Low Dose Naltrexone | LDN | 703-844-0184 | Fairfax, Va | IV drip and hydration therapies | LOW dose Naltrexone for chronic diseases

Low Dose Naltrexone has been utilized for numerous treatments. Look at the data below for Chrone’s disease, fibromyalgia, and M.S and chronic pain. Naltrexone seems to be very helpful.

Low dose Naltrexone for induction of remission in inflammatory bowel disease patients.

Low dose Naltrexone for induction of remission in IBD

Abstract

BACKGROUND:

Around 30% of patients with inflammatory bowel disease (IBD) are refractory to current IBD drugs or relapse over time. Novel treatments are called for, and low dose Naltrexone (LDN) may provide a safe, easily accessible alternative treatment option for these patients. We investigated the potential of LDN to induce clinical response in therapy refractory IBD patients, and investigated its direct effects on epithelial barrier function.

METHODS:

Patients not in remission and not responding to conventional therapy were offered to initiate LDN as a concomitant treatment. In total 47 IBD patients prescribed LDN were followed prospectively for 12 weeks. Where available, endoscopic remission data, serum and biopsies were collected. Further the effect of Naltrexone on wound healing (scratch assay), cytokine production and endoplasmic reticulum (ER) stress (GRP78 and CHOP western blot analysis, immunohistochemistry) were investigated in HCT116 and CACO2 intestinal epithelial cells, human IBD intestinal organoids and patient samples.

RESULTS:

Low dose Naltrexone induced clinical improvement in 74.5%, and remission in 25.5% of patients. Naltrexone improved wound healing and reduced ER stress induced by Tunicamycin, lipopolysaccharide or bacteria in epithelial barriers. Inflamed mucosa from IBD patients showed high ER stress levels, which was reduced in patients treated with LDN. Cytokine levels in neither epithelial cells nor serum from IBD patients were affected.

CONCLUSIONS:

Naltrexone directly improves epithelial barrier function by improving wound healing and reducing mucosal ER stress levels. Low dose Naltrexone treatment is effective and safe, and could be considered for the treatment of therapy refractory IBD patients.

The use of LDN in clinical settings is gaining interest, with Crohn’s disease, multiple sclerosis
and fibromyalgia described as potential targets for treatment with LDN.

 

Fibromyalgia symptoms are reduced by low-dose naltrexone: a pilot study.

Fibromyalgia symptoms are reduced by low-dose naltrexone a pilot study.

Fibromyalgia is a common clinical entity that can be devastating to patients and frustrating for pain management specialists. Up to 5% of women and up to 2% of men may be diagnosed with fibromyalgia. Fibromyalgia can lead to lost productivity and medical costs due to pharmacologic agents utilized for treatment. Patients may describe pain, fatigue, gastrointestinal, and other symptoms. Fibromyalgia has been described as a member of the “central sensitivity syndromes”, which are disorders including chronic fatigue, irritable bowel syndrome, and interstitial cystitis. Centrally active cytokines that are proinflammatory are believed to lead to fatigue, increased pain sensitivity, and similar symptoms of fibromyalgia. Currently, the FDA has approved pregabalin, duloxetine and milnacipran for use in the treatment of patients with fibromyalgia. Naltrexone is an agent that the authors of this study suggest may be an adjunct in the treatment of patients with fibromyalgia. Compared to the other drugs, naltrexone is relatively inexpensive, costing less than $40 per month (per the article). LDN is suggested for study in this population because of its ability to antagonize opioids receptors, and decrease the superoxides and inflammatory mediators in microglia cells in the central nervous system (CNS). Theoretically, LDN is believed to block beta-endorphins from binding to receptors for a short time, leading to an increased production of beta-endorphins, and, therefore, clinical effect. LDN has also been evaluated in patients with multiple sclerosis and Crohn’s disease.

Patients included in the study were required to meet the American College of Rheumatology criteria for fibromyalgia (1990), and excluded were those with prior use of opioids, a history of autoimmune disease, those positive for rheumatoid factor, or those with an elevated (over 60mm/h) erythrocyte sedimentation rate (ESR). Each participant in the study received a baseline evaluation (2 weeks), a placebo (2 weeks), LDN 4.5mg (8 weeks), and washout (2 weeks). This design allowed patients to have a control phase allowing investigators to account for patient variability. Patients self-reported their symptoms via a Palm handheld computer. Questions included the severity of the patient’s pain on a visual analogue scale (VAS) from 0-100, fatigue, sadness, highest pain level, stress, sleep quality, the ability to think, concentration, gastrointestinal (GI) symptoms, and headache. Study patients also had mechanical, thermal- and cold-sensitivity testing in a lab every 2 weeks to note the effect of naltrexone on sensitivity. Side effects were minimal with drug administration, with vivid dreams and nausea and insomnia being reported. Naltrexone administration was shown to increase thermal pain thresholds by 0.9 degrees Celsius, and improve mechanical thresholds. The drug administration did not have an impact on cold pain thresholds, however. The investigators found that naltrexone had a statistically significant impact on daily pain, highest pain felt, fatigue, and stress, decreasing these in patients treated. The following parameters did not achieve statistical significance: sleep quality, GI problems, headaches, thinking and concentration, and sadness. The investigators propose that fibromyalgia is a disease entity that describes clinical conditions presenting similarly by noting that baseline levels of the ESR test correlated positively with response to naltrexone. They hypothesize that the presence of elevated ESR may identify patients who may be more responsive to LDN than those who are not. Younger and Mackey advise testing for liver functioning as well as observing for the theoretical risk of infection that may be present with administration of naltrexone. The study would be made stronger with a larger patient population and a double-blinded construction. Despite this limitation, the study does seem to suggest the need for future evaluation of the use of LDN in the treatment of patients with pain of fibromyalgia.

  1. A pilot trial of low-dose naltrexone in primary progressive multiple sclerosis.

    Gironi M, Martinelli-Boneschi F, Sacerdote P, Solaro C, Zaffaroni M, Cavarretta R, Moiola L, Bucello S, Radaelli M, Pilato V, Rodegher M, Cursi M, Franchi S, Martinelli V, Nemni R, Comi G, Martino G

    Mult Scler 2008 Sep; 8(14):1076-83

    PMID: 18728058

  2. Low-dose naltrexone therapy improves active Crohn’s disease.

    Smith JP, Stock H, Bingaman S, Mauger D, Rogosnitzky M, Zagon IS

    Am J Gastroenterol 2007 Apr; 4(102):820-8

    PMID: 17222320

    http://www.lowdosenaltrexone.org/ <LDN Resource

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    Low dose naltrexone for treatment of multiple sclerosis

    Low Dose Naltrexone for Treatment of Multiple Sclerosis A Retrospective Chart Review of Safety and Tolerability

    A potential alternative or adjunctive

    therapy for MS is related to knowledge
    about the endogenous opioid system and
    its ability to modulate autoimmune diseases
    using animal models of MS.7–10 This
    novel biological pathway involves an endogenous
    opioid growth factor, chemically
    termed methionine enkephalin, and its
    nuclear-associated receptor, Opioid growth
    factor receptor.11 Modulation of this pathway
    by exogenous administration of opioid
    antagonists such as naltrexone (NTX) has
    been shown to mediate cell replication including
    T lymphocytes, astrocytes, and
    other glia that are associated with MS
    inflammation and degeneration.9 The magnitude
    and direction of change in cell
    proliferation is dependent on the duration
    of opioid receptor blockade.12 Low dosages
    of NTX (LDN), given once daily block the receptor intermittently and result
    in inhibited cell replication.

  3. Three clinical trials of LDN in MS
    have been conducted and report that
    LDN increases the quality of life of MS
    patients.13–15 Cree et al14 concluded from
    a trial of 8 weeks that 4.5 mg LDN daily
    was a safe therapy that improved quality
    of life, whereas Sharafaddinzadeh et al13
    reported safety after 17 weeks of treatment
    and recommended that longer trials be
    conducted to evaluate efficacy. Gironi et al15
    studied primary progressive MS patients
    treated with LDN for 6 months and reported
    increased endogenous opioid levels
    in the patients and improved MS. The LDN
    treatment of patients with other autoimmune
    diseases including Crohn’s disease
    and fibromyalgia has demonstrated safety
    and efficacy of the therapy.16,17 A major
    symptom of MS is fatigue,18 which is one
    of the many characteristics that patients seek
    to alleviate. Improvement in fatigue was cited
    in these clinical studies after LDN therapy,
    which suggests that there is a potential link
    between upregulated endogenous opioid
    systems and fatigue. Gironi et al15 reported
    elevated β-endorphin levels at 1, 3, and
    6 months after the onset of treatment, with
    β-endorphin levels remaining elevated for
    an additional month after LDN was discontinued.

The use of low-dose naltrexone (LDN) as a novel anti-inflammatory treatment for chronic pain

The use of low-dose naltrexone (LDN) as a novel anti-inflammatory treatment for chronic pain

Use of LDN in chronic pain
LDN has been tested experimentally in a small number of
chronic pain conditions. One such condition is fibromyalgia
(FM). FM is a chronic pain disorder that is characterized by
diffuse musculoskeletal pain and sensitivity to mechanical
stimulation as well as profound fatigue, cognitive disruption,
and sleep difficulty. Although FM does not respond to common
anti-inflammatories and does not seem to be an inflammatory
disorder in the classic sense [13], inflammatory processes
may still be involved [14]. We have shown in two
separate, small clinical trials that LDN may be an effective
treatment for FM. In both trials, LDN was administered at
4.5 mg daily, once at night before bedtime. In the first crossover
trial, published in 2009 [15], LDN reduced fibromyalgia
pain significantly greater than placebo in 6 out of the 10
women. While the pilot study was encouraging, it had limitations
such as a single-blind design. To help validate the
findings, a second study in 30 women with fibromyalgia
was conducted [9]. In that double-blind, crossover,
counterbalanced study, 57 % of the participants were observed
to exhibit a significant (1/3) reduction of pain during LDN. At
the end of the LDN treatment, half of the participants reported
feeling “much improved” or “very much improved” from
LDN (Fig. 1). Together, these two studies suggest that LDN
is superior to placebo in reducing the pain associated with
fibromyalgia.

Evidence for a novel central anti-inflammatory action
of naltrexone

Anti-inflammatory effects of LDN in vivo and in vitro
In describing LDN’s clinical utility, it is important to understand
the dual physiologic mechanisms of naltrexone and
other opioid antagonists. Most clinicians are familiar with
naltrexone as a potent and nonselective opioid receptor antagonist
and treatment for opioid addiction. Naltrexone, at typical
dosages, significantly blocks activity at mu- and delta-opioid
receptors as well as (to a lesser extent) kappa-opioid receptors
[16]. Because beta-endorphin activity at mu-opioid receptors
is associated with endogenous analgesic processes, it may
seem counterintuitive to administer naltrexone to individuals
with chronic pain, as we might expect the medication to
reduce analgesia produced by beneficial endogenous opioid
activity.
Naltrexone, however, exerts its effects on humans via at
least two distinct receptor mechanisms. In addition to the
antagonist effect on mu-opioid and other opioid receptors,
naltrexone simultaneously has an antagonist effect on nonopioid
receptors (Toll-like receptor 4 or TLR4) that are found
on macrophages such as microglia [17]. It is via the nonopioid
antagonist path that LDN is thought to exert its antiinflammatory
effects. Microglia are central nervous system
immune cells that are activated by a wide range of triggers
[18]. Once activated, microglia produce inflammatory and
excitatory factors that can cause sickness behaviors such as
pain sensitivity, fatigue, cognitive disruption, sleep disorders,
mood disorders, and general malaise [19]. When chronically
activated, the resulting proinflammatory cascade may become
neurotoxic, causing several deleterious effects [20]. Given the
wide variety of inflammatory factors produced by activated
microglia (e.g., proinflammatory cytokines, substance P, nitric
oxide, and excitatory amino acids) [21], a range of symptoms
and medical outcomes could share the pathophysiological
mechanism of central inflammation. Conditions such as fibromyalgia
may involve chronic glial cell activation and subsequent
production of proinflammatory factors. The hypothesis
is indirectly and partially supported by the high degree of
symptomatic overlap between fibromyalgia and cytokineinduced
sickness behaviors.
Both naloxone and naltrexone have been demonstrated to
exert neuroprotective and analgesic effects [22]. The neuroprotective
action appears to result when microglia activation in the brain and spinal cord is inhibited [23]. By suppressing
microglia activation, naloxone reduces the production of reactive
oxygen species and other potentially neuroexcitatory
and neurotoxic chemicals [24]. The anti-inflammatory effect
of opioid antagonists may also extend to the periphery, as
evidenced by suppressed TNF-alpha, IL-6, MCP-1, and other
inflammatory agents in peripheral macrophages [25]. It should
be noted that most animal work has used naloxone, while
most human work has used naltrexone (because of its higher
oral availability). We cannot discount the possibility that
findings from one compound would imperfectly translate to
the other.

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