Naltrexone is a medication licensed in 1984 by the FDA as a treatment for heroin and alcohol addiction in a daily dose of 50 to 100mg. When used in a lower dose of 3-4.5mg, naltrexone may help to relieve pain associated with inflammatory conditions and improve autoimmune diseases such as systemic lupus, rheumatoid arthritis, Bahcet’s syndrome, Wegner’s granulomatosis, psoriasis, and Crohn’s disease. Low dose naltrexone (LDN) has also been used successfully in the treatment of neurodegenerative diseases such as multiple sclerosis, Parkinson’s disease and amyotrophic lateral sclerosis (ALS).
Naltrexone is a long-lasting opiate receptor antagonist in high doses. However, at lower doses, its opiate antagonist activity turns into an agonist. This triggers a prolonged release of endogenous opioids such as β-endorphins (3).
More specifically, LDN will temporarily block opioid receptors and may then induce β-endorphins and µ, đ, and ƙ opioid receptors after 6 hours (1). The temporary blockade of opioid receptors may cause an up-regulation of mood enhancing endorphins, augment dopamine activity and may also reduce inflammatory mediators in the immune-related diseases.
A recent study concluded that LDN may be an effective highly tolerable, and inexpensive treatment for fibromyalgia (5). Low dose naltrexone reduced fibromyalgia symptoms overall in the entire group, with a greater than 30% reduction of symptoms over placebo. Specific symptoms including pain, fatigue and stress, were also significantly impacted by LDN. The observed effects were accompanied by a very low incidence of side effects, suggesting LDN may be an effective and well tolerated treatment for fibromyalgi8a (5).
Some clinical studies suggest that endogenous opioids, such as β-endorphins, may be involved in multiple sclerosis (MS). These β-endorphins are peptide neurotransmitters produced by pituitary and hypothalamic neuronal cells. Recent evidence suggests that these endorphins may exert peripheral anti-nociceptive action and possess ant-inflammatory activity (2). In patients with multiple sclerosis, LDN may enhance the immune system, reduce disease progression, spasticity and fatigue and improve bladder control, heat tolerance, mobility, sleep, mood, pain and tremor. (2).
A randomized double-blind placebo controlled study demonstrated that LDN improves clinical activity index scores and improves gastrointestinal mucosal inflammation in subjects with moderate to severe Crohn’s Disease (4). The healing of the mucosal lining was evaluated by endoscopic appearance and histology from biopsies obtained during colonoscopies. The patients’ treated with LDN showed significant reversal of gastrointestinal inflammation and the placebo-treated group had no improvement (4). This study found that using LDN to alter the endogenous opioid system decreases inflammation and provides promise for the treatment of Crohn’s disease.
Sharafaddinzaden,N. Moghtaderi, A. Kashipazha, D. Majdinasab, Shalbafan, B.The effect of low-dose naltrexone on quality of life of patients with multiple sclerosis: a randomized placebo-controlled trial. Mult Scler (2010 June) 16:964.
UK Multiple Sclerosis resource centre. LDN treatment, Feb 2006. Date accessed 7/5/11. http://www.msrc.co.uk/index.cfm?fuseaction=show&pageid=651
Gironi,M, etal. A piot trial of low-dose naltrexone in primary progressive multiple sclerosis. Mult Scler (2008) 14:1076.
Smith, Jill P, et al. Therapy with opioid antagonist naltrexone promotes mucosal healing in active Crohn’s disease: A randomized placebo-controlled trial.Dig Dis Sci(2011) 56:2088-2097
Younger, Jarred, PhD, Mackey, Sean, MD, PhD. Fibromyalgia symptoms are reduced by low-dose naltrexone: a pilot study. Pain Med. (2009) ID (4):663-672.