• Welcome to Crohn's Forum, a support group for people with all forms of IBD. While this community is not a substitute for doctor's advice and we cannot treat or diagnose, we find being able to communicate with others who have IBD is invaluable as we navigate our struggles and celebrate our successes. We invite you to join us.

LDN- oral vs transdermal?

I am wondering if someone can explain the rationale for transdermal LDN in Crohn's. I would think that oral naltrexone would be better than transdermal since it would potentially have local effects on the intestine.



I don't know the answer to this but as far as it having an effect on the intestines it would need to be enteric coated? Does the pharmacy provide it in such capsules?


Senior Member
It has no direct effect on the intestines... Naltrexone is a neurological drug. As to whether or not transdermal methods would work, I have no info on any studies that used anything other than oral versions in their trials. I would suggest sticking with the tested method Vs transdermal UNLESS there was some overwhelming reason to try transdermal. There is a full transcript of an LDN study in another post that describes how it works, issuess, etc..


Staff member

There is another mother here whose daughter is on transdermal LDN (Livilou); perhaps she can give you some info re transdermal. :)
Hi Kev,

I agree that one should stick with the oral preparation, because that's what's been shown to work in clinical trials.

I initially asked the question because I've noticed some people are using transdermal naltrexone. Transdermal medications are absorbed systemically, avoiding "first pass" liver metabolism which many oral drugs, including naltrexone, undergo. So I can imagine, that transdermal naltrexone might be preferred over oral LDN for non-GI diseases such as MS.

I'm not sure what you mean by "neurologic drug". My understanding is that naltrexone works on opioid and opioid growth factor receptors and that some of these receptors are in fact in the GI track. I would think that the intestine would be the primary site of LDN action in people with Crohn's.

Even after trying to read the scientific journals, I am still not clear about where (which cells) LDN works on.
It works on opioid receptors, which are part of the central and peripheral nervous system, hence it is a "neurologic" drug. There are opioid receptors in the digestive tract, the brain, and the spinal cord.

LDN works on endogenous opioids called endorphins. It blocks this opioid receptor for up to 4 hours, suppressing endorphins. When the opioid receptor is "free", it boosts the production of endorphins, resulting in how LDN works to halt the disease. Endorphins are known to be healing. Which is part of why exercise is good for people. You produce endorphins when you exercise.

I'm not a doctor or a scientist so this may not be exactly correct but I think it's pretty close.

Someone please correct me if I'm wrong.
Last edited:
Actually, I'm a doctor, though not practicing for some time now. Despite my background, I find the mechanism of Naltrexone and Opioid/ Opioid Growth factor physiology really complex.

From my understanding, Naltrexone blocks both classical opioid receptors and the Opioid Growth factor OGF receptor. The OGF system is pretty ubiquitous and actually regulates (inhibits) cell proliferation. Met5-enkephalin was renamed OGF because it was found that it was a growth factor and not a neuromodulator.

Ctrlz your above description of LDN generally jives with how LDN Science describes it, except, substitute Opioid growth factor for endorphin. Short term OGF receptor blockade causes increase OGF receptors, increase receptor sensitivity and increase rebound production of OGF.

My question is where (what cells/organs) does Naltrexone act? Does OGF act like a traditional growth factor, acting locally, or more like a hormone, acting systemically. I'd love to understand this better.


Senior Member
I believe ctrl z has nailed how low dose Naltrexone works in treating IBD. Then again, I'm no doctor, or scientist, etc.. Just someone who has used LDN to treat my disease since late 2007. I've always/only used an oral dose compounded by one of several local pharmacies that have the proper equipment to make these little capsules for me. Thing of it is, despite they (pharmacies) and I being nearly 5 years into this experiment, there have been bumps along the road. Stale Vs fresh compound for example. My anecdotal info got the pharmacies to delve a little deeper into how long compound mixture retains its potency AND revise their practices. Now, what is involved in taking bulk Naltrexone and putting the proper dosage into a transdermal patch which then delivers that drug to the body in a method AND timeline consistent with treating Crohns (or any form of IBD) I don't know... and I wonder/worry whether anyone has the answer to that question. It may be that the process of putting 4.5mg of Naltrexone into a patch is quite easy, and it also may be that it doesn't affect how it delivers the drug... but has that been tested? My concern is that 4.5mg transdermal patches of Naltrexone may work for other issues like MS, whatever, etc., but have never been clinically trialed for treating IBD. And if some fundamental things like fresh Vs stale powder affect compounded capsules, what other potential unknowns might affect how well or whether if at all transdermal forms of the med will work. If I were starting from scratch today on LDN, I wouldn't take the chance of going a route that hasn't been trialed and proven successful. There is just too much to lose. No, I would go the tried N tested route first, and only deviate from it if there was some confirmed, overwhelming reason to experiment with transdermal. That is just my humble opinion, but I believe it makes good old fashioned horse sense.
We seemed to have posted at exactly the same time... I completely agree that one should try to copy the formulation used in the clinical trials. I'm glad it's working well for you. My son is hoping to find a doctor who will prescribe it and we will contact Hershey Med Center if necessary to get the correct oral formulation.

The transdermal route doesn't seem like it would be effective and I recently found LDNscience says not to use it. "For LDN to work, the full LDN dose must be delivered to the body in one go. Transdermal delivery methods by nature result in slow continuous delivery of a drug. This will result in continuous opiate receptor blockade - quite the opposite of the purpose of LDN which is to deliver a very short term blockade in order to create the beneficial rebound effect."
Naltrexone has very poor properties of penetration and does not have the physicochemical properties to penetrate deeply into the skin and enter the systemic circulation. The systemic circulation would be the source for the entire body. In recent studies it was discovered that naltrexone in a cream form (transdermal) does not alter cells in the skin distant to where the application was made. As a result it was discovered that it was great for wound healing but not for what we like to use LDN for. Also the pharmokinetics of applying naltrexone is not understood and there's no way of knowing how long it stays on your skin. Hope this helps.
Yes, it's true a lot of UCers have problems with absorption all together, not just with LDN. I had problems with absorption too, so I went from LDN pills to transdermal LDN.


Senior Member
Not being able to absorb LDN orally is something that only needs to be addressed IF/WHEN it occurs. Straying from the trialed/tested method of using LDN to fight Crohns isn't your best, first choice. If malabsorption of Naltrexone orally was a major issue (for this intent) then the people behind the original research would have looked at alternate delivery methods first. Yet they chose the oral route, and it had (and continues to have) a very high success rate. To offer some sage advice "If it ain't broke, don't fix it!"
Hi all
I would like to follow the advice on taking the liquid LDN however I am concerned about the ingredients (I have an eczema reaction to a lot of products) and the saccharine, I am prone to have a fermenting gut if I have too much sugar in my diet. Are my concerns about the saccharine and the other ingredients likely to be unfounded do you think? Grateful for any advice on this, and your experience.