Corydalis: An Herbal Medicine for Pain, with Some Thoughts on Drug Development

Corydalis. Better than opium?

Ever since William Withering published his classic treatise on Foxglove in 1775, science has been testing herbal medicines and trying to establish a scientific basis for the ones that work. As many as half of today’s prescription drugs were derived from plants. A new study published in Current Biology by Zhang et al. has identified a compound in a traditional herbal remedy that is effective in relieving pain in rats and works by a novel analgesic pathway. They used rigorous scientific methods and their findings do not represent an endorsement of traditional herbal medicine practices.

TCM Use of Corydalis

An herbalist website touts Corydalis as a remedy for fibromyalgia. It says TCM practitioners consider it the second most effective pain reliever after opium, and claim it has none of the side-effects of opiates. Also known as Yan Hu Suo, it is a Blood Vitalizer and is forbidden during pregnancy because it could detach a fetus.

Dr. Oz has recommended it for fibromyalgia, but the herbalist criticizes him for not mentioning that it should be avoided during pregnancy and nursing and for not mentioning that it should be used together with other herbs in formulas.

The Natural Medicines Comprehensive Database, which I consider the best source of information on natural medicines, has surprisingly little to say about it. It doesn’t mention that it has been used for pain or fibromyalgia; it says people use it for mild depression, neuroses, emotional disturbances, severe nerve damage, limb tremors, as a mild sedative and tranquilizer, hallucinogen, to lower blood pressure, and to relax small intestinal peristalsis. They say there is insufficient reliable information about its safety to give it a safety rating, but they rate it as “likely unsafe” in pregnancy. As for effectiveness, they found insufficient reliable information to rate its effectiveness.

Previous studies

PubMed lists mainly animal studies and in vitro studies. There are only a very few pilot studies in humans. This one found no difference in relief of knee osteoarthritis pain between Corydalis and an NSAID control; the incidence of adverse effects was 24% and 47% respectively.

This one was a double blind RCT that found no difference in esophagitis symptoms between a placebo and a mixture of Corydalis Tuber and Pharbitis Seed.

The new study

The new study had nothing to do with TCM; it was firmly in the “Western” scientific tradition. They start by explaining that current pain management is unsatisfactory: the opiates are only effective for 70-80% of patients and they are plagued by side effects. They started by screening TCMs that were known for their analgesic properties. They tested a total of 500 fractionated samples of eight herbal medicines. Only one fraction of Corydalis yanhusuo had a reproducible effect in their assay. They proceeded to purify it and identify the active ingredient, dehydrocorybulbine (DHCB). They determined its structure and synthesized it to get adequate amounts for study. They showed that the synthetic DHCB was identical to the purified plant derivative.

They gave the synthetic DHCB to dopamine receptor knockout mice and found it was effective against inflammatory pain and injury-induced neuropathic pain. Mice can’t report their pain, so they used a tail-flick assay. I suppose the SPCA would call this animal cruelty. They investigated the mechanism of action and the effect of the compound on opioid receptors. They found that DHCB crossed the blood-brain barrier and the mice did not develop tolerance (the need for higher doses to get the same effect) with repeated doses, which is a problem with opioids.

They suggested that their methods could be applied to any natural source and might result in the discovery of many more naturally occurring active compounds.

Natural medicines vs. pharmaceutical drugs

Herbal medicines are essentially adulterated drugs. The active ingredient or ingredients are mixed with many other components with unknown effects. Herbalists believe that these other ingredients work together to potentiate the effect. But when that theory has been put to the test, in most cases the isolated active ingredient proves to be just as effective as the whole plant extract. Rather than helping, those other ingredients might just as well cause side effects or even tend to counteract the effect of the active ingredient.

In the process of drug development, this kind of testing in animals is only a first step. Animals are not identical to humans. Clinical testing in humans must follow. Effectiveness and safety for humans must be established, and appropriate doses and administration intervals must be determined. It takes a long time for such studies to lead to the marketing of a useful drug.

Foxglove contained active ingredients that worked for heart failure, but the original “digitalis leaf” preparation was dangerous. Content varied, and the therapeutic dose was perilously close to the toxic dose. Scientists developed a synthetic version, Digoxin, that allowed them to provide precise doses of a pure product. Then they developed a test to monitor the amount of Digoxin in the blood, and an antidote that could stop its action in case of overdose or side effects. It would be foolish to go back to the uncertainty of the “natural” version. Natural medicines are only a starting point; scientific drug development can improve on them.

Our critics complain that scientists are reluctant to study natural medicines because there’s no money in it. They say plants can’t be patented. But methods of purifying herbal remedies can be patented. And synthetic compounds like the one these researchers developed are certainly patentable. If Big Pharma companies are impressed enough by preliminary studies like this one, surely they will compete to develop products like DHCB for profitable marketing.

Conclusion: the right way to study herbal medicines

Junk science abounds in research on herbal medicines. Less scrupulous researchers might have done an uncontrolled study, giving Corydalis to a few fibromyalgia patients to see if they said they felt better. Instead, these researchers did real science, basic science with what appears to me to be high-quality methodology. This is the way to evaluate claims for natural medicines. This is the way to find new effective drugs.

We need better analgesics to help combat the “opioid epidemic.” This study is promising, but Corydalis is not yet ready for prime time. I worry that people will read too much into this mouse study and think they should take existing supplement products. You can buy Full Spectrum Corydalis at WalMart, with the somewhat worrisome disclaimer “the displayed country of origin information may not be accurate or consistent with manufacturer information.” Buyer beware.

This article was originally published in the Science-Based Medicine Blog.

Dr. Hall is a contributing editor to both Skeptic magazine and the Skeptical Inquirer. She is a weekly contributor to the Science-Based Medicine Blog and is one of its editors. She has also contributed to Quackwatch and to a number of other respected journals and publications. She is the author of Women Aren’t Supposed to Fly: The Memoirs of a Female Flight Surgeon and co-author of the textbook, Consumer Health: A Guide to Intelligent Decisions.

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