Should I lick this?

Originally posted October 14, 2010.  A little weekend repost. –PalMD

When I lived in Northern California, I would often hear stories about people scouring the back country for psychedelic toads.  In popular imagination, these toad wranglers would then gather around bonfires and with great ceremony and earnestness, they would lick hapless bufoids until they (the humans) fell into ecstatic trances—and then vomited profusely. These stories, often parroted by local media, would end with the news that toad licking had finally been outlawed by the state.   The truth, as usual, is quite a bit more complicated.

Bufotenin, one of many molecules secreted by the skin and parotid glands of some toads of the genus Bufo, is classified by the DEA as a Schedule I drug.  This is the same class as heroin, mescaline, cannabis, and other drugs the DEA feels have a high potential for abuse and little or no therapeutic value.  Bufotenin is also present in certain mushrooms, so I wouldn’t swear that is was outlawed because of a pandemic of toad licking.

But many toads are toxic.  While there are few reports in the literature about poisoning due to toad licking, there are plenty of reports of accidental toad poisoning.  Toads are a food product in parts of Southeast Asia.  There have been many reports of accidental toad poisoning in rural Laos, especially when toad skin and toad eggs are part of a meal.

But there’s more than one way to get killed by a toad. A traditional Chinese herbal medicine called ch’an su *, which has been sold as an aphrodisiac, topical anesthetic, and a heart medicine, has been responsible for poisonings both in Asia and the U.S. (one of the versions sold in the U.S. was “marketed” as a topical medication, but was taken internally, perhaps for the hallucinogentic affects).  

Some of the chemicals present in toad venom are closely related to cardiac glycosides such as digoxin, a potent naturally-derived heart medication, and intoxication with toad venom closely resembles digoxin poisoning.  In fact, blood tests in victims are often positive for digoxin.  Given the similarities to digoxing poisoning, investigators have tried treating toad poisoning in a clever way. Digoxin (and toad) poisoning requires intensive medical care.  Even with close care, a patient can die of fatal heart arrhythmias.  But a couple of decades ago, an antidote was developed for digoxin poisoning.  Sheep are injected with digoxin and anti-digoxin antibodies are then isolated from their blood.  These antibodies are then chopped up so that only the “Fab” portion is present.  When given to a patient with digoxin toxicity, the Fab binds to circulating digoxin, preventing it from binding to other receptors in the body, and allowing it to be harmlessly excreted by the kidney.

Given how closely toad poisoning and digoxin poisoning resemble each other, and that toad toxins are similar enough to digoxin that they show up as digoxin in toxicology tests, it seems reasonable to think that the same antidote may work for both poisons.  This has been tested in several cases, with apparently good results (there data are limited by the small number of patients).

Cardiac glycoside poisoning is very dangerous.  It would appear that poisoning by sources other than regular medications has a high fatality rate.  Given this, it would seem reasonable to treat suspected toxicity with digoxin immune Fab.  The only catch is cost and availability.  If a kid in New York eats some Chinese toad venom, any hospital can administer the antidote.  If a woman in a small Laotian village eats a bad batch of toad soup, the cure may not be available.  The cost may also be prohibitive.  Each vial costs around $700, and it wouldn’t be unusual to give 10 vials.

It may be hard to prevent toad poisoning among rural Laotians without solving societal problems of poverty and hunger.  But in this country we can easily avoid consuming potentially deadly herbal remedies.

*(a special shout-out to my buddy David Kroll who may be interested in this bit of history, if he doesn’t already know it).

References

Kuo, H., Hsu, C., Chen, J., Wu, Y., & Shen, Y. (2009). Life-threatening episode after ingestion of toad eggs: a case report with literature review Case Reports, 2009 (may10 1) DOI: 10.1136/bcr.11.2008.1241

Keomany S, Mayxay M, Souvannasing P, Vilayhong C, Stuart BL, Srour L, & Newton PN (2007). Toad poisoning in Laos. The American journal of tropical medicine and hygiene, 77 (5), 850-3 PMID: 17984341

Roberts, B., Aronsohn, M., Moses, B., Burk, R., Toll, J., & Weeren, F. (2000). Bufo marinus intoxication in dogs: 94 cases (1997–1998) Journal of the American Veterinary Medical Association, 216 (12), 1941-1944 DOI: 10.2460/javma.2000.216.1941

Gowda, R. (2003). Toad venom poisoning: resemblance to digoxin toxicity and therapeutic implications Heart, 89 (4), 14-14 DOI: 10.1136/heart.89.4.e14

Chi, H., Hung, D., Hu, W., & Yang, D. (1998). Prognostic implications of hyperkalemia in toad toxin intoxication Human & Experimental Toxicology, 17 (6), 343-346 DOI: 10.1191/096032798678908800

Brubacher JR, Ravikumar PR, Bania T, Heller MB, & Hoffman RS (1996). Treatment of toad venom poisoning with digoxin-specific Fab fragments.Chest, 110 (5), 1282-8 PMID: 8915235

Brubacher, J. (1999). Efficacy of digoxin specific Fab fragments (Digibind®) in the treatment of toad venom poisoning Toxicon, 37 (6), 931-942 DOI:10.1016/S0041-0101(98)00224-

5 Comments

  1. “Should I lick this?”

    Pal, if you have to ask, the answer is probably no…

  2. Pal, this is an absolutely fascinating post! The reference in the 1929 JBC paper on Ch’an Su to John Jacob Abel’s 1912 JPET paper on the isolation of epinephrine was known to me but I had not remembered that he was working with toads (frogs and toads were common cardiovascular models and you may have even worked with frogs in medical school if you still had pharmacology lab).

    It’s fascinating that toads make this lovely concoction of hallucinogens and cardiac glycosides that are also found in the plant kingdom. Bufotenin is simply a serotonin analog, 5-hydroxydimethyltryptamine, that is also similar to the 4-hydroxy-DMT hallucinogenic mushroom compound psilocin and its phosphorylated relative, psilocybin. Similarly, the bufadienolide Na-K-ATPase inhibitors are, as you state, very closely related to the cardiac glycosides from foxglove, Digitalis purpurea & lanata. The conservation of these pathways through evolution speaks to the toxic efficiency of these relatively simple compounds.

    Since this whole comment is an aside, I’ll leave you with another one related to our shared concerns about alternative medicine: in 1997, a wholesale batch of plantain (the plant, not the tropical banana) used as an herbal laxative was found instead to be digitalis, apparently due to a central misidentification of the plant. The cardiac glycoside poisoning by these herbal products was published in NEJM in 1998 and represents a great detective story. Of note is the second author, Bill Obermeyer, the former FDA pharmacognocist and co-founder of ConsumerLab.com.

  3. Steve Parker, M.D.

     /  October 15, 2010

    Great post title.

    I live in the Sonoran desert. After a good summer rain, many large toads appear at night. It is said that ingestion or licking of these toads by dogs is toxic to them, causing odd behavior but usually not death.

    Haven’t heard reports of humans licking them, but I’m sure its been done.

    -Steve

  4. If you can use sheep to make an antitoxin, could you vaccinate people against toad toxin and have them make their own antibodies as a preventive measure? I mean, if exposure is frequent enough it might be worth it.

  5. Shirah

     /  February 17, 2012

    @Namnezia: Even if it was possible (I’m guessing not, without adding something antigenic to the digoxin to “flag” it to the immune system), it would be bad news if said population later needed digoxin.

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