For far too many patients, there’s one more major concern that threatens their health and livelihoods — the price of their prescription medications. We’ve all followed the intense healthcare debates in Washington, but little, if anything, has changed. To make matters worse, the processes for developing innovative new medications for devastating diseases like cancer are slow and expensive. But we may not have to wait for pharmaceutical companies. Drug repurposing is a drug development strategy that makes use of the untapped potential of currently available treatments. By finding new purposes for drugs that are off-patent or close to patent expiry, we may be able to meet the unmet needs of patients.
Recently, a drug called disulfiram has been receiving lots of attention for its broad range of potential uses. So, can one drug deter alcohol use, kill antibiotic-resistant bacteria, treat cancer, and eradicate Lyme disease? Let’s find out.
What is Disulfiram?
Disulfiram, also known by the brand name Antabuse, is a drug that has been used to treat chronic alcoholism since its FDA approval in 1951.1 A member of a family of drugs called dithiocarbamates, disulfiram blocks an enzyme called aldehyde dehydrogenase (ALDH).
To understand how disulfiram works, let’s briefly discuss what happens when you drink alcohol. There are several ways your body breaks down and eliminates alcohol, but the most common pathway involves two enzymes, ALDH and alcohol dehydrogenase (ADH). Shortly after a person drinks alcohol, ADH in the liver converts most of the ethanol into a highly toxic compound (or metabolite) and a known carcinogen called acetaldehyde. Fortunately, acetaldehyde is short-lived; it gets broken down by ALDH into a less-toxic compound called acetate. Afterward, acetate is broken down into carbon dioxide and water.
But the problem is, these processes take time. And heavy drinking leads to a buildup of acetaldehyde, which in turn inhibits ALDH activities. When alcohol fails to be properly metabolized, a person experiences unpleasant effects physicians refer to as “alcohol flush reaction.” Symptoms of this condition include:
- Facial flushing
- Chest pain
- Blurred vision
- Difficulty breathing
- Mental confusion
- General “hangover” symptoms
Although unpleasant, these symptoms are precisely why disulfiram works. The drug blocks ALDH, causing acetaldehyde levels in the blood to rise quickly when alcohol is consumed. Patients experience these effects even after drinking small amounts of alcohol. And while disulfiram is certainly not a cure for alcoholism, its effectiveness and favorable safety profile made disulfiram a popular part of treatment regimens for over 60 years.
Disulfiram and Cancer
While lack of patient compliance may have made disulfiram less popular in recent years, disulfiram may be able to find a new life as an anticancer therapy. This is significant not only for the enormous cost-saving benefits, but for the ability of disulfiram to kill many different types of cancer cells.
This isn’t news to scientists. In fact, it was in 1971 that they noticed the anticancer potential of disulfiram. Since then, several clinical trials have found that disulfiram can also increase survival rates among cancer patients.
So why has it taken almost 50 years for disulfiram to start getting attention?
Part of the reason was because scientists didn’t agree on how disulfiram worked. But as newer studies come out, it’s becoming increasingly evident that disulfiram should be repurposed as a cancer drug. And so far, disulfiram has been shown to be effective for several types of cancers, including:
- Glioblastoma (a type of brain cancer)
Laboratory and animal studies have shown that the main metabolite of disulfiram, diethyldithiocarbamate (DDC), is a strong chelator of certain metal ions (copper and zinc in particular). When combined with copper, DDC inhibits proteasome, a protein complex responsible for degrading thousands of damaged, misfolded, or otherwise unnecessary proteins. The inhibition generates reactive oxygen species (ROS), which damages DNA, proteins, and lipids. This ultimately leads to cell death or increased sensitivity of cancer cells to treatment.2
In other words, DDC and copper effectively “freezes” the machinery in cells, and the resulting protein buildup causes cancer cells to become stressed and die. Additionally, proteasome inhibition is an attractive property to researchers because it allows disulfiram to distinguish normal cells from cancer cells, which are much more dependent on proteasome activity.
Another anti-cancer property of disulfiram is its ability to block the formation of new blood vessels, which help tumors grow. Cancer cells and tissues have high levels of copper for this process, which means that copper is a potential tumor-specific target.3
While finding new purposes for old drugs is always exciting, this does not mean that disulfiram is a cure for cancer. Disulfiram certainly may help extend the lives of patients with metastatic cancer, but scientists are still trying to figure out the exact mechanism by which disulfiram exerts its anticancer effects.
Disulfiram and Lyme Disease
As we’ve discussed in my article Is Lyme Disease the Result of a Biological Warfare Experiment Gone Wrong?, chronic Lyme disease is becoming increasingly common and problematic. Among the small number of pathogens capable of persisting despite sophisticated host immune responses, the spirochete Borrelia burgdorferi gets special recognition because researchers still have not been able to elucidate the mechanisms that sustain its long-term survival. What we do know is that the spirochete has several remarkable abilities to adapt, which include:
- The ability to hide within cells of certain tissues during or between stages of disease4
- The ability of B. burgdorferi to change its morphology in response to varying environmental conditions5
- Formation of a biofilm that enables B. burgdorferi to be more resilient to stress
- Suppression of host immune response
So, what does this mean? It means that when antibiotics are used to treat persistent infections like B. burgdorferi, we likely end up with highly persistent mutants. This is a separate phenomenon from antibiotic resistance, and it is becoming increasingly clear that currently available treatments do not do enough to eliminate B. burgdorferi or its coinfections. And while physicians and patients alike have good reason to be very skeptical of medical breakthrough claims, recent research indicates that disulfiram just may be the real thing.
Researchers regularly screen medicinal compound libraries to identify molecules that may be effective against a specific target. In screenings that included 7,450 drug molecules, disulfiram was identified as highly active against both B. burgdorferi and babesiosis, a common Lyme disease coinfection.
As you might expect, this finding was surprising to scientists. Some hypothesized that B. burgdorferi or Babesia may have an enzyme similar to aldehyde dehydrogenase, but they have not been able to find one yet. Others think that the complex formation of disulfiram and metal ions that cause the death of cancer cells may also inhibit bacterial growth.6
Although we don’t know how disulfiram kills Babesia and the persister forms of B. burgdorferi, clinicians are already reporting its effectiveness against the diseases they cause. A report published in June 2019 presented the cases of three patients, all of whom had been treated for relapsing Lyme disease and babesiosis for several years with open-ended antimicrobial therapy. Once they started disulfiram, however, all three patients reported significant improvement. Two of the patients were able to stay off all antimicrobials and stay clinically well during the 6- to 23-month post-treatment observation period. The third patient relapsed after 6 months, but was placed on a second course of disulfiram at the time the article was published.7
Supporting the Immune System When You Have Lyme Disease
In an interview with Science Daily in April 2018, Lyme disease expert Dr. Utpal Pal of the University of Maryland stated, “Lyme disease is actually caused by your immune system.” He and his team had identified a surface protein of B. burgdorferi, BBA57, that impairs various early efforts by the immune system to eliminate the bacteria. He explained, “This bacteria wins the first battle, and your body overreacts so much that it causes intense inflammation in all the joints and areas that the bacteria spreads by sending in so many reinforcements to kill it. Borrelia is then killed, but the inflammation remains and causes many of your symptoms for Lyme disease.”8
What was even more surprising — and concerning — was the plasticity of B. burgdorferi. In their research, Pal and his team found that even in the absence of BBA57, B. burgdorferi was able to undergo adaptive changes in their genome to evade the immune system. This simply means that B. burgdorferi appears to have multiple lines of defense — if BBA57 isn’t there to beat back the first wave of immune defense, infection can recur at a later time.9
Another study from the Bay Area Lyme Foundation also underlined the importance of having a robust immune system to fight off the initial stage of Lyme disease. The study by the Bay Area Lyme Foundation found that patients with a competent immune response — namely the response of B cells which produce antibodies — were less likely to remain sick after a 21-day course of doxycycline.10
Simply put, your immune system is driving B. burgdorferi to undergo genomic changes, but the healthier it is, the faster it will figure out what’s going on and clear the infection. Healthier patients may also experience fewer symptoms during infection.
It’s important to note that while antibiotics may be effective at killing B. burgdorferi, they do not discriminate between good and bad bacteria. This means that antibiotics can take a great toll on your body unless you support your immune system before and during treatment. To do this, I recommend Transfer Factor L-Plus, a targeted formula of immune messenger molecules that can stimulate the immune system. I also use Pantethine to boost the immune system and help reduce inflammation.
Side Effects of Disulfiram
Although generally well-tolerated, several adverse effects of disulfiram have been documented. The most serious side effects of disulfiram include:
- Symptoms of encephalopathy, such as paranoid ideas, disorientation, impaired memory, weakened balance or coordination, slow or slurred speech, abnormal brain activity on electroencephalograms11
- Cranial neuropathy (damage to nerves in the brain or brainstem)14
- Peripheral neuropathy (damage to nerves that connect the brain and spinal cord to the rest of the body)15,16
- Toxic optic neuropathy (damage to the optic nerve caused by a toxin)17
- Irreversible damage to the basal ganglia (brain structures that help control movement)18
- High blood pressure19
- Drug-induced psychosis20,21,22
- Liver damage resulting in liver transplantation and/or death23,24,25,26,27,28
Based on the pathways through which disulfiram acts, it also has the potential to interact and have major impacts on the activities of other prescription drugs, such as warfarin, opioids, antidepressants, phenytoin, barbiturates, antihistamines, etc. Therefore, concurrent use of disulfiram and other therapies need to be carefully monitored and dosage adjustments may be required.
If your doctor prescribes disulfiram, be sure to avoid consuming any alcohol, including over-the-counter products that may contain alcohol. People with an allergy to vulcanized rubber should also avoid disulfiram.
Is Disulfiram the Breakthrough Drug We’ve Been Looking for?
Using drugs designed to treat one condition for other unrelated ones might sound like an odd concept, but it’s been happening for decades. And not just for cancer, either. From asthma drugs repurposed to treat Parkinson’s disease to morning sickness treatments now used to treat melanoma, drug repurposing can deliver better treatments faster.
Disulfiram displays all the properties required for it to be repurposed as an anti-cancer, anti-parasitic, or anti-mycobacterial treatment. Of course, clinical trials still need to be conducted to determine the optimal dosage as well as the duration of treatment, but there is no denying that disulfiram has the potential to be a highly economical, practical, and safer alternative to many of the other drugs available.
Now it’s time to hear from you. What are your thoughts on disulfiram? Have you or a loved one had experience being treated with a repurposed drug? Share your story in the comments below!