Low Dose Naltrexone (LDN): The Potential Role in Reducing Alcohol Consumption - A Review of Current Evidence

Edited by Yoon Hang Kim MD MPH

About Dr. Kim

Dr. Yoon Hang "John" Kim, a recipient of the 2024 Functional Medicine for All scholarship from the Institute for Functional Medicine, brings over 20 years of experience in integrative and functional medicine to his telemedicine practice. After serving as chief wellness officer at a community hospital in Carthage, IL, where he provided care to rural and underserved populations, Dr. Kim now offers virtual integrative and functional medicine services, making personalized, evidence-based care accessible to patients regardless of location. His approach combines functional medicine lab testing with complementary therapies such as meditation, yoga, tai chi, and lifestyle interventions using food and physical activity as medicine, addressing the root causes of disease. Dr. Kim earned his medical degree from the Medical College of Wisconsin, completed a master’s in public health at San Diego State University, and trained with Dr. Andrew Weil during his residential fellowship at the University of Arizona. Certified by the American Board of Preventive Medicine, the American Board of Medical Acupuncture, and the American Board of Integrative and Holistic Medicine, he has also contributed to the field as a faculty member, consultant, and founder of the Integrative Health Studies Certificate program at the University of West Georgia. With clinical interests in autoimmune conditions, chronic pain, integrative oncology, and gastrointestinal disorders, Dr. Kim specializes in treating complex conditions such as fibromyalgia, chronic fatigue syndrome, long COVID symptoms, and toxic mold illness, and has authored two books and over 20 articles while helping establish integrative medicine practices across various institutions.

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Abstract

Low-dose naltrexone (LDN), typically administered at 1–4.5 mg daily, has gained attention for off-label applications beyond its standard use in alcohol use disorder (AUD). While standard-dose naltrexone (50 mg daily) is well established for reducing heavy drinking and cravings in AUD, evidence supporting LDN specifically for alcohol cessation or reduction remains limited and preliminary. This article reviews the mechanistic distinctions, available clinical data, and practical considerations surrounding LDN in AUD, emphasizing the need for caution and professional oversight.

Introduction

Alcohol use disorder (AUD) affects millions worldwide and contributes substantially to morbidity and mortality. Pharmacologic interventions, including naltrexone, acamprosate, and disulfiram, are recommended as adjuncts to psychosocial therapies (Reus et al., 2018). Standard-dose naltrexone, an opioid receptor antagonist, is FDA-approved for AUD at 50 mg daily, where it reduces alcohol-related reward and craving (Maisel et al., 2013; Jonas et al., 2014).

In contrast, low-dose naltrexone (LDN) is thought to exert effects through transient opioid receptor blockade and subsequent endorphin modulation, mechanisms primarily studied in chronic pain, inflammatory, and autoimmune conditions (Younger et al., 2014). Most published research and clinical trials on LDN have focused on its use in chronic conditions and autoimmune diseases, with organizations like the LDN Research Trust supporting research and education in this area. Interest has recently emerged regarding LDN’s potential role in AUD, particularly for craving reduction or moderated drinking, though high-quality evidence remains sparse.

Mechanisms of Action on Opioid Receptors

At standard doses, naltrexone competitively blocks μ-opioid receptors, reducing alcohol-induced dopamine release within mesolimbic reward pathways and thereby diminishing reinforcement (O’Malley et al., 2002).

LDN, administered at substantially lower doses, is hypothesized to induce a compensatory increase in endogenous opioid production or to modulate neuroinflammation via glial cell activity (Toljan & Vrooman, 2018). Specifically, LDN may act on microglial cells within the central nervous system, which are key glial cells involved in neuroinflammation. Activated microglial cells produce proinflammatory cytokines, pro inflammatory cytokines, nitric oxide, reactive oxygen species, and substance P, all of which contribute to pain, inflammation, and neurotoxicity. LDN may help suppress microglial activation, thereby reducing the production of these inflammatory mediators.

Additionally, LDN’s transient blockade of opioid receptors can lead to increased production of endogenous opioids and natural peptides, such as endorphins and opioid growth factor. These natural peptides interact with opioid growth factor receptors to regulate immune function and cell growth. Opioid receptors are present in both the central and peripheral nervous systems, so LDN’s effects may extend to both regions. While these mechanisms may plausibly influence craving or affective regulation, they remain speculative in the context of AUD and have not been directly validated in alcohol-specific models.

Evidence for Standard-Dose Naltrexone in AUD

Multiple meta-analyses demonstrate moderate efficacy for oral naltrexone 50 mg daily in reducing return to heavy drinking, with a number needed to treat of approximately 12, and in decreasing drinking days when combined with psychosocial interventions (Jonas et al., 2014; Maisel et al., 2023). Clinical practice guidelines from the American Psychiatric Association endorse its use for individuals with moderate-to-severe AUD (Reus et al., 2018).

Evidence for Low-Dose Naltrexone in AUD and Chronic Pain

Direct evidence evaluating LDN for AUD is limited. Available data consist primarily of anecdotal reports, theoretical discussions, and small exploratory studies. To date, no large randomized controlled trials demonstrate efficacy for LDN in alcohol cessation or reduction (Patten et al., 2024).

One pilot study—a pilot randomized trial—assessing LDN in combination with gabapentin among individuals with HIV and heavy alcohol use found no significant difference in pain or alcohol-related outcomes compared with placebo (Edelman et al., 2024). While off-label discussions frequently cite potential reductions in cravings, these claims remain unsupported by rigorous clinical evidence (Toljan & Vrooman, 2018). Crossover trials have been used in other LDN research, such as studies on fibromyalgia, to assess efficacy, but such study designs are lacking in the context of AUD.

Limitations and Risks

LDN is not FDA-approved for AUD, and its use in this context constitutes off-label prescribing. Although side effects are generally mild—such as insomnia or vivid dreams—potential risks include hepatic strain, particularly with ongoing alcohol consumption. It is important to note that opioid antagonist naltrexone is FDA-approved for opioid use disorder, where higher dosages are typically used compared to low dose naltrexone. Taking LDN or naltrexone while opioids are present in the system can precipitate opioid withdrawal, so medical screening is essential before starting therapy. Self-directed use is discouraged due to variability in compounding practices, dosing, and potential drug interactions.

Patient Perspectives and Experiences -

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Many patients with chronic pain conditions have turned to low dose naltrexone (LDN) as an anti-inflammatory treatment, particularly when conventional approaches haven't provided adequate relief. People with fibromyalgia, complex regional pain syndrome, and multiple sclerosis frequently report improvements in function, reduced pain intensity, better sleep, and enhanced quality of life.

Clinical research supports these observations. In randomized placebo-controlled trials, fibromyalgia patients taking LDN showed significant reductions in pain severity, fatigue, and sleep disruption. Patients with Crohn's disease have reported improvements in abdominal pain, diarrhea frequency, and fatigue—demonstrating LDN's potential across multiple inflammatory conditions.

Beyond pain relief, practitioners have documented improvements in psychological well-being, with patients showing meaningful reductions in anxiety and depression scores alongside physical symptom improvement. For many, LDN has also helped reduce opioid dependence—addressing legitimate concerns about addiction risks and long-term side effects of chronic opioid use.

Patients often describe LDN as transformative, enabling greater participation in daily activities and improved overall function. The mechanism appears to involve immune modulation, resulting in decreased inflammation and better health outcomes.

That said, responses to LDN vary considerably. While many patients benefit, some don't achieve meaningful improvement. As with any treatment, consultation with a knowledgeable provider is essential to determine appropriateness and monitor for adverse reactions.

As research continues, LDN's role in chronic pain and inflammatory conditions will become better defined—offering hope for patients seeking alternatives to conventional pain management.

Conclusion

While standard-dose naltrexone has a well-established evidence base for the treatment of alcohol use disorder, current data are insufficient to support the use of low-dose naltrexone for reducing alcohol consumption or cravings. Individuals interested in pharmacologic treatment for AUD should consult qualified healthcare professionals to pursue evidence-based options and integrate medication with behavioral and psychosocial interventions.

About Dr. Kim's Private Practice

At Direct Integrative Care, Dr. Kim is dedicated to guiding you on your path to wellness through a deeply personalized and supportive approach. We focus on integrative medicine, looking beyond symptoms to uncover the root causes of chronic conditions and develop a treatment plan tailored specifically to your unique health journey. By combining compassionate care with innovative therapies, our goal is to empower you with the knowledge and tools needed to achieve lasting health. We invite you to explore our website to learn more about how our patient-centered practice can help you find balance and vitality. 

Yoon Hang Kim MD

Integrative & Functional Medicine Physician

Virtual Practice Serving IA, IL, MO, FL, GA, and TX

www.directintegrativecare.com

References

Edelman, E. J., et al. (2024). Pilot RCT comparing low-dose naltrexone, gabapentin and placebo to reduce pain among people with HIV with alcohol problems. PLOS ONE, 19(2), e0297903. https://doi.org/10.1371/journal.pone.0297903

Jonas, D. E., et al. (2014). Pharmacotherapy for adults with alcohol use disorders in outpatient settings: A systematic review and meta-analysis. JAMA, 311(18), 1889–1900. https://doi.org/10.1001/jama.2014.3628

Maisel, N. C., et al. (2013). Meta-analysis of naltrexone and acamprosate for treating alcohol use disorders: When are these medications most helpful? Addiction, 108(2), 275–293. https://doi.org/10.1111/j.1360-0443.2012.04054.x

Maisel, N. C., et al. (2023). Pharmacotherapy for alcohol use disorder: A systematic review and meta-analysis. JAMA Network Open, 6(11), e2343420.

O'Malley, S. S., et al. (2002). Naltrexone decreases craving and alcohol self-administration in alcohol-dependent subjects and activates the hypothalamo-pituitary-adrenocortical axis. Psychopharmacology, 160(1), 19–29.

Patten, D. K., et al. (2024). Low-dose naltrexone: A potential gold medalist? American Family Physician, 110(2), 123–124.

Reus, V. I., et al. (2018). The American Psychiatric Association practice guideline for the pharmacological treatment of patients with alcohol use disorder. American Journal of Psychiatry, 175(1), 86–90. https://doi.org/10.1176/appi.ajp.2017.1750101

Toljan, K., & Vrooman, B. (2018). Low-dose naltrexone (LDN)—Review of therapeutic utilization. Medical Sciences, 6(4), 82. https://doi.org/10.3390/medsci6040082

Younger, J., et al. (2014). The use of low-dose naltrexone (LDN) as a novel anti-inflammatory treatment for chronic pain. Clinical Rheumatology, 33(4), 451–459.