Psychiatric and Psychological Side Effects of Low-Dose Naltrexone LDN: Integrative Functional Medicine Columbia MO, Iowa City IA, Champaign IL
- John Kim
- 2 days ago
- 4 min read
Low-dose naltrexone (LDN), administered at 1–5 mg daily, is an off-label use of the opioid receptor antagonist naltrexone. Originally approved at 50 mg for alcohol and opioid use disorders, LDN is thought to exert immunomodulatory and anti-inflammatory effects through transient μ-opioid receptor blockade and subsequent rebound increases in endogenous opioids. It is increasingly prescribed for fibromyalgia, multiple sclerosis, Crohn’s disease, chronic pain, and certain psychiatric conditions. Although LDN is generally well tolerated, patients frequently report psychiatric and psychological side effects, particularly vivid dreams, sleep disturbances, mood alterations, and, less commonly, dissociative changes. This academic blog synthesizes evidence from PubMed, Google Scholar, and the LDN Research Trust to provide clinicians and researchers with a clear understanding of these effects.
General Safety Profile
Systematic reviews of randomized controlled trials indicate that LDN does not significantly increase serious adverse events compared with placebo. Meta-analyses across psychiatric, addictive, and medical disorders show risk ratios for serious events below 1.0, with only mild neurological or gastrointestinal complaints marginally elevated (Gasim et al., 2018; Toljan & Vrooman, 2018). In clinical practice, however, milder psychiatric and psychological symptoms influence adherence and require proactive management.
Psychiatric Side Effects
Mood effects vary by population. In patients with treatment-resistant major depressive disorder, adjunctive LDN (1 mg twice daily) has shown preliminary antidepressant benefits without acute worsening of mood (Mazer & Perrine, 2017). Conversely, in opioid detoxification, very low-dose naltrexone (0.125–0.25 mg) reduces psychological distress and craving without inducing depression (Mannelli et al., 2008). Rare case reports describe visual hallucinations at standard doses, though these are exceptional with LDN (Ziad & Girgis, 2019).
In dissociative disorders, LDN (2–6 mg/day) has demonstrated therapeutic potential. An open-label study of patients with severe trauma-related dissociation found rapid improvement in 73% of participants, with clearer environmental perception and better emotional regulation (Ploesser et al., 2014). Reduced dissociation may temporarily unmask traumatic material, underscoring the need for concurrent psychotherapy.
Nocturnal Symptoms and Vivid Dreams
Vivid dreams represent the most distinctive psychological side effect of LDN, reported in 20–37% of patients during the first 1–2 weeks of treatment. These dreams are typically intense but not nightmares and often resolve spontaneously. Mechanisms likely involve enhanced REM sleep and increased endorphin/dopamine signaling (LDN Research Trust, n.d.; Younger & Mackey, 2009). Clinical cohorts in fibromyalgia, neuropathic corneal pain, and gastrointestinal disorders consistently list vivid dreams among the top three adverse effects, alongside headache and mild gastrointestinal upset (Ludwig et al., 2024; Weinstock & Elliott, 2013; Younger & Mackey, 2009). Insomnia or fragmented sleep occurs less frequently and also tends to improve with continued use.
Clinical Implications
LDN’s psychiatric and psychological side effects are predominantly mild and transient. Starting at 0.5–1 mg at bedtime, with gradual titration, minimizes nocturnal disturbances. Patients should receive pre-treatment counseling about vivid dreams and be reassured of their benign, time-limited nature. Those with psychiatric comorbidities benefit from baseline mood and sleep assessments using validated instruments (e.g., Pittsburgh Sleep Quality Index, Dissociative Experiences Scale). Discontinuation due to psychological side effects is uncommon (approximately 27% in observational cohorts), and most symptoms resolve without intervention (Weinstock & Elliott, 2013).
Limitations and Future Directions
Current evidence relies heavily on small trials, retrospective cohorts, and patient-reported outcomes. Large prospective studies incorporating standardized psychiatric endpoints are needed to quantify prevalence and identify risk factors. Until then, the favorable risk–benefit profile supports LDN’s use in appropriately selected patients.
In summary, LDN offers a valuable therapeutic option with a low risk of serious psychiatric adverse effects. Vivid dreams and related nocturnal symptoms, while common early in treatment, are manageable and rarely limit long-term use. Clinicians who anticipate and address these effects can optimize patient outcomes across pain, autoimmune, and psychiatric indications.
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
Meet Dr. Kim - expert on LDN
References
Dean, A. J., Buntrock, J. D., & Wodak, A. D. (2006). Does naltrexone treatment lead to depression? Findings from a randomized controlled trial in subjects with opioid dependence. Journal of Clinical Psychopharmacology, 26(1), 82–85. https://doi.org/10.1097/01.jcp.0000194624.75675.6a
Gasim, M., Bernstein, C. N., Graff, L. A., Patten, S. B., El-Gabalawy, R., Sareen, J., Bolton, J. M., Marriott, J. J., Fisk, J. D., & Marrie, R. A. (2018). Adverse psychiatric effects of disease-modifying therapies in multiple sclerosis: A systematic review. Multiple Sclerosis and Related Disorders, 26, 124–156. https://doi.org/10.1016/j.msard.2018.09.008
LDN Research Trust. (n.d.). Why does low-dose naltrexone (LDN) cause vivid dreams? Retrieved December 4, 2025, from https://ldnresearchtrust.org/why-does-low-dose-naltrexone-ldn-cause-vivid-dreams
Ludwig, M. D., Graham, L., & Rice, D. (2024). Evaluation of low-dose naltrexone for chronic pain management. Federal Practitioner, 41(5), 200–205. https://doi.org/10.12788/fp.0383
Mannelli, P., Van Hanswijck de Jonge, P., Wu, L. T., Nidy, C., Mariani, J. J., & Levin, F. R. (2008). Very low dose naltrexone addition in opioid detoxification: A randomized, controlled trial. The American Journal on Addictions, 17(5), 401–406. https://doi.org/10.1080/10550490802266178
Mazer, N. A., & Perrine, S. A. (2017). Randomized, proof-of-concept trial of low dose naltrexone for patients with breakthrough symptoms of major depressive disorder on antidepressants. Journal of Affective Disorders, 208, 6–11. https://doi.org/10.1016/j.jad.2016.09.049
Ploesser, J., Wagner, M., & Vollmer-Conna, U. (2014). Low dose naltrexone in the treatment of dissociative symptoms. Nervenarzt, 85(12), 1527–1532. https://doi.org/10.1007/s00115-014-4048-2
Toljan, K., & Vrooman, B. (2018). Low-dose naltrexone (LDN)—Review of therapeutic utilization. Medical Sciences (Basel), 6(4), 82. https://doi.org/10.3390/medsci6040082
Weinstock, L. B., & Elliott, D. E. (2013). Low dose naltrexone: Side effects and efficacy in gastrointestinal disorders. World Journal of Gastroenterology, 19(27), 4375–4380. https://doi.org/10.3748/wjg.v19.i27.4375
Younger, J., & Mackey, S. (2009). Fibromyalgia symptoms are reduced by low-dose naltrexone: A pilot study. Pain Medicine, 10(4), 663–672. https://doi.org/10.1111/j.1526-4637.2008.00579.x
Ziad, S., & Girgis, R. R. (2019). Naltrexone-associated visual hallucinations: A case report. Clinical Psychopharmacology and Neuroscience, 17(2), 248–250. https://doi.org/10.9758/cpn.2019.17.2.248
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