Dragon Boat Festival Column — The Deadly Little Toxicologist: Toads

Since ancient times, the Dragon Boat Festival has been an important part of Chinese culture. In traditional belief, this was the day when the "Five Poisons" were most active, and people took various measures to drive away these dangerous creatures. The Five Poisons include animals familiar to almost everyone: snakes, geckos, scorpions, centipedes, and toads. This article introduces one member of this notorious group—the toad—and explores the nature of its toxins.

Figure 1. The largest toad species in Taiwan, Bufo bankorensis（Image source：Evan Pickett， CC BY-SA 4.0 ）

Figure 2. Bufo melanostictus, the second toad species found in Taiwan（Image source：Lokionly， CC BY-SA 3.0 ）

Most people have encountered toads in parks or agricultural fields. Compared with animals such as snakes, centipedes, or scorpions, which are capable of active attacks, toads appear relatively harmless. Beneath this unassuming appearance, however, lies a highly sophisticated chemical defense system. Unlike predators that rely on venom to capture prey, toads primarily use toxins for self-defense and lack specialized structures such as venomous fangs. Their toxins are distributed mainly within the skin and in the parotoid glands located behind the ears, where the compounds are synthesized. The size of these glands varies among species, and the degree of gland development is generally correlated with the strength of toxicity. For example, the well-known cane toad (Bufo marinus) is famous for its large parotoid glands and powerful toxins.

Because of these potent secretions, humans recognized the dangers of toad venom long ago. In the Western world, toads were often feared and despised, frequently appearing in folklore as ingredients in witchcraft and magical potions. In East Asian traditions, the attitude toward toads has been more complex. In Chinese and Japanese folklore they are sometimes regarded as mysterious creatures possessing powerful forces, and their toxins have been considered both poisonous and medicinal. Although cultural interpretations differ between East and West, a certain degree of consensus exists regarding their pharmacological potential.

Figure 3. Traditional wealth-attracting toad statue（Image source：miheco， CC BY-SA 2.0 ）

Indeed, toad toxins possess genuine medicinal possibilities. In traditional Chinese medicine, products prepared from toad venom are known as Chan Su. Classical texts describe it as pungent and warm in nature with mild toxicity and an affinity for the heart meridian. Clinically, Chan Su can induce symptoms such as accelerated heartbeat, sweating, nausea, and hallucinations, and in high doses it may become lethal. The major components include bufalin and bufotenin (5-hydroxy-N,N-dimethyltryptamine, abbreviated 5-HO-DMT).

Bufalin is a steroid compound structurally similar to digoxin, a cardiac glycoside extracted from foxglove and used in the treatment of heart disease. It inhibits the Na+/K+ ATPase pump, causing intracellular sodium levels to rise. This disturbance subsequently affects the sodium-calcium exchanger, leading to an accumulation of calcium ions within cardiac muscle cells. The result is rapid and forceful contraction of the myocardium. Clinical manifestations may include increased heart rate, gastrointestinal discomfort, and neurological damage.

Figure 4. Structural formula of bufalin, Courtesy of Ed (Edgar181)

Figure 5. Structural formula of digoxin, Courtesy of Mrgreen71

Bufotenin, in contrast, is structurally similar to serotonin and can interfere with serotonin receptors (5-HT receptors) in the human body. These receptors are widely distributed throughout the nervous system, including the brain and gastrointestinal tract, where they regulate emotional states such as calmness and well-being. When bufotenin interacts with these neural pathways, it disrupts normal serotonin signaling, leading to symptoms such as anxiety, panic, hallucinations, and digestive disturbances. Because of these psychoactive properties, bufotenin has occasionally been misused as a recreational substance. In 2022, a bizarre trend in the United States involved people licking Colorado River toads in an attempt to experience hallucinogenic effects, prompting the National Park Service to strictly prohibit such behavior.

Figure 6. Structural formula of bufotenin, Courtesy of Fuse809

Figure 7. Structural formula of serotonin, Courtesy of CYL

The chemical arsenal of toads extends far beyond these two compounds. Chan Su contains a complex mixture of substances, including bufotalin, bufagins, 5-methoxy-dimethyltryptamine (5-MeO-DMT), and bufothionine, among many other organic molecules. These compounds serve an ecological purpose by helping toads deter predators, yet they also hold importance in the medical field. Bufalin, for instance, has been investigated as a cardiotonic agent, while bufotenin and related compounds have drawn attention for their potential roles in psychopharmacology when used under controlled conditions.

If you happen to encounter a toad during the Dragon Boat Festival, pause for a moment and appreciate how such a small creature carries within it a formidable collection of chemical defenses capable of discouraging predators. And when the deep croaking of a toad echoes through the night, it is almost as if it is declaring:

"Do not underestimate me—I am nature's master chemist."

Author: Rodrigo

References:

1. Okada, Masahiro; Suga, Toshiro; et al. （1960). Pharmacology of the priniciples isolated from Senso (Ch'an Su) the dried venom of the Chinese toad (IV). Asian Medical Journal. 3 (4): 155–160

2. Blough BE, Landavazo A, Decker AM, Partilla JS, Baumann MH, Rothman RB (October 2014). "Interaction of psychoactive tryptamines with biogenic amine transporters and serotonin receptor subtypes". Psychopharmacology. 231 (21): 4135–4144.