Cantharidin is classified as an extremely hazardous substance in the United States, and is subject to strict reporting requirements by facilities that produce, store, or use it in significant quantities.

[6] However, feeding studies indicate that the biosynthetic process is more complicated, and not a simple product of geranyl pyrophosphate or related ten-carbon parent structure, as the seeming monoterpene nature would suggest.

[9] Preparations made from blister beetles (particularly "Spanish fly") have been used since ancient times as an aphrodisiac, possibly because their physical effects were perceived to mimic those of sexual arousal,[10] and because they can cause prolonged erection or priapism in men.

Examples of such use found in historical sources include: Cantharidin was first isolated as a chemically pure substance in 1810 by Pierre Robiquet,[23] a French chemist then living in Paris.

[30] Great bustards, a strongly polygynous bird species,[31] are not immune to the toxicity of cantharidin; they become intoxicated after ingesting blister beetles.

[32][33] Great bustards may eat toxic blister beetles of the genus Meloe to increase the sexual arousal of males.

[34] As a blister agent, cantharidin has the potential to cause adverse effects when used medically; for this reason, it has been included in a list of "problem drugs" used by dermatologists and emergency personnel.

[35] Topical cantharidin is absorbed by the lipid membranes of epidermal cells, causing the release of serine proteases, enzymes that break the peptide bonds in proteins.

This causes the disintegration of desmosomal plaques, cellular structures involved in cell-to-cell adhesion, leading to detachment of the tonofilaments that hold cells together.

[45] The efficacy of cantharidin was formally established for the treatment of molluscum in patients 2 years and older in two double-blind, randomized, placebo-controlled trials.