Category: Supplements


For those unfamiliar with the medication, Naltrexone is typically used in the management of alcohol or opioid dependence. It works by blocking the euphoric effects and feelings of intoxication, providing a useful tool for individuals with substance use disorders to avoid relapses. It’s an “opioid antagonist,” meaning that it blocks the action of opioids in the brain.

What is Low Dose Naltrexone (LDN)?

Low Dose Naltrexone (LDN) is a term that refers to doses of this medication ranging from 1 to 5 milligrams. This is significantly lower than the average dose used for managing opioid addiction, which is typically 50 milligrams. LDN is non-addictive, safe, and cost-effective, and is becoming more recognized for its potential benefits.

How Low Dose Naltrexone (LDN) works

What makes LDN work is its unique method of action. It temporarily blocks the opioid receptors in the brain and immune cells, leading to an increase in the production of endorphins. As you may know, endorphins are the body’s natural painkillers.

But that’s not all LDN does—it also promotes an upsurge of opioid receptors, further enhancing the body’s capacity to regulate pain and mood. Additionally, there is evidence that LDN has immune-modulating effects, helping to boost immune function.

This makes LDN a multifaceted medication capable of addressing pain management but also offering potential benefits for mood regulation and immune system support.

What are the potential benefits and uses of Low Dose Naltrexone (LDN)?

The use of LDN has been linked to benefits in treating conditions like autoimmune diseases, such as rheumatoid arthritis and multiple sclerosis.

It has also shown promise in managing pain related to central sensitization conditions such as Ehlers-Danlos Syndrome and Fibromyalgia.

There’s even evidence to suggest LDN can aid in the treatment of mood disorders like depression and anxiety.

What are the potential side-effects of Low Dose Naltrexone (LDN)?

Due to its low dose, LDN is generally well-tolerated, with very few reported side-effects. Some patients may experience mild side-effects like nausea, headache, or insomnia when first starting LDN treatment. These symptoms are usually temporary and tend to improve with continued use of the medication.

When should I start seeing the potential benefits from taking Low Dose Naltrexone (LDN)?

The time required to observe benefits from LDN varies between individuals, but typically, positive effects can be noted within a few weeks to months. It is crucial to work closely with your healthcare provider to determine the best dosage and treatment plan for your specific condition.

Disclosure: The information in this article is not intended to replace your doctor’s medical advice, diagnosis or treatment. If you require more information, or have any questions, please speak to your doctor/ specialist.


  1. Younger, J., Parkitny, L., & McLain, D. (2014). The use of low-dose naltrexone (LDN) as a novel anti-inflammatory treatment for chronic pain. Clinical Rheumatology, 33, 451–459.
  2. Patten, D. K., Schultz, B. G., Berlau, D. J. (2018). The safety and efficacy of low-dose naltrexone in the management of chronic pain and inflammation in multiple sclerosis, fibromyalgia, Crohn’s disease, and other chronic pain disorders. Pharmacotherapy: The Journal of Human Pharmacology and Drug Therapy, 38, 382–389.
  3. Metyas, S., Yeter, K., Solyman, J., & Arkfeld, D. (2018). Low dose naltrexone in the treatment of fibromyalgia. Current Rheumatology Reviews, 14, 177-180. DOI: 10.2174/1573397113666170321120329
  4. Smith, J. P., Bingaman, S. I., Ruggiero, F., Mauger, D. T., Mukherjee, A., McGovern, C. O., & Zagon, I. S. (2011). Therapy with the opioid antagonist naltrexone promotes mucosal healing in active Crohn’s disease: a randomized placebo-controlled trial. Digestive diseases and sciences, 56, 2088–2097. DOI: 10.1007/s10620-011-1653-7
  5. 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 and Rheumatism, vol. 65, 2013, pp. 529-538. DOI: 10.1002/art.37734.

PEA: A Natural Pain Killer?

Chronic pain is a persistent problem for many people. According to the Australian Institute of Health and Welfare, one in 5 Australians aged 45 and over are living with persistent, ongoing pain. Current treatments for chronic pain often come with unpleasant side effects or the risk of drug interactions, so there is a great need for new and effective therapies.

Palmitoylethanolamide (PEA) is a natural fatty acid that has analgesic, anti-inflammatory, and neuroprotective effects. In this blog post, we will discuss the current research on PEA and its potential as a treatment for chronic and neuropathic pain (nerve pain).

Palmitoylethanolamide (PEA) is present in all mammals, including humans. It is produced naturally in the body and is also found in some foods, such as chicken egg yolk and soybeans.

What is PEA?

Palmitoylethanolamide (PEA) is a fatty acid amide that is naturally produced in the body. PEA is found in high concentrations in the central nervous system. It is produced by neurons, glial cells, and immune cells. PEA belongs to a class of endocannabinoids known as N-acylethanolamines (NAEs).

How does Palmitoylethanolamide (PEA) work?

PEA binds to both CB1 and CB2 receptors, although its binding affinity is higher for CB2 than for CB1. The activation of CB2 receptors by PEA is thought to be responsible for the management of pain. Research suggests that PEA may be an effective treatment for neuropathic pain, inflammatory pain, and neuro-inflammatory conditions. 

PEA functions as an agonist at both TRPV1 and TRPA1 ion channels.TRPV1 ion channels are located on nociceptive neurons and are activated by noxious stimuli such as heat, acidic pH, and capsaicin. Activation of TRPV1 ion channels results in an influx of calcium ions into the cell, which leads to the initiation of pain signals.

TRPA1 ion channels are also located on nociceptive neurons and are activated by noxious stimuli such as cold temperatures and mustard oil derivatives. Activation of TRPA1 ion channels also results in an influx of calcium ions into the cell, which leads to pain signals being transmitted from the periphery to the central nervous system. 

You may have heard of the endocannabinoid system (ECS), but what exactly is it and how does it work?

The ECS is a complex cell-signaling system that plays a role in maintaining homeostasis in the body. This system is involved in many physiological processes, including regulating many important functions in the body including pain, inflammation, mood, and sleep. 

The ECS is made up of endocannabinoids, which are ligands that bind to cannabinoid receptors. There are two known cannabinoid receptors, CB1 and CB2. CB1 receptors are found primarily in the brain and central nervous system, while CB2 receptors are found mainly in the peripheral nervous system. Both CB1 and CB2 receptors are G protein-coupled receptors (GPCRs). 

The CB1 and CB2 receptors are activated by endogenous ( produced naturally by the body) and exogenous (plant-derived) cannabinoids. The activation of CB1 receptors is primarily responsible for the psychoactive effects of cannabinoids, while CB2 activation is thought to be responsible for the immunomodulatory and anti-inflammatory effects.

What Does the Research Say? 

There is a growing body of evidence from clinical trials supporting the use of PEA as a treatment for chronic and neuropathic pain. A number of studies have shown that PEA supplements can help to reduce pain and improve the quality of life in people with chronic pain.

One study in cancer patients found that PEA was effective at reducing neuropathic pain when used alongside standard pain medication. Another study found that PEA was effective at reducing inflammatory joint pain in patients with rheumatoid arthritis. 

A 2017 systematic review looked at 28 clinical trials on the efficacy of PEA for treating various types of chronic and neuropathic pain. The authors concluded that “PEA is an effective adjuvant therapy for chronic non-cancer related pains.” 

Another study published in 2018 found that PEA was an effective treatment for nerve damage-related pain reduction. The authors conclude that “PEA should be included in guideline-recommended pharmacological treatments for diabetic patients with painful diabetic neuropathy.” 

A recent study by Austrian researchers, published in 2022, concluded PEA has clinically relevant analgesic properties, acting on both peripheral and central mechanisms (reducing wind-up) as well as in pain modulation, therefore increasing pain tolerance.

What conditions might be improved by taking PEA as a supplement?

Conditions where people might benefit from using PEA for their pain management include (but are not limited to):

  • Neuropathic pain (nerve pain)
  • Inflammatory pain
  • Fibromyalgia
  • Radiculopathic pain
  • Peripheral neuropathy
  • Persistent post-surgical pain
  • Chronic pelvic pain
  • Visceral pain
  • Diabetic neuropathy

How long does it take to see an effect after starting PEA?

Individual patients can take up to 4 – 6 weeks to experience benefits from PEA supplementation. It is well tolerated and has no known side effects which makes PEA an option for patients who have multiple medication sensitivities or allergies.


Although more research needs to be done on PEA and its potential therapeutic applications, current evidence suggests that PEA holds promise as a treatment for chronic pain conditions due to its ability to modulate both TRPV1 and TRPA1 ion channels. 

The current emerging evidence and clinical data suggest that PEA may be an effective treatment for treating chronic pain with few side effects. If you are interested in trying PEA, speak to your healthcare provider about whether it is right for you.

Disclosure: The information in this article is not intended to replace your doctor’s medical advice, diagnosis or treatment. If you require more information, or have any questions, please speak to your doctor/ specialist.


  1. Artukoglu BB, Beyer C, Zuloff-Shani A, Brener E, Bloch MH. Efficacy of Palmitoylethanolamide for Pain: A Meta-Analysis. Pain Physician. 2017 Jul;20(5):353-362. PMID: 28727699.
  2. Guida, F., Luongo, L., Boccella, S. et al. Palmitoylethanolamide induces microglia changes associated with increased migration and phagocytic activity: involvement of the CB2 receptor. Sci Rep 7, 375 (2017).
  3. Petrosino S, Di Marzo V. The pharmacology of palmitoylethanolamide and first data on the therapeutic efficacy of some of its new formulations. Br J Pharmacol. 2017 Jun;174(11):1349-1365. doi: 10.1111/bph.13580. Epub 2016 Sep 29. PMID: 27539936; PMCID: PMC5429331.
  4. The Effect of Palmitoylethanolamide on Pain Intensity, Central and Peripheral Sensitization, and Pain Modulation in Healthy Volunteers—A Randomized, Double-Blinded, Placebo-Controlled Crossover Trial Kordula Lang-Illievich, Christoph Klivinyi, Gudrun Rumpold-Seitlinger, Christian Dorn and Helmar Bornemann-Cimenti. Nutrients 2022, 14, 4084. nu14194084.