Naltrexone is primarily recognized for its role in addiction treatment, but there is growing interest in its potential use for other conditions, including anxiety. The standard, higher dose of Naltrexone is an opioid receptor antagonist. This means it blocks the effects of opioids and the body’s natural pain- and pleasure-regulating chemicals, known as endorphins. This action has led researchers to explore the medication’s impact on mood and anxiety, particularly when prescribed at much lower, off-label dosages.
Naltrexone’s Standard Medical Uses
Naltrexone is a prescription medication with established indications for treating substance use disorders at standard dosages, typically 50 milligrams (mg) per day. It is approved by the FDA to manage alcohol use disorder by reducing the pleasurable effects of alcohol and decreasing cravings. The drug is also FDA-approved for the treatment of opioid use disorder. In this context, Naltrexone functions as an opioid antagonist, binding to opioid receptors to block the euphoric and sedative effects of both illicit and prescription opioids. Patients must be opioid-free for a minimum of seven to ten days before starting the medication to avoid precipitating acute withdrawal symptoms.
Naltrexone and Anxiety: Clinical Findings
Naltrexone is not currently FDA-approved as a treatment for anxiety disorders, and research on its direct efficacy is still developing. Evidence supporting its use often comes from studies focused on co-occurring conditions. For example, in individuals with opioid dependence, Naltrexone treatment has been shown to reduce symptoms of anxiety and depression. A separate study involving people with alcohol use disorder and co-morbid anxiety also found significant improvement in anxiety symptoms.
In these addiction-focused contexts, anxiety reduction is often a secondary benefit of successfully treating the primary substance use disorder. Some early-phase clinical trials are beginning to directly investigate Naltrexone’s potential to reduce anxiety. Research suggests the drug’s effects on the body’s stress response system may provide a mechanism for relief. For instance, a study on individuals with multiple sclerosis found that those taking low-dose Naltrexone showed lower anxiety scores. The primary evidence for Naltrexone’s use in anxiety is largely linked to its off-label use in lower dosages.
Low-Dose Naltrexone (LDN) Protocol
The use of Naltrexone for conditions like anxiety and chronic pain is associated with Low-Dose Naltrexone (LDN). The LDN protocol involves significantly smaller doses than those used for addiction treatment, typically ranging from 1.5 mg to 4.5 mg daily. This requires a specialized compounded formulation since commercial tablets cannot be accurately divided into such small amounts.
The rationale for using LDN is that a brief, low-level blockade of opioid receptors may trigger a beneficial rebound effect. This temporary blockade, lasting only a few hours, is hypothesized to stimulate the body to increase its production and utilization of endorphins. LDN is often prescribed off-label for conditions involving chronic inflammation or immune dysregulation, such as fibromyalgia, multiple sclerosis, and certain autoimmune diseases. In these applications, anxiety reduction often appears as a secondary benefit tied to the overall improvement in the underlying condition. The typical starting dose is 1.5 mg once daily, usually taken at bedtime, with gradual increases until the target dose of 4.5 mg is reached. This slow titration helps minimize temporary side effects like vivid dreams or insomnia.
Mechanism of Action on Mood Regulation
The mechanism by which Naltrexone, particularly at low doses, influences mood and anxiety is distinct from its addiction treatment effects. High doses block opioid receptors throughout the day. In contrast, the low-dose formulation provides only a transient blockade of the mu-opioid receptors, lasting about four hours. This brief blockade prompts a homeostatic response, leading to an upregulation in the production of endogenous opioid peptides, such as endorphins.
Endorphins are the body’s natural compounds that help regulate pain, promote well-being, and modulate stress responses. The resulting increase in these chemicals is hypothesized to be the primary driver behind LDN’s positive effects on mood and anxiety. LDN is also believed to exert an anti-inflammatory effect within the central nervous system. It modulates the activity of glial cells, which are involved in the brain’s inflammatory response. Since chronic inflammation is recognized as a factor in various mood disorders, this anti-inflammatory action may contribute to reduced anxiety.
Essential Safety and Usage Guidance
Before considering Naltrexone for anxiety, consult with a healthcare provider. The most significant contraindication is the concurrent use of any opioid-containing medication, including prescription pain relievers. Taking Naltrexone while physically dependent on opioids will instantly precipitate a severe withdrawal syndrome.
Common side effects, even at lower doses, include mild gastrointestinal upset, nausea, headache, dizziness, and sleep disturbances like insomnia or vivid dreams. These effects are usually temporary and subside as the body adjusts. Naltrexone can also cause liver damage in rare cases, so patients with pre-existing liver disease may require additional monitoring.
Because Naltrexone for anxiety is an off-label use, it must be initiated under the supervision of a prescribing physician. A doctor can assess the potential benefits against the risks and ensure the dosage and titration schedule are appropriate.