LDN and Fibromyalgia

For sufferers of fibromyalgia, their condition is not just painful, but made doubly worse by the lack of proper treatment for it, and the uncertainty over the condition in the medical community. Now there is good news. A recent study indicates that Low-Dose Naltrexone does indeed ease the pain of fibromyalgia. 



Johnson B, Ulberg S, Shivale S, Donaldson J, Milczarski B, Faraone SV. Fibromyalgia, autism, and opioid addiction as natural and induced disorders of the endogenous opioid hormonal system. Discov Med. 2014;18(99):209‐220.


Introduction: Because of their circulation through the blood, the multiplicity of receptor sites, and the diversity of functions, opioids may most accurately be designated as a hormone. Opioids modulate the intensity of pain. In mammals, the opioid system has been modified to modulate social interactions as well (Panksepp and Watt, 2011).

Methods: Over 10,000 patient encounters were observed on a neuropsychoanalytic addiction medicine service. Cold pressor times (CPT) were recorded before and after stimulation of the opioid system with low-dose naltrexone (LDN) for patients after opioid detoxification and for fibromyalgia patients.

Results: Patients maintained on opioids relate autistically. The cold, unrelated nature of their human interactions was reversed by detoxification from opioids. Fibromyalgia patients have difficulty participating in human relationships, as if they lack an ability to respond interpersonally, as do post-detoxification patients. LDN improved pain tolerance as shown by a significant increase on CPT for post detoxification patients from 16 seconds to 55 seconds and in fibromyalgia patients from 21 seconds to 42 seconds, and improved relatedness. The correlation of opioid prescribing increasing over time and autism prevalence increasing over time is highly significant.

Conclusions: 1. Opioid-maintained patients relate autistically. 2. Autism is a hyperopioidergic disorder. 3. Fibromylagia is a hypoopioidergic disorder. 4. Low opioid tone caused by opioid maintenance or fibromyalgia can usually be reversed with low-dose naltrexone. 5. The increase in the incidence of autism may have been caused by the increase in use of opioids for analgesia during childbirth.


Deshpande S, Rivera DE, Younger JW, Nandola NN. A control systems engineering approach for adaptive behavioral interventions: illustration with a fibromyalgia intervention [published correction appears in Transl Behav Med. 2014 Dec;4(4):439]. Transl Behav Med. 2014;4(3):275‐289. doi:10.1007/s13142-014-0282-z

ABSTRACT: The term adaptive intervention has been used in behavioral medicine to describe operationalized and individually tailored strategies for prevention and treatment of chronic, relapsing disorders. Control systems engineering offers an attractive means for designing and implementing adaptive behavioral interventions that feature intensive measurement and frequent decision-making over time. This is illustrated in this paper for the case of a low-dose naltrexone treatment intervention forfibromyalgia. System identification methods from engineering are used to estimate dynamical models from daily diary reports completed by participants. These dynamical models then form part of a model predictive control algorithm which systematically decides on treatment dosages based on measurements obtained under real-life conditions involving noise, disturbances, and uncertainty. The effectiveness and implications of this approach for behavioral interventions (in general) and pain treatment (in particular) are demonstrated using informative simulations. 

KEYWORDS:  Adaptive behavioral interventions; Control systems engineering; Dynamical systems; Fibromyalgia; Model predictive control; Pain treatment; System identification


Younger J, Noor N, McCue R, Mackey S. 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 Rheum. 2013;65(2):529‐538. doi:10.1002/art.37734

OBJECTIVE To determine whether low dosages (4.5 mg/day) of naltrexone reduce fibromyalgia severity as compared with the nonspecific effects of placebo. In this replication and extension study of a previous clinical trial, we tested the impact of low-dose naltrexone on daily self-reported pain. Secondary outcomes included general satisfaction with life, positive mood, sleep quality, and fatigue.

METHODS Thirty-one women with fibromyalgia participated in the randomized, double-blind, placebo-controlled, counterbalanced, crossover study. During the active drug phase, participants received 4.5 mg of oral naltrexone daily. An intensive longitudinal design was used to measure daily levels of pain.

RESULTS When contrasting the condition end points, we observed a significantly greater reduction of baseline pain in those taking low-dose naltrexone than in those taking placebo (28.8% reduction versus 18.0% reduction; P = 0.016). Low-dose naltrexone was also associated with improved general satisfaction with life (P = 0.045) and with improved mood (P = 0.039), but not improved fatigue or sleep. Thirty-two percent of participants met the criteria for response (defined as a significant reduction in pain plus a significant reduction in either fatigue or sleep problems) during low-dose naltrexone therapy, as contrasted with an 11% response rate during placebo therapy (P = 0.05). Low-dose naltrexone was rated equally tolerable as placebo, and no serious side effects were reported.

CONCLUSION The preliminary evidence continues to show that low-dose naltrexone has a specific and clinically beneficial impact on fibromyalgia pain. The medication is widely available, inexpensive, safe, and well-tolerated. Parallel-group randomized controlled trials are needed to fully determine the efficacy of the medication.


Ramanathan S, Panksepp J, Johnson B. Is fibromyalgia an endocrine/endorphin deficit disorder? Is low dose naltrexone a new treatment option?. Psychosomatics. 2012;53(6):591‐594. doi:10.1016/j.psym.2011.11.006


Fibromyalgia is a chronic pain syndrome. Neuman and Buskila noted that fibromyalgia afflicts approximately 5% of women and 1.6% of men. The diagnosis of fibromyalgia is primarily based on chronic widespread pain that has (1) pain on both sides of the body, (2) is above and below the waist, (3) should involve the axial skeleton, and (4) must have been present for more than 3 months. Physical examination must include at least 11 of 18 tender points. In clinical practice, nearly half the population may have fewer tender points. A new proposed fibromyalgia syndrome also includes sleep deficits, daytime fatigue, and altered cognition/mood as a part of the syndrome. Comorbid psychiatric disorders are common in fibromyalgia. Arnold et al. reported that 75% of patients with fibromyalgia have a mood disorder, 60% have an anxiety disorder, and 26% have a substance use disorder. A clearly defined causative explanation for fibromyalgia has eluded investigators. One of the earliest explanations for fibromyalgia looked at the most obvious source—muscle. However, this theory was disproved quickly, leading to more central explanations. The two most accepted evidence-based theories include: neuropeptide abnormalities (involving entities such as Substance P, serotonin, and endogenous opioids); and neuroendocrine defects (including the hypothalamo-pituitary adrenal [HPA], hypothalamo-pituitary gonadal [HPG], hypothalamo-pituitary-thyroid, and the growth hormone axes). Endorphins play a significant role in pain perception. Hence, it is not surprising that a number of investigators have looked at perturbations of endorphin function as a possible explanation for fibromyalgia. Vaeroy et al. observed that CSF -endorphin levels are either normal or lowered in individuals with fibromyalgia.


Younger J, Mackey S. Fibromyalgia symptoms are reduced by low-dose naltrexone: a pilot study. Pain Med. 2009;10(4):663‐672. doi:10.1111/j.1526-4637.2009.00613.x


OBJECTIVE: Fibromyalgia is a chronic pain disorder that is characterized by diffuse musculoskeletal pain and sensitivity to mechanical stimulation. In this pilot clinical trial, we tested the effectiveness of low-dose naltrexone in treating the symptoms of fibromyalgia.

DESIGN: Participants completed a single-blind, crossover trial with the following time line: baseline (2 weeks), placebo (2 weeks), drug (8 weeks), and washout (2 weeks). 

PATIENTS: Ten women meeting criteria for fibromyalgia and not taking an opioid medication. 

INTERVENTIONS: Naltrexone, in addition to antagonizing opioid receptors on neurons, also inhibits microglia activity in the central nervous system. At low doses (4.5 mg), naltrexone may inhibit the activity of microglia and reverse central and peripheral inflammation. 

OUTCOME MEASURES: Participants completed reports of symptom severity everyday, using a handheld computer. In addition, participants visited the lab every 2 weeks for tests of mechanical, heat, and cold pain sensitivity. 

RESULTS: Low-dose naltrexone reduced fibromyalgia symptoms in the entire cohort, with a greater than 30% reduction of symptoms over placebo. In addition, laboratory visits showed that mechanical and heat pain thresholds were improved by the drug. Side effects (including insomnia and vivid dreams) were rare, and described as minor and transient. Baseline erythrocyte sedimentation rate predicted over 80% of the variance in drug response. Individuals with higher sedimentation rates (indicating general inflammatory processes) had the greatest reduction of symptoms in response to low-dose naltrexone. 

CONCLUSIONS: We conclude that low-dose naltrexone may be an effective, highly tolerable, and inexpensive treatment forfibromyalgia.