Autumn 2004
O'Shaughnessy's
Journal of the California Cannabis Research Medical
Group
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Dr. Weil's Recommendation:
Honor Complexity
By Andrew Weil, MD
One of the most dramatic advantages of learning to use
plants in medicine is their relative lack of toxicity compared to isolated
derivatives of plants. This should be obvious. If you find something
in nature that has a biological effect, that affects animals, and you
attempt to concentrate that therapeutic power, you inevitably concentrate
toxicity because they’re one and the same thing.
Andrew Weil, MD, delivered the J. Thomas Ungerleider
lecture at UCLA Neuropsychiatric Institute May 5 on the topic
of "Medical Marijuana."
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“One of the basic principles of pharmacology —and by the way, that word comes
from Greek roots meaning ‘the study of poisons’— is that there is no difference
between a drug and a poison except dose. Any drug given in a high enough dose
will cause toxicity. Some poisons in low-enough dose become useful therapeutic
agents.
The great advantage of plant drugs is that they’re dilute.
The great advantage of plant drugs is that they’re dilute. They’re
diluted by inactive materials. The typical concentration of drugs in
a natural pharmaceutical is on the order of one-half to one percent
by dry weight of the plant. That’s an enormous difference from a chemical
compound that’s 100 percent pure
Moreover, when you ingest a plant, generally you put it into your body in ways
that cause slow absorption into the bloodstream. In general the pharmacological
power and toxicity of drugs is more correlated with the rate of increase in
concentration than with the absolute dose. A large dose of a drug given by
a route that causes slow absorption actually produces a more muted effect than
a small dose of the drug put into the body very directly.
Nature does not give us drugs as pure, single molecules. Nature
produces constellations of related molecules.
Another difference between plant drugs and isolated chemicals —and
this is not something that is talked about in medical offices— is a
qualitative difference in composition. Nature does not give us drugs
as pure, single molecules. Nature produces constellations of related
molecules in plants.
There may be one compound that’s present in the largest amount, and if isolated,
reproduces most of the plant’s drug effects. We have gotten into the habit
of calling that dominant compound the ‘active principle’ of the plant. We have
been taught in medicine and in pharmacology for generations now that it’s more
scientific and more useful medically to isolate that compound and purify it
and, if possible, tinker with the molecule in the laboratory to make the effects
even more powerful.
We pay a very high price in medicine for our reliance on those purified compounds
that have very dramatic effects. That price is a completely unacceptable level
of toxicity... At the moment, deaths caused by pharmaceutical medications ranks
between the sixth and fourth leading cause of death in US hospitals. An article
in JAMA a couple of years ago estimated that we’re now seeing a hundred thousand
deaths a year in US hospitals —deaths directly caused by pharmaceutical drugs.
These deaths were not ‘mistakes;’ they were not attributable to the wrong drug
given to the wrong patient. This was the right drug at the right dose to the
right patient from the right physician —and 100,000 people die a year! I think
that is completely unacceptable. And it would not happen if we were using more
plant drugs in medical practice.
There’s a qualitiative difference that’s very difficult to talk about in scientific
audiences but I see change beginning to come. One of the characteristics of
these compounds that occur in arrays in nature is that they often include both
agonists and antagonists, so you’ve got a kind of built-in ambivalence, a paradoxical
effect. [An agonist is a molecule that activates a receptor; an antagonist
blocks the receptor, or otherwise cancels the agonist’s effect.]
There are herbs in Chinese medicine that raise low blood pressure
and lower high blood pressure.
There are herbs in Chinese medicine that raise low blood pressure
and lower high blood pressure. That makes no sense to Western pharmacology.
We think of drugs as having unidirectional action; so how can a drug
possibly do both things?
Coca leaf is a big medicinal plant for Andean Indians, like peppermint or chamomile
for Europeans. Its main indication is for gastro-intestinal disorders. They
say it treats both diarrhea and constipation. How can that be? Cocaine is a
stimulant, it increases gut motility, so you could see how it would help a
constipated person move their bowels; but what possibly could it do for someone
with diarrhea except make it worse? Well, if you look at the array of alkaloids
in the coca leaf, they all look similar —14 or 15 variations on a molecular
theme, cocaine being the dominant component.
But the cocaine molecule is a strange molecule, closely related structurally
to drugs like scopalamine and atropine that come from jimson weed and datura.
These have the opposite effect on the gut —they paralyze the gut.
Cocaine itself has a built-in paradox. According to the way the molecule looks,
it should be a gut paralytic; in practice, it increases gut motility and causes
diarrhea.
What happens when cocaine is taken in that whole mix of other, related molecules
that have this combined agonist/antagonist property? Which effect predominates?
When you present the body with a complex array, you’re giving
it choice in how it responds.
Which effect predominates may have a lot to do with which receptors
are available for binding. When you present the body with a complex
array, you’re giving it choice in how it responds. That’s fundamentally
a different kind of pharmaco-therapeutics from giving a person a purified,
isolated molecule that’s a shove in one direction.
I think both those kinds of medicine have their place. But I have to tell you,
as somebody who’s practiced botanical medicines for many years, there’s often
great value in using these natural mixtures.
The reason that pharmacologists and most physicians have such trouble with
this concept is that we are strongly under the spell of reductionism.
Reductionism is a useful tool. It makes life simpler. It is very difficult
to study complex substances. How do you study a plant with 50 complex molecules,
all of which might contribute to its activity? It is much simpler to say that
one of these equals the whole, and to isolate that and study it. But you’re
missing out on the clinical relevance of the whole plant, which may be very
different from that of the isolated molecule...
In other areas of science —outside of medicine there’s a rising interestin
complexity... If you want to describe changes in weather patterns or the shapes
of clouds, you can’t use simplistic, classical formulas, you have to use new
mathematical models based in complexity.
The rise of complexity theory and its success in physics, mathematics and other
disciplines has not made the slightest inroad into medicine. Pharmacology is
locked into reductionist ways of thinking, especially when it approaches natural
products. We’re dealing with the most complex phenomenon that nature has produced,
the human organism. It seems to me it makes much more sense, if you’re treating
a complex thing, to treat it with a complementary complex thing.