Combine Opioid and Opioid Blocker for Less Fibromyalgia Pain?

By Ginevra Liptan, MD
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My last blog post was about the use of low doses of naltrexone, an opiate blocker, to turn down the volume on fibromyalgia pain. But the limiting factor for many fibromyalgia patients is that they are already taking opiate-based pain medications, which don’t mix well with naltrexone. The concern of course is that as an opiate blocker, naltrexone will knock the opiates off their receptors, inducing withdrawal symptoms and worsening pain. However, there may be a way to allow taking low-dose naltrexone along with an opiate, and the key is in keeping the dosage very low, what’s called ultra-low-dose naltrexone. In fact there is some evidence that ultra-low-dose naltrexone may actually help opiates to work better, for longer, in patients.

Laboratory research and clinical trials have demonstrated unexpected, paradoxical effects when opiate blockers are combined with opiates that enhance their pain-relieving effects. This is dosage dependent, as too much of the opiate blocker will block the pain-relieving effects of the opiate and even induce withdrawal symptoms. In general, studies show the best success when combining opiates with ultra low doses of naltrexone at around 1mg or less. This is in comparison to usual dose of low-dose naltrexone (LDN) which is between 1 and 5mg (The typical dosage of prescription naltrexone is 50mg when it is used for treatment of addiction to block the euphoric effects of opiates and alcohol).

How could an opiate blocker combined with opiate pain medications decrease pain? We know that long-term high dose opioids can actually increase pain levels, because they irritate certain cells in the spinal cord called glia, which increase sensitivity to pain signals. In my last blog post, I talked about how the central nervous system in fibromyalgia has become supersensitized to pain signals because of glial cell activation. Glial cell activation is one important reason why, over time, opiates are less effective for managing fibromyalgia pain, because while the opiate pain meds are blocking some pain signals, they are at the same time increasing the pain volume. Think of the opiates like putting in ear plugs to block out the noise from the TV, but at the same turning up the volume on the TV speakers. Pretty soon it will feel just as loud as if you didn't have the ear plugs in at all.

Ultra-low-dose naltrexone seems to help block the activation of glial cells caused by long term opioid use, and prevent the amplification of pain that can be induced by long-term opiate use. At very low doses it can do this without blocking the pain-relieving actions of the opiates. The key is finding the dosage sweet spot where LDN is able to calm the glial cells, but not knock the opiates off their receptors. That sweet spot seems to be around 0.5–1mg, called ultra-low-dose naltrexone (usual low-dose naltrexone is 3–4.5mg).

A review published in a pain management journal found that "low doses of opioid antagonists seem to ‘reset’ the opioid receptor system, enhancing analgesia (pain relief) while overcoming prior opioid tolerance.”

One study found that oxycodone and ultra-low-dose naltrexone combined provided better pain relief from osteoarthritis than oxycodone alone. Similar findings were shown in a study of chronic low back pain, with subjects on the combination of oxycodone and ULDN getting better pain relief, and requiring lower doses of oxycodone compared to subjects on oxycodone alone. 

The use of ultra-low-dose naltrexone is an exciting area that needs more study, as it could enable us to get a lot more therapeutic benefit from opiates with less negative side effects. And it may mean that patients currently taking opiates can get the benefit of LDN, as long as they take less than 1mg. I am just starting to try this with a few of my brave patients; stay tuned for updates on how they are doing.

Author Bio: Ginevra Liptan, MD, developed fibromyalgia while in medical school. She is a graduate of Tufts University School of Medicine and board-certified in internal medicine. Dr. Liptan is the founder and medical director of The Frida Center for Fibromyalgia and the author of The FibroManual: A Complete Fibromyalgia Treatment Guide For You...And Your Doctor and The Fibro Food Formula: A Real-Life Approach to Fibromyalgia Relief.