Low Dose Naltrexone and the Treatment of Pain

Your body makes its own morphine.  It’s true.  Substances in your body called endorphins, enkephalins and dynorphins work on the same receptor as morphine.  You have probably heard of a runner’s high.  This results from a flood of endorphins that stimulate  the morphine receptors.

When morphine or another opioid is given to a person, it acts on an area of the brain called the hypothalamus to inhibit the release of many hormones including beta endorphin[1].  The endorphins can also inhibit their own release resulting in increased pain, allodynia or hyperalgesia.  It is called a negative feedback loop.

Recently, there has been a flood of research examining the use of a drug called naltrexone in low doses (Low Dose Naltrexone or LDN) to treat pain.  Naltrexone blocks the effects of the opioid receptors and has been used to treat alcohol and opioid addiction.  When naltrexone blocks the endorphin response in the hypothalamus, it actually stimulates the body to produce more endorphins.  LDN has been proven, through scientific study, to actually increase the levels of circulating endorphins[2][3].  The theory is that, by increasing the body’s own circulating endorphin levels, the endogenous opioids will produce more inhibition at the body’s own pain receptors.

Typical doses of LDN are 0.5 to 4.5mg per day.  Because of rhythms of the body’s production of master hormones, LDN is best taken between 9:00 pm & 3:00 a.m. Most patients take it at bedtime.

The only major side effect seen in most of the patients is sleep disturbances  Because of this, I recommend gradually titrating the dose up to 4.5mg.  This can be accomplished by taking 1.5mg by mouth at bedtime for one to two weeks, then 3mg at bedtime for one to two week, followed by 4.5mg at bedtime thereafter.

If the patient is already on an opioid for pain such as morphine, codeine or hydrocodone, they should consult the prescribing physician to ensure there will not be a precipitated withdrawal from the narcotics when LDN is added to their regimen.  However, it is possible to use LDN concurrently with narcotic analgesics.  There are many case studies demonstrating that concurrent use of LDN with narcotics decreases the amount of narcotics the patient needs for pain control.[4][5][6][7]

[1] Goodman and Gillman’s, The Pharmacological Basis of Therapeutics, 7th ed (1985).  Chapter 22, page 500.
[2] Giorni et al.  A pilot trial of low-dose naltrexone in primary progressive multiple sclerosis. Mult Scler. 2008 Sep;14(8):1076-83
[3] Bouvard MP, et al.  Low-dose naltrexone effects on plasma chemistries and clinical symptoms in autism: a double-blind, placebo-controlled study. Psychiatry Res. 1995 Oct 16;58(3):191-201
[4] Crain SM, Shen KF. Antagonists of excitatory opioid receptor functions enhance morphine’s analgesic potency and attenuate opioid tolerance/dependence liability. Pain. 2000;84(2-3):121-31
[5]Cruciani RA, Lussier D, Miller-Saultz D, Arbuck DM. Ultra-low dose oral naltrexone decreases side effects and potentiates the effect of methadone. J Pain Symptom Manage. 2003;25(6):491-4
[6]Gan TJ, Ginsberg B, Glass PS, Fortney J, Jhaveri R, Perno R. Opioid-sparing effects of a low-dose infusion of naloxone in patient-administered morphine sulfate. Anesthesiology. 1997;87(5):1075-81
[7]Powell KJ, Abul-Husn NS, Jhamandas A, Olmstead MC, Beninger RJ, Jhamandas K. Paradoxical effects of the opioid antagonist naltrexone on morphine analgesia, tolerance, and reward in rats. J Pharmacol Exp Ther. 2002;300(2):588-96
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2 Responses to Low Dose Naltrexone and the Treatment of Pain

  1. Lynette Bilski says:

    Hi, I am not sure if I understood the article correctly. I am now on a trial of a pain patch called Butrans 5mcg/hour. I’ve had it on about 48 hours and am having problems with headaches and itching in the spot where I am wearing the patch. I am very sensitive to narcotics and become dependent easily and it is a long and painful process to get off the drug. I am seen in a pain clinic and have a good working relationship with my doctors and they are very helpful, but for now, I have to restart a narcotic but I am extremely worried about becoming dependent again. Will this new drug possibly help me, and if so, how? Are pain clinic doctors using it?

  2. Lynn Bakeman says:

    We tried LDN for 8 months (told it can take up to a year for results) to help with IBD. We did not have much success as malabsorption became a huge issue. My son is now on morphine for the pain of a fistula. My question is about your comment on combining the two. I understand he should clear his system of the morphine for 2 wks before trying LDN again. He does feel the morphine helps with his UC symptoms, but given its addictive quality, I’d rather he give LDN a try again! Would love your input!

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