Ivermectin

In brief

What ivermectin is

Ivermectin is a drug made by changing a molecule a bacterium already makes. The natural products are the avermectins, found in a single soil isolate of an actinomycete named Streptomyces avermitilis, and described in 1979 as a family of macrocyclic lactones with no useful antibacterial or antifungal activity but extraordinary activity against worms ⁶. Chemists at Merck then hydrogenated one double bond of avermectin B1 — adding two hydrogen atoms across the carbons numbered 22 and 23 — and the product was ivermectin ⁸. Its exact chemical name, as the researchers who cloned its target wrote it, is 22,23-dihydroavermectin B1a ¹. The commercial material is not one compound but a mixture: at least 80% B1a and at most 20% B1b, which differs in one side chain ^2,7.

It is given by mouth, usually once, at 150 to 200 micrograms per kilogram of body weight — for a 70-kilogram adult, around 10 to 14 milligrams ^12,13. It is used against onchocerciasis, the blackfly-borne worm disease that causes river blindness; against lymphatic filariasis, the worm disease that causes grossly swollen limbs; against strongyloidiasis, a threadworm infection of the gut that can turn lethal in people whose immune systems are suppressed; and against scabies, the burrowing skin mite ^17,37,38. More than 5.9 billion doses had been distributed through global programs by 2025 ¹⁹.

What it does not do is kill adult worms. In onchocerciasis it clears the microfilariae — the microscopic larvae circulating in skin that both cause the damage and carry the infection onward — while the adult females live on inside nodules and resume producing larvae, which is why treatment has to be repeated for years ^12,39. In lymphatic filariasis it is given with other drugs rather than alone, and a single dose of the combination kept larvae out of the blood for three years in 96% of the people treated ⁴⁰. Understanding that distinction matters for everything that follows: ivermectin is extremely good at suppressing one stage of one kind of organism, at a dose that is tiny by the standards of most drugs.

The structure, part by part

Start with the ring. A lactone is an ester — the bond you get when an acid group and an alcohol group join and release water, the same bond that holds a fat together — formed inside a single molecule so that the chain closes on itself. A macrocycle is any ring of twelve atoms or more. Ivermectin's ring has sixteen, which is why the avermectins and their cousins the milbemycins are classed together as the sixteen-membered macrocyclic lactones ^3,50. Two of the other ring systems — the hexahydrobenzofuran at one end, and one ring of the spiroketal at the other — are fused into that ring, sharing atoms with it; only the two-sugar tail at carbon 13 and a small side chain at carbon 25 truly hang off it.

The ring is built by a bacterial assembly line, a polyketide synthase. The gene cluster in S. avermitilis contains four enormous proteins organized as twelve modules with 55 active sites between them, each module adding two carbons to a growing chain before the chain is folded and closed — described in 1999 as the most complex multifunctional enzyme system then known ⁵¹. A cytochrome P450 enzyme — one of a family of enzymes that add oxygen to molecules — then probably closes a five-membered oxygen-containing ring, the furan, across the carbons numbered 6 and 8a, producing the fused double-ring unit chemists call the hexahydrobenzofuran ⁵¹. A separate cluster of nine genes, eight of them functional, makes an unusual sugar, oleandrose, and attaches two of them end to end onto the ring ⁵¹.

Three features give the molecule its shape and its behavior. The spiroketal is a pair of rings that share exactly one carbon atom — a carbon bonded to one oxygen in each ring — so they sit almost at right angles like two keyrings pinched at a single point; it makes that end of the molecule rigid. The hexahydrobenzofuran carries a hydroxyl group at carbon 5 which, judging from a comparison with selamectin, which carries a different group there, is needed for full efficacy at the glycine receptor, a chloride channel of vertebrate nerve cells used in the laboratory to study how the drug binds ⁵². The disaccharide — two oleandrose sugars joined end to end — is the tail, and it does different work in different places. At the glycine receptor, contacts between the sugar tail and the M2–M3 loop proved unimportant for ivermectin sensitivity ⁵², while docking against the worm's own efflux pump predicts that the sugars are what give the sugar-bearing avermectins their extra affinity over the sugar-free relatives, and places the benzofuran and the spiroketal in their own distinct pockets ⁵³.

Now the differences that matter. Avermectin B1a is the natural product; ivermectin B1a is the same molecule with two hydrogen atoms added across the 22,23 double bond, made industrially by hydrogenating avermectin B1 over a rhodium catalyst, which is why ivermectin costs more than the fermentation product it comes from ^7,8. Abamectin, used as a crop insecticide, is the natural avermectin B1 material, predominantly B1a, before hydrogenation ^1,7. The milbemycins are a parallel family from a different organism: they carry the same sixteen-membered ring, but where the avermectins have their two sugars, at the carbon numbered 13, the milbemycins have nothing but a hydrogen ⁴. Moxidectin belongs to that family but is not itself a fermentation product: it is made by chemically modifying nemadectin, a milbemycin produced by Streptomyces cyaneogriseus, adding a methoxime group at carbon 23 ^4,54. Those small differences change the pharmacology substantially, and in the clinic they change the dose, the duration and the safety margin.

One date in the literature does not hold up. A widely cited 2018 review states that the avermectins were discovered in 1967 ⁵⁰; the first full description of the producing organism was published in 1979 ⁶, and the discoverers' own account places the discovery in the late 1970s ¹⁷, with the isolation described first hand in the Nobel lecture ⁵⁵. Where a review and the primary papers disagree, the primary papers win.

The whole history, including the reversals

The history divides cleanly into two halves. For forty years ivermectin was a quiet, enormous success: first a veterinary drug, in commercial use against the parasites of cattle, horses and sheep by 1983 ⁵⁸, then, from 1987, a human medicine given away free, which transformed the treatment of two of what its discoverers called the world's most devastating and disfiguring diseases and was recognized with a Nobel Prize ^17,18,22. Then in 2020 it was taken up worldwide for a disease it does not treat, and the collapse of that claim — across randomized trials, a retracted meta-analysis and a withdrawn database study — took three years ^59,60,61,62.

The second half did not end when COVID-19 did. The same arguments, the same kinds of evidence and at least one of the same authors moved to cancer: Peter McCullough, a coauthor of a retracted case series of ivermectin-based multidrug therapy in COVID-19 ⁶³, is a senior author of the telemedicine company cohort that reported an 84.4% clinical benefit rate; that paper is now flagged as retracted in PubMed and is the subject of a continuing editorial review ^20,21,64. Meanwhile the original use went on quietly succeeding: Colombia was verified free of river blindness in 2013, three more countries in the Americas followed, and Niger became the first country in Africa to eliminate transmission, a success dated to 2024 and documented in detail in 2026 ^23,24,25.

How it works, and why it spares us

In a worm, ivermectin opens glutamate-gated chloride channels. These are pores in nerve and muscle membranes that open when the signaling molecule glutamate binds, letting negatively charged chloride ions through; vertebrates do not have this particular channel. When ivermectin holds them open, chloride floods in, the inside of the cell becomes more negative than it should be — hyperpolarized — and the cell can no longer fire or contract. The worm is paralyzed, limply, and its pharynx stops pumping ^1,3. The crystal structure, solved in 2011, shows the drug bound not at the glutamate site but in the membrane-spanning part of the channel, acting as a wedge that stabilizes the open pore ⁹. In C. elegans, different channel subunits matter for ivermectin and for moxidectin, which is part of why the two drugs do not produce identical effects ³.

The sparing of vertebrates is the interesting half, because it is two mechanisms rather than one. The first is the missing channel. The second is a pump. P-glycoprotein, encoded by the gene called MDR1 or ABCB1, sits in the membranes of the cells lining the brain's blood vessels and throws foreign chemicals back into the blood; macrocyclic lactones are fat-loving molecules and good substrates for it ^11,56. Take the pump away and the protection goes with it: mice lacking one pump gene are a hundred times more sensitive to ivermectin ¹⁰, and in mice lacking two, the subcutaneous dose that kills half the animals is 0.46 micromoles per kilogram for ivermectin against 2.3 for moxidectin ⁴¹.

What the drug does once it is inside a vertebrate brain is act on the GABA-A receptor — GABA is gamma-aminobutyric acid, the brain's main calming signal — the main calming receptor of the vertebrate nervous system and the one alcohol, benzodiazepines and general anesthetics work on. In brain membranes the parent avermectin enhances benzodiazepine binding with half-maximal effect at 40 nanomolar, halves high-affinity GABA binding, and more than doubles antagonist binding — effects the authors concluded require a separate site of its own on the receptor complex ³¹. In rat receptors expressed in frog eggs, ivermectin potentiates the GABA response to 414% of control against moxidectin's 257% ⁴¹. In rats given 1 milligram per kilogram — five times the human antiparasitic dose — the behavioral profile is that of an anxiety-reducing, sedating drug with GABA-like properties ².

The collie story is the clinical face of this. A subpopulation of collies is extremely sensitive to the drug, poisoned by doses that other dogs tolerate; in 2001 the cause was found to be a four-base-pair deletion in the canine mdr1 gene that shifts the reading frame and stops P-glycoprotein being made. Dogs with two copies of the deletion show the toxic phenotype; dogs with one copy do not ³². The test does not catch every case: of 28 dogs of other breeds that developed neurotoxicity during daily high-dose treatment for mange, 27 carried no copy of the deletion at all, and the authors pointed instead to other pump-blocking drugs taken alongside, excessive doses and uncharacterized variants ³³. The human equivalent has been reported: serious ivermectin toxicity in people carrying nonsense mutations in ABCB1, in a family treated for scabies ³⁴. The warning generalizes beyond genetics, because the pump can also be blocked by other drugs or foods, which would produce the same vulnerability without any inherited variant ¹¹.

Two further receptor actions matter for the cancer claims. Ivermectin is a positive allosteric modulator of the ATP-gated channel P2X4 — ATP, adenosine triphosphate, is the cell's energy molecule, which doubles as a signal outside cells — it does not open the channel itself, but turns up the response when ATP binds — and that property has been used as a laboratory tool to distinguish P2X4 from its relative P2X7. That use rests on a selectivity that turns out to be species-specific: ivermectin potently enhances the human P2X7 receptor while being poorly effective on the rat and mouse versions ⁴⁹. And it is both substrate and inhibitor of P-glycoprotein, which is where cancer pharmacology first noticed it: in resistant leukemia lines it restored retention of expelled drugs nearly as well as the reference blocker in a human line, and a few fold less well in a mouse line ⁴⁵.

What a dose actually achieves

This section is the hinge of the whole page, so the numbers are given exactly as their sources give them. After a single oral dose of 150 micrograms per kilogram in 25 patients with onchocerciasis, the peak plasma concentration was 52.0 nanograms per milliliter, reached at 5.2 hours, with an elimination half-life of 35.0 hours; 14 healthy volunteers showed a similar profile ¹⁴. In nine patients given a mean dose of 11.11 milligrams, the peak was 38.2 plus or minus 5.8 nanograms per milliliter at 4.7 hours ¹⁵. Those two figures — 38 and 52 nanograms per milliliter — are what a standard dose produces, and they are what every laboratory concentration in this literature has to be compared against. Higher doses go higher roughly in proportion ¹³: in 24 children with dengue given 400 or 600 micrograms per kilogram daily for three days, peak concentrations were 107.5 and 165.5 nanograms per milliliter, about 0.12 and 0.19 micromolar ¹⁶.

Three features of its disposition matter. It is lipophilic, meaning fat-loving, and it collects in fat: in human tissue samples fat showed the highest and most persistent concentrations, while skin, nodule tissue and the worms themselves were comparable and subcutaneous fascia lowest ¹⁴. Taking it with food raises exposure by a factor of 2.6 ¹³. And both patients and volunteers showed a second rise in blood concentration hours after the first, the signature of enterohepatic recirculation — the drug excreted into the gut in bile and then reabsorbed ¹⁴. It binds specifically to human serum albumin, which means only a fraction circulates free and able to enter cells ¹⁵; equilibrium dialysis in five healthy people put plasma protein binding at 93.2 plus or minus 4.4%, so roughly 7% is free — about 3.5 nanograms per milliliter at a 52 nanogram peak, or some 4 nanomolar ⁸⁴.

The half-life is genuinely unsettled, and it is worth saying so rather than picking a number. The same drug is reported at 56.5 plus or minus 7.01 hours in nine patients by one group ¹⁵, 35.0 hours in 25 patients by another ¹⁴, and approximately 18 hours in 68 healthy volunteers by the manufacturer ¹³. The studies differ in assay — radioimmunoassay in one, liquid chromatography in the others — in population, and in how long they sampled. A modern population analysis with a validated assay would settle it; until then, any single figure quoted as the half-life is a choice among three.

High doses have been studied, and that study is the one most often cited to argue that higher doses are safe. Sixty-eight healthy adults were randomized three to one against placebo to receive 30 or 60 milligrams three times weekly, or 90 or 120 milligrams once, in a dose escalation. Ivermectin was generally well tolerated with no indication of nervous-system toxicity up to ten times the highest approved dose of 200 micrograms per kilogram; pupil dilation, the primary safety endpoint, matched placebo; exposure rose roughly in proportion to dose; and accumulation on every-fourth-day dosing was minimal ¹³. Two things that study does not establish: that those doses are safe for months rather than days, and that they achieve micromolar concentrations. Modeling of exactly that scenario found that neither total nor unbound plasma concentrations reach 2 micromolar even at ten times the approved dose, and that predicted lung concentrations reach 0.820 micromolar against a 2 micromolar target ²⁹.

What it treats, and the programs built on it

Onchocerciasis is the disease ivermectin was made famous by. A blackfly bite delivers larvae that mature into adult worms living in nodules under the skin; the females release microfilariae that migrate through skin and eye, and the immune reaction to them causes ferocious itching, skin damage and, over years, blindness. One dose of ivermectin clears the microfilariae but leaves the adults, which resume producing larvae, so treatment is repeated annually or twice yearly for as long as the adults live ^12,17,39. Programs built on free donation have been running for decades: the Mectizan Donation Program began in 1987 and was extended to lymphatic filariasis in 1998 ²², and four countries in the Americas have since been verified free of transmission, Colombia first, in 2013, after 23 rounds of twice-yearly treatment ^23,24. Niger reported elimination of transmission as the first country in Africa; its own account attributes control to aerial larviciding against the blackfly from 1976 to 1989 and does not discuss ivermectin, so the drug's share of that result is not established by this source ²⁵.

The drug's grip is not permanent. In Ghanaian communities given 10 to 19 annual doses, about a quarter of infected people carried adult female worms that resumed producing larvae faster than they should, which the authors called phenotypic evidence of emerging resistance to the drug's effect on fertility; its larva-killing effect was still intact ⁶⁹. Genome-wide work later concluded that the trait is shaped by many genes, and that genetic drift rather than selection for resistance accounts for most of the difference between parasite populations ⁷⁰. Resistance to the macrocyclic lactones is already spreading in veterinary parasites ⁵³.

Lymphatic filariasis is treated with ivermectin in combination rather than alone. A trial in 182 adults in Papua New Guinea compared a single dose of ivermectin plus diethylcarbamazine plus albendazole against the older two-drug regimen: the triple combination cleared microfilariae from blood in 96% of participants at 12, 24 and 36 months, against 32%, 56% and 83% for a single dose of the two-drug regimen, and was not inferior to three annual rounds of it ⁴⁰. Moderate adverse events were more common with three drugs than two, 27% against 5%, with no serious events ⁴⁰. This is the clearest example on the page of ivermectin earning its place as part of a combination.

For strongyloidiasis, a threadworm infection that can disseminate and kill in people on immunosuppressive drugs, ivermectin is first choice on the evidence: pooling four trials and 478 participants, it cured more people than albendazole, with a risk ratio of 1.79, and was at least as well tolerated; against thiabendazole, cure rates were similar but side effects were a third as common ³⁷. The evidence was graded moderate at best, a second dose did not clearly add anything, and none of the trials studied the severe disseminated form ³⁷. Given to whole communities rather than to individuals, ivermectin cut Strongyloides prevalence by about 84% across five studies, which is the argument for adding it to deworming programs that now rely on albendazole ⁸⁵. For scabies, mass oral treatment of whole communities in Fiji reduced prevalence from 32.1% to 1.9% in a year, and reduced impetigo — a crusting bacterial skin infection that often follows scratched scabies — along with it ³⁸. It did not repeat everywhere: in the Solomon Islands, one or two rounds left prevalence essentially unchanged at 21 months, 18.7% and 13.4%, which the authors attributed partly to a pandemic-era influx of untreated people ⁷⁸.

The newest use is not antiparasitic at all in the usual sense. Ivermectin in a person's blood is lethal to mosquitoes that bite them, so treating people can suppress malaria transmission. A cluster-randomized trial in 84 clusters and 28,932 people in coastal Kenya, in an area already well covered by treated bed nets, gave three monthly rounds at 400 micrograms per kilogram and found malaria infection in children aged 5 to 15 reduced by 26% — 2.20 against 2.66 infections per child-year — with no safety signal ⁸⁰. The companion trial in Mozambique lost 57 of its clusters to flooding from the Gombe cyclone, along with low coverage and a delayed start, and could not answer the efficacy question ⁸³. Two other trials found nothing: in Burkina Faso, up to eight monthly rounds of high-dose ivermectin delivered alongside seasonal malaria chemoprevention did not lower malaria incidence in children, an incidence rate ratio of 0.96 (95% CI 0.58–1.59) ⁸¹; and on the Bijagós islands of Guinea-Bissau, adding ivermectin to mass antimalarial treatment left infection prevalence no lower, 6.6% against 5.1%, an adjusted risk difference of 1.67% (95% CI −1.44 to 4.78) ⁸².

The COVID-19 story, and how it ended

In April 2020 a Melbourne laboratory reported that adding ivermectin to infected monkey kidney cells two hours after infection produced a roughly 5,000-fold reduction in viral RNA at 48 hours ⁵⁹. That is a real and striking in vitro result. Within weeks, one group did the arithmetic the first paper had not. The concentration that halved viral replication was 2 micromolar — more than 35 times the peak plasma concentration an approved dose produces when taken fasting, and the experiment itself had used 5 micromolar — and simulations showed that neither total nor unbound plasma concentrations reach it even at ten times the approved dose, with predicted lung concentrations topping out at 0.820 micromolar ²⁹. A second model, published that September and also resting on a lung-to-plasma ratio measured in cattle, put simulated peak lung exposure at 772 nanograms per milliliter against the 1,750 nanograms per milliliter the virus work had needed ³⁰. Both papers were published in 2020. The question of whether the dose could reach the target was answered before most of the trials began.

The randomized trials then answered the clinical question six times over, in four countries, before the largest trial of all. In Colombia, 400 adults with mild illness were randomized to 300 micrograms per kilogram for five days or to placebo, 200 each way; the median time to symptom resolution was 10 days against 12, not statistically significant ⁷¹. In Malaysia, I-TECH randomized 490 high-risk patients aged 50 and over with comorbidities and found 21.6% progressed to severe disease on ivermectin against 17.3% on standard care — numerically worse, not significant ⁷⁶. In Brazil, the placebo-controlled TOGETHER platform gave 400 micrograms per kilogram for three days to 679 patients and found 14.7% reaching the primary outcome against 16.3% among 679 given placebo ⁷⁵. In the United States, ACTIV-6 ran two ivermectin arms: 400 micrograms per kilogram for three days, in which 1,800 outpatients were randomized and 1,591 analyzed, 817 of them on ivermectin, with median recovery at 12 days against 13 and a hazard ratio of 1.07 ⁸⁶; and up to 600 micrograms per kilogram for six days, in which 602 of 1,206 received the drug and median recovery was 11 days in both arms, a hazard ratio of 1.02 ⁶⁰. COVID-OUT, in 1,323 analyzed adults with overweight or obesity, found no reduction in a composite of low blood oxygen, emergency visit, hospitalization or death, an odds ratio of 1.05 ⁸⁷ — and ten months later, no reduction in long COVID either, a hazard ratio of 0.99 ⁸⁸.

The largest trial is also the one most often quoted in the drug's favor, and it deserves to be read precisely. PRINCIPLE's primary analysis included 8,811 people in the community in the United Kingdom, of whom 2,157 were randomized to ivermectin and 3,256 to usual care. Self-reported recovery came sooner with ivermectin, by an estimated median of 2.06 days (95% credible interval 1.00 to 3.06). The trial's own conclusion is that this fell short of the pre-specified threshold for a clinically meaningful effect — the probability of reaching it was 0.192 — that hospital admissions and deaths did not differ, and that the proportion feeling fully recovered was similar at three, six and twelve months: 74.3% against 71.2% at six months, a risk ratio of 1.05 (1.02 to 1.08) ⁷⁹. The trial was open-label. A symptom diary filled in by an unblinded participant is among the most fragile endpoints in clinical research, and a two-day shift in it with nothing else moving is what that fragility looks like.

Meanwhile the supporting literature was withdrawn. The meta-analysis of 23 trials that circulated most widely reported, in its original July 2021 version, a significant reduction in deaths; that result rested heavily on a trial later identified as potentially fraudulent. The paper drew an expression of concern in August 2021 ⁸⁹, and in February 2022 it was retracted and replaced by a reanalysis that excluded trials at high risk of bias and found no significant effect on survival (risk ratio 0.90) or hospitalization ^61,73. A companion analysis by the same authors showed what the original estimate had rested on: the potentially fraudulent trial alone implied about twelve times the survival benefit seen in the low-risk trials, a risk ratio of 0.08 against 0.96 ⁹⁰. A conference abstract reporting lower mortality in a national database was withdrawn at its authors' request, with an unusually candid notice explaining that their result showed only an association, had been misread as proof, and risked harm ⁶². Individual trial reports went the same way: PubMed now types as retracted a Lebanese trial in asymptomatic patients ⁹¹, a Brazilian pilot trial ⁹², an Egyptian hospital trial that had reported shorter survival with ivermectin ⁹³ — retractions cut both ways — and a case series of ivermectin-based multidrug therapy coauthored by Peter McCullough ⁶³. Cochrane's update excluded seven of the fourteen trials in its previous version, six because they had not been prospectively registered and one because it was not randomized, and concluded there is no beneficial effect for outpatients ⁷⁴. A short letter in Nature Medicine stated the general lesson in its title: meta-analyses based on summary data alone cannot detect a fabricated study, and so inherit the fabrication ⁹⁴. The World Health Organization recommends the drug for COVID-19 only in the context of clinical trials ⁷⁹, and regional guidelines discourage it ⁷⁷.

The harms were not hypothetical. One poison center described 37 cases over 24 weeks: median age 64, mostly men, 21 hospitalized and one death; 17 had taken veterinary formulations and those patients took the largest doses and developed the fastest neurological effects, while patients taking it chronically, at about 13.5 milligrams daily for a median of 3.8 weeks, developed milder toxicity than those with acute ingestions ³⁵. A registry across 15 academic medical centers in 12 states collected 40 cases, 18 from animal products, with nervous-system effects the most common finding and 25 of 40 classed as severe ⁹⁵.

The cancer claims, at their true strength

The laboratory evidence is real, substantial, and consistent in one respect that matters more than any of its mechanisms: the concentrations. In acute myeloid leukemia cells and fresh patient samples, ivermectin killed at low micromolar concentrations in preference to normal blood-forming cells, by raising intracellular chloride, hyperpolarizing the plasma membrane and generating reactive oxygen species, and slowed growth in three mouse leukemia models ⁴⁴. In a repositioning screen it blocked the WNT-TCF growth pathway and selectively slowed the growth of mouse xenografts that depended on that pathway ⁴². It inhibits PAK1, an oncogenic kinase, with half-maximal effects between 5 and 20 micromolar ²⁸. It appears to inhibit an RNA-unwinding enzyme that gliomas use to make a growth-promoting microRNA, and slowed glioma xenograft growth in mice ⁴³. It preferentially kills stem-like breast cancer cells between 0.2 and 8 micromolar, the opposite of the pattern paclitaxel produces ²⁶. It suppresses estrogen and HER2 signaling in hormone-resistant breast cancer cells ⁹⁶. In mice, alone it did nothing, but with a checkpoint antibody it produced complete responses ⁴⁶.

Now the concentrations, against the measured human peak of 52 nanograms per milliliter ¹⁴. One micromolar is about 875 nanograms per milliliter. So the lowest figure among these studies, 0.2 micromolar, is about 175 nanograms per milliliter — already more than three times the human peak ²⁶. The leukemia work gives no figure beyond 'low micromolar', which if it means 1 to 5 micromolar is 17 to 84 times it ⁴⁴. The PAK1 range of 5 to 20 micromolar is 80 to 340 times it ²⁸. A 2025 lymphoma study calculated a half-maximal concentration of 10.55 micrograms per milliliter, which is 10,550 nanograms per milliliter, or 203 times the 52 nanograms per milliliter peak and 276 times the 38.2 nanogram figure ^14,15,27. In that same 24-hour assay the chemotherapy drug cisplatin needed 8.32 micrograms per milliliter, so the test system is an unusually insensitive one: it illustrates the gap rather than ivermectin's typical potency ²⁷. And population modeling says 2 micromolar — 1,750 nanograms per milliliter — is not reached in plasma even at ten times the approved dose ²⁹. Because about 93% of the drug in blood is bound to plasma protein, the free concentration available to enter a cell is roughly a fourteenth of these totals ^15,84.

The influential 2018 review that organized the field claimed the opposite: that ivermectin's antitumor activities 'are achieved at concentrations that can be clinically reachable based on the human pharmacokinetic studies done in healthy and parasited patients' ⁵⁰. Measured against the human peak concentrations that have actually been published, that claim is wrong, and it is the single most consequential error in this literature. Two cancer papers built on that premise have since been retracted: a liver cancer study that claimed activity at 'clinically relevant concentrations' and called for trials ^97,98, and a glioma study ⁹⁹. The COVID-19 meta-analysis that circulated alongside them was retracted too ^61,73. The mouse immunotherapy paper now carries an author correction and an editorial expression of concern ^47,48, and the receptor axis it invokes behaves differently in mice and in people ⁴⁹.

The human evidence, as of October 2026, is this. No randomized controlled trial of ivermectin in any cancer has reported a result in the indexed literature; a PubMed search for randomized trials of ivermectin in cancer, run in October 2026, returns none. The most-circulated human report is a cohort of 197 patients prescribed compounded ivermectin and mebendazole through a United States telemedicine platform, of whom 122 answered a six-month survey; it reported a 'Clinical Benefit Ratio' of 84.4%, a composite the authors built from patients' own answers rather than from imaging assessed by the standard rules ²⁰. Patients received compounded capsules of 25 milligrams of ivermectin and 250 milligrams of mebendazole, and 37.1% reported their cancer was actively progressing at baseline ²⁰. All twelve of its authors list The Wellness Company, the telemedicine company that prescribed the treatment, among their affiliations; two also list the McCullough Foundation, and one Yale. More than a quarter of the patients were also receiving chemotherapy, a fifth radiation and a fifth surgery ²⁰. PubMed now types the record as a retracted publication; the journal's notices record an audit opened in June 2026 and closed in September with its requests withdrawn and no misconduct alleged, and a continuing review of the methodological points above ^21,64. Because the retracted flag and the editorial record have not been reconciled, this page states both and asserts neither a retraction date nor stated grounds. Reviewing the same evidence in 2025, gynecologic oncologists concluded that the clinical data in their field amount to cell-line work and cautioned strongly against using the drug ⁶⁶.

Beside that cohort sit a six-patient case series in which the drugs were chosen by measuring electrical conductance at acupuncture points, written by two authors who both list a commercial company, Your Energy Systems, as their affiliation ¹⁰⁰; a case report of a melanoma that shrank and whose circulating tumor DNA fell during self-administered ivermectin and fenbendazole, and then grew again, in a tumor whose extremely high mutation count makes spontaneous immune regression at least as likely an explanation, as its authors say ¹⁰¹; a case of severe liver injury in a man who took veterinary fenbendazole and ivermectin on alternate days for three months, at an estimated 0.18 milligrams of ivermectin per kilogram per 'squirt' ¹⁰²; and a case of seizures and respiratory failure in a woman with metastatic breast cancer who had taken high doses on the strength of what she read online ³⁶. Where the laboratory work has gone next is combinations — three-drug regimens that eradicate a lung cancer line while sparing normal fibroblasts, with each drug given at the concentration that on its own inhibits 30% of the cancer cells, which for ivermectin was 2.08 micromolar, about 1,800 nanograms per milliliter ¹⁰³. The concentration problem has not been solved; it has been inherited.

What was believed and is not

Every item below was a reasonable belief held by competent people, and every one was overturned by a specific, citable piece of work rather than by argument. Some were corrected by the drug's own developers, inside the papers that first established its usefulness: the Merck team that cloned the worm channel wrote in the same abstract that avermectins also touch vertebrate GABA receptors ¹, and the manufacturer's own high-dose study is the one that showed exposure rising roughly in proportion to dose, so that ten times the dose buys about ten times the peak — which is exactly why modeling could then show that even that does not reach micromolar levels ^13,29. That is what a self-correcting literature looks like when it works.

Others were corrected by the drug's critics, and one — the retraction of the most-shared meta-analysis — was corrected by its own authors ⁶¹. One entry is a reversal of an over-correction rather than of an error: after serious harms stopped mass treatment in whole districts, a cheap field instrument made it possible to protect the individuals at risk and treat everyone else ^67,68. Reading them together is a usable guide to which of the current claims will survive, because the pattern is consistent: the laboratory finding holds up and the dose does not.

Safety, overdose and veterinary products

At approved doses in people without heavy Loa loa infection, ivermectin's safety record across billions of treatments is the reason anyone takes the repurposing idea seriously ^13,19. The important qualifications are specific. Most of what people feel after treatment is not the drug: the fever, itching, rash and swelling of a Mazzotti reaction are the immune response to dying parasites, and in the moxidectin comparison trial they occurred in 99% and 97% of participants in the two arms ¹². Looking specifically at the eye, larvae in the front chamber — the fluid-filled space between the cornea and the iris — increased after treatment in about a fifth of participants in the first days, and ocular reactions occurred in 12.4% and 10.2% of the two arms, with no difference in type or severity ¹⁰⁴.

The serious hazard in mass treatment is Loa loa. In a Cameroonian district where it overlaps with river blindness, 20 of 17,877 treated people had serious reactions that left them needing help for more than a week, and two others were comatose for two to three days with larvae in their cerebrospinal fluid. This is Loa loa encephalopathy. Risk rose with the pre-treatment larval burden: marked or serious reactions became significantly more likely above 8,000 larvae per milliliter, and the odds of serious ones were extreme above 50,000 ⁶⁷. The modern answer is not to avoid whole districts but to count larvae at the point of care and withhold treatment from individuals above a threshold, which allowed 15,522 people to be treated safely in a district where distribution had been stopped after fatal events ⁶⁸. The mechanism is not the drug's barrier story. In baboons carrying heavy Loa loa burdens, ivermectin left degenerating larvae lodged in the small vessels of the brain and other organs, with fibrin deposits, damaged vessel walls and bleeding around them, and three times as many larvae in the brain as in untreated animals ¹⁰⁵; in people, the comas came with larvae in the cerebrospinal fluid ⁶⁷. Whether a weak pump contributes as well is unproven ¹¹.

Overdose looks like nervous-system poisoning, and nearly half of the reported cases involve an animal product. Across 37 cases at one poison center, the median age was 64, most patients were men, 21 were hospitalized and one died; those taking veterinary formulations took the largest doses and developed altered mental status fastest, while patients taking it chronically, at about 13.5 milligrams daily for a median of 3.8 weeks, developed milder toxicity than those with acute ingestions ³⁵. A 15-center registry found the same pattern in 40 patients, 18 of them on animal products, with 25 classed as severe ⁹⁵. In oncology specifically: a man taking veterinary fenbendazole and ivermectin by the squirt developed severe liver injury that reversed over six weeks after stopping ¹⁰², and a 73-year-old woman with metastatic breast cancer arrived with seizures and respiratory failure after high-dose self-administration, recovering fully in 48 hours ³⁶.

Two further points of practice. The drug is not the same in everyone: the rare human equivalents of the collie mutation exist ³⁴, and the pump can also be disabled by other drugs or foods, which would not show up on any genetic test ¹¹. And the pregnancy question is still open. Early animal work suggested harm at doses several-fold above human ones, and a prospective dataset of 238 pregnancies exposed around conception in two cluster-randomized trials found adverse outcomes in 22.9% of ivermectin-exposed against 19.5% of albendazole-exposed pregnancies, an odds ratio of 1.22 with a confidence interval from 0.59 to 2.50. The authors say plainly that the interval does not exclude a meaningful difference in either direction and that the numbers remain too small to support any policy conclusion ¹⁹.

What is still unknown

The honest list is short and specific. First, nobody has published the concentration of ivermectin inside a human tumor. Human tissue concentrations exist for fat, skin, onchocercal nodules and the worms themselves ¹⁴, and a lung concentration has been modeled from cattle data ³⁰, but the comparison that the entire cancer argument needs — drug measured in resected tumor against drug needed in a dish — has never been made. Computing the gap against plasma, as this page does, is the conservative choice and not the complete answer.

Second, the human half-life is unresolved: 18, 35 and 56.5 hours from three studies differing in assay and population ^13,14,15. Third, whether any tolerable intermittent schedule can hold plasma concentrations at micromolar levels is unanswered; the modeling says the approved dose and ten times it cannot ²⁹, and the one formal high-dose study ran for days rather than months ¹³.

Fourth, the status of the most-publicized human cancer report is genuinely unsettled in the indexed record: PubMed types it as a retracted publication while the journal's September 2026 notice records that its audit is closed and its document requests withdrawn, that no misconduct is alleged, that the authors have appealed against the course the journal proposed, and that no final decision has been taken on whether to correct or retract ^20,21. Fifth, no randomized trial of ivermectin in cancer has reported, so the question of whether a pharmacokinetically justified dose with blinded imaging assessment would show anything remains open — and the pharmacokinetics suggest such a dose may not be reachable by mouth, which is itself a finding ^29,30. Sixth, whether the two-day difference in self-reported recovery in the largest COVID-19 trial reflects anything other than unblinding cannot be settled from an open-label trial ⁷⁹. And one limit is this page's own: clinical trial registries were not reachable from the machine it was written on, so it can state what has been published and indexed, but it cannot enumerate trials that are registered and still unreported.

How it connects to parasites and cancer

There are two separate questions, and conflating them is the commonest mistake in this area. The first is whether parasites cause cancer. For three species the answer is yes and has been for decades: of the twelve infectious agents currently classed as established human carcinogens, three are flukes — Schistosoma haematobium, the urinary blood fluke, which causes bladder cancer, and the liver flukes Opisthorchis viverrini and Clonorchis sinensis, which cause bile duct cancer ^106,107. The effect size is substantial: in a review of 22 studies and 34,367 people, infection with C. sinensis, O. viverrini or O. felineus carried about a fourfold odds of cholangiocarcinoma, an odds ratio of 4.24 ¹⁰⁸. Infections of all kinds accounted for an estimated 2.3 million new cancers in 2024, around 12% of the global total ¹⁰⁶.

Ivermectin is almost irrelevant to that first question. It treats roundworms and mites ^17,38; the three carcinogenic parasites are flukes, a different class of organism, and ivermectin is not the drug used against them. A drug that clears Onchocerca larvae from skin or threadworms from the gut does nothing about the organisms that are known to cause cancer in people. If someone's reasoning runs 'parasites cause cancer, ivermectin kills parasites, therefore ivermectin treats cancer', both of the premises are partly true and the conclusion does not follow from them.

The second question is whether ivermectin itself has anticancer activity, independent of parasites. Here the honest answer has three parts, and they should be said in this order. The in vitro and mouse evidence is real and reproducible across several mechanisms and several laboratories ^{26,42,43,44,96}. The concentrations at which that evidence was generated run from about three to more than three hundred times the peak a standard human dose produces ^26,27,28; raising the dose narrows the gap only at its lowest end, since 600 micrograms per kilogram daily reaches about 0.19 micromolar ¹⁶, while modeling puts the 2 micromolar level most of this work used out of reach even at ten times the approved dose ^29,30. And the human evidence consists of one uncontrolled cohort of self-reported outcomes, written by twelve authors who all list the company that sold the treatment, which PubMed flags as retracted while the journal's review continues ^20,21, one six-patient series allocated by electroacupuncture readings ¹⁰⁰, and individual case reports — including one of a tumor that shrank and then grew, whose authors note that spontaneous immune regression is at least as plausible ¹⁰¹.

What that adds up to is not a dismissal. The pump-blocking property, discovered in 1996, remains a legitimate idea, and it is a different kind of claim: an effect on a transporter that expels chemotherapy, rather than on the cancer cell's own survival machinery ⁴⁵. The mouse result in which ivermectin did nothing alone but produced complete responses with a checkpoint antibody is the most interesting hypothesis in the field, and the fact that the paper now carries a correction and an expression of concern is a reason to test it, not to believe it ^46,48. What is missing is not imagination but one measurement and one trial: the concentration ivermectin reaches inside a human tumor, and a randomized trial at a dose justified by that number, with response assessed blind. Until those exist, anyone who tells a patient that ivermectin treats their cancer is going beyond the evidence. The harms documented so far have come from self-directed dosing — veterinary products, high doses, months of use ^36,102 — and from patients setting aside the treatment that works ¹⁰¹.

The tests, one by one

• Skin snip microfilarial densityA shaving of skin examined for emerging larvae, counted per milligram, and the endpoint on which ivermectin and its successors are compared ¹².This is the test actually used in onchocerciasis trials and programsQuantitative and reproducible enough to separate two drugs: 0.6 against 4.5 larvae per milligram twelve months after one dose ¹².It is a surrogate. It counts larvae in skin, not sight preserved, and it says nothing about the adult worms, which survive and resume producing larvae ^12,39.
• Loa loa microfilarial count (LoaScope)A phone-based microscope that counts Loa loa larvae in a drop of finger-prick blood before treatment is given ⁶⁸.This is the test that decides whether an individual can safely be treated at allGood enough to run a whole district: 16,259 people tested, 340 (2.1%) held back above 20,000 larvae per milliliter, and no serious adverse events ⁶⁸.It measures one species at one moment. The danger threshold itself is drawn from an observational study in which the highest-burden events were very few ⁶⁷.
• Ov16 antibody serology in childrenAn antibody test in children aged 5 to 9 — Ov16 is a protein of the river-blindness worm that infected people make antibodies to — used to show that transmission has stopped rather than that an individual is infected ²⁵.This is what elimination is certified on, alongside PCR testing of captured blackflies for parasite DNANegative in all 16,406 children aged 5 to 9 tested in the areas suspected of ongoing transmission ²⁵; Colombia's verification rested on the same logic ²³.A negative test in children cannot date when transmission stopped, and antibodies persist in adults, so the test is useless in them ²⁵.
• Plasma ivermectin concentrationMeasured by radioimmunoassay in one study and by chromatography in the others; assay, population and sampling all differ, which is part of why the reported half-life ranges from about 18 to about 56 hours ^13,14,15.Used in research, and almost never in clinical careConsistent on the peak: 38 to 52 nanograms per milliliter about five hours after a standard dose ^14,15.Blood is not tissue. Fat holds the highest and most persistent concentrations ¹⁴, and no one has published a concentration measured inside a human tumor.
• MDR1/ABCB1 genotypingUsed in veterinary practice for herding breeds, where a four-base deletion predicts ivermectin neurotoxicity ³²; reported in people only in case reports ³⁴.Used before high-dose ivermectin in dogs; not a human clinical testIn collie-lineage dogs two copies of the deletion predict severe sensitivity and carriers of one copy do not show it ³²; but the test does not catch every case — of 28 dogs of other breeds poisoned during daily high-dose treatment, 27 had no copy of the mutation ³³.It finds one kind of defect. Acquired pump failure, from another drug or a food that blocks the transporter, would not show up at all ¹¹.

Where it connects

Sources

108 sources, numbered as they are cited. Every one was checked against PubMed or its publisher before it was cited here; the note under each says what it shows and what it does not.

1. 1
   Cully DF, Vassilatis DK, Liu KK, et al. Cloning of an avermectin-sensitive glutamate-gated chloride channel from Caenorhabditis elegans.Nature · 1994 · 371(6499):707-11doi:10.1038/371707a0 · PMID 7935817

   The target, cloned. Also the source of ivermectin's exact chemical name and of the sentence that avermectins touch vertebrate GABA receptors as well as invertebrate chloride channels — so the selectivity was never absolute. The authors worked for the manufacturer.

2. 2
   Spinosa HS, Stilck SRAN, Bernardi MM. Possible anxiolytic effects of ivermectin in rats.Vet Res Commun · 2002 · 26(4):309-21doi:10.1023/a:1016094726033 · PMID 12184502

   Describes ivermectin in one line as a macrocyclic lactone disaccharide and a mixture of B1a at 80% or more with B1b at 20% or less, then shows that 0.5 and 1.0 mg/kg in rats produces a benzodiazepine-like behavioral profile. Rat behavior at five times the human antiparasitic dose; it does not establish anything about people.

3. 3
   Ardelli BF, Stitt LE, Tompkins JB, Prichard RK. A comparison of the effects of ivermectin and moxidectin on the nematode Caenorhabditis elegans.Vet Parasitol · 2009 · 165(1-2):96-108doi:10.1016/j.vetpar.2009.06.043 · PMID 19631471

   States the ring size for the whole family — the avermectins and milbemycins are 16-membered macrocyclic lactones — and shows that ivermectin and moxidectin act on different channel subunits in a worm. Worm genetics; nothing about mammals.

4. 4
   Prichard R, Ménez C, Lespine A. Moxidectin and the avermectins: Consanguinity but not identity.Int J Parasitol Drugs Drug Resist · 2012 · 2:134-53doi:10.1016/j.ijpddr.2012.04.001 · PMID 24533275

   The clearest published statement of what separates the two families: sugars at C13 in the avermectins, a bare carbon there in the milbemycins, and a methoxime at C23 in moxidectin. A review, and the authors' own transporter work is part of what it reviews.

5. 5
   National Center for Biotechnology Information. PubChem Compound Summary for CID 6321424, Ivermectin B1a.PubChem · National Library of Medicine · accessed 2026pubchem.ncbi.nlm.nih.gov/compound/6321424

   The source of the canonical isomeric SMILES string, the CID and the stated formula and mass for the B1a component. The string, CID, formula and mass are those of the PubChem record for CID 6321424. PubChem itself was not reachable from the machine this page was written on, so the string was checked independently instead: it computes to C48H74O14, an average mass of 875.1, a single sixteen-membered lactone ring, one spiro carbon bonded to two oxygens, and no aromatic atoms anywhere in the molecule, with the InChIKey AZSNMRSAGSSBNP-XPNPUAGNSA-N reported for ivermectin B1a. It is a database record, not a measurement.

6. 6
   Burg RW, Miller BM, Baker EE, et al. Avermectins, new family of potent anthelmintic agents: producing organism and fermentation.Antimicrob Agents Chemother · 1979 · 15(3):361-7doi:10.1128/AAC.15.3.361 · PMID 464561

   The first paper: names the producing organism Streptomyces avermitilis NRRL 8165, classes the avermectins as macrocyclic lactone derivatives that lack significant antibacterial or antifungal activity, and reports the fermentation yields. It says nothing about human use.

7. 7
   Zhang X, Chen Z, Li M, Wen Y, Song Y, Li J. Construction of ivermectin producer by domain swaps of avermectin polyketide synthase in Streptomyces avermitilis.Appl Microbiol Biotechnol · 2006 · 72(5):986-94doi:10.1007/s00253-006-0361-2 · PMID 16708195

   States the commercial composition plainly — avermectins B1 are a mixture of B1a above 80% and B1b below 20% — and that ivermectin is made by hydrogenating the C22-C23 double bond with a rhodium catalyst. An engineering paper; the strains it built made only small amounts.

8. 8
   Chabala JC, Mrozik H, Tolman RL, et al. Ivermectin, a new broad-spectrum antiparasitic agent.J Med Chem · 1980 · 23(10):1134-6doi:10.1021/jm00184a014 · PMID 6893469

   The chemistry of the single change that made the drug: selective hydrogenation of avermectin B1 with Wilkinson's catalyst. Animal efficacy only; no human data.

9. 9
   Hibbs RE, Gouaux E. Principles of activation and permeation in an anion-selective Cys-loop receptor.Nature · 2011 · 474(7349):54-60doi:10.1038/nature10139 · PMID 21572436

   The structure: ivermectin caught in the act, wedged in the membrane-spanning part of the worm channel and holding the pore open. A crystal structure of one purified worm protein, not a picture of a living nerve.

10. 10
    Schinkel AH, Smit JJ, van Tellingen O, et al. Disruption of the mouse mdr1a P-glycoprotein gene leads to a deficiency in the blood-brain barrier and to increased sensitivity to drugs.Cell · 1994 · 77(4):491-502doi:10.1016/0092-8674(94)90212-7 · PMID 7910522

    The hundred-fold number: deleting one pump gene makes a mouse a hundred times more sensitive to ivermectin. Mice, and a complete gene deletion rather than the partial variation seen in people.

11. 11
    Edwards G. Ivermectin: does P-glycoprotein play a role in neurotoxicity?Filaria J · 2003 · 2 Suppl 1(Suppl 1):S8doi:10.1186/1475-2883-2-S1-S8 · PMID 14975065

    Argues the human case: the same pump guards the human brain, so anything that disables it — a variant gene, or another drug or food that blocks it — could in principle let ivermectin in. A narrative review; the human examples are possibilities, not measured events.

12. 12
    Opoku NO, Bakajika DK, Kanza EM, et al. Single dose moxidectin versus ivermectin for Onchocerca volvulus infection in Ghana, Liberia, and the Democratic Republic of the Congo: a randomised, controlled, double-blind phase 3 trial.Lancet · 2018 · 392(10154):1207-1216doi:10.1016/S0140-6736(17)32844-1 · PMID 29361335

    The head-to-head trial that put a newer macrocyclic lactone ahead of ivermectin on skin larval counts a year after one dose. The endpoint is a surrogate — larvae per milligram of skin — not blindness avoided, and nearly every participant in both arms had a treatment reaction.

13. 13
    Guzzo CA, Furtek CI, Porras AG, et al. Safety, tolerability, and pharmacokinetics of escalating high doses of ivermectin in healthy adult subjects.J Clin Pharmacol · 2002 · 42(10):1122-33doi:10.1177/009127002401382731 · PMID 12362927

    The high-dose study everyone cites for safety: up to ten times the highest approved dose in 68 healthy adults randomized three to one against placebo, with no sign of nervous-system toxicity, the finding that food raises exposure 2.6-fold, and the finding that peak concentration and total exposure rise roughly in proportion to dose. Run and written by the manufacturer, in healthy adults, over days rather than months.

14. 14
    Baraka OZ, Mahmoud BM, Marschke CK, Geary TG, Homeida MM, Williams JF. Ivermectin distribution in the plasma and tissues of patients infected with Onchocerca volvulus.Eur J Clin Pharmacol · 1996 · 50(5):407-10doi:10.1007/s002280050131 · PMID 8839664

    The most-quoted human peak concentration after a standard dose, plus the only human tissue measurements: fat holds the most and holds it longest. Twenty-five patients and fourteen volunteers by radioimmunoassay; no tumor tissue was sampled, because none was being looked for.

15. 15
    Okonkwo PO, Ogbuokiri JE, Ofoegbu E, Klotz U. Protein binding and ivermectin estimations in patients with onchocerciasis.Clin Pharmacol Ther · 1993 · 53(4):426-30doi:10.1038/clpt.1993.46 · PMID 8477558

    Measured human blood levels in nine patients, and the finding that the drug rides on albumin. Nine people, an early chromatographic assay, and a half-life far longer than other studies report; the bound percentage comes from the same group's companion paper [85].

16. 16
    Lapphra K, Mairiang D, Tarning J, et al. Repeated-Dose High-Dose Ivermectin Pharmacokinetics and Safety in Children with Acute Dengue.Paediatr Drugs · 2026doi:10.1007/s40272-026-00771-4 · PMID 42773329

    What higher doses actually reach: peaks of 107.5 and 165.5 ng/mL at 400 and 600 µg/kg daily for three days. Twenty-four children of 15 kg or more with dengue, open-label and not designed to test efficacy; six developed grade 4 neutropenia, none judged related to the drug.

17. 17
    Crump A, Ōmura S. Ivermectin, 'wonder drug' from Japan: the human use perspective.Proc Jpn Acad Ser B Phys Biol Sci · 2011 · 87(2):13-28doi:10.2183/pjab.87.13 · PMID 21321478

    The origin story told by the discovering institution, and the source of the 'wonder drug' phrase. Reliable on the soil sample, the dates and the donation; its claim that ivermectin is the sole tool against both onchocerciasis and lymphatic filariasis overstates the lymphatic filariasis case, where it is given in combination.

18. 18
    Van Voorhis WC, Hooft van Huijsduijnen R, Wells TNC. Profile of William C. Campbell, Satoshi Ōmura, and Youyou Tu, 2015 Nobel Laureates in Physiology or Medicine.Proc Natl Acad Sci U S A · 2015 · 112(52):15773-6doi:10.1073/pnas.1520952112 · PMID 26699511

    Fixes the 2015 prize and its three recipients to a citable record. PubMed indexes no abstract for it, so only the title, authorship and the subject indexing (Nobel Prize, Ivermectin, Artemisinins) are verifiable here; two of the three authors work for an antimalarial drug-development organization.

19. 19
    Nicolas P, Mundaca H, Brazeal A, et al. Risk of adverse pregnancy outcomes following inadvertent exposure to ivermectin during the periconception period: findings from two cluster-randomized trials in Mozambique and Kenya.EClinicalMedicine · 2026 · 97:104069doi:10.1016/j.eclinm.2026.104069 · PMID 42518939

    Puts a number on the scale of use — more than 5.9 billion treatments distributed through global programs by 2025 — and reports pregnancy outcomes after accidental exposure around conception. Only 238 pregnancies, and the authors say plainly that the confidence interval is too wide to exclude harm or to support policy.

20. 20
    Hulscher N, Victory K, Thorp JA, et al. RETRACTED: Real-world Clinical Outcomes of Ivermectin and Mebendazole in Cancer Patients: Results from a Prospective Observational Cohort.Anticancer Res · 2026 · 46(6):3243-3255doi:10.21873/anticanres.18194 · PMID 42203321

    The source of the 84.4% figure circulating online: 197 patients prescribed the drugs through a telemedicine company, 122 of whom answered a six-month survey, with benefit judged from their own answers. PubMed types the record as a Retracted Publication. All twelve of its authors list The Wellness Company among their affiliations; two also list the McCullough Foundation, and one Yale.

21. 21
    Update to the Expression of Concern: Real-world Clinical Outcomes of Ivermectin and Mebendazole in Cancer Patients: Results from a Prospective Observational Cohort.Anticancer Res · 2026 · 46(9)doi:10.21873/anticanres.18380 · PMID 42703869

    The September 2026 update: the audit is closed and its document requests withdrawn, no misconduct is alleged, and the continuing review concerns how the composite benefit measure was built and how patients without follow-up and on concurrent chemotherapy were handled. It states that no final decision had been taken.

22. 22
    Gustavsen KM, Colatrella BD, McCoy T. For as Long as Necessary: Examining 30 years of MSD's Focus on Achieving Elimination of Onchocerciasis and Lymphatic Filariasis.Int Health · 2018 · 10(suppl_1):i3-i6doi:10.1093/inthealth/ihx038 · PMID 29186497

    The donation program in its own words: established in 1987 for onchocerciasis, extended to lymphatic filariasis in 1998, and the longest-running disease-specific program of its kind. Written by employees of the donating company.

23. 23
    Nicholls RS, Duque S, Olaya LA, López MC, Sánchez SB, Morales AL, Palma GI. Elimination of onchocerciasis from Colombia: first proof of concept of river blindness elimination in the world.Parasit Vectors · 2018 · 11(1):237doi:10.1186/s13071-018-2821-9 · PMID 29642939

    The first country verified free of river blindness, with the PCR fly-testing and antibody numbers behind the verification. One small focus treated twice a year for over a decade; it does not show that annual treatment of a large African focus would do the same.

24. 24
    Mackenzie CD, Post RJ, Boakye DA. Important entomological events in the history of onchocerciasis ('river blindness').Int Health · 2026 · 18(Supplement_1):i5-i15doi:10.1093/inthealth/ihag018 · PMID 41671175

    The source for the count and the dates: transmission has been eliminated in four countries in Latin America and, dated here to 2024, in Niger. A historical review by authors involved in the programs, so it is a summary of the record rather than primary evidence.

25. 25
    Adamou S, Laouali B, Garba N, et al. Niger: the first human onchocerciasis-endemic country in Africa to achieve elimination of infection transmission.Int Health · 2026doi:10.1093/inthealth/ihag013 · PMID 41804793

    The current high-water mark for the program: hundreds of thousands of blackflies tested by PCR and sixteen thousand children tested for antibodies, with no sign of transmission. Published in 2026, it reports data gathered from 2014 to 2024 and documents a success already recognized before then; its abstract credits aerial larviciding from 1976 to 1989 and never mentions ivermectin, so this is not a test of drug treatment alone.

26. 26
    Dominguez-Gomez G, Chavez-Blanco A, Medina-Franco JL, et al. Ivermectin as an inhibitor of cancer stem-like cells.Mol Med Rep · 2018 · 17(2):3397-3403doi:10.3892/mmr.2017.8231 · PMID 29257278

    Found by chemical resemblance to another compound and tested on one breast cancer line: active between 0.2 and 8 micromolar, hitting the stem-like fraction harder than the bulk, the opposite of what paclitaxel did. A single cell line; the lower end of that range is the lowest credible figure in this literature.

27. 27
    Shukla A, Sharma A, Gupta S, Mishra A, Singh A. Antitumor potential of ivermectin against T-cell lymphoma-bearing hosts.Med Oncol · 2025 · 42(5):169doi:10.1007/s12032-025-02726-0 · PMID 40257544

    A recent, thorough cell and mouse study, and the clearest illustration of the problem: the concentration that killed half the lymphoma cells was 10.55 micrograms per milliliter, which is two hundred times the peak a standard human dose produces. The mouse results are real; neither drug's concentration in this 24-hour assay is reached in human blood — cisplatin needed 8.32 micrograms per milliliter in the same test.

28. 28
    Hashimoto H, Messerli SM, Sudo T, Maruta H. Ivermectin inactivates the kinase PAK1 and blocks the PAK1-dependent growth of human ovarian cancer and NF2 tumor cell lines.Drug Discov Ther · 2009 · 3(6):243-6PMID 22495656

    The origin of the PAK1 claim, with half-maximal effects at 5 to 20 micromolar in cell culture. A four-page paper in a low-profile journal with no DOI, written from a non-institutional advocacy address, which also relays a xenograft result at second hand rather than reporting it.

29. 29
    Schmith VD, Zhou JJ, Lohmer LRL. The Approved Dose of Ivermectin Alone is not the Ideal Dose for the Treatment of COVID-19.Clin Pharmacol Ther · 2020 · 108(4):762-765doi:10.1002/cpt.1889 · PMID 32378737

    The arithmetic that should have ended it in 2020: the concentration that worked in the dish is more than 35 times the peak a standard dose produces, and ten times the dose does not close the gap. A simulation from a published population model, not new measurements in infected people.

30. 30
    Jermain B, Hanafin PO, Cao Y, Lifschitz A, Lanusse C, Rao GG. Development of a Minimal Physiologically-Based Pharmacokinetic Model to Simulate Lung Exposure in Humans Following Oral Administration of Ivermectin for COVID-19 Drug Repurposing.J Pharm Sci · 2020 · 109(12):3574-3578doi:10.1016/j.xphs.2020.08.024 · PMID 32891630

    The same conclusion reached independently for the lung, five months later: a simulated peak of 772 ng/mL against the 1750 ng/mL the virus work required. As in [42], the lung-to-blood ratio was borrowed from cattle, which is the model's weakest joint.

31. 31
    Olsen RW, Snowman AM. Avermectin B1a modulation of gamma-aminobutyric acid/benzodiazepine receptor binding in mammalian brain.J Neurochem · 1985 · 44(4):1074-82doi:10.1111/j.1471-4159.1985.tb08727.x · PMID 2983026

    Mammalian brain membranes respond to the parent avermectin at 40 nanomolar, which is the measurement behind the statement that the vertebrate target exists. Binding assays on ground-up brain, not on an intact animal with a working blood-brain barrier.

32. 32
    Mealey KL, Bentjen SA, Gay JM, Cantor GH. Ivermectin sensitivity in collies is associated with a deletion mutation of the mdr1 gene.Pharmacogenetics · 2001 · 11(8):727-33doi:10.1097/00008571-200111000-00012 · PMID 11692082

    The collie story solved: a four-base deletion that truncates the pump, with only the dogs carrying two copies affected. An association study in dogs; it does not measure brain drug levels.

33. 33
    Bissonnette S, Paradis M, Daneau I, Silversides DW. The ABCB1-1Delta mutation is not responsible for subchronic neurotoxicity seen in dogs of non-collie breeds following macrocyclic lactone treatment for generalized demodicosis.Vet Dermatol · 2009 · 20(1):60-6doi:10.1111/j.1365-3164.2008.00731.x · PMID 19152588

    The limit of the collie genetic test: of 28 dogs of other breeds poisoned during daily high-dose treatment, 27 carried no copy of the deletion. A case series with no unaffected comparison group, so it cannot give a risk; it does show the genotype is not the whole story.

34. 34
    Baudou E, Lespine A, Durrieu G, André F, Gandia P, Durand C, Cunat S. Serious Ivermectin Toxicity and Human ABCB1 Nonsense Mutations.N Engl J Med · 2020 · 383(8):787-789doi:10.1056/NEJMc1917344 · PMID 32813957

    The human counterpart of the collie finding, reported as a letter with a family pedigree after treatment for scabies. PubMed indexes no abstract, so the record supports the existence and subject of the report but no numbers; a single family cannot give a population risk.

35. 35
    Hoang R, Temple C, Correia MS, Clemons J, Hendrickson RG. Characteristics of ivermectin toxicity in patients taking veterinary and human formulations for the prevention and treatment of COVID-19.Clin Toxicol (Phila) · 2022 · 60(12):1350-1355doi:10.1080/15563650.2022.2134788 · PMID 36374218

    The clearest description of what overdose looks like and where it comes from: 37 cases, mostly men over 60, with veterinary products producing the largest doses and the fastest neurological effects. Cases reported to one poison center, so it counts the people who sought help, not the people who took it.

36. 36
    Saperstein Y, Bou Sanayeh E, Boazak P, Itani H, Moussa E, Gut T. Life-threatening neurotoxicity following off-label ivermectin use in metastatic breast cancer: a case report.Postgrad Med · 2026 · 138(4):391-395doi:10.1080/00325481.2026.2672183 · PMID 42170801

    A 73-year-old woman with metastatic breast cancer who took high doses on the strength of what she read online, and arrived with seizures and respiratory failure; she recovered fully in 48 hours. One case, and the dose was not measured.

37. 37
    Henriquez-Camacho C, Gotuzzo E, Echevarria J, et al. Ivermectin versus albendazole or thiabendazole for Strongyloides stercoralis infection.Cochrane Database Syst Rev · 2016 · 2016(1):CD007745doi:10.1002/14651858.CD007745.pub3 · PMID 26778150

    The systematic comparison that makes ivermectin first choice for threadworm: more people cured than with albendazole, and fewer side effects than with thiabendazole. Seven trials and about eleven hundred people, with evidence graded moderate at best; none of the trials studied the severe disseminated form.

38. 38
    Romani L, Whitfeld MJ, Koroivueta J, et al. Mass Drug Administration for Scabies Control in a Population with Endemic Disease.N Engl J Med · 2015 · 373(24):2305-13doi:10.1056/NEJMoa1500987 · PMID 26650152

    The scabies result: treating whole island communities with oral ivermectin cut scabies by 94% in a year, better than cream or treating only the affected. Three communities rather than randomized individuals, one year of follow-up, and more mild side effects than with permethrin.

39. 39
    Basáñez MG, Pion SD, Boakes E, Filipe JA, Churcher TS, Boussinesq M. Effect of single-dose ivermectin on Onchocerca volvulus: a systematic review and meta-analysis.Lancet Infect Dis · 2008 · 8(5):310-22doi:10.1016/S1473-3099(08)70099-9 · PMID 18471776

    The source for what one dose does and does not do: larvae in skin fall by 98–99% within one to two months, the fraction of female worms carrying live larvae falls by only about 70%, and the skin is repopulated afterwards. A model fitted to 26 microfilarial and 15 macrofilarial studies, so it is a synthesis rather than a measurement.

40. 40
    King CL, Suamani J, Sanuku N, et al. A Trial of a Triple-Drug Treatment for Lymphatic Filariasis.N Engl J Med · 2018 · 379(19):1801-1810doi:10.1056/NEJMoa1706854 · PMID 30403937

    Shows what ivermectin does in lymphatic filariasis: added to two other drugs, one dose cleared larvae from the blood in 96% of people for three years. 182 adults in Papua New Guinea, with more moderate side effects in the three-drug arm; it measures larvae in blood, not swollen limbs prevented.

41. 41
    Ménez C, Sutra JF, Prichard R, Lespine A. Relative neurotoxicity of ivermectin and moxidectin in Mdr1ab (-/-) mice and effects on mammalian GABA(A) channel activity.PLoS Negl Trop Dis · 2012 · 6(11):e1883doi:10.1371/journal.pntd.0001883 · PMID 23133688

    The two halves of the toxicity story measured together: lethal doses in pump-free mice, brain concentrations at those doses, and the strength of the two drugs' action on the mammalian calming receptor. Mice and frog eggs; the receptor work used rat subunits, not human.

42. 42
    Melotti A, Mas C, Kuciak M, Lorente-Trigos A, Borges I, Ruiz i Altaba A. The river blindness drug Ivermectin and related macrocyclic lactones inhibit WNT-TCF pathway responses in human cancer.EMBO Mol Med · 2014 · 6(10):1263-78doi:10.15252/emmm.201404084 · PMID 25143352

    The best-built mechanistic case: ivermectin blocks a specific growth-signaling pathway, and only tumors that depend on that pathway shrink in mice. Cell lines and mouse grafts; its abstract singles out selamectin for clinical testing while also proposing ivermectin itself as a WNT-TCF blocker.

43. 43
    Yin J, Park G, Lee JE, et al. DEAD-box RNA helicase DDX23 modulates glioma malignancy via elevating miR-21 biogenesis.Brain · 2015 · 138(Pt 9):2553-70doi:10.1093/brain/awv167 · PMID 26121981

    A second mechanism, found while studying something else: ivermectin as a blunt inhibitor of an RNA-unwinding enzyme that brain tumors use. The drug is a tool here, not the subject, and the paper's own wording is that it works by 'potentially' inhibiting that enzyme.

44. 44
    Sharmeen S, Skrtic M, Sukhai MA, et al. The antiparasitic agent ivermectin induces chloride-dependent membrane hyperpolarization and cell death in leukemia cells.Blood · 2010 · 116(18):3593-603doi:10.1182/blood-2010-01-262675 · PMID 20644115

    The most careful of the early cancer papers: low micromolar killing of leukemia cells in preference to normal blood cells, a worked-out chloride and oxidant mechanism, and slower tumor growth in three mouse models. Its claim that those concentrations 'appear pharmacologically achievable' is the sentence the later human pharmacokinetics contradict.

45. 45
    Didier A, Loor F. The abamectin derivative ivermectin is a potent P-glycoprotein inhibitor.Anticancer Drugs · 1996 · 7(7):745-51doi:10.1097/00001813-199609000-00005 · PMID 8949985

    Where the cancer interest began: in resistant leukemia cell lines ivermectin blocked the pump that tumor cells use to expel chemotherapy, nearly as well as the reference blocker. Cell lines only, and the effect is on the pump, not on the cancer cell's survival machinery.

46. 46
    Draganov D, Han Z, Rana A, Bennett N, Irvine DJ, Lee PP. Ivermectin converts cold tumors hot and synergizes with immune checkpoint blockade for treatment of breast cancer.NPJ Breast Cancer · 2021 · 7(1):22doi:10.1038/s41523-021-00229-5 · PMID 33654071

    The most-cited animal result and the most interesting hypothesis: ivermectin alone did nothing in mice, but combined with an immune checkpoint antibody it produced lasting responses. Mice, and the paper now carries both an author correction and an editorial expression of concern, so its figures should not be relied on.

47. 47
    Draganov D, Han Z, Rana A, Bennett N, Irvine DJ, Lee PP. Author Correction: Ivermectin converts cold tumors hot and synergizes with immune checkpoint blockade for treatment of breast cancer.NPJ Breast Cancer · 2026 · 12(1)doi:10.1038/s41523-026-00908-1 · PMID 41760676

    The authors' own correction to that paper, published February 2026. A correction notice; PubMed indexes no abstract, so the record establishes that something was corrected, not what.

48. 48
    Editorial Expression of Concern: Ivermectin converts cold tumors hot and synergizes with immune checkpoint blockade for treatment of breast cancer.NPJ Breast Cancer · 2026 · 12(1)doi:10.1038/s41523-026-00988-z · PMID 42248882

    The journal's notice, dated 5 June 2026, that something about the paper is under investigation while it remains in print. An expression of concern is not a retraction and states no finding.

49. 49
    Nörenberg W, Sobottka H, Hempel C, Plötz T, Fischer W, Schmalzing G, Schaefer M. Positive allosteric modulation by ivermectin of human but not murine P2X7 receptors.Br J Pharmacol · 2012 · 167(1):48-66doi:10.1111/j.1476-5381.2012.01987.x · PMID 22506590

    A correction with direct bearing on mouse cancer experiments: ivermectin's supposedly selective action on one ATP receptor is species-dependent, strong on the human form and weak on the mouse and rat forms. Recombinant receptors and cultured human macrophages.

50. 50
    Juarez M, Schcolnik-Cabrera A, Dueñas-Gonzalez A. The multitargeted drug ivermectin: from an antiparasitic agent to a repositioned cancer drug.Am J Cancer Res · 2018 · 8(2):317-331PMID 29511601

    The review that collected the cancer mechanisms and gave the field its central claim — that the antitumor concentrations are clinically reachable. That claim is the one the pharmacokinetic modeling and the measured human peak concentrations contradict.

51. 51
    Ikeda H, Nonomiya T, Usami M, Ohta T, Omura S. Organization of the biosynthetic gene cluster for the polyketide anthelmintic macrolide avermectin in Streptomyces avermitilis.Proc Natl Acad Sci U S A · 1999 · 96(17):9509-14doi:10.1073/pnas.96.17.9509 · PMID 10449723

    How the bacterium builds the ring: twelve modules, 55 active sites, a P450 that closes the furan ring, and a separate nine-gene set for the oleandrose sugars. Molecular genetics; it says nothing about what the molecule does in an animal.

52. 52
    Lynagh T, Webb TI, Dixon CL, Cromer BA, Lynch JW. Molecular determinants of ivermectin sensitivity at the glycine receptor chloride channel.J Biol Chem · 2011 · 286(51):43913-43924doi:10.1074/jbc.M111.262634 · PMID 22033924

    Which part of the molecule matters: comparing ivermectin with selamectin suggested that the hydroxyl on the benzofuran is needed for high efficacy, while van der Waals contacts between the sugar tail and the M2–M3 loop are unimportant for sensitivity. Site-directed mutagenesis with electrophysiology on recombinant receptors; it also shows that the crystal structure's contacts do not generalize across the receptor family.

53. 53
    David MA, Orlowski S, Prichard RK, Hashem S, André F, Lespine A. In silico analysis of the binding of anthelmintics to Caenorhabditis elegans P-glycoprotein 1.Int J Parasitol Drugs Drug Resist · 2016 · 6(3):299-313doi:10.1016/j.ijpddr.2016.09.001 · PMID 27746191

    Names the benzofuran and the spiroketal as distinct binding sub-sites, and shows the sugars are what give the avermectins their extra affinity for the pump compared with sugar-free relatives. Docking against a crystal structure: a computed prediction, not a measured binding constant.

54. 54
    Zhang Z, Yu J, Song X, et al. Mechanistic insights into ammonium-driven metabolic regulation for enhanced nemadectin biosynthesis in Streptomyces cyaneogriseus.Bioresour Bioprocess · 2026 · 13(1):20doi:10.1186/s40643-026-01015-6 · PMID 41615585

    Cited for one structural fact the clinical literature assumes: moxidectin is made from nemadectin, a milbemycin produced by Streptomyces cyaneogriseus, by adding a methoxime at carbon 23. A fermentation-engineering paper; nothing in it concerns human use.

55. 55
    Ōmura S. A Splendid Gift from the Earth: The Origins and Impact of the Avermectins (Nobel Lecture).Angew Chem Int Ed Engl · 2016 · 55(35):10190-209doi:10.1002/anie.201602164 · PMID 27435664

    The discoverer's own Nobel lecture, describing the isolation first hand. A memoir of a discovery, not an independent evaluation of it.

56. 56
    Kiki-Mvouaka S, Ménez C, Borin C, et al. Role of P-glycoprotein in the disposition of macrocyclic lactones: A comparison between ivermectin, eprinomectin, and moxidectin in mice.Drug Metab Dispos · 2010 · 38(4):573-80doi:10.1124/dmd.109.030700 · PMID 20089736

    Measures how much of the drug's fate the pump controls, drug by drug, in mice with and without it. Mouse pharmacokinetics at one dose; human transporter handling is inferred, not shown.

57. 57
    Tan B, Opoku N, Attah SK, et al. Pharmacokinetics of oral moxidectin in individuals with Onchocerca volvulus infection.PLoS Negl Trop Dis · 2022 · 16(3):e0010005doi:10.1371/journal.pntd.0010005 · PMID 35333880

    Records the 2018 United States approval of moxidectin for onchocerciasis in people aged 12 and over, and measures why it lasts: a terminal half-life of about three weeks. Pharmacokinetics in fewer than a hundred infected adults; no efficacy endpoint.

58. 58
    Campbell WC, Fisher MH, Stapley EO, Albers-Schönberg G, Jacob TA. Ivermectin: a potent new antiparasitic agent.Science · 1983 · 221(4613):823-8doi:10.1126/science.6308762 · PMID 6308762

    The 1983 state of knowledge from the Merck team: a 22,23-dihydro derivative of avermectin B1, in commercial veterinary use, mechanism attributed to GABA-mediated neurotransmission, and human usefulness explicitly not yet known.

59. 59
    Caly L, Druce JD, Catton MG, Jans DA, Wagstaff KM. The FDA-approved drug ivermectin inhibits the replication of SARS-CoV-2 in vitro.Antiviral Res · 2020 · 178:104787doi:10.1016/j.antiviral.2020.104787 · PMID 32251768

    The experiment that started the COVID-19 story: a 5000-fold drop in viral RNA in monkey kidney cells in a dish. One cell line, no animals, and no statement of what dose a person would need to reach that concentration.

60. 60
    Naggie S, Boulware DR, Lindsell CJ, et al. Effect of Higher-Dose Ivermectin for 6 Days vs Placebo on Time to Sustained Recovery in Outpatients With COVID-19: A Randomized Clinical Trial.JAMA · 2023 · 329(11):888-897doi:10.1001/jama.2023.1650 · PMID 36807465

    The answer to the 'not enough, not long enough' objection: three times the approved dose for six days, 1206 participants, median recovery eleven days in both arms. Mostly vaccinated outpatients, so it speaks to that population and that era of the virus.

61. 61
    Hill A, Garratt A, Levi J, et al. Retraction to: Meta-analysis of Randomized Trials of Ivermectin to Treat SARS-CoV-2 Infection.Open Forum Infect Dis · 2022 · 9(3):ofac056doi:10.1093/ofid/ofac056 · PMID 35146053

    The formal retraction notice for that meta-analysis, published in February 2022. A notice, not an analysis: it establishes the withdrawal, not what the corrected estimate would have been.

62. 62
    Efimenko I, Nackeeran S, Jabori S, Gonzalez Zamora JA, Danker S, Singh D. REMOVED: Treatment with Ivermectin Is Associated with Decreased Mortality in COVID-19 Patients: Analysis of a National Federated Database.Int J Infect Dis · 2022 · 116S:S40doi:10.1016/j.ijid.2021.12.096 · PMID 35654561

    A retrospective database abstract withdrawn at its own authors' request, with their reasoning printed in the notice: the result was an association only, was being read as proof, and could lead patients to demand the drug. Unusual and worth reading as a record of how a weak finding travels.

63. 63
    Hazan S, Dave S, Gunaratne AW, Dolai S, Clancy RL, McCullough PA, Borody TJ. RETRACTED: Effectiveness of ivermectin-based multidrug therapy in severely hypoxic, ambulatory COVID-19 patients.Future Microbiol · 2022 · 17:339-350 · Retracteddoi:10.2217/fmb-2022-0014 · PMID 35135310

    A 24-patient uncontrolled case series of an ivermectin combination, compared against database controls, now typed as a Retracted Publication. It is the documented link between the COVID-19 episode and the cancer cohort: Peter McCullough is a coauthor of both.

64. 64
    Expression of Concern: Real-world Clinical Outcomes of Ivermectin and Mebendazole in Cancer Patients: Results from a Prospective Observational Cohort.Anticancer Res · 2026 · 46(6)doi:10.21873/anticanres.18276 · PMID 42300708

    The journal's notice of 9 June 2026 opening an audit of ethics approval, source-verified diagnoses and documentation of the reported tumor regressions, and stating that the journal does not endorse unvalidated off-label use.

65. 65
    Hopkins A. Beyond providing drugs: the Mectizan donation stimulates new strategies in service delivery and in strengthening health systems.Curr Pharm Biotechnol · 2012 · 13(6):1110-9doi:10.2174/138920112800399220 · PMID 22039801

    The source of the pledge as it is usually quoted — as much as was needed, for as long as it was needed — and of how the community-directed distribution model spread to other programs. A review by the program's own director.

66. 66
    Mujumdar V, Huang M, Smith LC, Musa F. Ivermectin and gynecologic cancer: What's the data?Gynecol Oncol Rep · 2025 · 60:101803doi:10.1016/j.gore.2025.101803 · PMID 40851910

    A specialty's answer to patients asking about the drug: it records the 1996 US approval for intestinal strongyloidiasis and onchocerciasis, finds the cancer evidence limited to cell lines, and cautions strongly against use in gynecologic cancers. A short review and a recommendation, not new data.

67. 67
    Gardon J, Gardon-Wendel N, Demanga-Ngangue, Kamgno J, Chippaux JP, Boussinesq M. Serious reactions after mass treatment of onchocerciasis with ivermectin in an area endemic for Loa loa infection.Lancet · 1997 · 350(9070):18-22doi:10.1016/S0140-6736(96)11094-1 · PMID 9217715

    The harm that changed how mass treatment is run: serious reactions, and two comas with worm larvae in the spinal fluid, concentrated in people carrying very heavy Loa loa burdens. An observational field study in one Cameroonian district; the risk estimate at the highest burdens rests on very few events.

68. 68
    Kamgno J, Pion SD, Chesnais CB, et al. A Test-and-Not-Treat Strategy for Onchocerciasis in Loa loa-Endemic Areas.N Engl J Med · 2017 · 377(21):2044-2052doi:10.1056/NEJMoa1705026 · PMID 29116890

    The fix: count the Loa loa larvae at the point of care with a phone-based microscope, skip the few people above the danger threshold, and treat the rest. A single-arm field program with no control district, so it shows feasibility and the absence of serious events, not a measured risk reduction.

69. 69
    Osei-Atweneboana MY, Awadzi K, Attah SK, Boakye DA, Gyapong JO, Prichard RK. Phenotypic evidence of emerging ivermectin resistance in Onchocerca volvulus.PLoS Negl Trop Dis · 2011 · 5(3):e998doi:10.1371/journal.pntd.0000998 · PMID 21468315

    The reversal inside the success story: in Ghanaian communities given 10 to 19 annual doses, about a quarter of infected people carried adult female worms that responded suboptimally to the drug's effect on fertility, while its larva-killing effect held. 268 people in nine treated communities; a field study, not a randomized comparison.

70. 70
    Doyle SR, Bourguinat C, Nana-Djeunga HC, et al. Genome-wide analysis of ivermectin response by Onchocerca volvulus reveals that genetic drift and soft selective sweeps contribute to loss of drug sensitivity.PLoS Negl Trop Dis · 2017 · 11(7):e0005816doi:10.1371/journal.pntd.0005816 · PMID 28746337

    What the genomes say about that resistance: it is a quantitative trait spread across about 31 regions, with little overlap between countries, and drift rather than selection for resistance explains most of the population difference. Pooled sequencing of 108 worms.

71. 71
    López-Medina E, López P, Hurtado IC, et al. Effect of Ivermectin on Time to Resolution of Symptoms Among Adults With Mild COVID-19: A Randomized Clinical Trial.JAMA · 2021 · 325(14):1426-1435doi:10.1001/jama.2021.3071 · PMID 33662102

    The first adequately sized randomized trial: no significant difference in how fast symptoms resolved. 400 adults with mild illness at a single site in Colombia, so it could not address severe disease or death.

72. 72
    Temple C, Hoang R, Hendrickson RG. Toxic Effects from Ivermectin Use Associated with Prevention and Treatment of Covid-19.N Engl J Med · 2021 · 385(23):2197-2198doi:10.1056/NEJMc2114907 · PMID 34670041

    The first prominent report of the harms, from a regional poison center; the record's indexing names confusion, seizures and hospitalization. A letter with no abstract in PubMed, so the case details come from the fuller papers by the same group.

73. 73
    Hill A, Garratt A, Levi J, et al. Meta-analysis of Randomized Trials of Ivermectin to Treat SARS-CoV-2 Infection.Open Forum Infect Dis · 2021 · 8(11):ofab358doi:10.1093/ofid/ofab358 · PMID 34796244

    The pooled analysis of 23 trials that was widely read as support. The abstract now indexed is the corrected replacement, whose primary analysis found no significant effect on survival or hospitalization; the version that circulated in July 2021 reported a significant reduction in deaths. PubMed types the record as a Retracted Publication; it should no longer be cited as evidence.

74. 74
    Popp M, Reis S, Schießer S, et al. Ivermectin for preventing and treating COVID-19.Cochrane Database Syst Rev · 2022 · 6(6):CD015017doi:10.1002/14651858.CD015017.pub3 · PMID 35726131

    The synthesis, after the reviewers excluded seven of the fourteen trials they had previously included — six because they were not prospectively registered and one because it was not randomized — leaving eleven trials and 3,409 participants: no benefit for outpatients, and real uncertainty for inpatients. It also records 28 trials held in limbo for unanswered questions about their methods.

75. 75
    Reis G, Silva EASM, Silva DCM, et al. Effect of Early Treatment with Ivermectin among Patients with Covid-19.N Engl J Med · 2022 · 386(18):1721-1731doi:10.1056/NEJMoa2115869 · PMID 35353979

    The large placebo-controlled outpatient trial at a dose twice the approved one: no reduction in hospitalization or prolonged emergency observation. Brazil, twelve public health clinics, three days of treatment.

76. 76
    Lim SCL, Hor CP, Tay KH, et al. Efficacy of Ivermectin Treatment on Disease Progression Among Adults With Mild to Moderate COVID-19 and Comorbidities: The I-TECH Randomized Clinical Trial.JAMA Intern Med · 2022 · 182(4):426-435doi:10.1001/jamainternmed.2022.0189 · PMID 35179551

    Tested the high-risk group the drug's advocates said would benefit, and found no protection against progressing to severe disease. Open-label with no placebo, which can inflate differences in either direction; the deaths were too few to interpret.

77. 77
    Barbosa AN, Chebabo A, Starling C, et al. Pan-American Guidelines for the treatment of SARS-CoV-2/COVID-19: a joint evidence-based guideline of the Brazilian Society of Infectious Diseases (SBI) and the Pan-American Association of Infectious Diseases (API).Ann Clin Microbiol Antimicrob · 2023 · 22(1):67doi:10.1186/s12941-023-00623-w · PMID 37550690

    A formal guideline, built on a systematic review and graded with GRADE, that discourages the use of ivermectin. A recommendation rather than new data, from one regional panel.

78. 78
    Lake SJ, Engelman D, Zinihite J, et al. One versus two doses of ivermectin-based mass drug administration for the control of scabies: A cluster randomised non-inferiority trial.PLoS Negl Trop Dis · 2023 · 17(3):e0011207doi:10.1371/journal.pntd.0011207 · PMID 36930667

    The scabies result that did not repeat: in 20 villages in Solomon Islands, neither one nor two rounds reduced prevalence at 21 months, although prevalence fell among people present at baseline. The authors attribute the failure partly to a pandemic-era influx of untreated people, so it is as much a lesson about mass treatment as about the drug.

79. 79
    Hayward G, Yu LM, Little P, et al. Ivermectin for COVID-19 in adults in the community (PRINCIPLE): An open, randomised, controlled, adaptive platform trial of short- and longer-term outcomes.J Infect · 2024 · 88(4):106130doi:10.1016/j.jinf.2024.106130 · PMID 38431155

    The largest and the most careful about the distinction that matters: self-reported recovery came about two days sooner, which fell short of the pre-specified threshold for a meaningful effect, while hospital admissions and deaths did not differ and recovery at six months was similar, 74.3% against 71.2%. Only 2,157 of the 8,811 people in the primary analysis received ivermectin, against 3,256 on usual care. Open-label, so the two-day difference in a self-reported symptom diary is exactly the kind of result that unblinding produces.

80. 80
    Chaccour C, Maia M, Kariuki M, et al. Ivermectin to Control Malaria - A Cluster-Randomized Trial.N Engl J Med · 2025 · 393(4):362-375doi:10.1056/NEJMoa2411262 · PMID 40700688

    The newest use: treating people to kill the mosquitoes that bite them, which lowered malaria infection in children by 26% against an active control. The endpoint is infection detected by testing rather than illness, and the effect was measured in one Kenyan county over six months.

81. 81
    Somé AF, Somé A, Sougué E, et al. Safety and efficacy of repeat ivermectin mass drug administrations for malaria control (RIMDAMAL II): a phase 3, double-blind, placebo-controlled, cluster-randomised, parallel-group trial.Lancet Infect Dis · 2025 · 25(7):737-750doi:10.1016/S1473-3099(24)00751-5 · PMID 39919778

    The null malaria trial: up to eight monthly rounds of high-dose ivermectin alongside seasonal chemoprevention, and no reduction in malaria incidence in children (incidence rate ratio 0.96). Fourteen clusters in Burkina Faso, and new dual-chemistry bed nets were distributed to every cluster mid-trial, which the authors say may have masked an effect.

82. 82
    Hutchins H, Pretorius E, Bradley J, et al. Adjunctive ivermectin mass drug administration for malaria control on the Bijagos Archipelago of Guinea-Bissau (MATAMAL): a quadruple-blinded, cluster-randomised, placebo-controlled trial.Lancet Infect Dis · 2025 · 25(4):424-434doi:10.1016/S1473-3099(24)00580-2 · PMID 39551062

    The second null malaria trial: adding ivermectin to mass dihydroartemisinin-piperaquine did not lower parasite prevalence (6.64% against 5.05%) or mosquito parity. 24 clusters, quadruple-blinded; coverage reached only about 60–79%.

83. 83
    Chaccour C, Nicolas P, Martinho S, et al. Ivermectin to reduce malaria transmission: safety and efficacy results from the BOHEMIA cluster randomized trial in Mozambique.EClinicalMedicine · 2025 · 90:103632doi:10.1016/j.eclinm.2025.103632 · PMID 41278243

    The companion trial to the Kenyan one, and the source for why it cannot be read as a result: flooding from the Gombe cyclone cost it 57 clusters, coverage was low and distribution late, and the authors call the efficacy data inconclusive (incidence rate ratios 0.99 and 1.05).

84. 84
    Klotz U, Ogbuokiri JE, Okonkwo PO. Ivermectin binds avidly to plasma proteins.Eur J Clin Pharmacol · 1990 · 39(6):607-8doi:10.1007/BF00316107 · PMID 2095348

    The missing number for protein binding: 93.2 ± 4.4% bound, by equilibrium dialysis. Five healthy individuals and a two-page report, from the group that also measured the blood levels in [26].

85. 85
    Le B, Clarke NE, Legrand N, Nery SV. Effectiveness of ivermectin mass drug administration in the control of soil-transmitted helminth infections in endemic populations: a systematic review and meta-analysis.Infect Dis Poverty · 2024 · 13(1):16doi:10.1186/s40249-024-01185-5 · PMID 38369483

    What community-wide treatment does to threadworm: a pooled 84% reduction in Strongyloides prevalence across five studies of ivermectin alone. Prevalence before and after, with high heterogeneity and no randomized comparison.

86. 86
    Naggie S, Boulware DR, Lindsell CJ, et al. Effect of Ivermectin vs Placebo on Time to Sustained Recovery in Outpatients With Mild to Moderate COVID-19: A Randomized Clinical Trial.JAMA · 2022 · 328(16):1595-1603doi:10.1001/jama.2022.18590 · PMID 36269852

    ACTIV-6's first ivermectin arm, at twice the approved dose: median recovery 12 days against 13, hazard ratio 1.07. Of 1,800 randomized, 1,591 were analyzed, 817 of them on ivermectin; mostly vaccinated US outpatients.

87. 87
    Bramante CT, Huling JD, Tignanelli CJ, et al. Randomized Trial of Metformin, Ivermectin, and Fluvoxamine for Covid-19.N Engl J Med · 2022 · 387(7):599-610doi:10.1056/NEJMoa2201662 · PMID 36070710

    COVID-OUT: a placebo-controlled factorial trial in adults with overweight or obesity, in which ivermectin did not reduce a composite of low blood oxygen, emergency visit, hospitalization or death (odds ratio 1.05). 1,323 of 1,431 randomized were analyzed; the trial's positive signal was for metformin, not ivermectin.

88. 88
    Bramante CT, Buse JB, Liebovitz DM, et al. Outpatient treatment of COVID-19 and incidence of post-COVID-19 condition over 10 months (COVID-OUT): a multicentre, randomised, quadruple-blind, parallel-group, phase 3 trial.Lancet Infect Dis · 2023 · 23(10):1119-1129doi:10.1016/S1473-3099(23)00299-2 · PMID 37302406

    The long-COVID follow-up of the same trial: no reduction with ivermectin (hazard ratio 0.99). The long-COVID outcome was a diagnosis reported by participants over ten months, a prespecified secondary endpoint rather than the trial's primary question.

89. 89
    Hill A, Garratt A, Levi J, et al. RETRACTED: Expression of Concern: 'Meta-analysis of Randomized Trials of Ivermectin to Treat SARS-CoV-2 Infection'.Open Forum Infect Dis · 2021 · 8(8):ofab394doi:10.1093/ofid/ofab394 · PMID 34410284

    The expression of concern the authors' own journal issued in August 2021, six months before the retraction. A notice with no abstract: it establishes that the paper was already in question while it was being circulated as support.

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    Hill A, Mirchandani M, Pilkington V. Ivermectin for COVID-19: Addressing Potential Bias and Medical Fraud.Open Forum Infect Dis · 2022 · 9(2):ofab645doi:10.1093/ofid/ofab645 · PMID 35071686

    The same authors' account of what their original estimate had rested on: stratified by trial quality, the significant survival effect depended on largely poor-quality studies, and the potentially fraudulent trial alone implied about twelve times the benefit of the low-risk ones (risk ratio 0.08 against 0.96). A reanalysis of the same published summaries, not new patient data.

91. 91
    Samaha AA, Mouawia H, Fawaz M, et al. RETRACTED: Effects of a Single Dose of Ivermectin on Viral and Clinical Outcomes in Asymptomatic SARS-CoV-2 Infected Subjects: A Pilot Clinical Trial in Lebanon.Viruses · 2021 · 13(6):989 · Retracteddoi:10.3390/v13060989 · PMID 34073401

    One of the favorable early trials, in 100 asymptomatic people, that PubMed now types as a Retracted Publication. Listed here as part of the record of what was withdrawn, not as evidence.

92. 92
    Pott-Junior H, Paoliello MMB, Miguel AQC, et al. RETRACTED: Use of ivermectin in the treatment of Covid-19: A pilot trial.Toxicol Rep · 2021 · 8:505-510 · Retracteddoi:10.1016/j.toxrep.2021.03.003 · PMID 33723507

    A 32-patient open-label pilot reporting faster viral clearance, now typed as a Retracted Publication. Listed as part of the retraction record.

93. 93
    Elshafie AH, Elsawah HK, Hammad M, et al. RETRACTED: Ivermectin role in COVID-19 treatment (IRICT): single-center, adaptive, randomized, double-blind, placebo-controlled, clinical trial.Expert Rev Anti Infect Ther · 2022 · 20(10):1341-1350 · Retracteddoi:10.1080/14787210.2022.2098113 · PMID 35788169

    A trial that reported harm — shorter survival time with ivermectin in hospitalized patients — and is also typed as a Retracted Publication. Worth naming because it shows retraction cutting against the drug as well as for it.

94. 94
    Lawrence JM, Meyerowitz-Katz G, Heathers JAJ, Brown NJL, Sheldrick KA. The lesson of ivermectin: meta-analyses based on summary data alone are inherently unreliable.Nat Med · 2021 · 27(11):1853-1854doi:10.1038/s41591-021-01535-y · PMID 34552263

    The methodological verdict, which is the whole of its title: pooling published summaries cannot detect a fabricated study, so the pooled estimate inherits the fabrication. A short letter; PubMed indexes no abstract, so the record supports the argument's existence and authorship rather than any count.

95. 95
    Farah R, Kazzi Z, Brent J, Burkhart K, Wax P, Aldy K. Ivermectin associated adverse events in the treatment and prevention of COVID-19 reported to the FACT pharmacovigilance project.Clin Toxicol (Phila) · 2022 · 60(8):942-946doi:10.1080/15563650.2022.2070187 · PMID 35535587

    The same pattern across fifteen academic medical centers in twelve states: 40 patients, nearly half taking animal products, and nervous-system effects the most common finding. A voluntary case registry, which cannot give a rate.

96. 96
    Rujimongkon K, Adchariyasakulchai P, Boonyaratsewee C, Horpratraporn K, Ketchart W. Ivermectin inhibits ER, HER2, and TGF-β pathways in ER-positive and endocrine-resistant breast cancer cells.PLoS One · 2026 · 21(4):e0348260doi:10.1371/journal.pone.0348260 · PMID 42060658

    The most recent mechanistic addition, in hormone-resistant breast cancer cells: ivermectin suppressed estrogen-driven growth and several resistance markers. Cultured cells only, and the paper reports no concentrations in its abstract that could be compared with human blood levels.

97. 97
    Lu H, Zhou L, Zuo H, et al. Ivermectin synergizes sorafenib in hepatocellular carcinoma via targeting multiple oncogenic pathways.Pharmacol Res Perspect · 2022 · 10(3):e00954doi:10.1002/prp2.954 · PMID 35568994

    A liver cancer paper that claimed activity 'at clinically relevant concentrations' and called for trials. PubMed types it as a Retracted Publication; it is listed here only because it was influential, and it should not be cited as evidence.

98. 98
    RETRACTION: Ivermectin Synergizes Sorafenib in Hepatocellular Carcinoma via Targeting Multiple Oncogenic Pathways.Pharmacol Res Perspect · 2026 · 14(1):e70222doi:10.1002/prp2.70222 · PMID 41689298

    The retraction notice for that paper, published February 2026. It establishes the withdrawal; PubMed indexes no abstract, so it states no grounds here.

99. 99
    Liu J, Liang H, Chen C, et al. RETRACTED: Ivermectin induces autophagy-mediated cell death through the AKT/mTOR signaling pathway in glioma cells.Biosci Rep · 2019 · 39(12) · Retracteddoi:10.1042/BSR20192489 · PMID 31755894

    A second retracted cancer paper, on glioma cells and mouse xenografts. PubMed types it as a Retracted Publication; it is listed only because the cancer literature cites it.

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     Guilford FT, Yu S. Cancer Therapy Using Antiparasitic Medications Guided by Acupuncture Meridian Assessment: A Case Series of Six Patients.Integr Med (Encinitas) · 2026 · 25(3):27-33PMID 42491797

     Six patients given mixtures of antiparasitic drugs chosen by measuring electrical conductance at acupuncture points, all reported to have outlived their prognoses. Six selected patients with no control, no blinding and no validated allocation method; both authors list Your Energy Systems, a commercial company, and the record carries no DOI.

101. 101
     Cheng R, Araujo DV. Case Report: Metastatic melanoma with initial ctDNA decline and radiographic response during self-directed antiparasitic use: treatment effect or spontaneous regression?Front Oncol · 2026 · 16:1907192doi:10.3389/fonc.2026.1907192 · PMID 42745863

     The honest version of the single-patient story: a melanoma that shrank, and its blood tumor-DNA that fell, while the patient took ivermectin and fenbendazole instead of standard treatment — and then grew again. The authors note the tumor's very high mutation count makes spontaneous immune regression at least as likely an explanation.

102. 102
     Powderly GE, Hassevoort K, Loy M, Balonier J, Sievers C. Drug-Induced Liver Injury Following Co-ingestion of Veterinary Fenbendazole and Ivermectin for Prostate Cancer: A Case Report.Cureus · 2026 · 18(5):e108896doi:10.7759/cureus.108896 · PMID 42299164

     What dosing from an animal product by the squirt can do: severe liver injury in a man with prostate cancer, reversing over six weeks once he stopped. One case, with two drugs taken together, so it cannot apportion the injury between them.

103. 103
     Asano Y, Han Q, Li S, et al. Selective Synergy of the Combination of Recombinant Methioninase With Cisplatinum and Ivermectin Which Eradicates Lung-Cancer Cells but Has No Synergy and Limited Effect on Normal Fibroblasts.Anticancer Res · 2025 · 45(12):5389-5398doi:10.21873/anticanres.17875 · PMID 41318162

     A current example of where the laboratory work has gone: three-drug combinations that wipe out a lung cancer line while sparing normal cells. Each drug was given at its 30% inhibitory concentration, which for ivermectin was 2.08 micromolar in the cancer cells — above what oral dosing reaches; most of the authors list AntiCancer Inc., which develops the partner enzyme.

104. 104
     Kanza EM, Nyathirombo A, Larbelee JP, et al. Onchocerca volvulus microfilariae in the anterior chambers of the eye and ocular adverse events after a single dose of 8 mg moxidectin or 150 µg/kg ivermectin: results of a randomized double-blind Phase 3 trial in the Democratic Republic of the Congo, Ghana and Liberia.Parasit Vectors · 2024 · 17(1):137doi:10.1186/s13071-023-06087-3 · PMID 38491528

     Looks specifically at the eye after treatment and finds larvae in the front of the eye rising in a fifth of participants in the first days, with reactions in roughly one in ten on either drug. A secondary analysis of one trial; it cannot say what those transient increases mean for sight years later.

105. 105
     Wanji S, Eyong EJ, Tendongfor N, et al. Ivermectin treatment of Loa loa hyper-microfilaraemic baboons (Papio anubis): Assessment of microfilarial load reduction, haematological and biochemical parameters and histopathological changes following treatment.PLoS Negl Trop Dis · 2017 · 11(7):e0005576doi:10.1371/journal.pntd.0005576 · PMID 28686693

     The nearest thing to a mechanism for Loa loa encephalopathy: in treated baboons, degenerating larvae lodged in small vessels of the brain and other organs with fibrin deposits, vessel-wall damage and bleeding, and brain larval counts tripled. Twelve animals, and a parallel rather than a proof for the human events.

106. 106
     Rumgay H, Georges D, Huang Y, et al. Global burden of cancer attributable to infections in 2024: a worldwide incidence analysis.Lancet Oncol · 2026 · 27(10):1237-1248doi:10.1016/S1470-2045(26)00307-4 · PMID 42805198

     The current count of which infections are established causes of cancer and how much they cause: twelve agents, 2.3 million cases in 2024, about 12% of all cancers. Only three of the twelve are parasites, and all three are flukes; roundworms, which is what ivermectin treats, are not among them.

107. 107
     Mertelsmann AM, Bowers SF, Wright D, et al. Effects of Schistosoma haematobium infection and treatment on the systemic and mucosal immune phenotype, gene expression and microbiome: A systematic review.PLoS Negl Trop Dis · 2024 · 18(9):e0012456doi:10.1371/journal.pntd.0012456 · PMID 39250522

     The reference point for the one fluke that causes bladder cancer: urogenital schistosomiasis affects about 110 million people, and infection with Schistosoma haematobium has been associated with bladder cancer and with HIV acquisition. A systematic review of 94 studies on immunity, gene expression and microbiome; it describes mechanisms with oncogenic potential rather than measuring cancer risk.

108. 108
     Huang YL, Zhang KY, Sun YL, Qian MB, Wang Z. The risk of hepatobiliary complications in Clonorchis and Opisthorchis infection: A systematic review and meta-analysis.Acta Trop · 2024 · 260:107457doi:10.1016/j.actatropica.2024.107457 · PMID 39521195

     The size of the real parasite-cancer effect, for comparison: liver fluke infection carries a roughly fourfold odds of bile duct cancer across 22 studies and 34,367 people. Observational studies, and the flukes are treated with praziquantel, not ivermectin.