San Antonio, TX Integrative and Functional Medicine: LDN for treating IBD (aka colitis)

LDN and Inflammatory Bowel Disease such as Ulcerative Colitis and Crohn's Disease (aka Colitis)

The Potential Role of Low-Dose Naltrexone in the Management of Inflammatory Bowel Disease

Introduction

Inflammatory Bowel Disease (IBD), encompassing Crohn’s disease and ulcerative colitis, poses a persistent challenge due to its chronic nature and impact on quality of life. Standard treatments—such as immunosuppressants and biologics—can induce remission but often carry side effects or insufficient responses. Low-Dose Naltrexone (LDN), administered at 1–5 mg daily (a fraction of the 50 mg dose used in opioid dependence), has gained attention as a promising adjunctive therapy with immune-modulating and anti-inflammatory properties.

Mechanism of Action

LDN transiently blocks opioid receptors, which appears to trigger increased endorphin production and modulation of immune activity. It acts on glial cells, reducing pro-inflammatory cytokines like IL-6 and TNF-α. It may also stabilize the intestinal barrier through effects on tight junction proteins. Notably, LDN’s antagonism of toll-like receptor 4 has been proposed as part of its mechanism in tempering gut mucosal inflammation (Wikipedia).

Evidence from Clinical Trials

• 2018 Therapy-Refractory IBD Study: Individuals with Crohn’s or ulcerative colitis treated with 4.5 mg LDN for 12 weeks achieved clinical improvement in 74.5% and remission in 25.5%, with benefits tied to epithelial barrier function and reduced cellular stress (BioMed Central).

• Quasi-Experimental Prescription Study (2018): Initiation of LDN in IBD patients correlated with reduced dispensing of other IBD medications, suggesting an adjunctive or disease-modifying impact (Oxford Academic).

• Current RCT Protocol (2022): A randomized, double-blind, placebo-controlled multicenter trial (LDN Crohn) is underway, investigating whether 4.5 mg daily LDN induces endoscopic remission in mild-to-moderate Crohn’s disease over 12 weeks (PMC, PubMed, Physician Guide to Breastfeeding).

Review Literature & Expert Commentary

A recent scoping review (2025) acknowledged that in some IBD-oriented studies, LDN led to reduced symptoms or total disease remission in Crohn’s and ulcerative colitis (Cureus). However, comprehensive systematic reviews like Cochrane still emphasize the limited quality and quantity of controlled evidence (Cochrane Library).

Patient Experiences

• Case Series & Survey-Based Insights: Clinical case series and patient surveys describe variable but notable benefits—ranging from significant symptom relief to prolonged remission—often after conventional treatments failed (e.g., partial remission in pediatric Crohn’s; long-term remissions in select cases).

• Real-World Observations: Gastroenterologists have reported rapid symptomatic improvement in patients starting LDN off-label, although such anecdotal data naturally require cautious interpretation.

Safety & Side Effects

LDN is generally well tolerated. Adverse events are mild and may include vivid dreams or temporary insomnia, typically managed by dose tweaks. Compared to steroids and immunosuppressants, its side effect profile appears favorable. However, opioid interactions must be monitored.

Conclusion

LDN shows promise as a low-risk adjunct therapy for IBD, backed by preliminary trial data, real-world patterns, and mechanistic rationale. While current evidence is encouraging, definitive validation requires further high-quality randomized controlled trials—particularly with endoscopic and long-term outcome measures. Clinicians might consider LDN in refractory cases, guided by multidisciplinary evaluation and patient-specific considerations.References

1. Lie MR et al. (2018) – Low-dose naltrexone for induction of remission in inflammatory bowel disease patients. Demonstrated clinical improvement in 74.5% of IBD patients and 25.5% remission with 4.5 mg LDN over 12 weeks. Read more (BioMed Central)

2. Raknes G et al. (2018) – The effect of low-dose naltrexone on medication in inflammatory bowel disease. Found reductions in dispensing rates of standard IBD medications following LDN initiation. Read more (Oxford Academic)

3. Paulides E et al. (2022) – Low-dose naltrexone for the induction of remission in Crohn’s disease: Protocol for a randomized, double-blinded, placebo-controlled, multicentre trial (LDN Crohn study). Currently ongoing trial assessing endoscopic remission. Read more (PubMed, PMC)

4. Leiber KK (2025) – Therapeutic Uses and Efficacy of Low-Dose Naltrexone (Scoping Review). Includes cases of successful symptom relief and remission in Crohn’s and ulcerative colitis with LDN. Read more (Cureus)

5. Cochrane Review (2014) – Low-dose naltrexone therapy effectiveness and safety. Highlights limited evidence and calls for larger, more rigorous trials. Read more (Cochrane Library)

6. Wikipedia – Naltrexone / Low-dose naltrexone – Overview of LDN’s pharmacodynamics, off-label use, typical dosing, and immune-modulating mechanisms (including TLR4 antagonism). Read more (Wikipedia)

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