LDN and Benzodiazepines: Can You Take Them Together Safely?

Low Dose Naltrexone (LDN) has become increasingly popular for treating a variety of chronic conditions, from autoimmune diseases to mood disorders. Its appeal lies in its ability to reduce inflammation, balance the immune system, and even improve mental clarity and energy—all while using a fraction of the dose used in addiction treatment. But if you're already taking medications that affect the central nervous system, such as benzodiazepines, it's natural to wonder whether these drugs can safely be taken together.

The reassuring news is that LDN and benzodiazepines do not have a direct drug interaction. LDN works by temporarily blocking opioid receptors, leading to a rebound increase in natural endorphins once the blockade lifts. Benzodiazepines, by contrast, act on an entirely different system—namely the GABA-A receptors—which help calm neural activity and are often used for anxiety, insomnia, and seizure disorders. Because these two drugs target different receptor systems and are metabolized through different pathways, there is no known pharmacological conflict between them.

However, that doesn’t mean the combination is without concerns. One key issue is central nervous system sensitivity. Some people who start LDN experience temporary side effects such as restlessness, vivid dreams, or anxiety—especially when taken at night. If you're relying on a benzodiazepine to calm the nervous system, particularly to manage insomnia or panic attacks, LDN’s early activating effects could be disruptive. In such cases, taking LDN in the morning rather than at night can help reduce these issues.

Another consideration is mood regulation. LDN’s indirect increase in endorphins may enhance dopamine activity, which could be beneficial for people dealing with low mood or fatigue. However, in people with fragile neurochemistry or a history of mood swings, this shift could cause overstimulation or emotional lability. That’s why it’s important to start LDN at a low dose—typically 0.5 mg—and increase slowly, while monitoring for any unusual psychological or physical responses.

Perhaps the most important caution involves benzodiazepine withdrawal. If you are in the process of tapering off benzodiazepines, introducing LDN at the same time is not advised. Withdrawal from benzodiazepines can be physically and emotionally intense, and the central nervous system is already under considerable stress. Adding LDN during this period, even though it is not a stimulant or sedative, could tip the balance and trigger unwanted symptoms. For this reason, it's best to wait until you are stable on your current benzodiazepine dose before starting LDN.

That said, many patients with chronic illness—especially those dealing with fibromyalgia, chronic fatigue syndrome, or autoimmune conditions—have found LDN to be a helpful complement to long-term benzodiazepine use. Some report better pain control, more emotional resilience, and improved sleep, especially after adjusting the timing and dosage of LDN to suit their needs. Others, particularly those with heightened sensitivity to CNS medications, find that starting too high or titrating too quickly leads to discomfort. Patience and careful observation are key.

In summary, LDN and benzodiazepines can generally be used together safely, provided you approach the combination thoughtfully. Start with a very low dose of LDN, increase gradually, and adjust timing based on how your body responds. Avoid introducing LDN during benzo withdrawal, and always consult a knowledgeable provider before making changes to your medication regimen.

Everyone’s body is different, and what works for one person may need adjusting for another. The good news is that with proper care and awareness, LDN can be a powerful ally—even for those already managing complex medication regimens.