In recent years, public attention has been focused on the presence of Fentanyl-laced cocaine. It has overshadowed another new threat just as heinous yet relatively unknown – that of levamisole. Since the turn of the century, the use of levamisole has grown as a “filler” to cut or increase the amount of cocaine sold. Other than for veterinary use, this compound has been largely abandoned by human medicine due to its toxicity, especially that of necrotic vasculitis. With constant use of this adulterated cocaine, levamisole will portend a most lurid form of chemical vivisection. The only good diagnostic test is a physical examination; the only cure is stopping the drug abuse.
For the past half-century, levamisole has served the veterinary community well as an anti-helminthic and also (temporarily) in medical practices as a treatment for a variety of diseases. Since the 1960s, levamisole has killed parasitic worms in cattle, sheep, goats, pigs, and poultry. While good for ranchers, it has also served urban dwellers as a deworming agent for their dogs and cats. It is an Imidazothiazole that targets the roundworm nervous system, causing it to be paralyzed and die. While good for your animals, it has also been used in medicine to treat rheumatoid arthritis, Crohn’s disease, nephrotic syndrome, leprosy, lichen planus, collagen vascular disease, and warts. In oncology, it had been used with 5-fluorouracil for the adjuvant treatment of colon cancer. In the 21st century, its medical uses have been discontinued, in large part due to its toxicities of neutropenia/agranulocytosis and vasculitis.
Because of its chemical properties, levamisole had procured an additional use in illegal narcotics. The compound has the same physical parameters as cocaine, making it easy to bulk the cocaine with this drug, thereby increasing their profits. The math is simple: one portion of levamisole plus one portion of cocaine equals two portions of adulterated cocaine. Levamisole is readily available to both urbanites and ranchers alike. Prior to 2008, less than 10 percent of cocaine seized tested positive for levamisole; since that time, as much as 90 percent is positive. Levamisole also reportedly enhances the “high” obtained by causing the release of dopamine within the brain. With the emergence of an enhanced, adulterated product and increased profit, little is mentioned by way of the toxicity to the user. In the end, the addict pays a higher cost for this type of cocaine, particularly in terms of their health.
The initial signs and symptoms of levamisole toxicity are nonspecific and involve night sweats, fevers, weight loss, rhinorrhea, fatigue, and arthralgias. A purpuric rash appears with skin necrosis and infectious sequelae (e.g., oral) can occur. The foremost and most grotesque toxicity of levamisole-tainted cocaine is due to its vasculitis. Levamisole causes a leukocytoclastic vasculitis of small blood vessels, leading to thrombosis of small vessels, particularly among the superficial and deep dermal vasculature. This, in turn, causes a purpuric rash, later ulceration, gangrene, and finally autoamputation of smaller appendages. Almost all patients develop retiform purpura about the body. These are tender purple papules with an irregular border. In the torso, these can progress to significant ulcerative craters. Among the other injuries, approximately three-quarters of patients progress to necrosis of the ear(s) and nose; half develop nephritis, and about one in five develop genital necrosis (e.g., penile/scrotal gangrene). Secondarily, about a third of patients will show some degree of neutropenia that leads to infectious complications. These can present as nasopharyngeal ulcers, thrush, pharyngitis, or odynophagia. While cocaine itself can cause cerebral ischemia, strokes, and acute demyelinating encephalitis, levamisole accentuates the number and intensity of this damage. The additive adds to the profit, but the disfigurement is permanent and painful.
Laboratory evaluation for levamisole-adulterated cocaine is difficult at best. Urine levamisole can be detected by gas chromatography/mass spectrometry, but this is not available to many hospitals. Under these circumstances, a clinical exam and a toxicology screen positive for cocaine may provide the only diagnostic hint. Besides neutropenia, other findings include anti-neutrophil cytoplasmic antibody (ANCA), antinuclear antibody (ANA), anti-double-stranded DNA (dsDNA), anti-human neutrophil elastase (HNE), and anti-myeloperoxidase antibodies. Despite the presence of these autoantibodies, no one confirmatory test exists for this malady.
The treatment for levamisole-adulterated cocaine is primarily supportive. There is no antidote for levamisole. The retiform purpura resolves within 2-3 weeks after drug cessation. However, symptoms will quickly recur if abuse is renewed. Patients with deep ulcerations may benefit from grafting. Steroids are of dubious help. GM-CSF can help temporarily with the neutropenia. The white cell count will normalize within 2 weeks, on its own, after the tainted cocaine is stopped. The essence of treatment is the cessation of tainted cocaine use. The detritus from this toxicity will eventually clear, but the scars from its use can persist forever.
Though overshadowed by the attention given to Fentanyl, levamisole use in cocaine has been steadily rising over recent years. For those affected, the disfigurement, to the body and soul, can be permanent. Acumen and suspicion are essentially the only tools guiding the practitioner to the proper diagnosis. Drug cessation offers the only “cure.” Levamisole is plentiful in quantity due to veterinary medicine. Levamisole that is good for your dog is bad for your cocaine.
Robert Killeen is a hematologist.
