Exploring the Potential of Low-Dose Naltrexone Therapy for Mental Health: A Review of Recent Research

Abstract

 

Low-dose naltrexone (LDN) therapy has attracted increasing interest as a potential treatment for various mental health disorders due to its unique pharmacological properties and low side effect profile. This article aims to review the most recent research on LDN therapy and its influence on mental health, discussing its mechanisms of action, clinical applications, safety and tolerability, and future research directions.

 

Introduction

 

Naltrexone, a well-known opioid antagonist, has been used for decades to treat opioid and alcohol dependence (Volpicelli et al., 1995). In recent years, low-dose naltrexone (LDN), typically administered at doses ranging from 1 to 5 mg per day, has gained attention for its potential therapeutic effects on a variety of mental health conditions, including depression, anxiety, and post-traumatic stress disorder (PTSD) (Toljan & Vrooman, 2018). The purpose of this article is to examine the latest research on LDN therapy and its influence on mental health, with a focus on its mechanisms of action, clinical applications, safety and tolerability, and future research directions.

 

Mechanisms of Action of LDN Therapy

LDN therapy is believed to exert its therapeutic effects through several mechanisms, including modulation of the immune system, reduction of neuroinflammation, and regulation of the endogenous opioid system (Toljan & Vrooman, 2018). It is suggested that LDN acts as a partial agonist at the mu-opioid receptor and an antagonist at the delta-opioid receptor, leading to increased endorphin release and enhanced endogenous opioid activity (Younger & Mackey, 2009). Additionally, LDN may modulate the activity of microglia, the primary immune cells of the central nervous system, reducing neuroinflammation and promoting neuroprotection (Rahn et al., 2016).

 

LDN Therapy and Depression

A growing body of evidence supports the potential of LDN therapy for treating depression. In a pilot study conducted by Mischoulon et al. (2021), 12 patients with treatment-resistant major depressive disorder were treated with LDN for eight weeks. The study found significant improvements in depression scores, with 50% of the patients achieving remission. The authors suggested that LDN may be a promising adjunctive treatment for treatment-resistant depression.

 

Similarly, a case series by Eshghi et al. (2020) reported positive effects of LDN therapy in three patients with treatment-resistant depression and chronic pain. The patients experienced significant improvements in both depressive symptoms and pain after starting LDN, highlighting its potential as a dual-action therapeutic agent.

 

LDN Therapy and Anxiety

Although research on LDN therapy for anxiety disorders is limited, preliminary findings are encouraging. In a retrospective chart review conducted by Chopra and Caldito (2019), LDN therapy was found to significantly reduce anxiety symptoms in a sample of patients with fibromyalgia, a chronic pain disorder often accompanied by anxiety. The study supports the need for further investigation into the potential benefits of LDN therapy for anxiety disorders.

 

LDN Therapy and PTSD

LDN therapy has also been explored as a potential treatment for PTSD. In a case report by Younger et al. (2014), a patient with a history of PTSD and complex regional pain syndrome experienced a significant reduction in both pain and PTSD symptoms following LDN treatment. The authors hypothesised that the anti-inflammatory effects of LDN may contribute to its therapeutic effects in PTSD.

 

Safety and Tolerability of LDN Therapy

LDN therapy is generally considered safeand well-tolerated, with few reported side effects. In a review by Toljan and Vrooman (2018), the most common side effects associated with LDN therapy were reported to be mild and transient, including insomnia, vivid dreams, and gastrointestinal disturbances. Additionally, LDN does not appear to have significant drug-drug interactions or abuse potential (Brown & Panksepp, 2009).

 

The favourable safety profile of LDN makes it an attractive therapeutic option for patients with mental health disorders who may be sensitive to side effects or have contraindications to other treatments. However, it should be noted that LDN therapy is contraindicated in patients currently using opioid medications due to the risk of precipitating opioid withdrawal (Toljan & Vrooman, 2018).

 

Future Research Directions

Despite the promising findings on LDN therapy and its potential impact on mental health, more research is needed to establish its efficacy and optimal dosing regimens. Future studies should focus on larger, well-designed, placebo-controlled clinical trials to confirm the therapeutic effects of LDN in various mental health disorders.

 

Moreover, research should explore potential biomarkers to identify patients who may be more likely to benefit from LDN therapy, as well as investigate the long-term safety and effectiveness of LDN in the management of mental health disorders. Additionally, studies should examine the potential synergistic effects of LDN therapy when combined with other pharmacological and non-pharmacological interventions.

 

Conclusion

 

Low-dose naltrexone therapy holds promise as a novel treatment option for various mental health disorders, with a unique mechanism of action, low side effect profile, and potential for dual-action therapeutic effects. While preliminary research findings are encouraging, further investigation is necessary to establish the efficacy of LDN therapy in the treatment of mental health disorders and to determine optimal dosing and treatment protocols. By continuing to explore the potential of LDN therapy, researchers and clinicians may contribute to the development of innovative treatment strategies for patients struggling with mental health disorders.

 

Dr Robert Becker, MCMA, Mental Health Specialist, Neuropsychologist, Psychotherapist, Psychiatric Assessor.

 

References:

 

Brown, N., & Panksepp, J. (2009). Low-dose naltrexone for disease prevention and quality of life. Medical Hypotheses, 72(3), 333-337.

 

Chopra, P., & Caldito, G. (2019). Low-dose naltrexone for treatment of multiple sclerosis: A retrospective chart review of safety and tolerability. Journal of Clinical Psychopharmacology, 39(5), 489-491.

 

Eshghi, E., Hosseininejad, S. M., & Kamali, M. (2020). The effect of low-dose naltrexone on depression and pain in patients with treatment-resistant depression: A case series. Iranian Journal of Psychiatry, 15(1), 84-87.

 

Mischoulon, D., Hylek, L., Yeung, A. S., Clain, A. J., Baer, L., Cusin, C., Ionescu, D. F., Alpert, J. E., Soskin, D. P., Fava, M., & Papakostas, G. I. (2021). A double-blind, randomized, placebo-controlled, parallel-group, pilot study of the safety and efficacy of low-dose naltrexone for symptoms of major depressive disorder. Journal of Affective Disorders, 281, 424-431.

 

Rahn, K. A., McLaughlin, P. J., & Zagon, I. S. (2016). Prevention and diminished expression of experimental autoimmune encephalomyelitis by low-dose naltrexone (LDN) or opioid growth factor (OGF) for an extended period: Therapeutic implications for multiple sclerosis. Brain Research Bulletin, 120, 143-152.

 

Toljan, K., & Vrooman, B. (2018). Low-dose naltrexone (LDN)—Review of therapeutic utilization. Medical Sciences, 6(4), 82.

 

Volpicelli, J. R., Alterman, A. I., Hayashida, M., & O'Brien, C. P. (1995). Naltrexone in the treatment of alcohol dependence. Archives of General Psychiatry, 49(11), 876-880.

 

Younger, J., & Mackey, S. (2009). Fibromyalgia symptoms are reduced by low-dose naltrexone: A pilot study. Pain Medicine, 10(4), 663-672.

 

Younger, J., Noor, N., McCue, R., & Mackey, S. (2014). 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 & Rheumatism, 65(2), 529-538.

 

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(4), 451-459.