A Case of Remission from Crohn’s Disease with Low Dose Naltrexone LDN by Jeffrey Dach MD
Tom came into my office about 6 months ago. He is a 32 year old male with a long history of inflammatory bowel disease. He has been evaluated and treated by many gasteroenterologists over the years, and was told he has Crohn’s Disease, and will never fully recover.
Left Image: Crohn’s with typical ulceration of distal ileum on barium xray courtesy of jeffrey dach md.
Tom had seen my previous article on Low Dose Naltrexone, and he was interested in using it for his Crohn’s Disease. None of his other doctors would give it to him. I started him on the drug immediately. LDN is safe with virtually no adverse side effects, and has been shown effective for Crohn’s Disease in a 2007 report, “Low-dose naltrexone therapy improves active Crohn’s disease” by Jill Smith MD at Penn State University.(1-2) A second larger study was reported in 2011.(2)
Crohn’s Disease is a chronic inflammatory condition of the small bowel, and complete recovery is very rare. The following is an email from Tom describing his experience after 6 months of treatment with LDN:
Thank you for helping me get rid of symptoms of one of the most
problematic and debilitating diseases. For more than 10 years I had been struggling with Crohn’s disease and fighting a losing battle. For a lot of people, Crohn’s disease doesn’t respond well to traditional methods of treatment.
The anti-inflammatory drugs I was taking before I saw Dr. Dach had very little effect and the prednisone was such a destructive drug, I could only be on it for short periods of time. I gained 85 pounds on my last round of prednisone and as soon as I came off, the bleeding and intestinal pain resumed and I started worrying about long car rides and being far from bathrooms. This had a big impact on my personal and professional life. I knew that if I ever wanted to get rid of the disease it would be with an unconventional treatment.
I first heard of LDN from doing a search on the internet and made an appointment with Dr. Dach. I had exhausted every possible option before and felt like I had no where else to turn. When I went to my appointment, Dr. Dach spent a lot of time with me and it felt very different than the “assembly line approach” that I was used to.
My first visit was in the summer of 2008 and I’ve been symptom-free ever since. I could feel my body healing almost immediately after starting treatment. For me, low-dose naltrexone has been a miracle drug. I can now lead a normal life and do all kinds of things Crohn’s disease would have prevented me from doing, like sitting through a movie or taking a long car trip. This has changed my life and I hope more people can benefit.
Regards, from Tom
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Other Uses for LDN:
LDN has been found beneficial in Ulcerative Colitis, Multiple Sclerosis, Fibromyalgia/Chronic Pain syndromes, Autonomic Dysfunction/POTS, Sarcoidoisis, Scleroderma, and most other autoimmune disease.(3-11)
Chronic Pain/Fibromyalgia: LDN has been found useful see my previous article, LDN Part Four.
Articles With Related Content:
Low Dose Naltrexone LDN Part One
Low Dose Naltrexone LDN Part 2
LDN for Neuropathic Pain PArt Four
Jeffrey Dach MD
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References:
1) Smith, Jill P., et al. “Low-dose naltrexone therapy improves active Crohn’s disease.” The American journal of gastroenterology 102.4 (2007): 820. Low-dose naltrexone therapy improves active Crohn’s disease Smith Jill Amer j gastroenterology 2007
Endogenous opioids and opioid antagonists have been shown to play a role in healing and repair of tissues. In an open-labeled pilot prospective trial, the safety and efficacy of low-dose naltrexone (LDN), an opioid antagonist, were tested in patients with active Crohn’s disease.
METHODS: Eligible subjects with histologically and endoscopically confirmed active Crohn’s disease activity index (CDAI) score of 220-450 were enrolled in a study using 4.5 mg naltrexone/day. Infliximab was not allowed for a minimum of 8 wk prior to study initiation. Other therapy for Crohn’s disease that was at a stable dose for 4 wk prior to enrollment was continued at the same doses. Patients completed the inflammatory bowel disease questionnaire (IBDQ) and the short-form (SF-36) quality of life surveys and CDAI scores were assessed pretreatment, every 4 wk on therapy and 4 wk after completion of the study drug. Drug was administered by mouth each evening for a 12-wk period.
RESULTS: Seventeen patients with a mean CDAI score of 356 +/- 27 were enrolled. CDAI scores decreased significantly (P= 0.01) with LDN, and remained lower than baseline 4 wk after completing therapy. Eighty-nine percent of patients exhibited a response to therapy and 67% achieved a remission (P < 0.001). Improvement was recorded in both quality of life surveys with LDN compared with baseline. No laboratory abnormalities were noted. The most common side effect was sleep disturbances, occurring in seven patients.
CONCLUSIONS: LDN therapy appears effective and safe in subjects with active Crohn’s disease. Further studies are needed to explore the use of this compound.
2) Smith, Jill P., et al. “Therapy with the opioid antagonist naltrexone promotes mucosal healing in active Crohn’s disease: a randomized placebo-controlled trial.” Digestive diseases and sciences 56.7 (2011): 2088-2097.
3) Matters, Gail L., et al. “The opioid antagonist naltrexone improves murine inflammatory bowel disease.” Journal of immunotoxicology 5.2 (2008): 179-187.
Inflammatory bowel disease (IBD) is a condition of the intestine with significant morbidity. Although hereditary, environmental, immunologic, and bacterial factors have been implicated, the etiology of IBD remains unknown. Since opioid peptides modulate inflammatory cytokine production and opioid antagonists promote tissue growth and repair, we hypothesized the opioid antagonist naltrexone could reduce inflammation of the bowel. Using a chemically-induced mouse model of IBD, C57BL/6J mice received either untreated drinking water or water containing 2% dextran sulfate sodium (DSS) in two parallel regimens modeling moderate and severe colitis. After colitis was established, animals in the moderate colitis study were administered either saline (control) or naltrexone (NTX; 8 or 400 microg/kg) daily, while those in the severe colitis study received 0.1 or 10 mg/kg NTX. DSS-treated animals had significant weight loss (p = 0.006) and higher disease activity index (DAI) scores (p < 0.001) compared to water controls. However, NTX treatment of mice with moderate colitis resulted in less weight loss, lower DAI scores, and less histologic evidence of inflammation compared to controls. Significantly, elevated levels of colonic RNA for pro-inflammatory cytokines interleukin (IL)-6 and IL-12 were also decreased toward normal with NTX. Similar to patients with severe and unresponsive disease, animals in the severe colitis study did not significantly respond to treatment. Thus, NTX therapy reverses physical symptoms, histologic evidence, and molecular markers of inflammation in moderate colitis. The mechanism by which NTX acts to reverse colitis is related in part to the decreased expression of pro-inflammatory cytokines.
4) Lie, Mitchell RKL, et al. “Low dose Naltrexone for induction of remission in inflammatory bowel disease patients.” Journal of Translational Medicine 16 (2018).
Low dose Naltrexone induced clinical improvement in 74.5%, and remission in 25.5% of patients. Naltrexone improved wound healing and reduced ER stress induced by Tunicamycin, lipopolysaccharide or bacteria in epithelial barriers. Inflamed mucosa from IBD patients showed high ER stress levels, which was reduced in patients treated with LDN. Cytokine levels in neither epithelial cells nor serum from IBD patients were affected.
Naltrexone directly improves epithelial barrier function by improving wound healing and reducing mucosal ER stress levels. Low dose Naltrexone treatment is effective and safe, and could be considered for the treatment of therapy refractory IBD patients.
5) Weinstock, Leonard B. “Naltrexone Therapy for Crohn’s Disease and Ulcerative Colitis.” Journal of clinical gastroenterology 48.8 (2014): 742. Naltrexone Therapy Crohns Disease Ulcerative Colitis Weinstock Leonard B J clin gastroenterology 2014
“Adjunctive therapy with low dose naltrexone appeared to be a safe and possibly effective therapy in ulcerative colitis”
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6) ALS – and LDN ALS Untangled No 8 Low dose naltrexone for ALS
Sarcoidosis
7) Weinstock, Leonard, Trisha L. Myers, and Anup Shetty. “Low-dose Naltrexone for the treatment of sarcoidosis.” Sarcoidosis vasculitis and diffuse lung disease 34.2 (2017): 184-187. Low-dose Naltrexone for Sarcoidosis Weinstock Leonard Sarcoidosis vasculitis lung disease 2017
Systemic Sclerosis (Scleroderma)
8) Frech, Tracy, et al. “Low-dose naltrexone for pruritus in systemic sclerosis.” International journal of rheumatology 2011 (2011).
Fibromyalgia
9) Younger, Jarred, and Sean Mackey. “Fibromyalgia symptoms are reduced by low-dose naltrexone: a pilot study.” Pain medicine 10.4 (2009): 663-672.
Fibromyalgia is a chronic pain disorder that is characterized by diffuse musculoskeletal pain and sensitivity to mechanical stimulation. In this pilot clinical trial, we tested the effectiveness of low-dose naltrexone in treating the symptoms of fibromyalgia.
DESIGN: Participants completed a single-blind, crossover trial with the following time line: baseline (2 weeks), placebo (2 weeks), drug (8 weeks), and washout (2 weeks).
PATIENTS: Ten women meeting criteria for fibromyalgia and not taking an opioid medication.
INTERVENTIONS: Naltrexone, in addition to antagonizing opioid receptors on neurons, also inhibits microglia activity in the central nervous system. At low doses (4.5 mg), naltrexone may inhibit the activity of microglia and reverse central and peripheral inflammation.
OUTCOME MEASURES: Participants completed reports of symptom severity everyday, using a handheld computer. In addition, participants visited the lab every 2 weeks for tests of mechanical, heat, and cold pain sensitivity.
RESULTS: Low-dose naltrexone reduced fibromyalgia symptoms in the entire cohort, with a greater than 30% reduction of symptoms over placebo. In addition, laboratory visits showed that mechanical and heat pain thresholds were improved by the drug. Side effects (including insomnia and vivid dreams) were rare, and described as minor and transient. Baseline erythrocyte sedimentation rate predicted over 80% of the variance in drug response. Individuals with higher sedimentation rates (indicating general inflammatory processes) had the greatest reduction of symptoms in response to low-dose naltrexone.
CONCLUSIONS: We conclude that low-dose naltrexone may be an effective, highly tolerable, and inexpensive treatment for fibromyalgia.
10) Chopra, Pradeep, and Mark S. Cooper. “Treatment of complex regional pain syndrome (CRPS) using low dose naltrexone (LDN).” Journal of Neuroimmune Pharmacology 8.3 (2013): 470-476.
Complex Regional Pain Syndrome (CRPS) is a neuropathic pain syndrome, which involves glial activation and central sensitization in the central nervous system. Here, we describe positive outcomes of two CRPS patients, after they were treated with low-dose naltrexone (a glial attenuator), in combination with other CRPS therapies. Prominent CRPS symptoms remitted in these two patients, including dystonic spasms and fixed dystonia (respectively), following treatment with low-dose naltrexone (LDN). LDN, which is known to antagonize the Toll-like Receptor 4 pathway and attenuate activated microglia, was utilized in these patients after conventional CRPS pharmacotherapy failed to suppress their recalcitrant CRPS symptoms.
Dysautonomia POTS
11) Weinstock, Leonard B., et al. “Case Report: Successful treatment of postural orthostatic tachycardia and mast cell activation syndromes using naltrexone, immunoglobulin and antibiotic treatment.” BMJ case reports 2018 (2018). Successful treatment postural orthostatic tachycardia mast cell activation syndrome naltrexone immunoglobulin antibiotic Weinstock Leonard BMJ case reports 2018
Multiple Sclerosis, and others
12) Toljan, Karlo, and Bruce Vrooman. “Low-Dose Naltrexone (LDN)—Review of Therapeutic Utilization.” Medical Sciences 6.4 (2018): 82. Low Dose Naltrexone LDN Review of Therapeutic Utilization Toljan Karlo Bruce Vrooman Medical Sciences 2018
Gut Dysbiosis
Dysbiotic gut microbiota causes transmissible Crohn’s disease-like ileitis independent of failure in antimicrobial defence. Gut doi:10.1136/gutjnl-2015-309333 by Dirk Haller, Chair of Nutrition and Immunology, ZIEL-Institute for Food and Health, Technische Universität München, ZIEL—Research Center for Nutrition and Food Sciences, Gregor-Mendel-Str.2, Freising-Weihenstephan 85350, German
We provide clear experimental evidence for the causal role of gut bacterial dysbiosis in the development of chronic ileal inflammation with subsequent failure of Paneth cell function.
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The reader is advised to discuss the comments on these pages with his/her personal physicians and to only act upon the advice of his/her personal physician. Also note that concerning an answer which appears as an electronically posted question, I am NOT creating a physician — patient relationship. Although identities will remain confidential as much as possible, as I can not control the media, I can not take responsibility for any breaches of confidentiality that may occur.
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