Why ‘just say no’ doesn’t work: pathophysiology of addiction

Part 2


Founder, providence recovery services

Winston Churchill is quoted as saying; “Everyone has an addiction, the key is to find one that is socially acceptable.” As a person in recovery nearly 20 years I can relate to this comment. I spent years trying to find a way to use mood altering substances in a manner that wouldn’t create problems in my life. However, once I understood the science behind addiction I realized why I was behaving in such a way. Understanding the problem gave me hope for a solution. 

Our brains and bodies are, perhaps, the most complex entities in the universe. When they fail to operate as designed, we call this a disease. Substance Use Disorder (SUD) and the associated addiction is a disease. Let’s see if I can convince you of the same. 


One definition of disease is: a cessation or disorder of the body or system with predictable signs or symptoms or consistent anatomical alterations. As a physician, my favorite definition is: 

Addiction is a chronic progressive disease with defined symptoms that have

predictable outcomes when specific medical interventions are used.  

The same definition can be used when considering diabetes. Diabetes, in general, is not something you get over in a week. It is chronic and progressive if not treated. So is addiction. It can be diagnosed because it has predictable symptoms. So does addiction. It can be treated effectively with known medications and lifestyle changes to slow or even stop the progression. So does addiction! This is good news to those of us who have battled addiction or have a loved one that is in the battle. 

Extensive studies have been done on the brain including real-time PET scans, neurochemical and genetic mapping. These studies help us predict with a high-level of certainty who will be at risk for substance Use Disorder (SUD). 


The brain is made of an almost endless amount of circuitry. The “wires” of these electrical circuits are cells called neurons. A message, in the form of an electrical impulse, is transmitted from one neuron to the next to deliver information to different parts of the brain.

The brain part most involved in the study of addiction is the limbic system. The limbic system is the part of the brain that gives us pleasure. When we eat a piece of cake and enjoy it it’s because of the action of the circuitry in the limbic system. Another important area of the brain is the prefrontal cerebral cortex. The limbic system constantly sends messages to this part of the brain. 

These important electrical messages are transmitted back and forth across the brain using a negative feedback mechanism. 


An example of a negative feedback mechanism is the central air in a home. We set the thermostat for a specific temperature. The air conditioner comes on when the room temperature is above this level and cools the room down. The thermostat also turns the system off when the room becomes too cold. If the room heats up again, the sensor turns the air conditioner back on. As a result the room is kept at a constant temperature. This is a negative feedback mechanism. 

Another way to think of a negative feedback mechanism is to think of the brain as a family. The limbic system is the boundary testing teenager. The prefrontal cortex are the parents who try to keep the teenager in check, safe and making good decisions. The parents and the teenager communicate daily and the end result is the teenager is kept on the straight and narrow. Stray too far from rules one way or another and the parents bring the teenager back to safety. Understanding negative feedback mechanisms is important in our discussion of addiction, when this mechanism is broken there are consequences. 

When a typical non-alcoholic drinker goes to a party and has an alcoholic drink the limbic system is stimulated and produces euphoria, happiness and a feeling of ease. However, The negative feedback mechanism also kicks in. This message tells the person that while the alcohol has made them feel good, they have a job they must get to in the morning, a family that has to be taken care of, and other responsibilities. As such our individual stops drinking before becoming so inebriated that they cannot uphold their other responsibilities. Their “brain thermostat” or “parents of the brain” reign them in to prevent a catastrophe. In the person with SUD the brain circuitry is physically disconnected. It can be seen on a real time MRI that the message going to the prefrontal cortex reminding the person of their responsibilities never gets through. The line is literally and figuratively cut. 

As an individual with SUD takes that same drink there is no connection to the prefrontal cortex reminding them about their work presentation and family needs. The only message they get is that it feels good, so keep doing it to feel better. The more they do, the better it feels and the better it feels the more their limbic system tells them to continue. They become unconcerned with the future and can only seek out what meets their desires at the moment. As the saying goes: one drink is too many and a thousand is not enough. 

The individual who has substance use disorder is suffering from a broken decision making capacity. Or to put it simply, a “broken decider.” This is why in 12 step programs they encourage sponsorship. In treatment centers like Providence Recovery, groups of other patients are used to help the individual work through decisions while their brain is healing. People are unable to make healthy decisions for themselves in the beginning of treatment and recovery. 


Before exploring the cellular level of addiction, it is helpful to understand the limbic system’s role in cravings. The limbic system not only has a role in pleasure, but also memory. In an addict this is very dangerous. Even when not using a substance, the memory of the pleasure it once produced (and lack of memory of consequences) causes them to have overwhelming cravings for the substance again. Cravings may be the biggest part in continued use and relapse.


The cellular circuitry of our brain (neurons) also contain chemical messengers called neurotransmitters. Specifically, dopamine is a neurotransmitter that plays a key role in addiction. All people have dopamine throughout their body with a very high concentration in the limbic system. Neurons have one purpose, to generate and pass on electrical impulse messages. Neurons are long cells that link to other neurons in long chains of circuitry. One neuron does not physically link to the next neuron it is communicating with. There is a very small space between the end of one neuron and the beginning of the next. This tiny space is called a synapse. Our electrical impulse message must cross the synapse gap. It does so by converting its electrical message to a chemical message and then back to an electrical message once it reaches the next neuron. The chemical messenger is one of several neurotransmitters. Dopamine reigns king in understanding addiction. 

Dopamine molecules can also be called “little packets of joy.” Every time the limbic system is stimulated with dopamine, we feel a tiny bit of pleasure. When we eat a piece of cake and enjoy the sweet taste, that comes from dopamine being released in our limbic system. The more dopamine that is released, the more pleasure we experience. 

When the neurotransmitters cross the synapse they connect with receptors on the next neuron making an electrical impulse and thus sending the message further down the circuit. The more neurotransmitters in the space the more exciting and robust message is given to the next neuron. While these neurotransmitters are crossing the synapse there are also receptors on the previous neuron calling them back into the previous neuron. As such, the neurotransmitter is only in the synapse for a short period of time before being called back “home” to get ready to carry more messages. The receptors calling the neurotransmitter back home are called “reuptake receptors.” This mechanism takes place in a split second.

Understanding how cocaine works in this reuptake mechanism can help us understand addiction better. Cocaine by itself does nothing to make us feel better. However, when a person ingests cocaine it attaches itself to these reuptake receptors and prevents them from calling the neurotransmitter floating in the synapse back home. So these neurotransmitters continue, almost indefinitely, stimulating the following neuron. And if this neurotransmitter is dopamine and in the limbic system it, the ongoing action of the “little packets of joy” makes a person very happy and euphoric. 

The problem is, eventually the dopamine breaks down and if a person continues to use cocaine they will have to take higher and higher amounts to squeeze the little remaining good dopamine out into the synapse. Eventually we run out of dopamine because our body cannot make the dopamine as fast as the cocaine is allowing it to be used up. That is why an individual will need progressively more and more of their substance of choice (cocaine, opiates, meth, alcohol, video games, work, money) to get the same effect. The process may be slightly different with each substance or action, but the result is always the same, maximizing the release of dopamine. If dopamine equals “joy” the lack of dopamine equals depression and even suicidal ideas.


This is where it gets scary. Higher and higher amounts of a substance begin to be needed to recreate the good feeling the person had with their first use. However, the amount needed to overdose never changes. This overdose amount is called the lethal dose. 

Every drug has two dosage levels that can be studied and put on a graph. As we slowly increase the dosage of a particular drug we will first arrive at the effective dose. This is the amount of a given drug that is required to create the desired effect. That can be anything from enough to kill bacteria in the case of antibiotics or enough to bring down a fever in the case of Tylenol. In the case of substance use disorder the effective dose is the amount of drug needed to create the desired feelings a person gets by using them. This dose, as we mentioned earlier, can vary. It may reside at a particular level initially and slowly increase over time as the patient uses more and more of it. 

The next important marker on the dose response graph is the lethal dose. This dosage level never changes. No matter how much tolerance a patient builds up, they are only building tolerance to the effective range, they are not changing the lethal dose amount. That is why heroin overdoses are so common and unsuspected by the patient. 

Heroin is highly addictive because of the pleasure it initially gives a person. They also quickly develop tolerance and increase the effective dose amount with each use. Most of the time these patients are completely unaware that the next dose is the one that causes overdose. The effective dose has moved to the point where it is equal with the lethal dose. This usually happens without warning because they don’t realize they are taking any more than they usually take because the feeling they get is the same as always (however the amount is, in-fact greater).


Without too much genetic detail, it is safe to say, doctors can now show, through extensive research, there are areas on four separate chromosomes that are unique in patients with substance use disorder or at risk for substance use disorder. In other words, in the very near future if a parent wishes, they could test an embryo for these genetic anomalies and know from birth whether their child will be at risk for substance use disorder.


Along with better genetic understanding, there are several drugs being used successfully in the treatment of substance use disorder. 

The first is Suboxone or buprenorphine. This drug is not an opiate like methadone but a partial opiate agonist. It is used to treat people with opiate addictions. It has a ceiling effect. This means the body will only use a certain amount of the drug regardless of how much has been taken. It binds to the opiate receptor in a neuron with an infinity greater than 250 times that of heroin. As such, it can be used to help individuals taper off of opiates without the terrible withdrawals and can be used as a maintenance therapy to prevent cravings and allow a person to fully invest themselves in their recovery and rebuilding of their life. 

Second is Narcan, or naloxone. Narcan also binds to the opiate receptor, however it has no effect whatsoever. In essence, it just blocks the receptor so no other opiate can use the receptor. Since Narcan has a greater affinity for the receptor than heroin or most other opiates it will push away any existing opiates in the synapse. It is commonly used to reverse opiate overdoses. It stops the overdose.  

Charles O’Brien, MD, of the University of Pennsylvania, is a senior consultant for Providence Recovery Services in Craig and has spent his life studying and researching substance use disorder. He was instrumental in developing Suboxone. He also has done extensive research into using Narcan for people with alcohol use disorder. He found that most people with an alcohol use disorder also get opiate receptor stimulation when they drink. This does not appear to occur with unaffected persons. Therefore, Narcan can also be used to treat alcohol use disorder by blocking the opiate stimulation that a patient would get normally when they drink alcohol.

Addiction is not the result of a weak will or moral character. The evidence is clear that it is a disease process. We know that addiction is the same regardless of the substance involved (alcohol, heroin, crack, methamphetamine, gambling or social media). Addictions create dopamine release and a cascade of life altering effects. 

With continued understanding of addiction, the treatments are becoming more and more effective. The tools are available and the fix is in sight. 

Feel free to contact me with any questions at david@providence-recovery.com

Special to the Herald Times