Use of Low-Dose Naltrexone

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Yen Nien (Jason) Hou, PharmD, DiplOM, LAc

Yen Nien (Jason) Hou, PharmD, DiplOM, LAc

Jyothirmai Gubili, MS

Jyothirmai Gubili, MS

The ASCO Post’s Integrative Oncology series is intended to facilitate the availability of evidence-based information on integrative and complementary therapies sometimes used by patients with cancer. In this installment, Yen Nien (Jason) Hou, PharmD, DiplOM, LAc, and Jyothirmai Gubili, MS, focus on low-dose naltrexone because it is promoted as a treatment for a variety of symptoms and conditions including pain and immune dysfunction.


Developed in the 1960s, naltrexone is a semisynthetic opioid antagonist. It has been used to treat alcohol and opioid addictions following its approval by the U.S. Food and Drug Administration (FDA) in the 1980s. Naltrexone in low doses is being promoted for off-label use to manage pain, reduce inflammation, and treat conditions and diseases including immune dysfunction and cancer. However, current evidence to support claims of its benefit in these areas is limited.

The Science

Preliminary findings suggest that low-dose naltrexone may be useful in patients with fibromyalgia. In a small, randomized crossover trial of 33 patients not on opioid analgesics, 12 weeks of low-dose naltrexone (4.5 mg daily) resulted in significant reduction in pain compared with placebo (28.8% vs 18.0%; P = .016) along with improvement in mood (P = .039).1

Similar findings were reported in another study of 10 patients. Those in the low-dose naltrexone cohort (4.5 mg daily for 8 weeks) had a greater than 30% reduction in symptoms compared with those in the placebo arm. Also, patients with higher sedimentation rates, indicative of inflammatory processes, reported the greatest reduction in symptoms.2

In a crossover study, 67 patients with painful diabetic neuropathy were randomly assigned to receive 2 mg of low-dose naltrexone or 10 mg of amitriptyline. After 6 weeks, the difference (confidence interval) in the change in the visual analog score between the groups was 1.64 (–0.92 to 4.20) in a per-protocol analysis and 1.5 (–1.11 to 4.13) in an intention-to-treat analysis. Further, the number of adverse effects was significantly lower with low-dose naltrexone compared with amitriptyline (P < .001).3


Jun J. Mao, MD, MSCE

Jun J. Mao, MD, MSCE

Dr. Mao is the Laurance S. Rockefeller Chair in Integrative Medicine and Chief of Integrative Medicine Service at Memorial Sloan Kettering Cancer Center, New York.

In a small study of 12 patients with major depressive disorder who relapsed on dopaminergic antidepressant regimens, the addition of low-dose naltrexone (1.0 mg twice daily for 3 weeks) decreased the severity of depression (21.2 ± 2.0 to 11.7 ± 7.7 for low-dose naltrexone, from 23.7 ± 2.3 to 17.8 ± 5.9 for placebo; P = .3).4

Preliminary findings also indicate potential utility of low-dose naltrexone in managing inflammatory bowel disease. In a 12-week study of 40 patients with moderate-to-severe Crohn’s disease, 80% of those randomly assigned to receive naltrexone (4.5 mg daily) had at least a 70-point decline in Crohn’s Disease Activity Index score compared with 40% of patients in the placebo arm (P = .009).5 Low-dose naltrexone has been studied in patients with multiple sclerosis as well. However, findings are inconclusive.6,7

Larger, methodologically sound trials are needed to confirm the previously mentioned findings. Studies are also needed to assess the claims of anticancer effects of low-dose naltrexone.

Adverse Reactions

Low-dose naltrexone has been reported to cause mild side effects, including diarrhea, nausea, epigastric pain, nausea, altered mood, joint pain, and headache.3,7

Herb-Drug Interactions

CYP450 Substrates:Naltrexone has been shown to interact with several cytochrome P450 enzymes, particularly 2C9 and 2D6, in preclinical studies. However, the clinical significance of these interactions is not known.8


Listed here are some of the contraindications associated with standard doses of naltrexone9:

  • In patients taking opioid analgesics
  • In patients currently dependent on opioids, including those currently maintained on opiate agonists such as methadone or partial agonists such as buprenorphine
  • In individuals who are in acute opioid withdrawal
  • In those who have failed the naloxone challenge test or who have a positive urine screen for opioids
  • In individuals with a history of sensitivity to naltrexone or any other components of this product. It is not known whether there is any cross-sensitivity with naloxone or the phenanthrene-containing opioids.


Naltrexone is an FDA-approved agent used in the treatment of alcohol and opioid abuse. The typical dose is 50 to 100 mg, and it requires a prescription. The off-label use of low-dose naltrexone (0.5–6 mg) is not approved by the FDA, and it requires a licensed medical practitioner to prescribe it and monitor patients on it. Because low-dose naltrexone is not an approved drug, only a compounding pharmacy can dispense it, typically in tablets, sublingual tablets, capsules, and transdermal form. Patients should not buy low-dose naltrexone from an unlicensed establishment nor without a prescription from a trained and licensed provider. 

DISCLOSURE: Dr. Hou and Ms. Gubili reported no conflicts of interest.


1. Younger J et al: Low-dose naltrexone for the treatment of fibromyalgia. Arthritis Rheum 65:529-538, 2013.

2. Younger J, Mackey S: Fibromyalgia symptoms are reduced by low-dose naltrexone. Pain Med 10:663-672, 2009.

3. Srinivasan A et al: Efficacy and safety of low-dose naltrexone in painful diabetic neuropathy. J -Diabetes 13:770-778, 2021.

4. Mischoulon D et al: Randomized, proof-of-concept trial of low dose naltrexone for patients with breakthrough symptoms of major depressive disorder on antidepressants. J Affect Disord 208:6-14, 2017.

5. Smith JP et al: Therapy with the opioid antagonist naltrexone promotes mucosal healing in active Crohn’s disease. Dig Dis Sci 56:2088-2097, 2011.

6. Cree BAC et al: Pilot trial of low-dose naltrexone and quality of life in multiple sclerosis. Ann Neurol 68:145-150, 2010.

7. Sharafaddinzadeh N et al: The effect of low-dose naltrexone on quality of life of patients with multiple sclerosis. Mult Scler 16:964-969, 2010.

8. AlRabiah H et al: Effect of naltrexone hydrochloride on cytochrome P450 1A2, 2C9, 2D6, and 3A4 activity in human liver microsomes. Eur J Drug Metab Pharmacokinet 43:707-713, 2018.

9. Revia (naltrexone hydrochloride), Duramed Pharmaceuticals, October 2013. Available at Accessed February 24, 2023.

Dr. Hou is Manager of the “About Herbs” website, maintained by Memorial Sloan Kettering Cancer Center’s Integrative Medicine Service, and Ms. Gubili is Editor, also at the Integrative Oncology Service, Memorial Sloan Kettering Cancer Center, New York.