Low Dose Naltrexone

Low dose Naltrexone

LDN is a competitive opioid receptor antagonist. At higher doses, (generally used for addiction), naltrexone blocks the effects of both the endogenous (bodies own) opioids, and pharmaceutical opioids. At lower doses, (a 10th or less of the standard dose), LDN causes microglial cells in the nervous system to ‘up-regulate’ (meaning to boost up) opioid receptors, and there are a wide range of cells in the body that have opiod receptors. In addition, LDN helps to regulate immune system functioning by decreasing and regulating inflammatory mediators that cause muscle and soft tissue pain. 

Endorphins are your natural peptides produced in many cells which regulate cell growth, including your immune cells. Many patients who have autoimmune disease tend to have low levels of endorphins which are important immuno-modulatory agents. Opioid receptors are in the central and the peripheral nervous system, the GI tract, and on lymphocytes. By using LDN you receive a brief blockade, creating a rebound effect giving you more endorphins, including OGF, and increased production of the OGF receptors.

It is via the non-opioid antagonist path that LDN is thought to exert its anti-inflammatory effects. Microglia are central nervous system immune cells that are activated by a wide range of triggers. Once activated, microglia produce inflammatory and excitatory factors that can cause pain sensitivity, fatigue, cognitive disruption, sleep disorders, mood disorders, and general malaise. One of the conditions that has been studied the with LDN is fibromyalgia, and studies have consistently shown that LDN has effectiveness at reducing the chronic pain associated with FM. Fibromyalgia involves chronic glial cell activation and subsequent production of pro-inflammatory factors. The hypothesis is indirectly and partially supported by the high degree of symptomatic overlap between fibromyalgia and cytokine-induced sickness behaviors.

Both naloxone and naltrexone have been demonstrated to exert neuroprotective and analgesic effects. The neuroprotective action appears to result when microglia activation in the brain and spinal cord is inhibited. By suppressing microglia activation, naltrexone reduces the production of reactive oxygen species and other potentially neuro-excitatory and neurotoxic chemicals.

Low Dose Naltrexone binds to the endorphin receptors for about 1 – 1/2 hours, and the blockade lasts about 4 - 6 hours. The effects of LDN are analgesia and anti-inflammatory.  One of the other effects is that it increases the production of your own endorphins.

While LDN is not FDA-approved for treating inflammatory conditions, studies have shown it to be effective at immune system modulation and can also help curb cravings such as sugar/carbohydrate and alcohol cravings. Unlike traditional pain medications, LDN does not cause addiction or cause damage to the lining of the intestinal tract. At higher doses, it is used to treat alcohol use disorder. We really don’t have any other tools like LDN, that reduce pain, fight inflammation and pain and have an incredibly safe SE profile. 

Patients will often start anywhere from 1-3 mg, and titrate up to 4.5 to 10 mg, usually taken at bedtime. 

One of the most exciting aspects of LDN is the low reported incidence of adverse side effects. There have been no noted incidences of ulcers, renal insufficiency, interference with warfarin and other common medications, increased heart attack or clotting risk, or other problems that can be seen with non-steroidal anti-inflammatory drugs. No known cases of severe adverse events and minimal to know withdrawal effects.

Side effects of LDN treatment are mild. In our research, participants have rated LDN as slightly more tolerable than placebo (91.0 versus 89.5 %, not significant). The most common side effect we have observed is the reporting of more vivid dreams, which is seen in approximately 37 % of the participants. In a minority of cases, patients report nightmares. As a side effect, vivid dreams develop rapidly (as soon as the first dosing) and decrease over time. It is unclear what mechanism may drive increased vividness of dreams. Individuals generally self-report increased effectiveness of sleep, so it is unlikely that the vivid dreams represent an adverse disruption of normal sleep patterns. It is important to note that increased vividness of dreams is also the most commonly reported side effect during placebo administration, so some cases may be driven by expectancy.

There are no reports of LDN interactions with other medications. However, the sample sizes in studies have been very small, and there are undoubtedly a large number of interactions that have not been tested. An obvious exception is LDN co-administered with an opioid analgesic.