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
- Nausea
- Headache
- Vomiting
- Chest pain
- Weakness
- Blurred vision
- Sweating
- Choking
- Difficulty breathing
- Anxiety
- 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:
- Prostate
- Breast
- Colon
- Lung
- Glioblastoma (a type of brain cancer)
- Melanoma
- Ovarian
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
- Convulsions12,13
- 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!
References:
- https://www.accessdata.fda.gov/scripts/cder/daf/index.cfm?event=reportsSearch.process&rptName=1&reportSelectMonth=8&reportSelectYear=1951&nav
- https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4295765/
- https://www.ncbi.nlm.nih.gov/pubmed/26254539
- https://iai.asm.org/content/iai/59/2/671.full.pdf
- https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4339653/
- https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4827596/
- https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6627205/
- https://www.sciencedaily.com/releases/2018/04/180402171044.htm
- https://www.pnas.org/content/115/16/E3788
- https://www.frontiersin.org/articles/10.3389/fimmu.2018.01634/full
- https://www.ncbi.nlm.nih.gov/pubmed/1252149/
- https://www.ncbi.nlm.nih.gov/pubmed/26664087/
- https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4623653/
- https://www.ncbi.nlm.nih.gov/pubmed/27846399/
- https://www.ncbi.nlm.nih.gov/pubmed/27029711/
- https://www.ncbi.nlm.nih.gov/pubmed/4328367/
- https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3116542/
- https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1015193/
- https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4201801/
- https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4003787/
- https://www.ncbi.nlm.nih.gov/pubmed/28138114/
- https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1238733/
- https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1630947/
- https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2417987/
- https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4087419/
- https://www.journal-of-hepatology.eu/article/S0168-8278(06)00007-9/fulltext
- https://www.ncbi.nlm.nih.gov/pubmed/2646364/
- https://www.ncbi.nlm.nih.gov/pubmed/25004669/
I’m in the process of clearing parasites and heavy metals. I thought I would go after viruses next. I have to say, when I saw the topic of your article, I got excited. After reading the list of possible side effects, it didn’t take long for me to decide NOT WORTH IT!
Indeed! There are many natural treatments available. No need for yet another dangerous psychotropic drug!
Wendy Bolt – While I agree that psychiatric drugs are WAY over prescribed and that they generally do more harm than good, Disulfiram is NOT a psychotropic drug. Simply because a drug can effect ones mental state in rare cases as a side effect does not make it a psychotropic drug.
By the way, if you had ever had to spend decades of your life being constantly mentally and physically exhausted all the time and were in severe pain from the time you woke up in the morning until you finally managed to fall asleep at night, you would most likely not give a damn about how natural a potential cure was. All you would care about is how well it works. And when you are in so much physical pain that you regularly contemplate suicide, then some rare but very dangerous side effects of a possible cure are not going to be much of a deterrent to its use. The bottom line is sometimes natural remedies are the safest and most effective treatments for a condition and sometimes they are not. It’s all case by case.
Well said Ken F!
Amen. Well said.
As a physician with progressive peripheral neuropathy related to Lyme, I find that a combination of Gabapentin and Lyrica works best for neuropathy pain. I have been on a Fentanyl patch for over 10 years, but it’s causing nausea and I’m just about weaned off of it. There is no need to go to Suboxone or these other new drugs to get off of narcotics. I find that a dose of Atenolol 25-50 mg, to control tachycardia, rapid heart rate, is all that is needed. I cut the Fentanyl patch by 20% each time and extend the time that it’s on until I have withdrawal symptoms…that’s usually about 4-5 days. Narcotics do not seem to help the neuropathy pain. Currrently I’m on IVIG at 80 GM every three weeks, but am going up to 160 GM every three weeks. I plan to start DSF this week and will go very very slowly. I also have an Ozone Sauna that I will use along with an Ionic Foot Cleanse to Detox twice a week. Detox is best if one uses a Far Infrared Sauna, an Ozone Sauna, or Ionic Foot Cleanse. One needs to take replacement minerals. Personally I take Klaire Labs Magnesium Chelate, and Klaire Labs LDA Trace Mineral Supplement on the day of the treatment and also MWF. It’s the most well-balanced trace mineral supplement on the market. For liver support, I use Apex Energetics Trisomal product and also take Lipoic Acid 150 mg/day. For power foods, I eat calves liver, brewers yeast in a smoothy, and also at times raw wheat germ in cereal even though it’s a gluten product. These three foods have the highest concentration of natural B-Vits of any source. Synthetic Bs Vits just do not compare. Be Well.
Doc Jim
Marlene – You said that you wanted to “go after viruses” yet you did not mention having any particular viral infection. Furthermore, the article above did not say anything about this drug being effective against viruses (only cancer and certain bacteria) – although I did read a separate article that said it may be effective in rendering the AIDS virus easier to kill. In any case, our bodies are full of viruses and bacteria which are usually completely harmless to us and in some cases they are even very beneficial. So, I cannot really see any reason to go after anything unless you have conclusively identified that thing as being detrimental to your health.
Marlene,
How have you been diagnosed for parasites and heavy metals? Personally, I’ve found that Genova has the best comprehensive stool analysis. The test will suggest various therapies, both drug and herbal. If parasites are found, in many cases an herbal product by NutraBiogenesis called Parabiotic Plus is effective if taken for 10 days. The bottle suggests 3 caps/day, but I’ve found that 1/day is fine. For H. Pylori, Mastic Gum by Nutricology is endorsed by the New England Journal of Medicine as being effective and with far fewer side effects than antibiotics. For heavy metals, Genova also has a Pre and Post provocative test for heavy metals. For the provocative test, some use DMPS or DMSA. In the US, you can assume that you have a burden of heavy metals due to all of the pollutants in our environment especially if you live near a big city. The body simply cannot handle removing these without the help of your skin pores. Taking supplements might help some, but methods to sweat may be far more effective. There is evidence that a diet high in iodine will displace heavy metals and toxic substances if one takes 5 mg/day. Caution must be taken for anyone allergic to seafood or iodine. Far Infrared Sauna, Ozone Sauna and/or Ionic Foot Cleanse are often very helpful. The FIR Saunas I’ve owned a Sunlighten http://www.sunlighten.com and found them to be the best. For an Ozone Sauna, I bought a steam sauna, then added an Ozonator and other equipment as it was far less costly than buying a fiberglass set-up. My experience for Ionic Foot Cleanse is that http://www.AMajorDifference.com makes the best in Denver Colorado.
I hope these comments are of help.
Doc Jim
Thank you for this extensive explanation! I’m just concerned about the multiple possible neurological side effects of disulfiram, specially that most Lyme patients already suffer from a lot of these neurological issues already. I’m curious to know, Would you still risk to try this with your neurological Lyme patients?
yes, in some cases it is worth it to see the end result of cure or remission of symptoms
Samia,
If one has neurological side effects, the dose may need to be adjusted or stopped. From the reading that I’ve done, in most cases, the neuropathies that result or worsen from DSF will reverse once the drug is stopped. Best to get the advice of a private physician and be cautious.
Doc Jim
Hi,
I just read your article on disulfiram. What caught my attention, was your suggestion to support the immune system with Transfactor L- Plus and pantethine during and after antibiotic therapy.
My 19 year old son found an embedded deer tick in his leg recently. Unsure of what to do I started him on astragalus and cats claw ( the only immune boosting herbs I could find in local store) while
I argued with his GP about starting him on antibiotics prophylactically since I found IILADS suggested 20 days of doxycycline if bitten but no rash. It took 6 days, but I finally got a docter to order 19 days of antibiotics. I did not keep up with herbs since I could not find someone to advise me about their effect with antibiotics or on any info about how to treat a tick bite prophylactically.
Upon reading your article I am wondering if I should give him TrasferL-Plus. He has not shown any signs of Lyme but I want I want to support his gut microbes and immune system.I have started him on probiotics. If you could advise me on this product or anything else I can do since he is almost done his 19 days of antibiotics, I would be most grateful.
It would be great if you could write an article about what to do when you get a tick bite. There is a lot of information out there about treatmenting Lyme disease, but not enough about how to prevent this dreadful disease if you get a tick bite. I think many of us are unprepared and uninformed about what to do, and feel a bit panicked when it happens.Thank you for any advise or information you can offer.
Joyce
yes, great idea, Joyce!
Joyce,
Often physicians use an inadequate dose of Doxycycline and then a person goes on to get Lyme Disease. The correct dose of Doxy for an insect bite is Doxy 200 mg twice a day for 3 weeks. To remove the tick, it’s best to use Lidocaine Gel on it first and even inject a small amount of Lido 1% with Epinephrine under the tick or insect, then use an instrument to pull the tick out. The concept is that the tick if paralyzed by Lidocaine, it will not be able to inject infectious agents into the body. This is the hope, but still treatment should be given in most cases. These are ILADS’s most recent recommendations. As far as Pantenthine is concerned by itself, any time a B-Vitamin is given at a high dose, it should be combined with all of the other B-Vits otherwise one may induce a deficiency of another. Too much Pantothine will induce a B2 deficiency. I personally prefer a product from Klaire Labs called Adrenamin. It contains Pantothenic Acid 100 mg, about 1/2 the amount of Pantothenic acid that is in Pantenthine, along with other factors needed to boost both the immune system and the adrenals. The transfer factor may be helpful and I agree with other physicians about this supplement.
The side effects sound dreadful. Also, would this be appropriate for those of us with a CBS mutation who cannot handle much sulfur?
it may be but your lyme literate doctor would suggest starting with very low doses…
Disulfiram sounds interesting. However, I’m a bit concerned about the “toxic optic neuropathy” side effect. I had surgery last year for ocular melanoma.
Also, does Disulfiram actually deplete zinc and copper in the body? Should someone be supplementing with them during use of this drug? Finally, how long is a typical course of Disulfiram and how successful was it’s use in chronic lyme studies versus acute cases.
Side effects can be serious but so can lyme disease. This drug offers a potential for cure and so some patients with physician guidance may decide to pursue treatment.
I took Disulfaram for 3 months…during that time I began seeing shadow figures that almost looked like ghosts. Then it progressed to seeing things in full color. For example, one time I saw a bug crawling across my son’s face and screamed. Another time I saw a blue bird hopping on the family room carpet but there was nothing there- my doctor never explained the potential side effects of this medication. I began to believe I had a brain tumor. I hope that other doctors who prescribe this medication will explain the side effects in advance.
The side effects are intimidating to read.. however… having had Memory loss, speech slurring, brain fog, depersonalization, couldnt comprehend what I read along with shortness of breath, blurry vision, extreme fatigue, muscle aches and digestive issues… I would gamble on this drug to help get rid of my persistant symptoms. After years of different cocktail RX and vitamin treatments my remaining symptoms are shortness of breath, blurry vision, sporadic headaches, sweating at the least excertion as well as just a constant lack of energy in general. Talk about a wet towel… I was a human wet towel… and I want my life back, I was a type A personality.. I would settle for a B- one now. My largest need now is a competent doctor to monitor me. My physician of 20 years moved out of state… Not sure who to truly trust and Ive slowly lost trust in myself.
Robin. Keep strong. Look for your states Lyme Support Center. They can give you a listing of LL physicians. Read as much as possible or have a loved one, a friend read the to you slowly…the are a lot to digest.
My husband has been battling this evil disease for 6 years now. Been on the medication train. The relapse bus, the anxiety and depression wagon. A trial of this repurposed med sounds like a welcomed relief for him, us and our family. Little exposed factoid, Lyme disease affects the patient, the spouse and the children. It is a family affair and it takes all of us to care for him, keep his spirits up and keep him safe. I applaud those medical professional whom were brave enough to try this.
I was rejected by the Columbia Lyme-Disulfiram trial, but my GP agreed to prescribe Antabuse for me @ 250 mg/2x/day. I started this dosage immediately in early Oct. 2019 with only side effect being great drowsiness – tendency to fall asleep for 3-4 hours at the drop of a hat. HOWEVER, began feeling truly rested in the mornings, after years of waking up feeling run-over-by- a-truck, daily aches/pains in joints as well as daily headaches relieved after several weeks, fatigue better described as EXHAUSTION from which I suffered for years gave way to a pleasant “tired” feeling, as after a good walk, or , better yet, on “good days”, I really have ENERGY again to accomplish things. After a couple weeks, I noticed a great lifting of spirits, which began to feel like euphoria. A friend, also trying Antabuse, warned me of the possibility of mania/depression. brought on by too- high doses. Cut back – stayed off completely for a few days, then went back on @ 250 every other day. Felt so good went out and got a P/T job, which however takes too much energy, leaving me too depleted at end of day. Have now quit job and am taking 250mg/day. Drowsiness has returned, but other plus effects have also remained. Best part is that for the first time in seventeen years I feel optimistic about my future. I feel that the brain fog is gradually clearing – also have been having better short-term memory retention. Am articulate again after years searching around for words. Plan to go back up to 250 mg/2x/day this week. I have already completed 30 days of therapy and am into week 2 of second 30 days. My liver tests have been normal (two tests run) and my Bb load is dropping – I have consistently shown 8 positive lines on IgG tests and have dropped to 5 lines after five weeks on Antabuse. The only other therapy which made my IgG go down in the past was Rife therapy. I stopped that because of the cost and also had family medical crisis which prevented continuing at that time. In the past I tried many different antibiotics , including IV Rocephin, as well as natural herbs, etc, none of which helped. NOTE: Pharmacies are now backordered for Antabuse – guess everybody out there is giving it a try. I would like to hear from others if anyone is having good results, and also if anyone is experiencing negative results. Good luck, everyone! Don’t give up!
Not only backordered, but drug suppliers in Pennsylvania have discontinued 250 mg disulfiram. I‘ve been trying to fill a script for almost two months. I fear the drug companies are about the stick it to the Lyme community. So bummed.