For Patients & Caregivers
Tell your healthcare providers about any dietary supplements you’re taking, such as herbs, vitamins, minerals, and natural or home remedies. This will help them manage your care and keep you safe.
What is it?
What is it used for?
Low-dose naltrexone is used to:
- Treat various types of unresolved lingering pain
- Relieve pain caused by fibromyalgia (chronic widespread pain, fatigue, and tenderness)
LDN has other uses, but doctors haven’t studied them to see if they work.
Talk with your healthcare provider before taking LDN. It may interact with some medications and affect how they work. For more information, read the “What else do I need to know?” section below.
What are the side effects?
What else do I need to know?
- Talk with your healthcare provider if you’re undergoing chemotherapy. It is unclear whether using LDN during treatment may affect how these drugs work.
- Talk with your healthcare provider if you’re taking tamoxifen (such as Nolvadex® or Soltamox™). It is unclear whether using LDN during treatment may affect how these drugs work.
For Healthcare Professionals
Naltrexone is an opioid antagonist that was originally developed in the 1960s and approved for medical use by the FDA in the 1980s. It has been used clinically to treat opioid and alcohol addictions (1). More recently, low-dose naltrexone (LDN) has been promoted for off-label use as a safe and inexpensive option to treat myriad conditions including pain, inflammation, immune dysfunction, gastrointestinal, neurological, and psychological conditions, and even cancer. However, studies are quite limited.
Small placebo-controlled trials suggest benefit with LDN for patients with fibromyalgia (2) (3). LDN efficacy for diabetic neuropathy appears to be similar to amitriptyline, but with fewer adverse effects (4). In a proof-of concept study of patients with major depressive disorder who relapsed on antidepressants, LDN-augmented treatment reduced depression severity (5). Other pilot RCTs suggest benefit for patients with moderate to severe Crohn’s disease (6) (7). However, results from studies in patients with multiple sclerosis are equivocal (8) (9), and anecdotal claims of efficacy with LDN for cancer have not been examined in clinical trials.
Although it is thought to be well-tolerated, larger well-designed clinical trials are needed to understand the conditions for which LDN may be safe and effective before it can be recommended.
Mechanism of Action
Naltrexone is a semi-synthetic opioid with structural similarity to other opioid agonists and competitive antagonist activity at mu opioid receptors (10), neuromodulators with functions that include nociception, or identifying and responding to painful stimuli.
The phenomenon of paradoxical hyperalgesia discovered with morphine in animal studies, where the opposite effect occurs at about one-tenth of the dose used to relieve pain has been proposed as the mechanism by which LDN may actually reduce pain (11). Anti-inflammatory effects have been attributed to additional antagonist effects on toll-like receptor 4, nonopioid receptors found on macrophages such as microglial cells (11) (12).
Contraindications associated with standard doses of naltrexone include (13):
- Patients receiving opioid analgesics.
- Patients currently dependent on opioids, including those currently maintained on opiate agonists such as methadone or partial agonists like buprenorphine.
- Patients in acute opioid withdrawal.
- Any individual who has failed the naloxone challenge test or who has a positive urine screen for opioids.
- Any individual with a history of sensitivity to naltrexone or any other components of this product. It is not known if there is any cross-sensitivity with naloxone or the phenanthrene containing opioids.
Chemotherapy drugs: Preclinical data suggest that naltrexone can interact with several CYP enzymes (14). Clinical relevance, including for low doses, has yet to be determined.
CYP450 substrates: Preclinical data show that naltrexone can interact with several CYP enzymes, and particularly 2C9 and 2D6 (14). Clinical relevance, including for low doses, has yet to be determined.