I always try to present the facts to anyone who reads this blog. I try not to stretch the truth. Maybe I haven’t been super successful in that regard, but I try to present accurate information without blowing it out of proportion. That’s what I want to do today, present some information and put it into context. For the record, I personally think naltrexone has promise for certain disease states.
Naltrexone is a drug that is specifically for narcotic overdose. It blocks receptors that normallyendongenous endorphins (and narcotics) will bind to create a sense of well being, euphoria, or analgesia (pain relief). Runners will often talk about the runner’s high they get after a good run. That’s endorphins. Mmm, endorphins (think Homer Simpson).
Naltrexone is wicked awesome, I used awesome not only as a superlative, but as in it’s crazy amazing to watch someone who should probably be dead because of no breathing from narcotic overdose, at reversing it completely. It’s bad to give the full dose all at once too because a person can go from not breathing to full withdrawal within a few seconds. It’s almost like watching someone raise the dead. ER docs will usually give it bits at a time and wait for response to avoid withdrawal.
So why use a revival agent for narcotics in something like rheumatoid arthritis or multiple sclerosis?
It has to do with what naltrexone actually does. You can think of it as an immune modulator. In autoimmune disorders like rheumatoid arthritis, the immune system is literally attacking the host body. Your immune cells are targeting you. No bueno. The only cases where we want this happening is when a cancer cell forms or a virus has infiltrated a cell.
For those that don’t want more nitty-gritty on the mechanism, you can skip this next part, but you should read it anyway and learn something new.
Naltrexone is known to bind the opiate receptors on cells.  This of course is how it helps prevent narcotics from doing their job, because they can’t do anything but float around aimlessly in the blood.
At a standard dose of 50mg, naltrexone causes blockade of opiates and if you were to take your Vicodin or Percocet, they wouldn’t do anything, other than the acetaminophen of course. What scientist have found is that when the dose is cut down to about 1/10 or so, blockade still occurs, but because there is little drug in the system, the body is able to clear it quickly and more endorphins are created to overcome the blockade.[2,3] In a normal dose or even a slightly higher dose, the naltrexone is present in enough quantities to stop the transient rise.
In the low dose, this rise creates the possibility of greater analgesia (pain relief) as well as immune modulation. These factors MAY increase quality of life, mood, and/or disease resilience.  It’s important to remember that word “may” because large trials haven’t been conducted in a placebo controlled, double-blind manner, which means we only have preliminary data to draw from.
It has been shown that naloxone can reduce inflammation cytokines (chemical messengers that incite inflammation from immune cells) in macrophages in the periphery. This may help explain some of the immune modulation thought to produce effects in things like arthritis or Crohn’s disease. It should be noted that this was done with naloxone and not naltrexone. While similar, you can’t always transfer effects of one drug to another, even though while in the same class.
In the nervous system, naltrexone has been shown to affect microglia, which are immune cells. By reducing inflammatory cytokines, they may help in neurodegenerative disease brought on by inflammation. Indeed, both naloxone and naltrexone, seem to have a neuroprotective effect, at least in mice. 
So what about actual studies looking at disease?
In one looking at fibromyalgia, one study looked at 10 women with the disease and found that 6 out of 10 received relief to some degree over placebo, and showed that mechanical and heat thresholds were improved. 
In another of fibromyalgia, 30 women were treated with placebo or naltrexone and there was a significant reduction in pain for the naltrexone group over the placebo group. 
Another fibromyalgia study with a 50mg dose showed no difference in groups.  As discussed above, this could be do the dose, rather than the drug. Remember that at higher doses, the blockade of opiate receptors happens for a longer period and the increased endorphins can’t do their job.
In another study with 60 participants with multiple sclerosis, naltrexone was found to improve mental health quality over placebo.  The authors did point out this study did not assess the drug as a disease modifying agent, such as Copaxone. They did state there did seem to be no interactions with typical MS drugs.
In patients with Crohn’s Disease, 18 naltrexone patients had significantly more reduction in severity score associated with the disease over 16 placebo patients. 
A trial with children found that it also may be very effective. 
Because of its mechanism, it’s not improbable that it could help with other autoimmune conditions like rheumatoid arthritis because of the inflammatory effects of the disease. Others like lupus might also benefit.
Naltrexone seems to be tolerated well, especially since it is being used at a lower dose. Some nausea has been reported as well as abnormal dreams. People that have liver disease might be cautious, as it has been shown to cause liver problems, but those are in the 50-100mg/day dose range. 4.5, the common dose used in many studies, doesn’t seem to have that effect.
Naltrexone also must be compounded by a compounding pharmacy. The lowest commercial dose available to pharmacies is 50mg/tab, so they have to make it into caps or suspensions, depending on the dose. You can call a compounding pharmacy and ask how much it would be for 30 caps of 4.5mg naltrexone. Most will probably already know or be able to get you a number relatively quick.
It also must be an immediate release formulation, no extended release. One note of caution: if you do choose to use naltrexone and you take narcotics, you’ll want to wean off of them. Naltrexone, even at a small dose, will block the effect of your pain med and cause problems. Talk to your doc about that if that’s a concern.
Because no large studies have been done, it’s hard to gauge just how effective it is. I’ve read several personal anecdotes of people claiming it has done great things for their lives. I have hope for it as I think it has much promise. Hopefully someone will be able to do larger scale trials to give us a better idea of how well it actually works at a more general population level with a given disease.
I’ve read about some people seroconverting with HIV, while others have claimed that their viral load decreased. Again, I haven’t seen clinical data to back that up, but if true, would be a great thing for people battling that horrible virus.
In short, if you’re willing to give naltrexone a try, their probably shouldn’t be much problem, other than maybe convincing your doctor of writing a script.
1.Wang D, Sun X, Sadee W. Different effects of opioid antagonists on mu-, delta-, and kappa-opioid receptors with and without agonist pretreatment. J Pharmacol Exp Ther. 2007;321:544–552
2.Tempel A, Gardner EL, Zukin RS. Neurochemical and functional correlates of naltrexone-induced opiate receptor up-regulation. J Pharmacol Exp Ther. 1985;232(2):439–444
3.Zagon IS, McLaughlin PJ. Gene-peptide relationships in the developing rat brain: the response of preproenkephalin mRNA and [Met5]-enkephalin to acute opioid antagonist (naltrexone) exposure. Brain Res Mol Brain Res. 1995;33(1):111–120
4.Brown N, Panksepp J. Low-dose naltrexone for disease prevention and quality of life. Med Hypotheses. 2009;72(3):333–337.
5.Liu SL, Li YH, Shi GY, Chen YH, Huang CW, Hong JS, Wu HL. A novel inhibitory effect of naloxone on macrophage activation and atherosclerosis formation in mice. J Am Coll Cardiol. 2006;48(9):1871–1879
6.Hutchinson MR, et al. Non-stereoselective reversal of neuropathic pain by naloxone and naltrexone: involvement of toll-like receptor 4 (TLR4) Eur J Neurosci. 2008;28(1):20–29.
7.Younger J, Mackey S. Fibromyalgia symptoms are reduced by low-dose naltrexone: a pilot study. Pain Med. 2009;10(4):663–672
8.Younger, Jarred, et al. “Low‐dose naltrexone for the treatment of fibromyalgia: Findings of a small, randomized, double‐blind, placebo‐controlled, counterbalanced, crossover trial assessing daily pain levels.” Arthritis & Rheumatism 65.2 (2013): 529-538.
9.Younger, Jarred W., Alex J. Zautra, and Eric T. Cummins. “Effects of naltrexone on pain sensitivity and mood in fibromyalgia: no evidence for endogenous opioid pathophysiology.” PloS one 4.4 (2009): e5180.
10.Cree, Bruce AC, Elena Kornyeyeva, and Douglas S. Goodin. “Pilot trial of low‐dose naltrexone and quality of life in multiple sclerosis.” Annals of neurology 68.2 (2010): 145-150.
11.Smith, Jill P., et al. “Low-dose naltrexone therapy improves active Crohn’s disease.” The American journal of gastroenterology 102.4 (2007): 820-828.
12.Smith, Jill P., et al. “Safety and tolerability of low dose naltrexone therapy in children with moderate to severe crohn’s disease: a pilot study.” Journal of clinical gastroenterology 47.4 (2013): 339.