Author: Bob Brensel | President, Pharmacist | ScriptWorks
Bob Brensel, RPh, earned his Pharmacy Degree at University of the Pacific in Stockton, California in 1980. Former California Pharmacists Association’s Award Winner for Recognition of Outstanding Achievement in Compounding Pharmacy. Read More →
What Is Dysbiosis?
Dysbiosis is the term for an imbalance of the microorganisms living in the gastrointestinal tract. When the ratio of “beneficial” to “opportunistic” microbes shifts unfavorably, it can lead to bloating, gas, diarrhea, constipation, food intolerances, and low-grade inflammation. Dysbiosis may also contribute to conditions such as irritable bowel syndrome (IBS), inflammatory bowel disease (IBD), small intestinal bacterial overgrowth (SIBO), and increased intestinal permeability (“leaky gut”).
While probiotics, dietary changes, and antimicrobial therapies remain standard options, some practitioners are exploring Low-Dose Naltrexone (LDN) as an adjunctive strategy for supporting gut health and microbial balance.
What Is LDN?
Naltrexone was originally approved at a standard dose of 50 mg to block opioid receptors in people with opioid or alcohol dependency. However, researchers discovered that when given in much smaller amounts—typically 0.5mg to 4.5 mg per day—its actions are different.
At these low doses, naltrexone is thought to create a temporary opioid receptor blockade. This blockade signals the body to produce more of its own natural opioids—endorphins and enkephalins—which may play important roles in immune regulation, tissue repair, and pain perception.
LDN refers specifically to this low-dose, off-label use of the medication. Compounding pharmacies often prepare it in capsule or liquid form, allowing for custom dosing.
Why Are Some Practitioners Prescribing LDN?
A growing number of integrative, functional, and even conventional gastroenterology practitioners are prescribing LDN for patients whose symptoms have not improved with standard measures. They may choose LDN because it:
- May help calm gut inflammation – by influencing immune signaling and inflammatory cytokine activity
- May support intestinal barrier repair – by modulating cell growth pathways
- May improve motility – which can be important in SIBO and constipation
- May promote a healthier gut environment – indirectly supporting a balanced microbiome
Practitioners are also drawn to LDN’s favorable tolerability profile at low doses, its low cost, and the possibility of combining it with existing diet, probiotic, or antimicrobial therapies.
How LDN May Work in Dysbiosis
1. Endorphin and Enkephalin Boost
When LDN briefly blocks opioid receptors, the body responds by producing more endorphins and enkephalins. These compounds don’t just influence mood—they also play a role in regulating immune system activity. A well-regulated immune system is less likely to overreact to harmless gut microbes, which may help restore a balanced gut environment.
2. Toll-Like Receptor 4 (TLR4) Modulation
TLR4 is part of the immune system’s “danger detection” system. Overactivation can drive chronic inflammation in the gut lining. LDN may act as a TLR4 antagonist, dampening this overactivation and reducing inflammatory signaling.
3. Opioid Growth Factor (OGF) Pathway Support
LDN is believed to upregulate the opioid growth factor (OGF) and its receptor (OGFr). This pathway is involved in cellular repair and tissue regeneration, which may support gut mucosal healing and improved barrier function.
4. Glial Cell Calming
In the nervous system, overactive glial cells can amplify pain and inflammation. By helping to normalize glial cell activity, LDN may reduce visceral hypersensitivity—the heightened pain perception often seen in IBS and other dysbiosis-related disorders.
5. Motility Regulation
Healthy gut motility is critical for preventing bacterial overgrowth and maintaining microbial balance. Clinical observations suggest that some patients notice improved bowel regularity on LDN, possibly due to reduced inflammation in the enteric nervous system and improved signaling between gut and brain.
Clinical Pearls for Patients and Providers
Dosing:
Most providers start patients on 0.5MG TO 1.5MG nightly, , increasing gradually to a target of 1mg to 6mg depending on tolerance and symptom response. Lower doses may be more appropriate in sensitive individuals.
Timing:
Bedtime dosing is common, as the endorphin rebound effect is believed to peak in the early morning hours. Some patients switch to morning dosing if sleep disturbances occur.
Onset of Action:
Some patients report changes in gut symptoms within 2–4 weeks, while others may require 8–12 weeks before evaluating its impact.
Side Effects:
LDN is generally well-tolerated, but some experience vivid dreams, mild insomnia, or temporary digestive changes. These effects often subside with dose adjustment.
Combination Approaches:
LDN is often paired with:
- Targeted probiotics or prebiotics
- Anti-inflammatory dietary patterns (Mediterranean, low-FODMAP, or elimination diet as indicated)
- Nutrients that support gut lining integrity (e.g., zinc carnosine, glutamine)
- Antimicrobials or antifungals for microbial overgrowth, when needed
A Hypothetical Case Example
A 42-year-old woman with IBS-M (mixed constipation and diarrhea) and confirmed SIBO has tried multiple antibiotics, probiotics, and dietary interventions. She experiences partial but incomplete relief. Her provider recommends adding LDN at 1.5 mg nightly, titrating to 4.5 mg over a month.
Over the next eight weeks, she notices reduced bloating, more predictable bowel movements, and less post-meal discomfort. While her SIBO breath test still shows mild overgrowth, her symptom improvement allows her to tolerate a broader range of foods and engage more in daily activities.
Key Takeaways
The gut is a complex ecosystem influenced by immune health, nervous system function, and barrier integrity—not just the microbes themselves. LDN’s multifaceted actions—immune modulation, cell repair support, and possible motility regulation—make it an intriguing option for patients with dysbiosis-related symptoms who are not getting full relief from conventional methods.
- LDN is naltrexone in much smaller doses (0.5mg-4.5 mg), compounded by a ScriptWorks pharmacy for off-label use.
- It may influence gut health by modulating immune activity, supporting barrier repair, and regulating motility.
- Practitioners are prescribing it as part of a comprehensive gut health plan for patients with dysbiosis, IBS, IBD, SIBO, or related conditions.
- While individual results vary, LDN is generally well-tolerated, inexpensive, and easy to incorporate into a broader gut restoration protocol.
Why This Matters for Dysbiosis
For California patients and providers seeking options beyond the usual probiotic or dietary strategies, LDN may represent a thoughtful, science-informed addition to the gut health toolbox.
Practitioners, offer your patients elevated options.
Patients, ask your doctor about whether LDN is a good fit for your specific case.