The first clinical use of low-dose naltrexone (LDN) was in 1985 by Dr. Bernard Bihari, a Harvard University physician working at SUNY/Health Science Center and King's County Hospital in Brooklyn, New York.
Dr. Bihari became worried about the human immunodeficiency virus/acquired immune deficiency syndrome (HIV/AIDS) epidemic. He compared various doses of LDN and found that a dose of 3.0 mg of LDN increased levels of natural endorphins during the night. He also found that the LDN improved the immune function of these individuals and those taking LDN got less secondary infections.
Anti-inflammatory Activity
The increase of β-endorphins to reduce pain levels is only one aspect of the use of LDN in pain management, especially when the source of the pain is related to an inflammatory process. It has been shown that LDN reduces inflammation by reducing multiple pro-inflammatory cytokines. Cytokines are chemical messengers, often made by immune cells, whose net effect can be to either increase or decrease immune function. The coordination of the immune system rests on the body's ability to keep a balance between cytokines that promote inflammation and those that reduce it. Cytokines are produced by various cells in the body and are associated with the physiologic experience of pain. In addition, Tumor Necrosis Factor alpha (TNF-α) is associated with increased inflammation when the body is presented with an insult such as nerve damage.Excess synthesis or upregulation of TNF-α is associated with certain conditions such as cerebral ischemia, Alzheimer's disease, and atherosclerosis, and reducing levels of this cytokine by using LDN may be of benefit in treatment.
The treatment of pain is a complex challenge and can benefit from an approach that includes attention to both biological and psychological aspects of a patient's symptoms. Healthcare practitioners have multiple tools available when facing the challenge of pain management. Treating the symptoms of pain using LDN as a monotherapy does not always work; however, if the patient's condition is highly inflammatory (eg, rheumatoid arthritis) using LDN can be extremely helpful by itself.
Of course, the use of opioids in this country has risen to an unprecedented level. It was reported in 2016 that 90 individuals die of opioid overdose in this country each day. The model of using a low dose of an opioid antagonist such as LDN is paradoxical. The benefit of using LDN for pain management has its foundations in the ability of this formulation to increase endogenous endorphins and decrease pro-inflammatory cytokines. It is important to note that the use of LDN is not recommended with opioid medications, however, at times I will use LDN at the end of the opioid medication withdraw period. This needs to be done under the supervision of a physician.
There have been several published articles on the use of LDN in patients suffering from fibromyalgia. In a 2013 placebo-controlled, crossover pilot study involving 31 women with fibromyalgia, a 4.5 mg dose of LDN at bedtime reduced daily pain levels and improved mood and overall reported quality of life in this study. In a study conducted in 2009 by the same researchers, the same dose of LDN reduced pain levels and improved symptoms of fatigue and stress in 10 women with fibromyalgia.
Dissociative Disorders and Post-Traumatic Stress Syndrome
There is limited information, mostly from case studies, on the use of LDN for post-traumatic brain injury syndrome and post-traumatic stress syndrome. One published study looked at using 2.0 to 6.0 mg of LDN when working with individuals with a history of repetitive, prolonged childhood trauma such as sexual abuse or cruelty. According to the author of the study, Wiebke Pape, MD, most of the people suffered from dissociative disorder, which she described at the 2017 LDN conference as the act of "shutting down" or where the "brain goes blank." Of the 12 inpatients studied with LDN, most reported favorable benefits of taking LDN, including better regulation of traumatic memories and reduction of self-destructive impulses. The use of LDN in these situations needs to be done in conjunction with psychiatric support (psychotherapist, psychiatrist, etc.).
Cancer
Opioid growth factor (OGF) is a peptide in the body that helps regulate cell growth. Upregulation or stimulation of this peptide and its receptor (OGFr) on cells has been shown to be a promising approach to cancer therapy. Because LDN upregulates the expression of OGF and OGFr, researchers are exploring the use of LDN in the treatment of ovarian, pancreatic, and other types of cancer. There have also been 2 published reports (in 2006 and 2009) of long-term survival using LDN and intravenous alpha-lipoic acid in patients suffering from pancreatic cancer.
In a study published in 2016, researchers compared standard doses of naltrexone with LDN on various genes involved in cell turnover. They found that genes responsible for apoptosis (tumor cell destruction) were upregulated by LDN but not by standard doses of naltrexone. In an in vitro (laboratory) study using ovarian cancer cells, investigators could demonstrate that LDN inhibited tumor growth when used with the chemotherapeutic agent cisplatin. Human studies are needed to support this finding.
Case
A 56-year-old female patient was diagnosed in 2015 with non-small cell lung cancer (NSCLC) seeking integrative care. She started on a chemotherapy regimen using carboplatin/pemetrexed/bevacizumab but was switched to pembrolizumab (Keytruda). She was started on LDN 1.0 mg per day in August of 2016 and increased to 3.0 mg per day in December 2016. She was increased to 3.5 mg per day of LDN and continues that dose. Her PET scan in January 2015 revealed two lung masses. In addition, two liver masses were present. Her last scan performed in July 2017 revealed a 2.5 cm stable right lower lobe mass (in remission) and an inferior right hepatic lobe mass "barely perceptible".
At the time of this article the patient has been in remission for 16 months. Although the addition of LDN into her protocol may or may not have contributed to her remission, it can be concluded that adjunctive treatment using LDN with Keytruda in her case has been safe and perhaps played a positive role in her medical outcome.
Use
Capsules and tablets can be prepared in any prescribed dose but the most common is 1.0 to 4.5 mg, typically taken at bedtime. They can only be prescribed through a compounding pharmacy. Tablets are usually very small and well-tolerated by patients, but not all pharmacies distribute tablets. Liquids or sublingual preparations can be made for those who want or need to avoid using capsules or tablets. Typical solutions are a 1.0 mg LDN per 1.0 ml glycerol solution. Liquids are often preferred over capsules or tablets for young children, or adults with swallowing difficulties.
Most LDN is prescribed at bedtime; however, if patients report nightmares, then taking the dose in the morning can be an alternative. Vivid dreams are the most commonly reported side effect in clinical trials but this seems to decrease after a few nights. No side effects of stomach ulcers, renal impairment, or interference with anti-clotting medications have been reported in research.
LDN can be used with other therapies such as acupuncture and intravenous (IV) therapy. If you have any questions or would like to make an appointment, call the office at (928) 445-2900.
Dr. Timothy Schwaiger
