A Drug with a Complex History
Levamisole was first developed in the mid-1960s by Janssen Pharmaceuticals as an effective and broad-spectrum anthelmintic, or anti-worm medication. Its effectiveness against roundworms led to its use for both humans and livestock to treat parasitic infestations such as ascariasis and hookworm infections. Following this, its immunomodulatory properties were discovered in the early 1970s, leading to new applications in human medicine.
For a time, it was used to treat conditions including rheumatoid arthritis and as an adjuvant therapy for certain cancers, most notably in combination with fluorouracil for resected Dukes' stage C colon cancer. However, the use of levamisole in human medicine was ultimately restricted and later withdrawn in many countries, including the United States, by 2000 due to its association with severe adverse effects. Today, while no longer approved for human use in the U.S., it remains an important medication in veterinary medicine for treating parasitic infections in animals like cattle, sheep, and pigs.
What Makes Levamisole a Multi-Purpose Drug?
Levamisole's different applications stem from its distinct mechanisms of action on different biological systems.
As an Anthelmintic
As an anthelmintic, levamisole targets the nervous system of parasitic worms. Its mechanism of action is based on its agonist activity toward the L-subtype nicotinic acetylcholine receptors in nematode muscles. This binding leads to a continuous stimulation of the worm's muscles, which results in spastic paralysis. The incapacitated worm is then expelled from the host's body through normal intestinal peristalsis. In the aquatic community, it is notably used to treat Camallanus roundworm infestations in fish.
As an Immunomodulator
Levamisole’s immunomodulatory effects are complex and not fully understood, but it generally acts to restore depressed immune function rather than simply boosting it. It affects both the humoral and cellular parts of the immune system by performing the following actions:
- Enhancing T-cell responses by stimulating their activation and proliferation.
- Potentiating the functions of monocytes and macrophages, including phagocytosis and chemotaxis.
- Increasing antibody formation against various antigens.
- Improving neutrophil mobility and adherence.
This restorative effect on immune function was the basis for its past use in autoimmune disorders and as a cancer therapy adjuvant.
Levamisole as a Dangerous Illicit Drug Adulterant
Since the early 2000s, levamisole has gained notoriety for its use as a cutting agent, or adulterant, in illicit street drugs. It is most commonly found in cocaine, but has also been detected in heroin and fentanyl. Its use as an adulterant is driven by several factors:
- Bulking Agent: It is readily available and inexpensive, allowing dealers to increase the bulk and weight of cocaine to improve profit margins.
- Appearance: Its powdered form looks very similar to cocaine.
- Street Purity Tests: It does not interfere with common street-level colorimetric tests for cocaine.
- Perceived Synergistic Effects: Some believe that levamisole's pharmacological properties, possibly through its effects on adrenergic and cholinergic systems, create a perceived enhancement or prolongation of the cocaine-induced euphoria.
The presence of this toxic substance in street drugs is a significant public health concern, with serious and sometimes fatal consequences for users.
Comparison of Levamisole's Uses and Risks
| Feature | Past/Current (Medical) | Past/Current (Veterinary) | Illicit (Adulterant) |
|---|---|---|---|
| Purpose | Anthelmintic and immunomodulatory agent for diseases like colon cancer and rheumatoid arthritis. | Anthelmintic for treating parasitic worm infections in livestock and fish. | Increases bulk and weight of illicit drugs (mainly cocaine), potentially enhancing or prolonging effects. |
| Status in US | Withdrawn for human use since 2000 due to severe side effects. | Approved and legally used for animals. | Uncontrolled substance, illegally added to street drugs. |
| Dose | Prescribed therapeutic doses (e.g., 50-150mg for anthelmintic use). | Veterinarian-approved doses based on animal's weight. | Highly variable and unpredictable in concentration; user is unknowingly exposed. |
| Main Risks | Agranulocytosis, bone marrow depression, flu-like symptoms. | Minimal side effects at correct doses, but resistance is a concern in some areas. | Severe agranulocytosis, neutropenia, widespread vasculitis, skin necrosis, death. |
The Toxic Effects of Levamisole Exposure
Exposure to levamisole, particularly through adulterated illicit drugs, poses severe health risks. Unlike therapeutic use where doctors monitor for adverse effects, exposure via street drugs is uncontrolled and dangerous.
Agranulocytosis
One of the most dangerous side effects of levamisole is agranulocytosis, a severe and potentially fatal condition characterized by a critically low count of certain white blood cells (granulocytes), particularly neutrophils. Without these immune cells, the body loses its primary defense against bacterial infections, leaving the individual highly vulnerable to life-threatening sepsis. This risk was the main reason for its removal from human therapeutic use.
Vasculitis and Skin Necrosis
Levamisole is well-known to cause vasculitis, an inflammation of the blood vessels. This condition can lead to thrombotic vasculopathy, where blood clots block small blood vessels, resulting in painful and distinctive purpura (purple-colored skin rashes), ulcers, and tissue necrosis (tissue death). These lesions often appear on the earlobes, face, and limbs. In severe cases, the necrosis can be extensive, requiring reconstructive surgery or leading to amputation.
Other Toxic Effects
Additional toxic effects associated with levamisole exposure include:
- Neurological Complications: Leukoencephalopathy (white matter damage in the brain), confusion, seizures, and speech disturbances.
- Systemic Effects: Liver damage, renal failure, and flu-like symptoms.
- Increased Risk of Infection: The compromised immune system makes individuals more susceptible to various infections.
For more in-depth information, the Center for Forensic Science Research & Education has published alerts on this topic, detailing the risks of levamisole adulteration.
Conclusion
What kind of drug is levamisole? It is a drug with a dual history: a therapeutic agent for parasites and immune disorders, and a potent source of harm when misused. While it remains a useful and controlled medication in veterinary medicine, its legacy in human health is marked by dangerous side effects that led to its withdrawal. The subsequent rise of levamisole as a toxic adulterant in the illicit drug supply has created a serious and ongoing public health crisis, exposing unaware users to life-threatening risks like agranulocytosis and vasculitis. It serves as a potent reminder of the unseen dangers associated with contaminated street drugs and the importance of public and medical awareness.
