Benzodiazepines and naltrexone can generally be taken together without a dangerous drug interaction. The two medications work through entirely different receptor systems in the brain, so they do not block or amplify each other in the way that, say, benzodiazepines and opioids do. That said, the combination does come with practical considerations that matter, particularly around how naltrexone subtly alters what benzodiazepines do in the body and why the two often end up prescribed together in the first place.
Different Receptor Systems, No Direct Clash
Naltrexone is an opioid receptor antagonist. It parks itself on the brain’s opioid receptors and blocks them. Benzodiazepines, on the other hand, act on GABA receptors, enhancing the calming neurotransmitter GABA to reduce anxiety, promote sleep, and relax muscles. Because these two drug classes target separate pathways, there is no pharmacological tug-of-war when they are taken at the same time. Naltrexone does not cancel out the anti-anxiety effects of a benzodiazepine, and a benzodiazepine does not prevent naltrexone from blocking opioid receptors.
This is a meaningful distinction from combinations that genuinely are dangerous. Benzodiazepines taken alongside opioids, for instance, create compounding sedation that can suppress breathing to a fatal degree. The NIH has noted that a substantial share of people recovering from opioid overdose still receive benzodiazepine prescriptions, which increases their risk of another overdose when combined with opioids.1National Institutes of Health (NIH). Medications reduce risk of death after opioid overdose Naltrexone does not carry that same respiratory-depression risk because it is not a sedating drug. The concern with benzodiazepines is really about what else a person might be taking alongside them, not about naltrexone specifically.
How Naltrexone Changes the Benzodiazepine Experience
Even though the two drugs do not dangerously interact, naltrexone does alter the subjective experience of taking a benzodiazepine. A human pharmacology study using diazepam (the generic form of Valium) found that when participants were pretreated with naltrexone, the “positive” effects of diazepam were dampened. Feelings of friendliness, vigor, liking the drug’s effects, and feeling high were all lower compared to taking diazepam with a placebo. At the same time, negative mood states like sedation, fatigue, and anxiety were somewhat higher under naltrexone.2PubMed. Naltrexone effects on diazepam intoxication and pharmacokinetics in humans
The same study also found a pharmacokinetic wrinkle: naltrexone delayed how quickly diazepam reached its peak blood levels. Under normal conditions, diazepam hit its peak concentration at around 75 minutes. With naltrexone on board, that peak was pushed out to roughly 135 minutes, nearly double the time.2PubMed. Naltrexone effects on diazepam intoxication and pharmacokinetics in humans Cognitive performance, interestingly, was not affected either way. So the drug still reached the brain and still did its job, but the timeline shifted, and the rewarding or euphoric edge was blunted.
This blunting effect makes sense in the context of what naltrexone does broadly. By blocking opioid receptors, naltrexone dampens the brain’s internal reward signals. Many substances that people experience as pleasurable, including alcohol and certain sedatives, produce at least part of their rewarding effect through downstream opioid-receptor activity. When naltrexone blocks those receptors, the pleasure aspect fades while the core pharmacological action of the drug remains more or less intact. For someone taking a benzodiazepine purely for anxiety relief, the practical impact may be minor. For someone who has developed a pattern of enjoying benzodiazepines recreationally, naltrexone could meaningfully reduce that appeal.
Research on Intentional Co-Prescribing
Researchers have not simply stumbled on this combination by accident. Several clinical studies have deliberately paired naltrexone with a benzodiazepine to see whether the combination is safe and whether it offers any therapeutic advantage.
One study in stimulant users tested naltrexone alongside alprazolam (Xanax) and found that the combination did not produce clinically problematic physiological effects or negative subjective effects. Both drugs, given separately, reduced some of the subjective effects of d-amphetamine. When combined, they attenuated an even broader range of stimulant effects than either drug alone.3PubMed Central. Separate and combined impact of acute naltrexone and alprazolam on subjective and physiological effects of oral d-amphetamine in stimulant users The takeaway from that study was not just that the combination was tolerable but that it might actually be useful in dampening the rewarding effects of stimulants.
In a different clinical population, a six-month trial looked at opioid-dependent patients and compared four groups: no medication, naltrexone alone, naltrexone plus a placebo pill, and naltrexone plus the benzodiazepine prazepam. All groups received psychological support and twice-weekly urine testing. The group receiving naltrexone plus prazepam had the best outcomes. Out of 14 patients in that group, 12 remained opioid-free over the full six months, with only one relapse before three months and one after. The naltrexone-plus-benzodiazepine group had a significant advantage over naltrexone alone.4PubMed. Naltrexone plus benzodiazepine aids abstinence in opioid-dependent patients
That result may seem counterintuitive: adding a potentially habit-forming sedative to a treatment for addiction. But the rationale is that anxiety, insomnia, and general distress are major drivers of relapse, and a benzodiazepine can address those symptoms directly during the vulnerable early months of recovery. Whether that benefit outweighs the risk of developing benzodiazepine dependence is a clinical judgment call that depends on the individual, and it is exactly the kind of trade-off that physicians navigate when managing complex addiction cases.
Why the Two Medications Often End Up Together
People taking naltrexone typically fall into two broad groups: those being treated for alcohol use disorder and those being treated for opioid use disorder. In both populations, anxiety disorders are remarkably common. Generalized anxiety, panic disorder, and social anxiety appear at much higher rates among people with substance use problems than in the general population. This overlap creates a clinical dilemma, because the most effective short-term medications for acute anxiety happen to be benzodiazepines.
A case report and literature review published in Addiction Science & Clinical Practice noted that no clinical trial has yet determined whether naltrexone treatment for alcohol use disorder can improve a co-occurring anxiety disorder on its own.5PubMed Central. Alcohol use disorder with comorbid anxiety disorder: a case report and focused literature review In other words, clinicians cannot assume that naltrexone, by reducing drinking, will also take care of the anxiety. Many patients still need separate treatment for their anxiety symptoms, and when non-benzodiazepine options like SSRIs or buspirone are insufficient or too slow to take effect, benzodiazepines may be added as a bridge.
This is one of the messier realities of treating people with overlapping conditions. Guidelines generally urge caution with benzodiazepines in anyone who has a history of substance misuse, because the drugs themselves carry dependence risk. But “caution” does not mean “never.” It means careful dosing, defined time limits, regular reassessment, and close monitoring. The fact that benzodiazepines and naltrexone lack a dangerous pharmacological interaction makes the combination more viable than it would otherwise be. The concerns are behavioral and clinical, not chemical.
What Actually Makes Benzodiazepines Risky in These Patients
If naltrexone is not the concern, what is? For people in recovery, the real risks of benzodiazepine use come from a few different directions.
- Opioid overlap: Benzodiazepines combined with opioids create a potentially fatal level of respiratory depression. A person taking naltrexone is supposed to be avoiding opioids, but relapse happens. If someone relapses to opioid use while also taking a benzodiazepine, naltrexone could actually mask the danger: the person might take a higher opioid dose to overcome the naltrexone blockade, and the benzodiazepine layered on top could tip the scales toward overdose.
- Cross-dependence: Some people who have been dependent on one substance develop dependence on another. Trading opioid dependence for benzodiazepine dependence is a recognized risk, particularly when benzodiazepines are prescribed without clear stopping points.
- Withdrawal severity: Benzodiazepine withdrawal, once dependence has developed, can be medically dangerous in its own right. Seizures, severe rebound anxiety, and other complications mean that stopping benzodiazepines requires a careful taper rather than an abrupt halt.
None of these risks are caused by naltrexone. They are risks inherent to benzodiazepines in vulnerable populations. Naltrexone neither worsens nor protects against them, with one indirect exception: by blunting the euphoric edge of the benzodiazepine, naltrexone may slightly reduce the reinforcing quality that leads to misuse. The diazepam study mentioned earlier supports this idea, since participants on naltrexone reported less “liking” and less “high” from the benzodiazepine.2PubMed. Naltrexone effects on diazepam intoxication and pharmacokinetics in humans
Practical Guidance If You Are on Both
If your doctor has prescribed both a benzodiazepine and naltrexone, the prescriptions are not contradictory. There is clinical precedent for the combination and no known dangerous pharmacological interaction. A few things are worth keeping in mind, though.
First, the benzodiazepine may feel different than you expect. The rewarding or relaxing “glow” that some people associate with benzodiazepines tends to be muted when naltrexone is on board. The anti-anxiety effect generally persists, but you might not feel the medication “working” in the way you are used to. This is not a reason to increase the dose on your own. The therapeutic effect is still happening; it is the pleasurable overlay that has been dampened.
Second, the onset may be slower than usual. Because naltrexone can delay the time it takes for a benzodiazepine to reach its peak blood levels, you might find that the medication takes longer to kick in. Again, this is not a reason to take more or to take it earlier than prescribed. The drug is still being absorbed; it is just on a slightly different schedule.
Third, be transparent with every prescriber about all your medications. People with substance use disorders sometimes see multiple clinicians: an addiction specialist prescribing naltrexone, a psychiatrist managing anxiety, a primary care physician handling everything else. If these providers are not communicating with each other, the risk of inappropriate combinations or duplicated prescriptions goes up. Make sure each one knows the full picture.
Why Prescribers Sometimes Hesitate
Even though the pharmacological safety profile is reassuring, you may encounter resistance from a prescriber who is reluctant to combine these medications. The hesitation is rarely about a direct drug-drug interaction. It is about the broader clinical picture.
Prescribers treating addiction are trained to minimize the number of potentially habit-forming medications a patient takes. Every benzodiazepine prescription in this context requires a justification that outweighs the dependence risk. Some providers draw a hard line and will not prescribe benzodiazepines at all to anyone with a substance use history. Others take a more flexible approach, weighing the severity of the anxiety against the risk of misuse and building in safeguards like short-duration prescriptions, frequent follow-ups, and urine drug screening.
If your anxiety is severe enough to impair your daily functioning or threaten your recovery, and non-benzodiazepine treatments have not been adequate, the combination of naltrexone plus a carefully managed benzodiazepine is a legitimate option with published evidence supporting it.4PubMed. Naltrexone plus benzodiazepine aids abstinence in opioid-dependent patients If a provider refuses without discussing alternatives or explaining their reasoning, it is reasonable to ask questions or seek a second opinion.
Naltrexone Formulation and Timing Considerations
Naltrexone comes in two main forms: a daily oral tablet (usually 50 mg) and a monthly extended-release injection (marketed as Vivitrol). The interaction with benzodiazepines is the same regardless of which form you take, but the practical implications differ slightly.
With the oral tablet, naltrexone’s effects wear off within roughly 24 to 72 hours after you stop taking it, depending on the dose. If a situation arose where a benzodiazepine needed to be used at its full unaltered potency, such as for a medical procedure requiring sedation, the oral form could be stopped temporarily. With the injectable form, naltrexone stays active for about a month and cannot be removed from the body once injected. Any benzodiazepine taken during that window will be subject to the same subjective blunting and delayed absorption discussed earlier.
For planned medical procedures, this distinction matters. Anesthesiologists and procedural teams should always be informed if a patient is on naltrexone in any form. The injectable version in particular can complicate pain management, since the opioid blockade persists even if the clinical situation calls for opioid-based analgesia. Benzodiazepines may actually play a larger role in sedation protocols for these patients, precisely because they still work through a separate pathway that naltrexone does not block.
People who use the monthly injection sometimes worry that adding any other medication will “overload” the body. Naltrexone, regardless of formulation, is processed by the liver. Benzodiazepines are also metabolized in the liver, but by different enzyme pathways. There is no evidence that combining them puts unusual strain on liver function beyond what either drug does individually. Standard monitoring of liver enzymes, which is already recommended for naltrexone patients, applies here as it would otherwise.