The Neuroscience behind Narcotic Addiction and Suboxone

By: Austin Chapin III, RN

previously published in ER PULSE

September 21, 2014

It was asked of me to present information about the medication Suboxone by a fellow colleague. In response to this request, I decided that it would be irresponsible as an educator to provide this information without painting a complete picture of the addiction process. Without being educated on the processes of the brain and effects of drugs on the brain, we can’t possibly understand how Suboxone works. With this essay I hope to enlighten the curious on the pharmokinetics and indications of the drug Suboxone. We will take a brief look at the class of drugs that are opioids and the effects they have on the brain. In the process I will also discuss the limbic system that controls our reward center in our brain. To conclude our journey, I will discuss the potential problems associated with Suboxone treatment and why it is a process that should be carefully monitored.

One might ponder the purpose of Pain, why do we have it? What is its primary purpose? Pain is a natural response to noxious stimuli whether from inside the body or outside notifying your brain of body damage or disease. Without this system of communication one could postulate that we would continue actions that could cause permanent damage or disability. Without the sensation of pain we might ignore violent internal infection processes if the information never reached our bowl of grey matter. The sensation of pain is transmitted and originated by special nerve cells called nociceptors. (Hasudungan)These neurons when activated send signals up to the brain that make us feel pain. We can then react to the pain properly by jumping up and down screaming expletives when we, let’s say crack our pinky toe on the leg of the coffee table. Our brain tells us, “Self!, hey don’t do that again, ever!!”. The end result is that you become more aware of the danger and thus damage can be avoided in the future. There are also knee jerk reflexes that don’t need to ever reach the brain for a reaction but I won’t go into those right now.

I can visualize early humans roaming the earth that slipped on a rock or stuck his hand into the fire. Instead of modern derogatory words, I’m sure that there was a great deal of jumping around and making similar sounds. Maybe something like, “ ooohh, ooohhh, grrrrrrr. Aaaahhhhhhhhhhh!!!!” The bottom line is this, pain is very important to our survival as a species. After a painful experience, a memory is implanted in our brain that reminds us not to do that action again.

There are many different types of pain, emotional, psychological, and physical which can be acute or chronic in nature. (Kring A., 2012) Psychological pain is attributed to the feeling that one is having pain; there is no physical evidence to explain the cause. Emotional pain is like when you experience a horrible psychological situation. Maybe a relative dies or you and your significant other break up. You can often have a hurt feeling in your body as a result of this major upset. It sad and you really do feel pain. Physical pain is caused by injury or disease. Some people learn early in life how to mentally deal with pain while others will cry for a week over a bruised rib. A big part of managing the feeling of pain can be attributed to our coping skills. For example: take an ice cube and put in your hand. Hold it as long as you can and time yourself. Now, do the same experiment but don’t think about the pain in your hand but think of a warm place where you are soaking up sun. Palm trees are swaying in the tropical breeze.  Which one had a better time? I bet the latter due to you finding a way to mentally concentrate on something other than the pain.

Our amazing body comes standard with the ability to produce its own pain killers; natural chemicals that help dull pain. Your body produces cortisol from the adrenal glands that is a steroid that helps reduce swelling in times of stress. Your body also produces endogenous opiate-like chemicals called endorphins and enkephalins. (Saladin K., 2007) HA HA!!, yes morphine-like chemicals made by you.!! These are produced by your body to help dull pain as well.  Unfortunately, it is short acting and never completely takes away all the pain because it wants you to know that you are damaged in some way. It’s like the scene from a science fiction movie, whoop….whoop…Damage in the lower left extremity detected captain!!, possible toe injury after passing table….Damage report!!!, Whoop, whoop…Partial destruction of pinky toe discovered, little piggy down….whooop…..whooop.

Ok, that was fun. I digress. When the body is feeling pain and the natural endorphins are not relieving it and you want comfort, you must find an exogenous (outside the body) substance to block or disrupt the pain signal from constantly reminding you of the now broken toe. The best way I have found to describe endogenous (from within) opioid-like feeling is that if you have ever been a runner you will experience this rush. Runners get these second and third “winds” that dulls the pain in their legs and then they can finish the race or marathon. It does not, however stop you from throwing up all over place after you finish. That rush and decreased sensation of pain is from an endogenous opioid-like substances called endorphins and enkelphalins. Note: this is different from the sympathetic response you get from being chased by a vicious animal. That is adrenaline being released into your body to help you fight off the animal or attempt to outrun the rabid thing. I can cover that on another essay in the future. (Saladin K., 2007)

There are many ways to manage pain whether it is acute or chronic. The most popular way is to take some type of analgesic (pain killer). There are several kinds of pain relievers to choose from, like aspirin, naproxen, acetaminophen, and narcotics. OTC drugs like acetaminophen are easy to come by and work well for most aches and pain. Narcotics are normally reserved for severe pain, like bone sticking out of your body kind of discomfort. Acetaminophen and NSAIDS block the pain signals at different places along the neuropathway. Narcotics in comparison do not really block the pain they change your perception of pain. They make you sort of…ummm forget about the bone poking out of arm. (Adams, 2005)

After a major injury to the body like broken bones or surgical procedures people are usually sent home with strong pain medication (Narcotics). The idea is to get you through the most painful portion of the healing process so that you can continue your life. It doesn’t always end like that for some people. Sometimes prescribing physicians that write for opiate medications are more liberal with narcotics. A person that has poor coping skills with pain may try to continue the narcotics longer than necessary. If this continues for too long the person can become tolerant and then eventually addicted to the opioids.  I will explain in a moment the internal process that leads to addiction and why it is difficult to just quit pain medication. First let’s discuss the term tolerance. Tolerance is the condition in which the individual needs more of the narcotic to get the same level of pain control or euphoria over time. (Opioid Mechansim of Action 3D Animation ) At first the injured person might just need a low dose to relieve the pain. In situations where there is months of pain it will gradually require higher doses to relieve the pain. Motor vehicle accidents seem to be the culprit of many cases of chronic pain that I encounter in the emergency room. Accidents can cause long lasting effects or disabilities. These individuals have daily pain exacerbated by psychological pain often coupled with depression. This is a perfect situation that will encourage a person to remain on narcotics. Over time an unfortunate thing happens with the effect of the medication. The brain begins to grow new receptor sites. That means more opiates are needed in order to have the initial pain killing effect. The person is no longer taking the pain medication just for pain control; they have become addicted to opioids. A person who has developed an addiction now has to take the drug just to feel “normal”.  By not taking the medication it begins a chain of horrible symptoms that is the beast called withdraw.

Receptor sites?? What are those? OK Austin, please explain yourself you say. Ok, this is the part where it gets tricky but stay with me and you will understand how opioids work and then we will discover how Suboxone is meant to help people with addiction to narcotics. I understand that it taking me a long while to get to the meat of this essay, but like I said, I feel it is my duty to make sure you have a good understanding of how Suboxone works and why it works. Then the next time you get a patient that reports they are on Suboxone you will have a better idea how to care for this individual. We are professionals here so we should not settle for; “yeah it works, so let’s give a medication type of doctrine.” I don’t know about you, but I have been an ER nurse for about 5 years now and I still look in the medication guides if I have a question about a medication. It is just good practice. Ok, here we go good stuff to follow.

Neuroscience 101- In your brain you have a special area that is designed to allow you to feel rewards and pleasure. (Saladin K., 2007) This system very is important for an organism like you for survival. When you do things that are good for your body you get a sensation of pleasure. This is so you continue to thrive in this harsh world. These little chemical Scooby snacks keep you on track by rewarding you when you eat, exercise, have sex, give a gift, help the poor…you get it. All these things help you survive and then pass on your genetic material with reproduction. I’m not saying this helps you stay on track as far as the quantity of food, drugs or sex, which mostly is a personal choice…for now. This part of your brain only cares about making you feel good. (Kring A., 2012) As you will see that while this is a great system it can be hacked and tweaked. By giving into these pleasures too much we can become dependent on the “feel good” sensation. It is then that we are addicted.

There are several nerve centers in an area around the middle of your brain that make up the limbic system. (Kring A., 2012) This is important for comprehending addiction so pay close attention. Your brain has these specialized centers that are activated when we receive pleasurable stimuli. Here are the parts of the brain that make up this awesome system. The Hippocampus is for memory and learning. Think of a Hippo with a big brain for memories. The Amygdala is responsible for emotion, emotional learning, and fear. The Striatum is associated with habitual behavior, and we don’t have to think about an established action. The striatum helps us repeat actions like eating, exercise, and sex. Then we have the Ventral Tegmental Area that is like a train station that connects these centers together. Finally, there is the pleasure center itself, the Nucleus Accumbens. All of these centers communicate by way of neurotransmitters. The Neurotransmitters are chemicals that neurons use to communicate with each other; they are Dopamine, GABA, Glutamate, Serotonin, and Norepinephrine. (Opioid Mechansim of Action 3D Animation )

 Dopamine is the main neurotransmitter for the pleasure center of the brain… it’s like candy to a child. In fact; it is released when you eat candy. All narcotics and other feel good drugs, cause the release of dopamine. Receptors are on the receiving post-synaptic neurons that accept the dopamine and activate the sensation of “OMG that felt really good”. This feeling is reinforced by your brain creating a memory of what caused that sensation. In a sense, you are being conditioned to do the action again. Like Pavlov ringing the bell, you are driven to repeat an activity to receive an award. That incredible sensation is, Wait!! This is the best part,… communicated to your prefrontal cortex which is the area where we solve problems and lead this wonderful body to situations that enable us to feel that pleasure again. Let’s put it all together in regards to exogenous substances how about narcotics. The Ventral Tegmental Area is stimulated by an opiate and sends a signal to the Nucleus Accumbens (NA). The NA releases dopamine that allows you to feel the high of the drug. The Amygdala helps you remember the environment and situation that caused this feeling. Then the Striatum forms a habit behavior so you will repeat the situation. The prefrontal cortex motivates you to create the situation where the wonderful sensation can be reproduced.  I know what you are thinking and I agree, this system can be very problematic as well as helpful. Without this reward system you wouldn’t seek food, or any other important thing needed for survival or reproduction. Have you ever wondered why you want to be around someone that you are really attracted to? When you are around this person you feel a rush like you are on a drug. Then when you are not around that person you have an empty feeling and you just ache and cry and want to sleep. These feelings are due to the release of dopamine. This nice little set up in the brain is how we fall in love. That is another example of endogenous stimulation of the limbic system. (Opioid Mechansim of Action 3D Animation )

Morphine, heroin, opium, oxycodone, fentanyl, Vicodin, Norco, hydrocodone, these are all examples of medications derived from the opium poppy plant. (Adams, 2005) Are you with me so far? Ok then, we will now introduce an exogenous opioid substance into this system of pleasure. BAM!! The introduced opioid stimulates dopamine neurons and the neurotransmitter is released into the synapse. Dopamine flows across the synapse and binds to Receptors on the receiving neuron and activates the pleasure system. You have essentially four (4) main receptor sites on receiving neurons. MU, Kappa, Delta and the forth one is primarily for only synthetics so I will just stick to the three first ones mentioned. (World Science Fair) The receptors are like locks that can only be opened by the right key. If you have ever fed small children spinach instead of applesauce then you have the right idea. If the site doesn’t like it the chemical will not be accepted.

Let’s start with MU. This receptor site only accepts morphine agonist (Opiate substances). It will only send a message if an opioid molecule binds to it. The MU sites are located in the Thalamus, Spinal Cord, Brain Stem, and Cortex. Stimulation results in Supraspinal analgesia, Respiratory depression, euphoria, sedation, decrease in GI motility, and constriction of the pupils. (Kring A., 2012)

The Kappa receptor site is different in that it will accept agonist or antagonist substances. The substances included are endogenous opioid substances such as endorphins as well as exogenous opiates. It will also accept antagonist like Naloxone (Narcan) that blocks or inhibits opiate stimulation. Suboxone as we will see in a few moments is a combination opioid agonist/ antagonist substance that is accepted by the Kappa sites. The Kappa sites are located in the Limbic system, Spinal cord, Brainstem, and Hypothalamus. Stimulation of these sites results in spinal analgesia, sedation, SOB, dysphoria, and inhibitory release of ADH. (Opioid Mechansim of Action 3D Animation )

Delta receptors also accept endogenous and exogenous opiate or opiate-like molecules and are located in the olfactory bulb, cerebral cortex, nucleus accumbens, and amygdala. Activation of the Delta sites results in mainly spinal analgesia, and decrease in GI peristalsis. Research is still being performed to discover if activation of delta receptors cause respiratory depression.

That was a lot of material but now we can understand tolerance and addiction. When opiates are continually used, a higher amount of dopamine is released into the synapse. The receptor sites will be overloaded by the free floating dopamine. Over-stimulation continues and the brain begins to build additional receptors to handle the load. Some of the dopamine is reabsorbed back into the releasing neuron. However; at higher amounts the re-uptake of dopamine is not sufficient enough and the receptors are repeatedly stimulated. With the growth of the additional receptors it will take more of the substance to fill the extra sites. Thus the person has become more tolerant of the substance. The receptors are like greedy little kids they all want candy too, right? Like a group of children, arms stretched out for candy. What happens if only a couple of the kids get candy…chaos, you have chaos. (Adams, 2005)

More time passes and more receptors are formed in the brain and soon the individual has used so much exogenous opiates that the brain says, “ya know, maybe I don’t need to produce my own feel good stuff”. The neurons that release dopamine start to shrink and produce less dopamine. (Siegal) Now don’t forget that the limbic system by this point has become quite efficient at getting the person to the substance and making use of that prefrontal cortex. But now there is less dopamine, hmmm…still taking the drug, and a lot of it and not getting that reward feeling. But we have all these greedy little sites wanting candy. Now we have a huge problem. Anxiety begins to set in when the person has to have opiates just to feel normal and not anxious. If they wait too long the withdraw symptoms begin. The unhappy brain says “ok you are now having cramps, achy bones, nausea, vomiting, with a little touch of diarrhea. “How about using that prefrontal cortex to get me more of that morphine stuff or umm what is that ummm, Dill. Da….Dulada, yeah that stuff”. . This is now an addiction to opiates. (Siegal)

Now that we understand all of that I can finally talk about Suboxone and why it is used. You might need to get up now, get a drink of water, and maybe hit the bathroom. We have been on a long journey through your brain. By the way, the Amygdala has a lot to do with how one handles stress and studies show that there is about a 50% genetic affinity to addiction. (St Jude Retreats )Chances are that if you have immediate family that are plagued with addictive personalities then guess what? This article is very important to you.

SUBOXONE, A mixed medication made up of two substances, Naloxone (Narcan) and Buprenorphine. It is used to treat addiction to narcotics and given sublingually. The Narcan is an opiate antagonist, and the Buprenorphine is an agonist/antagonist. The reason it works well is that the Narcan blocks some of the sites completely from opiates and the buprenorphine only partially blocks receptor sites allowing enough through to drastically reduce the withdraw effects. Some MU, Kappa, and Delta receptors are completely blocked by the Narcan and the Kappa and Deltas are partially blocked. Even if the person receives more opiates it will have little or no additional effects. (St Jude Retreats ) The person should be off opiates for a day or so before the Suboxone treatment is started. Otherwise they can be subjected to almost immediate withdraw. Essentially the person will be in the beginning stages of withdraw when they start the treatment. Suboxone has a lasting effect with a half-life of 37.5 hours allowing the user to maintain control and reducing anxiety. (RX LIST ) Normally withdraw from opiates can start after only a few hours after the last dose leading the user to find more opiates before the really bad symptoms begin. The prefrontal cortex is really working hard now to get more narcotics. Maybe you have witnessed this behavior in the ER. Addicted individuals will use whatever techniques they can come up with to satisfy that need for more narcotics. The withdrawing individual can have terrible adverse symptoms for 3-7 days, maybe longer. With the Suboxone having a long half-life it gives the person more time without the severe withdraw symptoms. The goal is to get the person past the withdraw stage. The next step is to slowly reduce the amount of Suboxone. The brain begins to decrease the amount of greedy receptor sites in response to the lower demand for the dopamine. New connections can be made to normalize the correct amount of dopamine flow. (World Science Fair)

Problems can and do exist with this treatment, people who also abuse benzodiazepines; Suboxone does not work well for those people. Suboxone itself can be addictive due to having a narcotic agonist element. Doctors who do not watch the patient close during this process can create another addiction problem. The patient can become addicted to the Suboxone because they either are not properly weaned off of it or they find it out on the street. The ratio of buprenorphine to naloxone is about 4:1, so there is more of the partial opioid component to the medication. (RX LIST )

I realize this was a very long article but it was necessary. I hope we all learn a little from this and other publications. Narcotic abuse in this nation is huge. The CDC estimates (St Jude Retreats ) that 600,000 people are addicted to narcotics. Approximately 5,000 people a year die from opiate overdose. Thank you for your time I hope you enjoyed my article. Please give me feedback on how I can improve my work or corrections that need to be made.

Austin Chapin, RN


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Kring A., J. S. (2012). Abnormal Psychology 12th ed. . New Jersey : Wiley and sons .

Opioid Mechansim of Action 3D Animation . (n.d.). Retrieved September 20, 2014, from youtube : tv?v=YCz5A8ZKavM

RX LIST . (n.d.). Suboxone drug and indications . Retrieved September 20, 2014, from htm.

Saladin K., P. (2007). Anatomy & Physiology The Unity of Form and Function 4thed. New York: McGraw Hill.

Siegal. (n.d.). What is Addiction? An Overview . Retrieved September 20, 2014, from Open Educational Resources :

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World Science Fair. (n.d.). What the Mind Hungers for: watch “The Craving Brain”. Retrieved September 20, 2014, from youtube:

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