Medications for Opioid Use Disorder: An Interview with Sam Snodgrass, PhD, of Broken No More

"Both methadone and buprenorphine are life-saving medications, if people can access them." - Sam Snodgrass, PhD

In my last post, I told the story of how my daughter eventually got on buprenorphine, after a terrible tragedy shook our family.  She knew she was not being given an adequate dose of buprenorphine, and she even told me that she thought she needed methadone.  In this month's issue of "Ask the Experts," I interviewed Sam Snodgrass, PhD, of Broken No More, on medications that are effective at treating Opioid Use Disorder (OUD), how they work, and why they are still so stigmatized in our society even though they save lives.

Moms for All Paths: Thank you for joining us Dr. Snodgrass!  Let’s start with the basics.  Who are you and what do you do?

Dr. Snodgrass:

I’ll start with education.  In 1987, I graduated from the University of Georgia with a PhD in biopsychology.  After I graduated, I was awarded a National Institute on Drug Abuse three-year Postdoctoral Fellowship at the University of Arkansas for Medical Sciences in their Pharmacology and Toxicology department.  I wanted to go there to work with Dr. Don McMillan who was chair of the department and  a leading researcher in the area of behavioral pharmacology, the study of how drugs affect behavior.  I completed my postdoc and was asked to remain on the faculty.  

In 1976 when I was 20 years old, I started to use heroin and dilaudid.  For thirteen years, I did okay.  Never used consistently enough to develop an issue. Then in 1989, I messed up and developed an Opioid Use Disorder (OUD).  I lived with that for the next 22 years.  I lost my position at UAMS in 1995 because my OUD became pretty apparent.  

 Now I am on the Board of Directors of a 501c3 nonprofit called Broken No More.  Our membership is primarily made up of parents and family members who have lost someone they love to overdose.   We support harm reduction,  medications for the treatment of OUD, and we try to do a lot of education around these issues.  

We are also working to develop a nationwide set of advocates among people who have lost someone they love to overdose to push back on the punitive drugs laws sweeping the country regarding fentanyl.   Smaller and smaller amounts of fentanyl are triggering larger penalties, and many states are adopting drug-induced homicide laws.  We are developing a national advocacy network that can push back on these laws with one voice, and promote policies that are based on public health, harm reduction, and science.  

The grief that people who have lost a loved one to overdose is called disenfranchised grief.  It’s not accepted by society; it’s a stigmatized grief.  We are trying to help these people destigmatize their grief and the person they loved.  Their loved ones' life was just as important, valuable and meaningful as anyone else’s.  We want to give them a chance to express their power and their voice.  

Moms for All Paths: Thank you for that introduction and the important work you are doing with Broken No More.  Can you tell us about the use of medications in the treatment of opioid use disorder, and shine some light on why using medication is still so stigmatized in this country?

Dr. Snodgrass: 

To understand why people need these medications and to destigmatize the use of these medications, you need to understand how they work, why they work, and why people need to use them.  

Because we are supposedly rational beings and we have the ability to look into the future and see the ramifications of our actions, there are two questions you can ask about human behavior.   First, “Why?”  “Why” questions are questions of teleology.  A teleological question is a question of purpose or goal: what is the purpose or goal of your behavior?  For example, “Why did Mary bake a cake?”  Perhaps it was for a child’s birthday, or a bake sale, or to give it to a friend.  Why do people use opioids?  Usually the answer is some type of self-medication.  They may be medicating trauma, anxiety or depression, or there may be environmental reasons, such as racism, poverty, or other reasons why someone is using opioids.  This is what is meant when it is said that, “People use drugs for reasons.”  That’s the “Why?” 

 The other question you can ask is “How?”  This is a question of mechanism.  So if you ask “ How did Mary bake the cake?” you are asking “By what mechanism did she bake the cake?  What are the ingredients, how did she measure them, how did she put the ingredients together, what kind of pan did she use, at what temperature did she bake the cake?  How did she do this?” 

I’m bringing this point up because there are so many times we get into arguments or discussions about drug use and addiction. We need to understand that we are asking two very different questions that have two very different answers.

What I’m going to talk about now is the how, not the why.  

Moms for All Paths:  That sounds like it will help us understand why there are medications that are effective to treat Opioid Use Disorder (OUD).

Dr. Snodgrass: 

Everybody is born with an endogenous opioid system (endogenous means “from within”). Opioid neuropeptides, endorphins, enkephalins, and dynorphins are chemical structures which bind with the opioid receptor sites within our brain and activate, modulate and keep our endogenous opioid system normal.  

This system is essential for our survival.  The endogenous opioid system mediates functions like pain, emotions, hunger, respiratory control, immune function, social motivation, bonding, gastric motility, stress response, as well as pleasure and euphoria.  It’s not in our brain to take up space!  It’s there for a reason: to keep us functioning normally and to help us to survive. 

Here’s what happens to you when you start taking an opioid, whether it’s pain pills heroin or fentanyl, on a consistent basis (the key is on a consistent basis):  the chemical structure of exogenous (from without) opioids is so similar to our endogenous neuropeptides that the receptor sites can’t tell them apart.  The exogenous opioids bind with opioid receptor sites and  activate them.  If you keep them continuously activated, the receptors start to change.  The brain is trying to maintain a balance, which is called homeostasis, so the brain tries to decrease the over-activation caused by the opioids by changing the receptor sites. They  become down-regulated and desensitized. The brain also  produces less endorphin. This is what we mean when we refer to tolerance.  Tolerance is not opioid addiction, but it drives opioid addiction. Say we’ve been doing a tenth of fentanyl a day.  We become tolerant to that amount, so we go up to two-tenths. By repeating this process, by continuously increasing the amount of opioids we are using we continue to down-regulate and desensitize our opioid receptors while causing a reduction in the amount of endorphin that is released and we reach a point where we are not using opioids to get  high, we’re using them  to feel normal.  We have shut down our endogenous opioid system to the point where if we don’t have these exogenous opioids flooding our brain and continuously binding with the opioid receptors and substituting for the endorphin our brain is no longer producing, we are not normal. Our brain has transitioned into a state of addiction. 

Opioid addiction is manifested as a voice in our head that won’t shut up. It drives us to do the things we do in our addiction. To find a way to obtain the opioids and use them. But, then, that’s what it’s supposed to do. Because we’re starving. 

What I want people to understand is that this voice is normal.  This voice is the voice of survival.  If you’re starving for food, you have that same voice in your head.  If you’re dying of thirst, that voice is in your head telling you to find water.  If you’re freezing to death, a voice in your head will demand that you get warm.  If you’re starving for food, that voice is driving you to find food and the more you starve the louder that voice becomes and the less important your home, your car, your job, your family become until your whole life collapses around trying to find food.  The voice that we hear in our heads is not about addiction.  It is about survival.

Let’s say you’re starving for food and there’s not enough food to go around: perhaps there is a famine, or the government is rationing food so you can’t get enough.  But there’s a black market in food.  In this black market, food is scarce, expensive and illegal to buy.  If you’re starving, what’s your option?  Are you going to starve to death or break the law to get food?  Are you going to steal to get the money to buy food?  Yes, because survival is not a choice.  You’re going to do what you have to do to survive.  What drives us to keep doing the things we do is not a lack of executive functioning or impulse control.  It is a rational decision of “We’ve got to do this to stop the starvation.”  

People say, “My child loves their drugs more than they love us,” but that’s not true.  We are not narcissistic hedonists.  You know us, you know who we are.  We’re your kids, we’re your brother,  your sister, your spouse, your partner. But we’re starving.  We get so desperate in our starvation that we will do things that hurt the people we love to stop the starvation. 

We hurt too, when we hurt the people we love. We may not act like it because we don’t understand what’s happening, no one’s ever explained to us that what we are experiencing is the result of an acquired disease of brain structure and function, and we're just trying to survive through the day.  We are not bad people. We love you.  We don’t want to hurt you, and yet if you were starving and you were in this situation, what is your option?  The longer we’re in this situation, the fewer options we have.  We reach a point where we can’t pay rent, we can't pay the car loan or anything else because we have to spend so much money just trying to stay well each day to survive.  We go to our grandfather’s house, steal his shotgun and hock it.  It’s not because we’re trying to get high: we are trying to find a way to stop starving. We aren’t dancing to the pawn shop saying, “Oh good, I hurt my grandfather,” but we don’t have any good options.  We could take a 45 and rob a drug store but that’s not a good survival strategy.  We end up hurting the ones we love because we have only bad options.  If you were starving for food, think of what you would do to stop the starvation.

If someone who is starving goes to a grocery store and steals a loaf of bread, no one says they lack executive function or impulse control.  They would say that person was starving. That’s what people need to see with us.  We are starving.

People say “How can anyone go out there and use fentanyl when they know it can kill them?”  Well let’s say you're starving for food and there is no food legally available, just a black market.  You know that some of the black market  food is tainted.  If you eat it, you could die.  But it’s the only food you can find, so what’s your option?  Are you going to sit in the corner and literally starve, or are you going to eat the food and hope you don’t die?  If you have a friend who is starving, do you let them starve or give them some of your food?  The food could be tainted. They could die, you could die, but what is your option? With opioids, if they die, you can be charged with drug-induced homicide.  By the laws of this county. you’re limited to what you can buy on the street.  It’s a very toxic drug supply, but what’s your option?  This is why we keep using fentanyl: we don’t have another option.  Give us another option! 

Moms for All Paths: So this is where medications come in? 

Dr. Snodgrass: 

This is where medications come in because they give us another option if we have access to them. There are many barriers that prevent people from accessing these medications such as living too far from a clinic, unable to find a provider, the cost of treatment, counseling requirements, and the stigma surrounding the use of these medications. And these barriers are killing people. Both methadone and buprenorphine are life-saving medications, if people can access them.

Methadone and buprenorphine are agonists.  An agonist is anything that binds to an opioid receptor and activates it. Methadone is a full opioid agonist, as are the exogenous opioids found in the black market opioid supply, meaning it binds with the opioid receptor sites and activates them fully.  Buprenorphine is a partial agonist, which means it binds to the opioid receptor sites and activates them partially.  It doesn’t produce the full effect as does methadone. 

People will say, “Oh no!  These are opioids and you’re just substituting one drug for another!”  What they don’t understand is that the medications have to be opioids in order to work.  If they weren’t opioids, they wouldn’t stop the starvation.  These medications are legal.  This makes a huge difference because if they're legal, you can get a safe supply that you can stabilize on.  Once you stabilize on one of the legal medications like methadone or buprenorphine, you stop the starvation. 

Moms for All Paths: What about Vivitrol, and its active ingredient, naltrexone? 

Dr. Snodgrass: 

Vivitrol is an opioid antagonist.  An antagonist is a chemical which binds to the opioid receptors but it doesn’t activate them.  It’s the old lock and key analogy.  The key is the chemical structure and the opioid receptor is like the lock.  Naltrexone is like a key that just sits in the lock and doesn’t open it.  It just keeps anything else from getting to it.  

Naltrexone also blocks the endogenous opioids too!  As I’ve said, the endogenous opioid system is not there to take up space.  I don’t believe that shutting down this endogenous opioid system is good for anyone.  We need our endogenous opioid system to function normally.

Retrospective studies have been done in real world situations where people look at how many prescriptions for Vivitrol have been filled from one to six months.  By the sixth month, less than 10% of people have filled their Vivitrol prescription.  100% fill the first prescription, yet after six months less than ten percent are still on the medication.  That tells you that it really doesn’t work well.  

I would advise people to avoid Viviatrol.  It increases the risk of overdose.  You can overcome Vivitrol if you take a lot, or and take it near the end of the month as the shot starts to wear off.  If you get off Vivitrol, you’re running a higher risk of overdose than if you’d never taken the drug in the first place.  

Think about it like this.  When you bind and over-activate your opioid receptor sites, you cause downregulation and desensitization.  What happens if you bind them with Vivitrol but you don’t activate them?  In animal studies you see an upregulation in the number of opioid receptor sites, so when you stop the medication you may very well have an increased risk of overdose. 

Vivitrol has been heavily pushed on people who are in the criminal justice system, and the outcomes have not been good.  They are setting people up for failure and overdose.  I would not recommend it at all.  

Moms for All Paths: Can you tell us about medications that are effective for combating Opioid Use Disorder (OUD)?

Dr. Snodgrass: 

Let’s start with methadone.  Methadone is completely synthetic.  It was discovered by Germany in World War II and has been used in this country for pain control since 1947.  In the 1960s, Vincent Dole, Marie Nyswander, and Mary Jeanne Kreek found that methadone worked well because it could be taken orally, once a day, and it kept people stable throughout the day.  What they found is that over time people stopped using illegal drugs, got jobs, and integrated into society.  Methadone did not have any serious negative side effects.  

This is where methadone started, and it really got a boost under the Nixon administration. Nixon didn’t give a damn about people who used heroin, but he saw the research that showed that methadone decreased crime, so he supported it.  Unfortunately, prescription and distribution of methadone was soon taken away from the medical profession and relegated to Opioid Treatment Programs (OTPs), what we used to call methadone clinics. 

Methadone is a full agonist; it is a very effective medication.  Once a person becomes stabilized, they’re not high.  Methadone binds with opioid receptor sites, replacing the endorphins we no longer have after long term, consistent use of exogenous opioids.   On methadone, the person’s endogenous opioid system is normalized and they function just fine.  

Usually, methadone prescribers will start you out with a 30-40 mg dose of methadone.  This is called the induction process.  Such a small dose doesn't hold a person if they have a pretty hefty addiction, but prescribers start this way because they’re afraid the person is going to overdose on methadone.  The problem is that without an adequate dose to hold off cravings, people use on top  of the methadone.  This is why in the first two weeks of treatment is when you see most of the overdose deaths.  People who start on methadone may also be taking a benzodiazepine like Xanax to combat withdrawals.  Methadone and benzodiazepines are a very bad combination because taken together they can cause respiratory depression and death.   

Methadone clinics try to get you on a blocking dose of about 80 mg.  On that dose, the tolerance that is built up means that you would have to take a lot of opioids to feel anything.  Eventually, it’s not worth the money, and you feel stable or normal on methadone alone.  With the fentanyl that’s out there now, I have been reading that people need higher doses of methadone.  120 mg used to be the top dose, but now the maximum dose may be getting higher.  If people are up and functioning, that’s fine.  

There are some people who keep trying to push their dose up.  Once you’ve stabilized on a dose you’re not feeling it.  Methadone at too high a dose is very sedating, and you start nodding out when you’re trying to do things.  I was nodding out and lost a couple of jobs and wrecked a car, then I figured out that I should not try to increase my dose of methadone!  Fortunately, most people are not like me.  The vast majority of people get onto a stable dose of methadone, stay there, and just go about their lives. 

 This is not a short term therapy.  This is long term maintenance.  You’ve altered the structure of your brain.  People go to rehab and they think “I feel great,” then the hunger comes back.  As David J. Nutt and colleagues in the UK discovered, 30 days after stopping opioids, the receptor sites rebound.  You've got more receptors coming back, but you do not get a  compensatory rebound in endorphins.  Nobody knows how long this endorphin deficiency will last.  It may be a few months, it might be a lifetime.  This is why most people will need long term medication.  It is like taking thyroxine for thyroid disease or insulin for diabetes  

OUD is an acquired disease of brain structure and function.  No one would say to someone with COPD (Chronic Obstructive Pulmonary Disease), “You have to stop your breathing treatments, you did it to yourself.”  There are many acquired diseases, but opioid addiction is treated differently from the others.  Addiction to opioids has been described as a psychopathology.  We’re still living in a world that views those with an opioid use disorder as having character defects or they are morally deficient.  

This is not a character defect, it’s not a moral failing, it is a medical condition.  You have changed the structure of your brain and you need to deal with that responsibly.  The responsible thing to do is follow the science which clearly shows that methadone and buprenorphine are the only effective treatments.  Counseling, psychotherapy, detox and rehab don’t work.   Within the first year over 90% of people are back using if they go to an abstinence-based treatment program. 

 Moms for All Paths: What about Suboxone? 

Dr. Snodgrass: 

Buprenorphine was first synthesized in 1966 by a company in Britain.  It was used in Europe in sublingual form first.  France had great success with buprenorphine because they viewed OUD as a disease and therefore covered it under their medical system.  Doctors didn’t have to go through special training and could prescribe it like any other medication.  It was approved in the United States in 2000 by a law called Data 2000 and became available for use in 2002.  First it was what was called Subutex, which was a mono product containing 8 mg of buprenorphine.  Suboxone was developed when they added 2 mg naloxone to 8 mg of buprenorphine to make what is now Suboxone.  

I worked in a buprenorphine clinic for ten years, and people would say that after they started on Suboxone they just felt normal - like they did before they ever started using.  Sometimes they said they get a bit of energy, like drinking a cup of coffee, but most people don’t even get that.  After a while so many people say they have some left at the end of the month because they just forgot to take it.  They’re going along with their day. They get busy and they say, “Wait, I haven’t taken my medication yet!”  You can tell they’re not getting high off something if they forget to take it.  I’ve heard people say, “I forgot to take my medication, I started to feel like I was getting a cold, then I realized I hadn’t taken my meds.”  

Buprenorphine doesn’t have the sedation effect you can have with methadone.  If you want to be normal, just go on with your day not have to fool with a methadone clinic, this is a great medication.  There is no euphoria with it.  I don’t object to people experiencing euphoria, but American culture seems convinced that no one should. 

Buprenorphine is a partial agonist with a very long half life, which means it stays in your system for a long time.  It has a very high binding affinity. Binding affinity is how strongly a drug molecule binds with a receptor site. Because of its incredibly high binding affinity, Buprenorphine has the ability to block the effects of other exogenous opioids, including fentanyl.  This is concentration dependent.  You need to have enough buprenorphine in your brain binding with enough receptors to block the effects of other exogenous opioids which means you need a high dose of buprenorphine to produce this effect.  

There is a problem with providers prescribing inadequate doses of buprenorphine.  Usually the FDA recommends a dose of 16 mg per day.  Sometimes under special circumstances up to 24 mg per day.  All the data demonstrate that 16 mg a day is less effective than 24 to 32 mg per day at reducing cravings, keeping people in treatment, helping people get back to their life, jobs, families, etc. because at 16 mg/day they’re still thinking about the opioids.  Maybe they take more than they are prescribed and by the end of the month they run out of their prescription.  They have to go out on the street and buy some or go through withdrawals and they drop out of treatment because 16 mg/day just isn’t holding them. 

Unfortunately, medical professionals are some of the most stigmatizing people in the world.  Instead of giving an effective dose which is what you would do with any other medication, they have a one size fits all 16 mg or less.  That just doesn’t work because there are a lot of people who need 24 - 32 or higher.  But we have this FDA recommendation which hasn’t changed since 2010  telling physicians that they should shoot for 16 mg per day.  The studies that are cited to support this recommendation were fatally flawed because they measured people’s responses to the medication just a few hours after taking it, when it was still at peak levels in the blood.  During the day, as blood levels fall, it becomes less effective at the 16 mg dose.  That dose just can’t hold a lot of people long enough, where a larger dose of 32 mg or even more can.  The blood levels remain in an effective range over the 24 hour period with the higher doses. The point is that we should give medications based on what’s effective, not based on trying to limit the amount of medication. 

Moms for All Paths: What do you say to people who say, “You’re not really ‘sober’ if you’re on medication,” or family members who ask, “Why aren’t you off that medication yet?” 

Dr. Snodgrass: 

We have in this country a real stigma about these medications.  When people say,  “You’re not ‘sober,’ what they’re really saying is “You're not as good a person if you're taking medications as a person who is not taking medication.”  It should be the exact opposite.  Every time you use illegal opioids, because of the toxicity of the supply, you’re taking the chance of overdose.  By using these medications to avoid using street opioids, you’re making a responsible choice.  If you choose abstinence instead of medication it should be an informed choice, with all of the possible information provided by someone who is not pushing the abstinence-only viewpoint.   People should see what the science shows and make their own decisions.  

 As it stands now, when a person is not taking medication, they get a pat on the back.  But when a person takes medication, they hear, “Why aren’t you off that medication?  You’re just substituting one drug for another.  It’s a crutch.”  The people who are taking medication know they are doing the right thing for them and the people they love, and yet they have to put up with the stigma, often from their own families.   People who are taking these medications can hold jobs, take care of their families, move forward in life and should not be treated as second class citizens.  We should be patting them on the back and taking them out to dinner to celebrate!  They’re the ones making the responsible choice. 

Taking medication is not easy, it’s hard.  You’ve got to go to the doctor, deal with the clinic, deal with telehealth, the pharmacy, and all of the stigma.  We should be applauding people who go through all of this to do what’s right for them and their families.  And we should be making it much easier to get these life saving medications.

Moms for All Paths: We are so grateful for your time, this lifesaving information, and all of your work Dr. Snodgrass!

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