Low Dose Naltrexone (LDN) - a promising therapy for pain & autoimmunity:
LDN (Low dose naltrexone) is a medication that is often used by Naturopathic Doctors to treat a variety of conditions including fibromyalgia, chronic pain, MS and autoimmunity.
It is important to note that naltrexone is not the same as naloxone!
Naloxone
Immediate acting opioid antagonist – most commonly used for acute opioid overdose reversal medication
Poor oral bioavailability
Serum half life ranges from 30-80 minutes
Naltrexone
Longer acting opioid antagonist – commonly used for alcohol use disorder treatment and relapse prevention in opioid use disorder
Classically prescribed in daily doses of 50-100mg orally (vs. Low dose is 1-5mg daily)
Serum half life is 4 hours
How does LDN work?
Use of naltrexone at a low dose seems to act by the hormetic principle, where certain substances exert qualitatively different pharmacodynamic effects in relation to the dosage. Essentially, this means that there are multiple dose dependant targets with different respective effects.
Clear mechanistic pathways for LDN seem to be unclear. Some proposed theories include:
Toll-like receptor 4 Blockade:
Resulting in decreased inflammatory markers (IL-1, TNF-alpha, IF-beta) -> resulting in decreased inflammation associated with autoimmune conditions & decreased pain sensitization
Thus modulating glial cells and regulating neuroinflammation through inhibition of release of inflammatory cytokines in the CNS
Transient blockage of opiate receptors:
Causing the body to release more endogenous opiates and upregulate receptor production -> thus decreasing pain sensation
Restoring the opioid growth factor (OGF) and opioid growth factor receptor (OGFr) axis to homeostasis (a dysregulation of this axis has been implicated that play a role in a variety of disease states).
Potential Adverse Effects:
As with any treatment, there are no guarantees that you will experience benefits or adverse effects. Most people seem to tolerate LDN very well, and the most common side effects are:
Difficulty with sleep onset
Vivid dreams
Both of these side effects occur when starting treatment and typically resolve within 2 weeks
Other adverse effects include:
- Symptom exacerbation (if starting at a higher dose in those with active disease)
- Hair loss (small subset of people develop this – hair loss ceases with dose reduction)
- One cause of immune related thrombocytopenia has been reported in an MS patient
SO… Why Use LDN?
LDN it typically very well tolerated, with limited side effects. It is also compatible with most medications (unless patients are taking narcotic pain medication on a regular basis). As LDN assists the body in changing it’s pain signalling and processing it is possible that patients may be able to discontinue LDN after a certain period with no or minimal recurrence of pain and other symptoms. Use of LDN may allow patients to reduce their overall medication use while also being able to control their symptoms better.
Conditions that LDN has been used to treat include:
- Fibromyalgia
- Crohn’s disease and Ulcerative Colitis
- MS
- Chronic regional pain syndrome
- Depression
- Chronic pain conditions
Please speak with your Naturopathic Doctor or primary care provider to see if LDN is a viable option for you.
Use of LDN is still an off-label use of naltrexone and like with any treatment, the benefits and harms of taking this medication should be discussed prior to initiation.
This article is not to be used as formal medical advice.
References:
Hesselink JMK, Kopsky DJ. Enhancing Acupuncture by Low Dose Naltrexone. Acupuncture in Medicine. 2011;29(2):127-130. doi:10.1136/aim.2010.003566
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, Crohns Disease, and Other Chronic Pain Disorders. Pharmacotherapy: The Journal of Human Pharmacology and Drug Therapy. 2018;38(3):382-389. doi:10.1002/phar.2086
Toljan K, Vrooman B. Low-Dose Naltrexone (LDN)—Review of Therapeutic Utilization. Medical Sciences. 2018;6(4):82. doi:10.3390/medsci604008
