Low-Dose Naltrexone (LDN)

Shanen Khwaja (Pharm.D) Enovachem Pharmaceuticals

Low-dose naltrexone (LDN) provides an alternative in medical management of chronic pain disorders as a novel anti-inflammatory and immunomodulatory. 1At the low dosage level, naltrexone exhibits paradoxical properties, including analgesia and anti-inflammatory actions, which have not been reported at larger dosages. 2 At 1 through 5 mg, naltrexone paradoxically increases opioid signaling, contributing to pain relief.1

Low-dose naltrexone (LDN) provides an alternative in medical management of chronic pain disorders as a novel anti-inflammatory and immunomodulatory. 1At the low dosage level, naltrexone exhibits paradoxical properties, including analgesia and anti-inflammatory actions, which have not been reported at larger dosages. 2 At 1 through 5 mg, naltrexone paradoxically increases opioid signaling, contributing to pain relief.1

In a randomized, double-blind, placebo-controlled, counterbalanced, crossover study found evidence that daily treatment with naltrexone (3.0–4.5 mg) reduced pain associated with fibromyalgia syndrome. 4In addition, LDN was also associated with improved general satisfaction with life (P = 0.045) and with improved mood (P = 0.039), but did not improved fatigue or sleep. 4Low-dose naltrexone was rated equally tolerable as placebo, and no serious side effects were reported. 4Only two side effects, vivid dreams (χ 2= 4.4, P = 0.037) and headache (χ 2= 4.05, P = 0.044), were more frequently reported in the LDN condition.4

In another study Younger found that after eight weeks of LDN administration, plasma levels of a range of broadly pro-inflammatory cytokines were decreased. 5In addition, participants reported less pain and symptoms following LDN.5

In addition, there are case reports on the use of LDN in other chronic pain disorder. 6These include one in diabetic neuropathy, one in chronic back pain, and two in complex regional pain syndrome (CRPS), in all four case reports the patient reported no adverse effects, and all experienced a significant improvement in daily pain.6

In a study selection, a total of 793 studies were obtained with the initial search and 8 articles were selected for evaluation. 1It was determined the primary outcome of all of the studies was pain intensity reduction.1 Patients reported nausea, fatigue, and insomnia when prescribed 1 through 4.5 mg.1

It is also noted, LDN does not exert any euphoric or reinforcing effects, and no cases of LDN misuse or abuse have been observed. 2LDN lacks both the addictive properties and adverse effects of opioids. 1However, patients must be opioid- and alcohol free before LDN initiation. 1If taken simultaneously with opioids or alcohol, acute withdrawal can be initiated.1

The totality of the basic and clinical research to date suggests that LDN is a promising treatment approach for chronic pain conditions thought to involve inflammatory processes. 2The medication is widely available, inexpensive, safe, and well-tolerated. 4As 4.5 mg was the dosage prescribed most commonly, there is justification for this dosage in a clinical setting. 1Ranges of dosages are beneficial based on diagnosis, symptomatology, and potential adverse effects.1

References:

1 Hatfield E, Philips K, Swidan S & Ashman L. Use of low-dose naltrexone in the management of chronic pain conditions. JADA

?2020; 151 (12): 891-902

2 Younger J, Parkitny L, & McLain D. The use of low-dose naltrexone (LDN) as a novel anti-inflammatory treatment for chronic

?pain. Clin Rheu 2014; 33:451-459

3 Trofimovitch D & Baumrucker SJ. Pharmacology Update: Low-dose naltrexone as a possible nonopioid modality for some

?chronic, nonmalignant pain syndromes. A J of Hospice & Palliative Medicine 2019; 36 (10): 907-912

4 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 & Rheu

?2013; 65 (2): 529-538

5 Parkitny L & Younger Jarred. Reduced pro-inflammatory cytokines after eight weeks of low-dose naltrexone for

?fibromyalgia. Biomed 2017

6 Patten DK, Schultz BG, & Berlau DJ. The safety and efficacy of low-dose naltrexone in the management of chronic pain and

?inflammation in multiple sclerosis, fibromyalgia, crohn’s disease, other chronic pain disorders. Pharm 2018