Nervous system: Drugs and Addiction

Learning Objectives

Know what a drug of abuse is and what it does in the brain. Understand how the brain’s response to drugs changes over time and how this contributes to addiction

As you’ve grown up, you’ve probably been bombarded with the simple message “DON’T DO DRUGS” from family, teachers, and advertisements. But why is this such an important message that it bears repeating over and over and over again? What are drugs actually doing in our brains that make the adults in your life so worried about you trying them?

When we talk about not “doing drugs,” we are talking about recreational use of a drug, or using a drug “just for fun,” which is considered abusing that drug, and can lead to becoming addicted to it. This is why we call them “drugs of abuse.” This group of drugs includes players such as: heroin, alcohol, cocaine, methamphetamine, nicotine (aka cigarettes/e-cigarettes), and marijuana. This does not include properly-taken medications, even though some medications are also drugs of abuse when taken improperly, like how morphine (which is related to heroin and can be addictive) is used for pain-relief, or how microdosing of ketamine (aka horse tranquilizer) is being tested as a treatment for depression.

The way drugs of abuse work in the brain is by targeting, either directly or indirectly, an area of the brain called the mesolimbic dopamine system. This pathway includes the Ventral Tegmental Area (VTA), which sends dopamine signals to the Nucleus Accumbens. Dopamine is one of the major neurotransmitters–or chemical signals–in the brain that relays information on whether something is rewarding or exciting. When it comes to addiction, dopamine is the little voice in your head saying “that felt good, do that again.” This is why the mesolimbic dopamine pathway is often lovingly referred to as simply: The Reward Pathway. Almost all drugs of abuse go through this pathway in some way to increase the amount of dopamine in the brain to make someone feel good and make them want to take a drug again.

A brain is depicted with the reward pathway circled. It is in the lower middle part of the brain.
Fig 1. Mesolimbic dopamine pathway (reward pathway; circled) in the brain

You might see how this itself could cause addiction, or a physical and/or psychological NEED for a drug. If a drug feels that good, it would make sense to keep using it to keep feeling good and chasing that high. That is definitely part of addiction. But wait, there’s more! We all have a baseline level of dopamine that our body likes to stay at. When we take a drug, that level increases. When a drug leaves the system, dopamine levels drop below baseline levels, throwing a person into what is called withdrawal, which includes symptoms such as anxiety, depression, physical ailments (stomach issues, pain, etc.), and craving that drug to get back to feeling good. As time goes on and a person goes back to using a drug over and over again (maybe to feel good, maybe to run away from withdrawal), the highs get smaller and the lows get bigger, and while that is happening, the baseline level of dopamine is also lowering itself. This physical change can stick around long-term, which is why addiction is considered a chronic disorder and why even years after stopping a drug some people still feel cravings for that drug.

The graphs shows a pattern of highs and lows associated to drug use as compared to a baseline. Initially, the high is great, but eventually the lows take over and even lower the baseline.
Fig 2. Mood/Dopamine levels increasing and decreasing over the course of drug-taking. Based on the Koob and LeMoal (1997) homeostatic model of addiction.


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