Mr. Melatonin, and Neuropathy - What's New With Sleep and Nerve Pain | Episode 200

clonidine dextromethorphan gabapentinoids melatonin neuropathy novel medications podcast Apr 30, 2023
Mr. Melatonin, and Neuropathy - What's New With Sleep and Nerve Pain | Episode 200

I get asked these questions all the time:

  • How do I get to sleep? 
  • How do I sleep better? 
  • How do I have restorative sleep? 
  • How do I wake up feeling refreshed? 
  • How come I can't go to sleep? 
  • How come I wake up in the middle of the night?
  • My legs hurt in the middle of the night and it wakes me up. My pain gets me up, what can I do?
  • What can I do for neuropathic pain? 
  • What about melatonin? 

The Problem with Self-Medication and Melatonin

There's a lot of self-medicating going on. 

We learned about people self-medicating quickly in my world of anesthesia. We would take people to the operating room and they were bleeding a lot. We learned over-the-counter herbs were not helping us out. 

That's why you get asked questions if you are going to have surgery, such as: Are you on St. John's wort? Also, it interferes sometimes with how drugs are metabolized because it's competitive at the liver. 

Melatonin Supplements

This week, the FDA oversight committee released an article on melatonin supplements. Even though they're “tested” and you can look at the label on the side of the bottle, what you see there might not be what you're getting. Supplements vary widely in actual dosage. Some were three times more powerful than what was on the bottle! That brings up the big question of how much is the government going to get involved in this? Because there may need to be more oversight. 

In the Journal of the American Medical Association, a study published just recently within the last couple of weeks showed that these melatonin gummies are working because they might have a lot more in them than necessarily thought. 

These dietary supplements, as they are called, are available in the retail stores, Amazon, Walmart, etc. They can be up to 10, 20, or even 30 percent more powerful than advertised. They mentioned 10% more in the study. But my experience with CBD is that unless it's an independent lab that has a good history and is qualified with these high-end analyzers (which are very expensive), you have got to be careful with what you're taking. 

Be careful what you put in your mouth. I cannot tell you as a physician how many times. I go into a room and when I ask what a patient is asking, they respond with a green pill, a little green pill. That doesn't help! There are generics, and there is on-brand. There are all sorts of different formulations, sizes, shapes and colors. 

We need to know what you're taking. More importantly, you're the consumer, you need to know what you put in your mouth. 

The Food and Drug Administration does not analyze or review supplements before they hit the market. Now, prescription drugs they do. They are very good with prescription drugs. They've had some controversy over COVID, but that's not what the FDA is. The FDA is an incredibly good organization because they make information transparent and the world can look at it.

FDA Medication Approval

So for me, I feel good when the FDA approves the medication, because I know the rigorous analysis that it's been through, and it IS rigorous. It can be years. They go through different phases and trials. By the time that drug gets to you and is mainstream and marketed, it could be a billion dollars. And sometimes they do put the brakes on things. 

Industry suppliers can put out pretty much anything they want because they know there's probably no consequences and no scrutiny. So the supplement might be pretty good, but it might be very potent. Or it might be very weak. Dietary supplements as they are marketed have a responsibility by the maker to make sure they're what they say they are before they hit the shelves. 

There can be adverse effects. I heard a physician on a well-listened to talk show, and a very respected physician from a New York university who has excellent credentials comment that melatonin is safe in children. Maybe, but you've got to know what you're giving that child, because there has been a significant increase in poison control calls. That's a big alarm with melatonin. It can have adverse effects in children. So talk it over with a qualified healthcare professional. 

Lobbying of Supplements

Some of these supplements do get heavily lobbied or get utilized in a care setting where they probably shouldn't have ended up in. Does that have anything to do with lobbying by manufacturers? I don't know. 

You want to know that whatever you're putting in your mouth, it contains a hundred percent of the ingredients. You want to know the expiration date. You want to know how to start it, how to come off it, and that you're getting what's on the label. That's from Steve Mister, he's the CEO of the Council for Responsible Nutrition. 

It comes down to quality. A 2017 study cited by a paper that came out in JAMA, said that melatonin supplements sold in Canada were unreliable. Several products contained undeclared amounts of serotonin. 

Serotonin can affect certain receptors, and it can affect mood. You've heard of serotonin reuptake inhibitors that I've had in my podcasts. These drugs can be adulterated. 

Some Melatonin Supplements Contain ~300% of the Advertised Amount

Some melatonin supplements had no melatonin in them, and some had 300% of the advertised amount.

Increasingly a popular sleep aid, it is everywhere. It quadrupled from 1999, and it's going up. It tripled from 2005 to 2018. There's not a lot of information for consumers to just jump on. Everybody goes to Google. 

The recommendations through Health Canada, Canadian study organization, is 10 milligrams per day. Some of these products go way over that. You've got to know what you're taking, so it's safe. You don't have enough data to know what is safe. There's increasing evidence that there is going to be increased calls to poison control centers. They're way up, in adults too, 530% from 2012 to 2021. 

Melatonin and Children

This fellow named Cohen said extra high potency products are probably responsible for those increased calls to the poison control center. 50 percent more melatonin could be the difference between what a child needs, and a trip to the ER.

There is an opinion that children should not take melatonin, and it's not meant for kids, and there are disclaimers in some products. You're going to see through Amazon and other product carriers different marketing. Be a consumer and be very careful on how you are marketed to. As any parent you always want your kid to go to sleep, but this may not be the pathway forward. Talk to your doctor first. 

Potential New Drug for Neuropathic Pain

The next study I want to talk about briefly is on neuropathic pain. I usually don't like talking about drugs that aren't available yet because it's frustrating to people. But you need to hear that the light at the end of the tunnel isn't always a truck. 

There's this new first in class or novel agent that's coming out that's associated with what's called a kinase receptor. It's being worked on by Bristol-Myers Squibb. It's in early phases, phase two.

It showed that if you take something called an alpha-2 adrenergic receptor and you inhibit it (that's a receptor that is important for so many things, including blood pressure), that it prevents signaling from this kinase, which seems to have an effect on pain.

Alpha-2 adrenergic signaling is a known antinociceptive way of dealing with neuropathic pain. A nociceptive is normal if it hurts. That means it's a nerve or whatever. If something is interfering with how something causes pain and it's doing it in a new way, it's got some real hope. 


Gabapentinoids are a common medication right now for neuropathic pain. Gabapentinoids have a brand name, Neurontin. There is long-acting gabapentin or Neurontin and there's also Lyrica which is another gabapentin, pregabalin. 

These are used, in my experience, to get anywhere from 50 to 70 percent reduction in pain.  They certainly have less baggage than tricyclic antidepressants, the go-to-sleep type of sedation stuff. The fuzzy impairment stuff that people get. But gabapentinoids have their moments too. If you talk to folks across the board, there's quite a few that just can't take it. 

Gabapentinoids are now felt to be potentially habit-forming and they have some withdrawal effects according to some people, etc. 

I've given a lot of doses of gabapentin over the years. I was an early adopter. I've had moments, but I can tell you the risk-award benefit in the proper healthcare professionals' hands is in the patient's favor. 

New Drugs and Blood Pressure

I talked about the new drug and what it does to blood pressure real briefly. We have this drug now called Clonidine, and it does help with pain some. What it does is it's an alpha-2 agonist, or receptor agonist. And Clonidine was originally developed for blood pressure. That's how a lot of these drugs come their way. We found that it also blunts a lot of the sympathetic response to withdrawal, and it helps with blood pressure, too, because it has effects on sympathetics. 

So we're looking at coming down with some pretty good options for relief. Particularly for those that suffer from diabetes and the elderly population. Also, in Type 1 and type 2 diabetes, there's a pretty high incidence of neuropathy, especially in those with an obesity body mass index that's around 20 and up, and hemoglobin A1C, that marker for blood sugar that's more than 11%. That's what they use in the article as descriptors. 

This new anti-nociceptive drug for neuropathic pain has promise. It’s not here yet. How long? I don't know, it depends on how the study goes. But from phase two to getting it out there, it might be a couple years.

Neuropathic Pain

When people start talking about neuropathic pain, they talk about the N-methyl-D-aspartate (NMDA) receptor. They start talking about other meds to block that. Methadone may have a mild effect. Demerol used to, I used to love Demerol, but it's off the market. Local anesthetics help with neuropathic pain, topicals and that sort of thing. 

Think about dextromethorphan, a little bit of that. It blocks the NMDA receptor too. I've used it. Don't use too much and do it only when somebody says in the healthcare field that it's okay to use because it does drug interactions. If you use too much of that stuff, you know, the Robitussin stuff, you can get pretty sick or get pretty high. It's an abused drug. So just a little on the side there.

Some Resources for You

  1. Pain Rating Scale at Go there and that gives you some quantitative assessment.
  2. My YouTube video about gabapentin
  3. More about neuropathy - Podcast #158  Low Dose Naltrexone- Fibro, Neuropathy, Novel Pain Control
  4. Here is my free course that goes pretty deep into neurophysiology
  5. FREE Guide to Pain Treatments and the Science Behind Pain, with a Health and History form with pain tracker
  6. Email me at [email protected]


Your roadmap to understanding pain, addiction and depression. Created for those suffering from pain and healthcare providers. 

Inside this guide you'll discover:

  • The science of pain
  • What can help pain
  • My 5 rules in treating pain
  • Treatments I have used in my practice
  • BONUS: FREE pain workbook and health & history form


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