What is cantharidin?

Cantharidin: A Blistering Agent with Therapeutic and Toxic Properties

Cantharidin is a potent vesicant (blistering agent) derived from blister beetles, particularly those of the Meloidae family, including the notorious "Spanish fly." Cantharidin is primarily used in dermatology as a topical treatment for warts and molluscum contagiosum, but it is highly toxic when ingested and lacks FDA approval for systemic use due to its dangerous side effects. 1, 2

Mechanism of Action

Cantharidin works through a specific cellular mechanism:

• Triggers acantholysis (cell separation) by targeting desmosomal dense plaques
• Causes detachment of desmosomes from tonofilaments
• Creates controlled blistering of the skin when applied topically
• Functions as both a vesicant and keratolytic agent 2

Clinical Applications in Dermatology

Available Formulations

• Canthacur (0.7% cantharidin) - for common warts, periungual warts, and molluscum contagiosum
• Canthacur PS (1% cantharidin, 30% salicylic acid, 2% podophyllotoxin) - specifically for plantar warts 2
• Also available in combination with podophyllum resin and salicylic acid (1%/5%/30%) 3

Treatment Efficacy

• For warts (verruca vulgaris):

  • Shown to be effective in treating plane facial warts with complete clearance in all patients within 16 weeks with 1-4 treatments 1
  • Recently, cantharidin combined with podophyllotoxin-salicylic acid has demonstrated effectiveness in adults 1

• For molluscum contagiosum:

  • Observational studies indicate effectiveness
  • In one small randomized controlled trial, improvement was greater than placebo but not statistically significant 1

Application Technique

When used for dermatologic conditions:

• Applied directly to lesions by medical professionals
• Painless during application
• Creates controlled blistering within 24 hours after application
• The superficial nature of injury reduces scarring risk 1
• Advantages include painless application with discomfort developing only when blistering occurs in the 24 hours following application 1

Toxicity and Safety Concerns

Systemic Toxicity

Cantharidin is highly toxic when ingested and can cause:

• Severe gastrointestinal mucosal irritation and hemorrhage
• Genitourinary tract damage with hematuria and dysuria
• Acute kidney injury
• Electrolyte disturbances (hypocalcemia, hypomagnesemia)
• Myocardial damage (in animals)
• Neurological symptoms in severe cases 4, 5, 6

Historical Misuse

• Traditionally misused as an aphrodisiac ("Spanish fly")
• Previously used as an abortifacient
• Ingestion can be potentially fatal 4, 7

Treatment of Cantharidin Poisoning

• No specific antidote exists
• Treatment is primarily supportive:
  • Intravenous fluid therapy
  • Electrolyte replacement
  • Pain management
  • Gastroprotectants if ingested 5, 6

Important Precautions in Clinical Use

• Not FDA approved despite clinical use in dermatology
• Should only be applied by healthcare professionals
• Must never be prescribed for oral consumption
• Contraindicated during pregnancy due to potential teratogenic effects
• Should be used with caution on sensitive areas or large surface areas
• Potential side effects include pain, blistering, and rarely, scarring 1, 2

Historical and Cultural Context

Cantharidin has been used in various cultures throughout history:

• As a component in traditional medicines
• Misused as an aphrodisiac in various cultures
• Used in South American civilizations for various therapeutic treatments 7

The controlled medical use of cantharidin as a topical agent represents a significant departure from its historical misuse, harnessing its vesicant properties while minimizing its toxic potential.