A ‘Novel’ Anti-inflammatory

“We discuss the concept of using low-dose naltrexone (LDN) as a novel anti-inflammatory treatment for chronic pain conditions that are suspected to be associated with inflammatory processes.”

outside the box

The Stanford researchers believe the action in LDN is in its central nervous system inflammation reducing properties not it’s effects on opioid receptors.

Low dose Naltrexone is one of the more intriguing treatment options to emerge for Fibromyalgia and pain patients in recent years.  Not  only is it dirt cheap compared to many drugs but side effects are usually minimal.

Because  any compounding pharmacy can produce  LDN, however, drug companies – the major source of drug innovation in the U.S. –  have largely ignored it. LDN’s ‘outsider status’ has hampered research efforts, but the drug simply appears to be too effective and too intriguing to be kept down for too long.

A recent review article by Stanford researchers on LDN and pain published in the Journal of Clinical Rheumatology, suggests that LDN’s effectiveness in Fibromyalgia could open the door for a new conception of chronic pain founded on neuroinflammation. They anticipate the development of an entirely new class of nervous system inflammation reducing pain drugs. The review article should also help expand recognition of LDN as option for people with Fibromyalgia and other pain conditions.

We cover the review article, other microglial inhibitors and LDN news in this blog.

Low Dose Naltrexone, Inflammation and Pain: A Different Look at Fibromyalgia and Chronic Pain

Clin Rheumatol. 2014 Apr;33(4):451-9. doi: 10.1007/s10067-014-2517-2. Epub 2014 Feb 15.The use of low-dose naltrexone (LDN) as a novel anti-inflammatory treatment for chronic pain. Younger J1, Parkitny LMcLain D.

The FDA approved naltrexone HCL in 1984 to treat opioid addiction. Low-dose naltrexone is typically given at about 1/10th the typical dose of naltrexone. By blocking opioid receptors naltrexone can increase pain, but at very low doses naltrexone has both pain-reducing (analgesic) and anti-inflammatory properties.

Tests with another drug, called ‘dextro-naltrexone’, which does not affect opioid receptors but does affect microglial receptors, suggest LDN’s effects in FM do not involve the opioid receptors.

Fibromyalgia – A ‘Central’ Inflammatory Disorder? 

“LDN may emerge as the first of many glial cell modulators that could be used to treat chronic conditions, with more specifically targeted medications developed in the future. As conventional anti-inflammatories have poor blood brain-barrier permeability, we expect centrally active immune modulators to be an area of interest in the future.”

The authors introduced LDN as a pain drug that is able to modulate ‘glial cell’ activity. When I asked Dr. Younger why he’s focused on the microglia in Fibromyalgia he stated,

“First, a growing collection of basic science studies (by investigators such as Drs. Linda Watkins and Mark Hutchinson) suggested that naltrexone can reduce the excitability of microglia in the brain, preventing the release of inflammatory and neurotoxic chemicals.”

Animal studies indicate LDN has neuroprotective properties that are directly tied to its ability to suppress microglial activation and possibly reduce inflammatory activity in the body as well.

glial cells

Glial cells could hold the key to reducing brain induced chronic pain

Glial cells provide structural support for neurons in the brain, relay oxygen and nutrients to them, and defend them from pathogen attack. Once activated, the glia (or microglia) spew a wide range of inflammatory and excitatory factors (substance P, cytokines, NO, etc.) that cause such symptoms as pain, fatigue, fever, cognitive and sleep problems; in short, just about every symptom associated with Fibromyalgia and Chronic Fatigue Syndrome.

Dr. Younger believes microglial cell activation may be causing the kind of central sensitization found in Fibromyalgia (and, we assume, Chronic Fatigue Syndrome patients) which causes a wide variety of symptoms:

“I think microglia activation is the best explanation for central sensitization when the symptoms are widespread (e.g., involves more than one of pain, fatigue, sleep problems, cognitive disruption, etc.). There are other types of central sensitization, but they would not lead to all-over-body symptoms and multi-symptom problems.”

Younger’s small Chronic Fatigue Syndrome leptin study suggested to him that the microglia had become sensitized to inflammatory factors. All it took were small fluctuations in leptin, which can cross the blood-brain barrier, for ‘sickness behavior’ (fluey feelings, fatigue, etc.) to be evoked.

“The microglia have been sensitized, and therefore small swings in cytokines and adipokines are sufficient to provoke a large sickness response.”

Fibromyalgia has not been thought of as an inflammatory disorder and anti-inflammatories are generally not very helpful, but LDN’s effectiveness in two small fibromyalgia studies (50% of participants improved) suggest a specific type of inflammation affecting the glial cells of the brain may be involved. If this is true then FM is probably best classified as a ‘central immune disorder'; i.e., an immune disorder of the brain, with lower levels of inflammation in the body.

A Novel Anti-inflammatory

The Stanford lab’s finding that higher erythrocyte sedimentation rate (ESR) readings at baseline were associated with greater reductions in pain in Fibromyalgia suggested a) inflammation played an important role in FM patients’ pain, and b) LDN was reducing that inflammation.


LDN may be particularly effective in immune/autoimmune based disorders

The erythrocyte sedimentation rate (ESR), commonly called a ‘sed rate’, is the rate at which red blood cells fall to the bottom of a tall thin tube in a period of one hour. It is a common hematology test, and is a non-specific measure of inflammation. When an inflammatory process is present, the high proportion of fibrinogen in the blood causes red blood cells to stick to each other.

The ESR findings suggest that people with inflammatory and autoimmune disorders such as lupus and rheumatoid arthritis could also benefit from low dose naltrexone.

LDN may be more effective in Crohn’s disorder (80% effectiveness rate thus far) than in FM, and may be helpful in multiple sclerosis and chronic regional pain syndrome. The authors recommended that future LDN trials include a variety of inflammatory measures such as ESR, c-reactive protein, cytokines, growth factors, etc. to explore its anti-inflammatory effects.

A Person with Fibromyalgia Describes Their Experience With LDN

Opioid Receptor Blocker

It’s also possible that LDN’s opioid receptor blockage could provide relief by inducing the body to produce opioids and opioid receptors.

Lost Cost and Low Side Effects

LDN can be obtained from compounding pharmacies for from $35-$55 a month

Calling the low side-effects one of the most exciting aspects of LDN, the authors emphasized they have seen no serious side-effects in their patients and contrasted that with the increased risk of ulcers, kidney problems, clotting, heart attacks, etc. resulting from use of the current crop of anti-inflammatories. The most common side effect they’ve seen has been vivid dreams.

Low Dose Naltrexone and …SEX! 

start me up

Start me up, baby! The reports are all anecdotal but some people report having better sex after using LDN. Could it be true?

Although not mentioned in this review, several LDN patients have mentioned dramatically increased libido. Although Younger wasn’t clear why this would be so and hadn’t noticed it in his patients, one ME/CFS and FM doctor has noticed its effects in her patients. If it is happening, Younger speculated that lifting inflammation-induced anhedonia could be in play.


Research into LDN has been limited, but with the first human drug trial only being published in 2007 , LDN is new to the medical community. Despite the limited research, strong clinical results and word of mouth among patients is making LDN a relatively well-known opioid alternative. LDN is the first choice for pain for Dr. Nancy Klimas, a Chronic Fatigue Syndrome researcher and physician at Nova Southeastern in Miami.

LDN’s mode of action is still unclear, but the authors encouragingly noted in the paper that several laboratories are ‘vigorously’ engaged in determining exactly how it works.

LDN Projects On Tap

Meanwhile stating “there will definitely be followup studies” Younger has some projects lined up.

  1. Do we see inflammatory markers in the blood decrease when someone improves with LDN?
  2. What is the proper dosage? (We will be conducting a dose-ranging study to see if lower or higher dosages work better for some people).
  3. Does LDN help in other conditions such as rheumatoid arthritis, osteoarthritis, CFS, and maybe even depression?
  4. We want to do a large (200+ person) clinical trial of LDN and fibromyalgia

(It was not clear which projects have been funded. The 200 person trial has not been funded.)

Drug Approval

An FDA-approved LDN drug would increase interest in LDN dramatically, making it available to many more patients and increasing research interest dramatically. The ability of compounding pharmacies to produce LDN would seem to remove it from the interest of drug companies, but Younger noted that one drug company, TNI Biotech, is interested and is trying to commercialize a 4.5 mg version of LDN for around $1/day.

Touting LDN’s effectiveness and safety in pediatric Crohn’s, TNI Biotech hopes to use that disease to bring an FDA-approved version of LDN to market. They did not respond to a request for an interview.

LDN News

International LDN Awareness week, this coming November 1-8, will coincide with a live streamed conference in Las Vegas.

The LDN Research Trust

LDN Research Trust is looking for case studies from LDN prescribing doctors, pharmacists, researchers, and LDN users around the world. To have case studies included you must provide

  •  Name
  • Country
  • Condition(s) LDN is used for
  • When LDN was started
  • Up to 40 words telling what LDN has done to help
  • A photo

Professionals List

Doctors who prescribe or pharmacists who compound LDN can add themselves to the LDN Researach Trust’s lists at the links below..

If you know of someone who should be added, send the Trust their details and they will contact them.


If you’ve tried LDN, you can also be interviewed over the phone. Your interview will be made into a video for the Trust’s YouTube Channel. They have over 400 videos listed.

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