Science connections: A neurotoxic natural product raised from the dead

From TV shows and movies to books and even video games, zombies have become a standard fixture in pop culture over the past few years. With Halloween right around the corner, zombies are once again, top of mind, begging the question—do the undead really walk among us? More than 30 years ago, Wade Davis, an ethnobotanist and anthropologist, asked the same question, traveling to Haiti to uncover the mystery behind zombies.

Zombies have long been a part of the voodoo religion that originated in Africa and emigrated to Haiti with the slave trade. Throughout history, many Haitians reported they had seen zombies, or in some cases, that they were themselves, zombies. There was a particularly compelling report of a man in Haiti —Clairvius Narcisse—who was documented as dead by multiple sources, but years later, returned alive and well. While the usual assumption is that zombies are folklore, stories like that of Narcisse prompted Davis to investigate.

After tireless research and much analysis of 'zombie potions' he had procured from voodoo practitioners on the island, Davis found his answer. He claimed that the potions included tetrodotoxin (TTX; CAS Registry Number^® 4368-28-9), a potent neurotoxin found in the flesh of pufferfish. In his 1983 article published in the Journal of Ethnopharmacology, Davis wrote that TTX was "fully capable of pharmacologically inducing the zombi [sic] state."

The path from folklore to medicine

Although Davis' research of 'zombie potion' has since been discredited, it may have reignited interest in TTX for potential applications in modern medicine. As a powerful blocker of voltage-gated sodium channels, TTX causes "rapid weakening and paralysis of muscles, including those of the respiratory tract, which can lead to respiratory arrest and death" when consumed. However, at sub-toxic doses, TTX has shown promise in the areas of pain management and anesthesia. In 1913, Japanese researcher Dr. Yoshizumi Tahara was granted a U.S. patent for his process of extracting and purification of TTX from the ovary and liver of pufferfish. According to the patent:

One result of the said invention, is to render possible the use of a very small amount of toxin, by physicians, for the purpose of curing and healing certain diseases with utmost safety and with satisfactory results.

Tahara's invention was briefly used to treat symptoms related to leprosy, tetanus and rheumatoid arthritis. However, it was not until the early 1960s, when studies revealed the chemical structure and sodium channel-blocking activity of TTX, that research into its use in medicine gained momentum.

Today, TTX continues to show promise in pre-clinical and clinical studies as a treatment for inflammatory, neuropathic and other types of pain. In 2007, the Canadian Tetrodotoxin Study Group published their findings on the treatment of severe pain in cancer patients, describing how TTX "effectively relieved severe, treatment-resistant cancer pain in the majority of patients and often for prolonged periods after treatment." In addition, a recent clinical study from researchers in China suggested a new medical use for TTX in patients with opioid addiction. According to the authors, their double-blind, placebo-controlled study of 216 heroin addicts showed that TTX "is effective in alleviating opiate withdrawal symptoms with few side‐effects."

Enabling re-discovery of long-forgotten natural products

With hundreds of scientists and analysts reviewing the scientific literature every day, CAS is uniquely positioned to find meaningful insights from historical research that can fuel modern scientific breakthroughs. In fact, our team of experts has identified and analyzed thousands of journal articles and patents related to the discovery, activity and use of TTX, all of which can be accessed through our world-class technology, like SciFinderⁿ, to help your researchers uncover new connections and applications. 

This commitment to converging human expertise with advanced technology is critical. It ensures no study or data point goes unturned—because you never know what insight could drive your next big breakthrough. Want to leverage expert insight and advanced technology to fuel your business? Learn how CAS can help.