herbal and pharmacologic medicine.  Paracelsus, quoted above, has been considered the father of pharmacologic medicine.  The following, written in 1874, is salient in this regard:

Paracelsus had seen how bodies were purified and intensified by chemical operations, and he thought if plants and minerals could be made to yield their active principles it would surely be better to employ these than the crude and unprepared originals.  He had besides arrived by some kind of intuition at the conclusion that the operations in the body were of a chemical character, and that when disordered they were to be put right by counter operations of the same kind.  It may be claimed for Paracelsus that he embraced within the idea of chemical action something more than the alchemists did (5).

Paracelsus was centuries ahead of his time, including the idea of purifying an “active principle” of plants.  Pharmaceutical drugs, for the most part are single chemicals, acting as a strong ligand for a human metabolic receptor.  We do not know the “mechanism of action” of all drugs, and more and more drugs are composed of more than one compound. These exceptions not-withstanding, the ideal drug has generally been a single “active principle” with a strong therapeutic effect on the disordered metabolism of an illness.  Reduction of a remedy to a single potent compound is the easiest medicine to study according to the current principles of pharmacologic medicine. Scientists tend to recoil from the complexity and general non-standardization of an herbal remedy.  If picked by the light of a waning moon, the effect may be different then if harvested in the broad daylight of spring.  The waxing and waning of terpenoids, flavonoids and alkaloids allow for a myriad of uncontrolled degrees of freedom, an impossible subject for scientific scrutiny.  A 60,000-year history with a current prevalence of use by about 80% of the world’s population only urges the pharmacologic chemist to even greater levels of reductionist scrutiny.

Unfortunately, the elephant in the room is the rate of morbidity and mortality secondary to pharmaceuticals discussed in the beginning of this paper.  Drug morbidity and mortality may be attributed to mis-prescribing by physicians, the patient overuse of opiates and tranquilizers, or some other preventable cause leading to these massive levels of mortality just behind heart disease and cancer.  Paracelsus, the “father” of pharmaceutical chemistry would likely think otherwise.  I suspect that he would understand the limits of the “active principle”, and, no doubt, given his history, would rail against the industrial “greed” that ignores the obvious statistics alluded to above.  I suspect he would be gratified by the “purified” extracts that heal infection, cure some malignancies and treat the symptoms of many diseases.  Then again, he would rage against the reduction of medicine to a single paradigm of the “active principle”, and the sacrifice of healing the patient on the altar of ideological scholarship and the ethnocentric culture of medicine.  It is my suspicion that he would find the wholesale rejection of herbal medicine a grievous loss to the healing arts and a misunderstanding of the practice and spirit of his writing.

For our purposes of understanding Paracelsus, we can substitute herbal medicine in the following quote for the word alchemy.  The word alchemy is too evocative of all that has been “overthrown” in the creation of modern medicine.

The physician should be versed in all branches of philosophy, physics and alchemy as well, as thoroughly, as profoundly as possible, and he should not lack any knowledge in all these fields.  What he is should stand on solid ground, founded in truthfulness and highest experience.  For of all men, the physician is supreme in the study and knowledge of nature and her light, and that is what enables him to ne a helper of the sick.

What is a pearl to the sow, since all she can do is eat?  I praise the art of alchemy because it reveals the mysteries of medicine and because it is helpful in all desperate illnesses.  But what shall I praise in those who have no idea of the mysteries of nature that are placed in their hands?  I also praise the art of medicine.  But how can I praise those who are physicians and alchemists at the same time?  If the art of medicine were found among those who are only alchemists, they would not understand it, and if it were found among those who are only physicians, they would not be able to make use of it, for they do not hold in their hands the key to the mysteries.  Thus I can only praise him who knows how to induce nature to be helpful, that is to say, is able to recognize what lies hidden in nature.  For never must knowledge and preparation, that is to say, medicine and alchemy be separated from each other. Mission of Medicine – Paracelsus

For those readers who dismiss the above outright when seeing the word alchemy, I can only refer them to Carl Jung’s last book written at the age of 85, Mysterium Coniunctionis.  Jung’s genius at this stage was to understand alchemy as metaphor, metaphor for the process of the union of opposites in the human psyche, which in uniting created the coniunctio, the mysterious “entity…stuff…substance…a mysterious, transcendent thing that can be expressed by many symbolic images” (6).  As Jung himself says about alchemy,

We must turn back to those periods in human history when symbol formation went on unimpeded, that is, when there was still no epistemological criticism of the formation of the images, and when, in consequence, facts that in themselves were unknown could be expressed in definite visual form.  The period of this kind closest to us is that of medieval natural philosophy, which…attained its most significant development in alchemy and Hermetic philosophy. (7)

I apologize to the reader for this seeming tangential thread in our discussion.  I raise these seemingly discursive ideas to outline how frozen we stand in the current medical paradigm, frozen in the face of “epistemological criticism”.  Although we use any number of medications with only poorly understood mechanisms of action, we are quick to discard the notion of herbal medicine with inadequately understood mechanisms of action.  We are ready to embrace an FDA approved drug after its phase III trial but ignore an herbal remedy with a 1000-year history of use and multiple studies in peer-reviewed journals.  We seem unable to accept both – unable to hold the union of “opposites”, unable to embrace both “alchemy” and medicine. And we do this to the dismay and sacrifice of our patients who look to us for healing, not for the substantiation of our working therapeutic ideology.  Real Medicine is our Coniunctio, the mysterious union of traditional and pharmaceutical medicine.  If we can reduce the dosage of medication and more successfully treat the underlying cause of illness by adding herbal medicine to the patient’s regimen, we are obliged to do so.  One does not exclude the other.  Healing remains mysterious despite our science.  We should remain open to try what works.  Medicine is a pragmatic art.  There is no philosophy more important than the healing of the patient.

class=This article is dedicated to the art of medicine and to those who benefit from its ministrations.
“center”

In memory of Wayne Souza RPh, LAc

Acknowledgement to Dan Kenner PhD, LAc and Jeff Hergenrather MD for important discussions, review and input.

(1) Principles and Practice of Phytotherapy:  Simon Mills and Kerry Bone, Churchill Livingstone, 2000, page 22
(2) Ibid page 22-23
(3) O’Shaugnessy’s – The Journal of Cannabis in Clinical Practice, Autumn, 2011
(4) Oxford Journals, Medicine, QJM: An International Journal of Medicine, Volume 94, Issue 1, pp. 45-48.
(5) John Ferguson, LL.D.; Professor of Chemistry, Glasgow University from 1874; author of papers on the history of chemistry.

(6) Edinger, Edward F. The Mystery of The Coniunctio, Inner City Books, 1994, Toronto Canada, page 18.
(7) Ibid, page 7

Sidney Kurn MD
Farmacopia December, 2011

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