Low dose naltrexone

Low Dose Naltrexone (LDN) refers to very small doses of the drug naltrexone hydrochloride, which is normally used to treat drug or alcohol dependence. When taken at much smaller doses naltrexone may reduce pain, or potentially neurological symptoms. Brand names of naltrexone include ReViva, Depade, and Vivitrol. LDN use other for treating drug dependence is considered off-label. Some patients report that LDN helps reduce their symptoms of ME/CFS, multiple sclerosis (MS), fibromyalgia (FMS), or autoimmune disease. Although its mechanism of action is unclear, some have speculated that it may act as an anti-inflammatory.

Prescription forms
LDN is typically prescribed using generic naltrexone hydrochloride or branded naltrexone, divided into much smaller doses. LDN may be taken in the form of liquid solution/syrup, sublingual doses or 1.5mg capsules, or a compounding pharmacy can create smaller sized capsules or tablets. LDN in the form of naltrexone cream, subcutaneous injections, IV naltrexone and eye drops (for dry eyes) are also available.

VLDN and ULDN
Very Low Dose Naltrexone (VLDN) and Ultra-Low Dose Naltrexone (ULDN) have recently been used in limited trials, both VLDN and ULDN involve doses of naltrexone significantly below 1mg.

Evidence


Jarred Younger published a small study that concluded "...low-dose naltrexone may be an effective, highly tolerable, and inexpensive treatment for fibromyalgia".

A second study concluded that "specific and clinically beneficial impact on fibromyalgia pain".

A 2014 review by Stanford researchers suggests that "LDN may operate as a novel anti-inflammatory agent in the central nervous system, via action on microglial cells. These effects may be unique to low dosages of naltrexone and appear to be entirely independent from naltrexone's better-known activity on opioid receptors. As a daily oral therapy, LDN is inexpensive and well-tolerated." The FDA approved naltrexone HCL in 1984 to treat opioid addiction. Low-dose naltrexone is typically given at about 1/10th the typical dose of naltrexone. By blocking opioid receptors, naltrexone can increase pain, but at very low doses naltrexone has both pain-reducing (analgesic) and anti-inflammatory properties.

In 2012 Solve ME/CFS Initiative contracted Biovista to use drug models to identify existing drugs that may be worth investigating for treatment. The results suggested Naltrexone was worth considering.

Jarred Younger's research suggests that people with an Erythrocyte Sedimentation Rate (ESR) over 40 millimeters an hour, tend to be strong responders to LDN, and that there may be other predictive factors for success.

News articles

 * 2019, In Tiny Doses, An Addiction Medication Moonlights As A Treatment For Chronic Pain - NPR, All Things Considered
 * September 9, 2021 https://www.empr.com/home/news/drugs-in-the-pipeline/low-dose-naltrexone-designated-orphan-drug-for-complex-regional-pain-syndrome/

Clinical use
Naltrexone is a prescription drug in many countries including the United States. Compounding chemists or compounding pharmacists can mix naltrexone with a powder filler or dilute in into a liquid to create the lower dose.

Fast-release fillers only
The LDN Research Trust advises that: "Pharmacies should be instructed NOT to provide LDN in an "SR" or slow-release or timed-release form. Unless the low dose of naltrexone is in an unaltered form, which permits it to reach a prompt "spike" in the blood stream, its therapeutic effects may be inhibited." and states that calcium carbonate filler should NOT be used because they reduce absorption, instead Avicel, lactose, or sucrose fillers as alternative fast-release fillers."

Do not take with
In general, Low Dose Naltrexone (LDN) should not be taken concurrently with opioid-containing drugs (opioid receptors in brain are blocked by LDN), alcohol, immunosuppressive drugs, or immunomodulator drugs. LDN blocks the effect of opioid drugs. Some opioid drugs are codeine, tramadol, oxycodone, vicodin, hydrocodone, fentanyl and morphine.

Australia
Compounding Pharmacies are able to fill these prescriptions, and post if needed.

UK
LDN suppliers in the UK include Dickson Chemist in Glasgow, Roseway Labs, and Specialist Pharmacy (The London Specialist Pharmacy Ltd). All these are compounding pharmacies and require a perscription, they are usually able to put patients in contact with private doctors who will consider writing a prescription, and can post medications to you. Compounding pharmacies are regulated by the UK's General Pharmaceutical Council.

United States
Neighborhood Compounding Pharmacies are able to fill these prescriptions and mail if needed. Your prescribing doctor can help you locate a compounding pharmacy in your area/state or you can look online.

Other countries
The LDN Research Trust lists pharmacies in multiple countries.

Clinical trials
A large number of clinical trials have been completed for LDN recently, although none have looked at the effect of LDN on symptoms of myalgic encephalomyelitis/chronic fatigue syndrome. Research has been carried out on patients with MS, Chronic Regional Pain Syndrome, FMS, Irritable Bowel Syndrome (IBS), Ulcerative Colitis, Skin Disorders and a range of other illnesses.

When, How To Take
Dr Whitaker states that the ideal dose is different for each person. Some doctors recommend starting at 1mg. Common dosages are 1.5mg, 3mg, 4.5mg. When beginning use of LDN, the drug must be stepped up over 6-8+ weeks as it may keep you awake; discuss how best to do this with your doctor and pharmacist.

LDN is usually taken at bedtime. Some people take LDN in the morning to minimize sleep disturbance, insomnia, and vivid dreams.

Talks and webinars
https://www.youtube.com/watch?v=z0p0ykSzy9o
 * 2012, LDNscience® Presents - How LDN (Low Dose Naltrexone) Works

https://www.youtube.com/watch?v=8a-ULCaarCQ
 * 2015, Functional Medicine & LDN (low-dose naltrexone) with Drs Carnahan and Vasquez

https://www.youtube.com/watch?v=Qnr51yU9ih8
 * 2015, Is Low Dose Naltrexone (LDN) for you?

Notable studies

 * 2009, Fibromyalgia Symptoms Are Reduced by Low-Dose Naltrexone: A Pilot Study - (Full text)
 * 2013, Low-dose naltrexone for the treatment of fibromyalgia: findings of a small, randomized, double-blind, placebo-controlled, counterbalanced, crossover trial assessing daily pain levels - (Full text)
 * 2014, The use of low-dose naltrexone (LDN) as a novel anti-inflammatory treatment for chronic pain - (Full text)
 * 2018, Double-blinded placebo-controlled cross-over pilot trial of naltrexone to treat Gulf War Illness - (Abstract)


 * 2018, Low-Dose Naltrexone (LDN)—Review of Therapeutic Utilization - (Full text)


 * 2019, Low-dose naltrexone in the treatment of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) - (Abstract)
 * 2020, Low-dose naltrexone as a treatment for chronic fatigue syndrome - (Full text)
 * 2021, Potential Therapeutic Benefit of Low Dose Naltrexone in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: Role of Transient Receptor Potential Melastatin 3 Ion Channels in Pathophysiology and Treatment - (Full text)

Learn more

 * Low-dose Naltrexone (LDN) Doctor's Fact Sheet 2014 - LDN Research Trust
 * LDN Research Trust
 * Low Dose Naltrexone and chronic pain
 * Wikipedia - Naltrexone
 * LDN Now
 * LDN Science - MedInsight Research Institute
 * 2015, The Use of Naltrexone in Low Doses Beyond the Approved Indication
 * Top 15 Scientific Health Benefits of Low Dose Naltrexone (2016)
 * Low Dose Naltrexone Resource Center for Fibromylgia and ME/CFS (2019)
 * 2016, Low-Dose Naltrexone as Adjunctive Pharmacotherapy for Fibromyalgia
 * The LDN Book - Lisa Elsegood (2016)
 * 2016, Low Dose Naltrexone Drug Combination Proposed for Chronic Fatigue Syndrome - Health Rising, by Cort Johnson (2016)
 * Low dose naltrexone: side effects and efficacy in gastrointestinal disorders by CFS Remission (2016)
 * Opioid blocking and alcohol - FAQ About Naltrexone Treatment for Alcoholism - 10.
 * Low Dose Naltrexone for Fibromyalgia (2018)
 * Low Dose Naltrexone Therapy for Crohn's Disease (2018)
 * LDN LOW DOSE NALTREXONE FOR ME/CFS MYALGIC ENCEPHALOMYELITIS & FIBROMYALGIA