What is happening when an addictive substance is used in the brain?

Every addictive substance acts on a chemical in the brain called dopamine. Those drugs that release a LOT of dopamine and act VERY quickly tend to be more addictive. This is because dopamine helps our brains decide what gives us pleasure, what is rewarding, and what we should be paying attention to in the world. It is what causes feelings of satisfaction and pleasure when we connect with friends, do an activity we enjoy, achieve a goal, eat, or love someone. These things feel good and so we want to do them more. This is beneficial to humans as these things are essential to human survival: building communities with others, seeking out food, and forming families helped the human race survive. BUT. The amount of dopamine released by the drug is WAAAAAYYYY more than what is released by these other activities. Our brain interprets this to mean this drug must be WAAAAAYYY better and more important than all those other things. If the drug continues to be present, over time the brain literally re-wires itself. This ability for brains to change over time is called ‘brain plasticity’. Now the brain is constantly seeking signs of the drug and figuring out how to get the drug and thinking about the drug. Additional changes that affect rational thinking, make one more impulsive, and cause chronic stress also happen. The longer the drug is used and the more of it that is used, the more these circuits strengthen. And those other, normal things no longer really cause the same level of pleasure response anymore. You can’t feel the drop of water when you are drowning in the ocean.

When someone addiction to opioids suddenly stops using the drug then problems develop. The brain has literally changed itself to accommodate this drug being present all the time. It has now become so changed that the person feels unwell, ill, anxious, and depressed when the drug is not there. In the later stages of addiction the drug no longer really even results in a ‘high’ when used; persons at this stage are instead using just to feel somewhat normal and not sick. The first few days or weeks the after abruptly stopping use will result in days to a couple weeks of feeling very physically ill with nausea, vomiting, severe aching pains, restlessness, feelings of skin sensations, and more. This is the acute withdrawal period. However, even once this period recedes, it takes months to years for the brain to re-wire itself. The feelings of anxiety, depression, lack of motivation, and altered sleep last weeks and months and more. The brain also still is trying to think about and search for the drug so cravings can remain; it takes a lot of time for this to fade. This is why persons with severe addiction relapse weeks and months or even years after a ‘detox’ when physical withdrawal has ended.

And that is where the medicines come in. The goal of the medicines is to help stabilize the changes in the brain circuits that have occurred with moderate to severe addiction so that the person is better able to feel, think, and function normally. It then allows them to participate in counseling, develop new coping strategies, get jobs, and heal relationships. All of those things help the brain to change itself back into a healthy brain. The three medications used to treat moderate to severe opioid use disorder are methadone, buprenorphine, and naltrexone.

First let’s look at Naltrexone. Naltrexone works by blocking the opioid receptor. An opioid has to bind to the receptor for any changes or effects to happen. If it now cannot get to the receptor, nothing will happen when one takes an opioid! Knowing this up front makes persons less likely to try to use a drug and even if they suffered a lapse they would be unlikely to feel much. This medication is not addictive and so there is no withdrawal if one suddenly stops taking it. It is not a controlled substance and so can be given in almost any location. It comes as a month long injection which can be helpful in sticking to the treatment plan since you don’t have to remember or commit to taking a pill every day.

And that is where the medicines come in. The goal of the medicines is to help stabilize the changes in the brain circuits that have occurred with moderate to severe addiction so that the person is better able to feel, think, and function normally. It then allows them to participate in counseling, develop new coping strategies, get jobs, and heal relationships. All of those things help the brain to change itself back into a healthy brain. The three medications used to treat moderate to severe opioid use disorder are methadone, buprenorphine, and naltrexone.

First let’s look at Naltrexone. Naltrexone works by blocking the opioid receptor. An opioid has to bind to the receptor for any changes or effects to happen. If it now cannot get to the receptor, nothing will happen when one takes an opioid! Knowing this up front makes persons less likely to try to use a drug and even if they suffered a lapse they would be unlikely to feel much. This medication is not addictive and so there is no withdrawal if one suddenly stops taking it. It is not a controlled substance and so can be given in almost any location. It comes as a month long injection which can be helpful in sticking to the treatment plan since you don’t have to remember or commit to taking a pill every day.

There are downsides, however. If one was to be in an accident or break a leg it would be very difficult to treat that pain because the naltrexone is blocking all those opioid receptors. You must carry a medical alert bracelet or medical alert card so that in such a situation the doctors would know they had to treat your pain differently. Also because of this, this medication does not work as well for those with chronic pain in addition to addiction. Most importantly, this medication is essentially the same as Naloxone (Narcan) which is used in overdose reversal. It pushes any opioid present in the system off the opioid receptor and takes its place. This results in withdrawal. This means you have to be AT LEAST 7 days without any opioids AT ALL in your system before you take this shot or it will push you into severe and irreversible withdrawal. Persons with severe addiction can have a hard time getting that 7 days or more with zero use.

Methadone can fully activate the opioid receptor just like heroin, oxycodone, and other opioids. The very key difference is that it takes a loooooooonnnngggg time for the methadone to kick in fully- well over 24 hours- and it lasts in the system for days. This means persons do not really get a rush or high when they take it for treatment. It can also be more helpful for those with both chronic pain and addiction; it is used in those without addiction as a treatment for severe chronic pain. Imagine the opioid receptor as a radio with a volume dial. Heroin turns the volume up all the way to 100% VERY quickly. Methadone turns the volume up to 100% as well but it does it verrrrryyyy sloooowwwwllly.

The downsides to methadone reflect the dangers of other opioids: you withdraw from it if you suddenly stop taking it and if you take too much it could stop your breathing, cause an overdose, or alter your heart rhythm. For that reason methadone is very tightly controlled to keep people safe. It can only be dispensed by regulated methadone clinics for the treatment of addiction. One generally has to go daily to this clinic to receive the medication; this can make it difficult for those who lack transportation or live in rural areas far from a clinic. Public methadone clinics may cost as little as 6 dollars a day, however, and usually have staff to help with psychiatric diseases and difficulties with housing, joblessness, and more which still make them one of the most effective treatment options for those with severe substance use disorders.

Buprenorphine is in between methadone and naltrexone. It can turn the opioid receptor on half-way. This means it has enough activity to stabilize the brain but it has a ‘ceiling effect’. This ceiling makes it very unlikely someone with a substance use disorder using it for treatment would be able to overdose or have their breathing stopped by this medication. Those cases where overdoses have been reported in such persons have found other sedating substances were mixed with the buprenorphine like alcohol, gabapentin, and benzodiazepines. Because it is safer than methadone, buprenorphine can be prescribed in regular doctors’ clinics which makes it easier for people to access. Buprenorphine also is very effective for pain and is used in general medicine separately as a pain treatment medication. It is a controlled substance, however, and addictive so you would withdraw from it if you suddenly stopped using the medication.

One of the main downsides of buprenorphine is it can be tricky to get started on the medication. Though buprenorphine is only turning the receptor on half-way, it binds the receptor tighter than any other opioid. This means that if another opioid is present like heroin, the buprenorphine will come in, push the heroin off the receptor, and take its place. Since the buprenorphine doesn’t turn the receptor on as much as the heroin, this will cause withdrawal symptoms. This means that persons have to wait a certain amount of time after their last dose of a regular opioid to start the buprenorphine medication. They must be feeling at least some moderate withdrawal before they take the first dose of buprenorphine or they will feel WORSE rather than better. The positive side of this is that if someone takes a regular opioid after taking their buprenorphine, they will not feel that other opioid they took nearly as strong. It blunts the high of that drug similar to how naltrexone does which prevents the person from having positive feedback from the drug.

Imagine the opioid receptor as a radio again: Buprenorphine turns the volume up only half-way to 50% unlike methadone and heroin which turned the dial up all the way to 100%. Now imagine that you have three hands going to adjust the volume of the radio: heroin, methadone, and buprenorphine. Buprenorphine will always slap those other hands out of the way and grab the dial, turn it to 50%, and then it will NOT let go. If the heroin hand was already there holding the dial at 100% volume, buprenorphine will push its hand out of the way, grab the volume dial, and turn it down to 50%. That sudden drop from 100% to 50% causes withdrawal.

No one is identical. The right medication and the dose of the medication will depend on the person, their situation, their use history, and more. These medications all have extensive evidence showing that they are more effective than counseling alone at keeping those with moderate to severe substance use disorder in treatment and in better health.