Low Dose Naltrexone (LDN) and Inflammatory Bowel Disease (Crohn's and Ulcerative Colitis)
LDN and Crohn's Disease Health Is PowHer Podcast Episode 10
HIP Health Is PowHer Podcast Episode #10: LDN's Evidence for Crohn's and Ulcerative Colitis
We learned from Dr. Andi Roths, PharmD in episode 9 that Low Dose Naltrexone or LDN blocks certain opioid receptors (yes we have those in our body and what’s interesting to note is that these natural opioids and opioid receptors are involved in not only pain, but inflammation and the immune system).
So that’s why LDN is studied because when it blocks these opioid receptors it regulates inflammation and our immune system potentially in a positive way. We still need more multi-site or larger controlled trials with LDN for specific conditions as it is still off label except for the FDA approved treatment for opioid use disorders, but new therapies start somewhere with smaller studies.
Let’s just do a brief overview of the pharmacology and mechanism of LDN:
LDN is an opioid antagonist blocking the opioid receptors - more specifically the MU-opioid receptors. It is absorbed by the body almost completely at 96%, but because it is metabolized by the liver - we only get about 5-40% of the actual drug to work. It mainly works for about 4 hours as that is its half life - and takes about 6 hours for 40% of it to be eliminated in the urine.
Mechanism:
At low doses ranging between 1-5 mg, LDN acts as a glial modulator binding to Toll-like receptors to block them in order to stop the inflammatory cascade from happening (neutralizing inflammation in the central nervous system).
LDN as we discussed also binds to the opioid receptors and the body recognizes that as not having enough endorphins or opioids - so our body naturally increases the opioids/endorphins/enkephalins which are our pain relieving, feel good, and neuroimmune and endocrine or hormone enhancing substances in our body to overcome that blockade.
This is why LDN has been studied for clinical use in fibromyalgia, multiple sclerosis, Crohn’s disease, cancer, Hailey-Hailey disease (a skin condition), and complex regional pain syndrome or amplified pain.
We are going to talk about some of the evidence in which LDN has helped chronic inflammatory conditions such as inflammatory bowel disease!
30% of individuals with IBD are refractory to current drugs or relapse meaning that those drugs don’t work for them.
Now that doesn’t mean that we should forgo those treatments b/c those are the best drugs/treatment out there for a majority of those living with IBD. However, we may need to find other treatments for those individuals who aren’t responding to the standard of care. Or they may have unique complications that doesn’t allow them to tolerate certain medications for IBD.
Hence, comes in low dose naltrexone with several studies we reviewed in the evidence-based literature.
RESEARCH STUDIES
Dr. Raknes and colleagues in 2018 looked at a Norwegian database in 2013 of 582 IBD patients, 256 patients who utilized LDN had reduced their Crohn’s disease drugs including immunosuppressants and steroids - which may mean a lot of things but the hope is that they were doing much better with disease regression and not suffering without their medications!
Dr. Mitchell et al. J Trans Med 2018:
47 patients with IBD were given low dose naltrexone 4.5 mg daily (crohns and ulcerative colitis). After 12 weeks on low dose naltrexone, they had a scope done and turns out that the gut barrier function improved and inflammation was reduced.
Ultimately, 75% of patients completing the low dose naltrexone had a significant healing response.
Adverse effects are what Dr. Roths previously reported in podcast episode: 9 people had vivid dreams, and 2 people drowsiness, and 1 person headache were complaints.
Of note, in a systematic review/meta-analysis that reviewed 89 trials with 11000 participants revealed that naltrexone does not appear to increase risk of serious adverse events over placebo encouraging studies for conditions outside of its FDA approval for opioid use disorders. However, higher dose naltrexone can potentially induce liver damage!
Dr. Jill Smith and her team at Hershey Medical Center in Pennsylvania completed several diseases in Crohns disease and found that in adults LDN lowered crohn’s disease activity significantly in 88% of participants (this was the gold standard double blind placebo controlled trial) .
She also conducted a pilot study meaning just starting to learn about a drug or treatment in a small population of 12 participants with Crohn’s disease who received LDN 4.5 mg or 0.1 mg/kg between the ages of 6-17 years old. They could stay on their same crohn’s medications.
They did find a biomarker known as prealbumin that improved 2.5 times more than the 6 patients on placebo. The six children had decreased Crohn’s activities scoring based upon a validated, but subjective, PCDAI scoring system. Ultimately a much larger trial is needed to assess efficacy in children but this is where research has to start in order to affect clinical change to help individuals with these chronic inflammatory conditions.
No difference in side effects between placebo and naltrexone but again the unusual dreams were reported here as well!
However, there are no studies demonstrating that LDN can induce or maintain remission as of yet but hopefully future studies will continue to shine a light on LDN or you guys can raise awareness to your academic institution if you’ve had a positive experience to possibly interest them to research LDN (of course money/funding usually is a huge factor in getting started with research studies which is so difficult to obtain through grants).
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