Levamisole in cocaine: Unexpected news from an old acquaintance
Bibliographic record
Abstract
Levamisole is a pharmaceutical with anthelminthic and immunomodulatory properties that was previously used in both animals and humans to treat inflammatory conditions and cancer. Levamisole has been identified as a cocaine adulterant in the United States since 2003. By 2009, the United States Drug Enforcement Administration (DEA) estimated that 69% of the cocaine seized contained levamisole. The first case reports of complications related to levamisole in cocaine users were published in 2009. The objectives of this article are to review the literature regarding the full spectrum of possible complications related to levamisole use for medical purposes, to review the current scope of levamisole-induced complications in cocaine users and to discuss the pharmacological properties that might explain the motivation behind the large-scale adulteration of cocaine with levamisole. Literature review revealed that significant complications were quickly reported when levamisole was used in inflammatory conditions. By 1976, several cases of leukopenia and agranulocytosis were reported. Recurrence with re-exposure was well described and agranulocytosis spontaneously reversed upon discontinuation of therapy. Vasculitis secondary to levamisole treatment was first reported in 1978 and mostly manifests as leukocytoclastic vasculitis, cutaneous necrotising vasculitis and thrombotic vasculopathy without vasculitis. These findings typically, but not invariably, involve the ear lobes. Discontinuation of levamisole therapy was again a critical part of the treatment. Various neurological side effects were described with levamisole therapy, the most concerning complication being multifocal inflammatory leukoencephalopathy (MIL). Literature review identified 203 unique cases of complications in cocaine users that can be attributed to levamisole adulteration. The two principal complications reported are haematological (140 cases of neutropenia) and dermatological (84 cases). Even though these complications can occur in isolation, many cases displayed both simultaneously. No formal case of leukoencephalopathy in the setting of cocaine use has been reported so far. A striking phenomenon is the apparent high level of recurrence (27.1%) of symptoms in cocaine users after re-exposure to cocaine that is presumably adulterated. The importance of accurately identifying levamisole-induced complications is therefore critical for symptomatic patients as discontinuation of exposure is fundamental and as a correct diagnosis prevents unnecessary and potentially dangerous use of other treatment modalities like powerful immunosuppressive therapy. Literature review suggests that levamisole might have the advantages of enhancing noradrenergic neurotransmission by inhibiting reuptake, by inhibiting MAO and/or COMT, by acting on ganglionic nicotinic receptors and by being partially metabolized into an amphetamine-like compound. It could also increase endogenous opioids and increase dopamine concentration in the cerebral reward pathway. These potential effects make levamisole an interesting choice as a cocaine adulterant. It seems unlikely that levamisole use as a cocaine adulterant will soon reach an end. More information is needed about the diagnosis and treatment of levamisole-induced complications, and the efforts of the medical and public health community is needed to face this challenging problem.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.002 | 0.006 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.001 | 0.002 |
| Scholarly communication | 0.002 | 0.006 |
| Open science | 0.001 | 0.001 |
| Research integrity | 0.006 | 0.012 |
| Insufficient payload (model declined to judge) | 0.002 | 0.002 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".