What we need to know about ivermectin and cancer

ot content with shaming people for hoping ivermectin (IVM) will benefit patients with Covid, some tabloid newspapers and tech news sites are now ridiculing the idea that IVM is a possible treatment for cancer. The reason is not that clinical trials have not yet been done. The reason is that some of the support for IVM is coming from their political opponents.

Some writers are even digging up old scare stories like we saw with hydroxychloroquine (HCQ) during Covid. This is unhelpful. People’s lives are at stake. Calling everything you don’t understand a ‘conspiracy theory’ or some other pejorative would return us to the nasty politicized science of the Covid era.

What is ivermectin and what does it do

Ivermectin is called a ‘small molecule’ because it’s not an antibody, but it is big enough (mw 875.09) to have trouble crossing the blood-brain barrier. In helminths and insects, IVM binds to glutamate-gated chloride channels, keeping them in an open state, which causes hyperpolarization of nerve cells. Because it has low ability to cross the blood-brain barrier, which invertebrates lack, it is relatively safe for humans.

This means that if it works against cancer, it must act by some other as yet undeter­mined mechan­ism. IVM has ‘pleiotropic’ effects on human cultured cells in vitro, which means it affects a wide variety of seemingly unrelated pathways including Wnt/β-catenin, PI3K/Akt, mTOR, STAT3, NFκB, caspases, PAK1, Bax/Bcl-2, and Importin-2.^[1] It could induce apoptosis (programmed cell death), inhibit cell proliferation, induce oxidative stress, or do something else that hasn’t been discovered.

People associate ivermectin with horses because everybody loves horsies

What does this mean? When authors propose large numbers of possible mechanisms to a drug, it’s a polite way of saying they have no clue how it works. Research­ers get skeptical when the mechanism of action is unknown. Often such drugs fail in clinical trials even if they have a potential benefit.

Ivermectin has very low toxicity and low cost, but it can be degraded by light and low pH. It has low solubility in water and therefore limited bioavailability when taken orally, which could hamper drug trials. Structurally it is a macrocyclic lactone that resembles other drugs that were tried in the past against cancer but failed.

Mechanism of action (MoA)

Mechanism of action is practically a worship word in pharmacology. Having the MoA means that you know the drug’s molecular target and what the target does when the drug binds to it. Knowing the mechanism of action is essential. If we know the molecular target, we can measure target engagement, which gives us confidence that it is working in people.

Just knowing the pharmacokinetic profile, which tells us the total amount of a dose that gets there (called the AUC, area under the curve), isn’t enough. We could only guess whether the amount the AUC tells you is enough or too much. Too high a concentration not only causes unwanted side effects; it can also induce the body’s protective mechanisms to get rid of it.

This happens, for example, with protein kinase C (PKC) activators. A high dose causes PKC levels to drop precipitously, so you have five minutes of increased enzyme activity followed by 24 hours of no activity. Which one is the effect you want to maximize? There’s no way to know. The same drug is called an activator or an inhibitor depending on which one the investigator decides is important.

Without knowing the target, you can’t set the dosage or dose schedule and you can’t rationally search for adverse effects. For some PKC activators, the target was the C1A and C1B domain on a specific protein. One guy published paper after paper warning that there are some 23 other proteins besides PKC that contain the same motif, so the drug could in principle do an astronomical number of different things. Little wonder it failed. The company promoting the drug dropped the whole program and pivoted to erectile dysfunction, and their stock price shot back up.

As for IVM, ‘modulating the environment,’ as is sometimes claimed for IVM, is a weasel word in science: ‘modulating’ has no particular meaning in biochemistry, and changing the environment usually means an effect on lysosomal pH. ‘Inducing apoptosis’ is another. Apoptosis can eliminate fast-growing cancer cells and is useful if the drug is given for a limited duration, but almost anything that stresses a cell can induce apoptosis. As for Wnt, PI3k, mTOR, and STAT3, we run into a bigger problem: as far as oncologists are concerned, anything that causes cell growth is bad and anything that kills them is good. This tunnel vision pervades the industry and the FDA, which is why we may never see a drug that regrows lost brain cells.

Why repurposing drugs can fail

Drugs invented to treat one illness are sometimes found to treat another. It’s called repurpos­ing, but what it often means is either (a) the drug’s effects are non-specific, or (b) the claims of an effect on the first disease were mistaken.

IVM deserves to be investigated, but using IVM for cancer without knowing what it does is a recipe for failure. The idea is that cancer is so terrible that we must try everything even if we don’t know how it works. But if we do, clinicians will be shooting in the dark and drug developers, whose job is to invent better versions of the drug, will have no clue what effect to enhance.

This is one reason Big Pharma doesn’t like repurposing. Repurpos­ing is popular among academics because the drug has already been in patients, so expensive preclinical and phase 1 testing, where you look for side effects, can be skipped. One drug I worked on was notorious in the lab for having what were euphem­ist­ically called ‘behavioral effects.’ It turned the mice ‘vicious’ and our lab techs refused to go near them. Management ignored the reports because the previous trials were not studying the brain and so never looked for or reported any neurological side effects. The patients were heroic in their determination to live and didn’t complain.

Non-specific treatments can also cause drug interactions because they bind to multiple targets. A few years ago there was a report of an Irish patient who was put on 13 different drugs. If each drug had one unwanted target, this patient would have had 169 different things going on. No pharmacist could ever have predicted the result. The patient eventually died of sepsis, which wasn’t even on the list of known side effects. The hospital chalked it up to bad luck.

This happens here in the US as well. If you get treated in a hospital, they’ll send you an email or text once a year to find out if you’re still alive. If you’re not, if for instance you died of “complications of surgery” a week after being discharged, all you have to do is not reply and they’ll make a note of it in their computer.

Repurposing statins

Even if a drug is highly specific for a target, the target itself can have many different and even opposing functions. The classic example is statins. Statins were developed to block HMG-CoA reductase, the rate-limiting enzyme in cholesterol synthesis. They were profitable, so Big Pharma rushed to create a whole slew of other drugs that blocked the enzyme more efficiently. But we now know that their therapeutic effect was not just due to reducing cholesterol.

Blocking the reductase also prevented the synthesis of prostaglandins, so some people decided statins were anti-inflammatory drugs. They also blocked protein anchoring because the reductase is a step in making isoprenoids, which attach membrane proteins to the membrane. So the idea now is to use a statin to prevent protein anchoring, which (the theory goes) is needed for breast cancer. Unfortunately, we need protein anchoring. Without it, we would be dead.

Statins also inhibit cell growth by blocking coenzyme Q10, which is a component of the mitochondrial electron transport chain. Atorvastatin (and probably other statins) cause mitochondrial dysfunction and cell death via ferroptosis in muscle cells. This causes muscle wasting in heart patients.

One cancer researcher writes:

In cancer cells, simvastatin disrupts the production of mevalonate pathway-derived intermediates that are essential for the prenylation of small GTPases, including members of the Ras and Rho families . . . By blocking the prenylation and proper membrane localisation of these GTPases, simvastatin impairs signalling pathways that are fundamental for cancer cell proliferation, survival, migration and invasion. . . the concentrations required for in vitro anticancer effects are approximately 200–900 times higher than those achieved with standard cholesterol lowering doses. ^[2]

Jacking up your dose of statin a thousand fold won’t be easy. Assuming such high levels of drug would be soluble, cancer treatment is painful enough as it is. A drug that blocks prenylation would have to have some specificity for cancer cells, otherwise it would just block signaling pathways everywhere. I shudder to think what that would do to your nervous system.

Repurposing cancer

It’s now recognized that cancer protects against Alzheimer’s disease (AD). The reason is a complete mystery: is AD being incorrectly diagnosed as cancer drug-induced dementia? Or is there some difference in their immune systems? Or do anti-cancer drugs somehow prevent AD? If people running clinical drug trials took the time to measure cognitive ability and the immune state, we would have a better idea. But on the AE sheets for neurological diseases they won’t mention any effects on patients’ cancer, and on AE sheets for cancer they don’t mention if they showed cognitive improvement. Entering and sharing this information would be enormously helpful.

Repurposing SSRIs

The selective serotonin reuptake inhibitor (SSRI) Prozac, aka fluoxetine, was originally a weight loss drug, then an antidepressant, and now also being repurposed for treating cancer. If it works it might be particularly valuable, as most anticancer drugs can’t cross the blood-brain barrier. There are thousands of anecdotal reports of harmful psychiatric effects from SSRIs. Using them for cancer might cause neurological problems, but we might also find commonalities between depression and cancer. Indeed, many researchers have found that the immune system is heavily involved in neuropsychiatric disorders and that cancer can cause brain problems well before it’s bad enough to be diagnosed.

Some people speculate that the side effects of some SSRIs are due to fluoride reaching the brain,^[8] which would be bad. Fluoxetine (Prozac), a fluoridated SSRI, also inhibits REM sleep, which could contribute to the reported harmful psychiatric effects. Note that the fluorine atoms are covalently attached to a carbon, so the molecule would have to get chemically degraded by intestinal bacteria or by ultraviolet light to release a fluoride. It wouldn’t just exchange with hydrogen ions.

Some researchers also believe that when antidepressants cause mania (called treatment-emergent affective switch or TEAS), maybe the SSRIs and SNRIs are converting unipolar depression into bipolar disorder. Others disagree, saying the patient could have actually had undiagnosed bipolar disorder. This question is still being debated.

Another idea is repurposing sertraline ^[3] and paroxetine ^[4] for cancer. Sertraline is a popular SSRI that is said to cause apoptosis by causing mitochondrial dysfunction, activation of caspases, and downregulation of Bcl-2. It also suppresses mTOR. Paroxetine (Paxil, another SSRI used for OCD), is thought to activate ubiquitination and proteasomal degradation of PD-L1, a biomarker of adaptive immune resistance in immunotherapy for NSCLC (non-small cell lung cancer).

The seemingly inexplicable ability of one drug to treat two radically different diseases is not necessarily a drawback. It could be a clue that the diseases have more in common than previously thought.

Repurposing fumarate

Dimethyl fumarate, which is used for plaque psoriasis and relapsing multiple sclerosis, is also being repurposed for cancer ^[5] and even for Alzheimer’s and Parkinson’s diseases.^[6][7] It is thought to up- or down-regulate the Nrf2 pathway, NFκB, and cGAS-STING inflammation signaling, and to cause necroptosis and ferroptosis. Most of these things are responses to oxidative stress. It is also clastogenic, which means it can damage your chromosomes. So it is suspected of causing cancer and also curing it: truly a molecule for all seasons.

No one questions whether these drugs can do so many contradictory things. A drug that does everything goes beyond two-edged sword, blasts past ‘Swiss army knife,’ and practically becomes a pharmacologic sea urchin. No wonder Big Pharma is migrating to antibodies.

Repurposing poison gas

Maybe the most dramatic repurposing of all time was the use of mustard gas, whose purpose was to kill people, as a treatment for leukemia. This led to a big push to find other, less-deadly drugs that could smash up your DNA. Nowadays, doctors inhibit the DNA damage response and administer DNA-smashing drugs at the same time to selectively kill rapidly growing cells.

Repurposing can be a valuable tool provided that the drug’s mechanism of action is known, but a repurposed drug by definition will create side-effects because its activity is a side effect. The risk is that doctors, taught that some drug is a standard treatment and therefore is harmless to the patient, might put a patient on it indefinitely.

Maybe repurposing ivermectin won’t work. But even if it doesn’t, we’ll learn a lot from testing it. Anyone who hopes it doesn’t work because they hate Trump or RFK Jr has a serious problem with their sense of right and wrong. Unfortunately, there’s no drug that can cure that.

feb 13 2026, 3:11 am