Here’s what we’ll cover in this blog post:
- Dr. Attia’s history with pain
- Why LDN is emerging as a chronic pain treatment
- Clinical evidence of LDN’s effectiveness
- The future of LDN for chronic pain
Low Dose Naltrexone (LDN) has long been a fringe favorite—championed quietly by patients and a handful of early adopters, but overlooked by much of the medical establishment.
Now, scientists and medical experts alike are starting to take notice, and research is beginning to illuminate a host of new pain medications that could knock painkillers off their pedestal. Low Dose Naltrexone is leading the pack.
In fact, that’s just what Dr. Attia discussed in his most recent episode of The Drive, where he sat down with pain expert Dr. Mackey to explore LDN’s place in pain treatment.
What’s the Story?
In a recent episode of The Drive, Dr. Peter Attia and Dr. Sean Mackey explored some of the most promising frontiers in treating chronic pain. One of the therapies they discussed was Low Dose Naltrexone (LDN), a treatment quietly gaining traction for its unique, systemic effects.
Both doctors know a thing or two about pain—not just from their patients, but from firsthand experience.
Dr. Mackey is Chief of Pain Medicine at Stanford University, who suffered from intense, painful cluster headaches for much of his life. Dr. Attia, a world-renowned longevity expert, visited Dr. Mackey’s office while earning his degree from Stanford, desperate for any relief from his debilitating pain.
It was Dr. Mackey who originally helped Peter Attia overcome his pain for good, using strategies he learned from his practice and his personal experience. They shared personal stories on their journey to better quality of life, along with other emerging solutions for treating pain.
Among these solutions is Low Dose Naltrexone.
How Does Low Dose Naltrexone Help with Pain?
When taken at 50mg, Naltrexone helps treat addiction by blocking the pleasure centers in our brain. This is critical for addiction treatment because it blocks the “reward” centers associated with addiction.
At 4.5mg, one-tenth of the dose, “Low Dose Naltrexone has been shown to block toll-like-4 receptors on the microglia,” Dr. Mackey says.
But what are toll-like-4 receptors, and what are microglia?
“They’re key neural immune modulators,” Dr. Mackey explains. “In times of stress, injury, fever, these microglia get activated and release all sorts of inflammatory mediators that sensitize the central nerves responsible for pain reception.” Toll-like-4 receptors are on microglia, and the culprits of not just pain perception, but chronic inflammation and pain.
Think of chronic pain like a fire alarm ringing long after the fire is out. Over time, that faulty signal can reshape the nervous system, locking the body into persistent inflammation and sensitivity.
But inflammation isn’t always a bad thing. “It’s a good thing after injury and infections, because it mobilizes all those repair cells to come in and clean up the mess (this is inflammation).”
“The problem that we see in pain?” Dr. Mackey says. “The switches don’t turn off and go back to normal.”
That’s where the magic of LDN comes in: “Low Dose Naltrexone blocks that neuroinflammatory soup, and in some patients, this drug’s been magical.”
Where the Magic Happens
What makes LDN especially compelling is its profile: low doses, minimal side effects, and growing evidence that it can help reset biological systems that have fallen out of balance.
Dr. Mackey discusses one such case where LDN transformed the quality of life for a stroke patient. “He’s dysarthric, he can’t speak, he’s got weakness, he’s got heavy, burning pain. He comes to me several years later after he’s tried everything. I said, ‘Let’s try Low Dose Naltrexone.'”
The patient came back 4 months later with not only less pain, but also “speaking for the first time since his stroke.” A few months later and he’s now speaking in full sentences. Within another few months, “now he’s having conversations, and his pain is massively better.”
Both doctors recall their own clinical experience with Low Dose Naltrexone. Because LDN has very few side effects, it may be the new go-to for treating pain, because it doesn’t add to the pain that patients are already experiencing.
“The only side effects I see with this are, in 2 or 3 months, patients get vivid dreams. For that, we recommend that patients take it first thing in the morning instead,” Dr. Mackey claims. “You cannot hurt yourself with this drug,”
When thought leaders like Dr. Attia shine a light on treatments like LDN, it signals a new chapter: longevity and root-cause medicine are moving into the mainstream.
From Research to Real Change
At AgelessRx, we’re not just early advocates of LDN’s potential—we’re the preeminent telehealth experts on LDN. As proud members of the LDN Research Trust since 2020, our focus on education and accessibility has allowed to amass an unmatched level of LDN data that continues to drive longevity science forward. Not only are we the first ever to propose LDN as a geroprotector, but we’re also among the only platforms using patient data to drive peer-reviewed LDN research, including clinical trials with the University of Washington.
Both Dr. Attia and Dr. Mackey believe this may also be occurring in neuroinflammation, potentially leading to diseases like Alzheimer’s. Both also agree that we need more studies to see how LDN can potentially help with not only Alzheimer’s, but stroke and mild cognitive impairment (MCI) as well. AgelessRx is contributing to LDN research with both past trials and planned studies, including the SF-36 Quality of Life Study and the LDN for Healthspan Study.
Low Dose Naltrexone is no longer just an underground therapy—it’s becoming a vital tool in reshaping how we approach chronic pain, neuroinflammation, and even cognitive decline. As both doctors emphasized, we’re only beginning to scratch the surface of LDN’s full potential.
We’re proud to be at the forefront of this shift—supporting not only greater access to LDN but also advancing the research needed to unlock its broader applications. Because sometimes the most meaningful changes start quietly—by fixing the signals, not just the symptoms.
Note: The above statements have not been evaluated by the Food and Drug Administration. This product is not intended to diagnose, treat, cure, or prevent any disease.