Crohn's Disease and Low Dose Naltrexone
What is Crohn's Disease?
Crohn's disease is a type of inflammatory bowel disease (IBD). Crohn's disease most commonly affects the colon, which is also called the large intestine, and the last part of the small intestine (ileum). It causes inflammation of your digestive tract, which can lead to abdominal pain, severe diarrhea, fatigue, weight loss and malnutrition. Inflammation caused by Crohn's disease can involve different areas of the digestive tract in different people. This inflammation often spreads into the deeper layers of the bowel.
Crohn's disease can be both painful and debilitating, and sometimes may lead to life-threatening complications. While there's no known cure for Crohn's disease, therapies can greatly reduce its signs and symptoms and even bring about long-term remission and healing of inflammation. With treatment, many people with Crohn's disease are able to function well.
What are the symptoms of Crohn’s Disease?
Signs and symptoms of Crohn's disease can range from mild to severe. They usually develop gradually, but sometimes will come on suddenly, without warning. You may also have periods of time when you have no signs or symptoms (remission). When the disease is active, signs and symptoms may include:
• Diarrhea
• Fever
• Fatigue
• Abdominal pain and cramping
• Blood in your stool
• Mouth sores
• Reduced appetite and weight loss
• Pain or drainage near or around the anus due to inflammation from a tunnel into the skin (fistula)
People with severe Crohn's disease may also experience:
• Inflammation of skin, eyes and joints
• Inflammation of the liver or bile ducts
• Kidney stones
• Iron deficiency (anemia)
• Delayed growth or sexual development, in children
What are the risk factors of Crohn’s Disease?
Risk factors for Crohn's disease may include:
• Age – Crohn's disease can occur at any age, but you're likely to develop the condition when you're young. Most people who develop Crohn's disease are diagnosed
before they're around 30 years old.
• Ethnicity – Although Crohn's disease can affect any ethnic group, whites have the highest risk, especially people of Eastern European (Ashkenazi) Jewish
descent. However, the incidence of Crohn's disease is increasing among Black people who live in North America and the United Kingdom.
• Family history – You're at higher risk if you have a first-degree relative, such as a parent, sibling or child, with the disease.
• Cigarette smoking – Cigarette smoking is the most important controllable risk factor for developing Crohn's disease. Smoking also leads to more-severe disease
and a greater risk of having surgery. If you smoke, it's important to stop.
• Nonsteroidal anti-inflammatory medications (NSAIDs) – These include ibuprofen, naproxen sodium, diclofenac sodium and others. While they do not cause Crohn's disease, they can lead to inflammation of the bowel that makes Crohn's disease worse.
What are the complications of Crohn’s Disease?
Crohn's disease may lead to one or more of the following complications:
• Bowel obstruction – Crohn's disease can affect the entire thickness of the intestinal wall. Over time, parts of the bowel can scar and narrow, which may block the flow of digestive contents. You may require surgery to remove the diseased portion of your bowel.
• Ulcers – Chronic inflammation can lead to open sores (ulcers) anywhere in your digestive tract, including your mouth and anus, and in the genital area (perineum). • Fistulas – Sometimes ulcers can extend completely through the intestinal wall, creating a fistula an abnormal connection between different body parts. Fistulas
can develop between your intestine and your skin, or between your intestine and another organ. Fistulas near or around the anal area (perianal) are the most common kind. When fistulas develop in the abdomen, food may bypass areas of the bowel that are necessary for absorption. Fistulas may form between loops of bowel, in the bladder or vagina, or through the skin, causing continuous drainage of bowel contents to your skin. In some cases, a fistula may become infected
and form an abscess, which can be life-threatening if not treated.
• Anal fissure – This is a small tear in the tissue that lines the anus or in the skin around the anus where infections can occur. It's often associated with painful bowel movements and may lead to a perianal fistula.
• Malnutrition – Diarrhea, abdominal pain and cramping may make it difficult for you to eat or for your intestine to absorb enough nutrients to keep you nourished. It's also common to develop anemia due to low iron or vitamin B-12 caused by the disease.
• Colon cancer – Having Crohn's disease that affects your colon increases your risk of colon cancer. General colon cancer screening guidelines for people without
Crohn's disease call for a colonoscopy every 10 years beginning at age 45. Ask your doctor whether you need to have this test done sooner and more frequently.
• Other health problems – Crohn's disease can cause problems in other parts of the body. These problems can include anemia, skin disorders, osteoporosis, arthritis,
and gallbladder or liver disease.
• Medication risks – Certain Crohn's disease drugs that act by blocking functions of the immune system are associated with a small risk of developing cancers
such as lymphoma and skin cancers. They also increase risk of infection. Corticosteroids can be associated with a risk of osteoporosis, bone fractures, cataracts, glaucoma, diabetes and high blood pressure, among other conditions. Work with your doctor to determine risks and benefits of medications.
• Blood clots – Crohn's disease increases the risk of blood clots in veins and arteries.
What treatments are available for Crohn’s Disease?
Treatment for Crohn's disease may involve medication, surgery, and lifestyle/home remedies. The aim is to control inflammation, resolve nutritional problems, and relieve symptoms. There is no known cure for Crohn's disease, but some treatments can help by reducing the number of flare-ups. Crohn's disease treatment will
depend on:
• Where the inflammation occurs
• Severity of the condition
• Complications
• Response to previous treatment for recurring symptoms
Some people can have long periods, even years, without any symptoms. Experts refer to this as remission. However, there will usually be recurrences. As periods of remission vary greatly, it can be hard to know how effective treatment has been. It is impossible to predict how long a period of remission is going to be.
Medications
There are a variety of medications for Crohn's disease, including:
• Anti-inflammatory drugs – A doctor will most likely mesalamine, which helps control inflammation.
• Steroids – These may include oral steroids, such as prednisone and budesonide, or intravenous steroids, such as methylprednisolone.
• Antibiotics – This type of medication can be useful in Crohn's disease flare-ups if a person has an abscess or fistula. • Anti-diarrheal drugs and fluid replacements – When the inflammation subsides, diarrhea usually becomes less severe. However, sometimes a person may still need something to address diarrhea and abdominal pain.
• Biologics – Biologics are a type of drug that scientists have developed from a living organism. Biologics reduce the body's immune response by targeting proteins that lead to inflammation. They appear to help people with Crohn's disease.
• Vitamins and Supplements – If you are not absorbing enough nutrients, then your doctor may recommend vitamins and nutritional supplements.
Surgical Procedures
Most people with a Crohn's disease diagnosis may need surgery at some point. A surgical procedure can relieve symptoms that have not responded to medication. It may also help address complications, such as an abscess, perforation, bleeding, or blockage.
Removing part of the intestine can help, but it does not cure Crohn's disease. Inflammation often returns to the area next to where the removed part of the gut was. In some cases, a person may need more than one surgery in their lifetime.
Sometimes, a person will need a colectomy, in which a surgeon removes the whole colon. They will make a small opening in the front of the abdominal wall and bring the tip of the ileum to the skin's surface to form an opening called a stoma, through which feces exit the body. A pouch then collects the fecal
matter. Doctors say a person who has a stoma can carry on leading a normal and active life If the surgeon can remove the diseased section of the intestine and then connect the intestine again, no stoma is necessary.
Most people with Crohn's disease can live normal and active lives, hold jobs, raise families, and function successfully.
Lifestyle and Home Remedies
• Diet – During a flare-up, a person should avoid high fiber foods, dairy, sugar, high fat foods, and spicy foods. Between flare-ups, it is advisable to drink more water, eat small meals, boil or steam food instead of frying it, and keeping a food diary to track how different foods make a person feel.
• Behavioral changes – If a person smokes, they may consider quitting. They can also try relaxation practices and techniques, such as meditation, mindfulness, or yoga. Exercise and mental health counseling could be helpful as
well.
What is Low Dose Naltrexone?
LDN is a prescription drug that helps to regulate a dysfunctional immune
system. It reduces pain and fights inflammation. It is not a narcotic or a
controlled substance. It is an opioid receptor antagonist that is taken orally to block opioid receptors. An antagonist is a chemical that acts within the body to reduce the physiological activity of another chemical substance.
Naltrexone was approved by the FDA in 1984 for the treatment of opioid addiction, usually at a dose of 50-100mg a day. It blocks the receptors that opioids like oxycodone bind to negating the euphoric effect. However, at much lower doses, naltrexone has been used for autoimmune disorders like
Hashimoto’s disease as well as chronic pain.
For more information on how LDN works, please click here.
Image Credit: https://pubchem.ncbi.nlm.nih.gov/compound/Naltrexone
How does LDN provide pain relief?
Before we discuss how LDN works, we need to go over the role of endorphins in the body. Endorphins are opiate-like molecules in the body. They are produced in most cells in the body and are important regulators of cell growth and the immune system. The particular endorphin that has been found to influence cell growth is called Opioid Growth Factor (OGF). For an endorphin such as OGF to exert its beneficial effects, it must interact with the body’s cells. It does this by binding to a receptor on the surface of the cells.
Naltrexone is an orally administered drug that binds to opioid receptors. In doing so, it displaces the endorphins which were previously bound to the receptors. Specifically, by binding to the OGF receptors, it displaces the body’s naturally produced OGF. As a consequence of this displacement, the affected cells become deficient in OGF and three things happen:
1) Receptor production is increased, in order to try to capture more OGF.
2) Receptor sensitivity is increased, also to try to capture more OGF.
3) Production of OGF is increased, in order to compensate for the perceived shortage of OGF.
Since LDN blocks the OGF receptors only for a few hours before it is naturally excreted, what results is a rebound effect; in which both the production and utilization of OGF is greatly increased. Once the LDN has been metabolized, the elevated endorphins produced as a result of the rebound effect can now interact with the more-sensitive and more-plentiful receptors and assist in regulating cell growth and immunity. The elevated level of endorphins can result in an enhanced feeling of well-being as well as a reduction in pain and inflammation. The duration of the rebound effect varies from person to person but generally lasts about one day. This effect can only be utilized by taking a low dose of naltrexone and not a high dose or extended-release naltrexone.
What does the research show?
Research has been done over the years evaluating how LDN and its use in Crohn's Disease. Some of the studies that have been published are smaller studies but show promise for the treatment of chronic pain using LDN. Studies include:
• Digestive Diseases and Sciences - found that patients with moderate to severe Crohn's Disease on LDN improved clinical and inflammatory activity compared to placebo.
• Inflammatory Bowel Diseases - found that patients with inflammatory bowel disease (IBD) showed significant improvement in Crohn's Disease Activity Index (CDAI) as well as in quality of life.
• Journal of Crohn's and Colitis - found LDN was a promising treatment with relatively mild side effects for patients with therapy-resistant IBD .
For a list of more studies, please click here.
What dosage forms are available?
LDN is available by prescription only from compounding pharmacies. It is available as an immediate-release oral capsule or a liquid. LDN is typically prescribed at doses from 0.001mg-16mg with the most common dose of 4.5 mg.
Ask your doctor or one of our compounding pharmacists if LDN is right for you.
Sources:
https://www.mayoclinic.org/diseases-conditions/crohns-disease/symptoms-causes/syc-20353304
https://www.mayoclinic.org/diseases-conditions/crohns-disease/diagnosis-treatment/drc-20353309
https://www.medicalnewstoday.com/articles/151620
https://pubmed.ncbi.nlm.nih.gov/21380937/
https://academic.oup.com/ibdjournal/article/19/suppl_1/S29/4604998
https://ldnresearchtrust.org/low-dose-naltrexone-therapy-resistant-ibd-case-series-abstract