Let’s be clear: addiction is a disease. One that can change how regions in the brain function, specifically those that are responsible for reward or pleasure, motivation, learning, judgement,and memory. Addiction is chronic and complex.

It is the severe form of Substance Use Disorder (SUD) and its many versions. Biological, behavioral, and environmental factors cause it. But it the substance use that changes the brain making it a chronic disease. Understanding how addiction changes the brain may help understand how addiction affects the person suffering from it.

How The Brain Gets Hooked

Look at the brain as a puzzle with sections and structures and connections. There are three distinct areas of brain: the forebrain—inner most part; midbrain—uppermost part; and hindbrain—upperpart of spinal cord. Each section is made up of structures that are responsible for numerous functions. We’ll focus on the forebrain and the midbrain.

How Neurotransmitters Work

Time for the neuroscience lesson. Within the midbrain you’ll find tiny structures—substantia nigra and ventral tegmental area—that release the neurotransmitter dopamine. Just to back up, neurotransmitters are chemical messengers that help carry information through the brain cells or neurons to other neurons. (There are other neurotransmitters too, like serotonin.) Each neurotransmitter has receptors that accept its “message.” Dopamine has five of these receptors in the central nervous system and the most abundant helps regulate the reward system, motor activity, memory, and learning receptors.

What Reward Does To Your Brain

When we experience a reward or pleasure, the ventral tegmental area sends dopamine into the basal ganglia—a structure that is responsible for numerous things such as executive functions, behaviors, and emotions. And it is this release that tells us that whatever we just experienced was wonderful and to please do it again. It is this chain of events that helps us change behavior, provide motivation, and affect our mood. All in all, it makes us feel good. And this is where substance use steps in.

“All addictive substances work on the same common reward pathway,” says Anna Lembke, M.D., medical director of addiction medicine at School of Medicine at Stanford University. “Different substances will release different amounts of dopamine, but they all release dopamine in a reward pathway and that’s what relates to their addictive potential. “

How the brain responds depends upon the substance to which one is addicted, says David A. Fiellin, M.D., director of the program in addiction medicine at Yale School of Medicine. “It is reasonable to say that the reward system of the brain gets hijacked by substances that cause addiction. Some of the brain changes are in the cells of the brain. The proteins that the cells make can also change over time with repeated exposure to a substance. The receptors on the cells can change also.” That’s a lot of brain chemistry shifting around.

Sometimes the dopamine release mechanism is not the only thing that explains the rewarding and reinforcing effects of a substance. There are other neurotransmitters, such as opioid, cannabinoid, GABA, and serotonin, that can create the feeling of pleasure in response to a substance (depending on the pharmacology of that su

How Different Substances Affect Different Neurotransmitters

bstance) and the neuroadaptation that can also result in addiction.

Dr. Lembke explains that various classes of substances can increase different neurotransmitters and receptors, such as:

  • Sedatives work on the GABA receptor, and GABA is the calming neurotransmitter in the brain.
  • Nicotine works on the nicotinic acetylcholine receptor, its own receptor in the brain.
  • Cannabis works on the anandamide receptor, its own receptor in the brain.
  • Opioids obviously work on opioid receptors.
  • Hallucinogens typically work on the serotonin system.

“So, even though they work by different mechanisms, the final common pathway to release dopamine in the reward pathway of the brain is the same,” she says.

How The Brain Responds To Withdrawal

“During abstinence and withdrawal, these neurotransmitters are decreased resulting in feeling pain, anxiety, and dysphoria,” Dr. Fiellin says. It is these changes, as well as other neurocircuitry, that occur in the brain that may drive the person to seek out the substance just to feel normal.

When the intoxicating effects of a substance wears off, there is an increase in signaling in some circuits of the forebrain. This firing triggers cravings for the substance and drives the individual to seek the substance out.

What’s wild, is that search alone can release dopamine into the basal ganglia when someone is craving the substance. This motivates them to keep going until they find it and consume the substance.

In brains that are not addicted, these circuits in charge of desire are held in check. The prefrontal cortex, which helps us make rational decisions and regulate emotions, prevail because the individual can balance the long-term goals against immediate reward.

But, repeated substance exposure can weaken these circuits. And in that case, the desire for the substance is too strong to ignore. This is what makes it so difficult for the individual who is living with addiction to stop taking the substance despite negative experiences with the substance, or even, lack of the pleasure they once experienced.

“In addition, some substances can be toxic to certain areas of the brain,” Dr. Fiellin says. For instance, alcohol can result in memory deficits, and cocaine can impact the area of the brain that affects decision making and insight—the orbitofrontal cortex. “Many of these brain changes help to explain the ongoing and sometimes remitting nature of addiction and the lack of success with simple detoxification strategies,” he says.

The Brain Chemistry Of Addiction Treatment

Addiction isn’t just about reliance on a substance. It is about interactions between biological factors—like the neurocircuitry described here, but also genetics and epigenetics, and environmental factors—such as stress, trauma, and cultural systems.

“Addiction is a biopsychosocial disease and so we need biopsychosocial treatments, meaning treatments that work at the biological, psychological, and social levels,” Dr. Lembke says.

Biologically, we have medicines that can target specific receptors. For instance, when treating nicotine addiction, the nicotinic acetylcholine receptor which is what binds nicotine, is targeted using medications like varenicline and nicotine replacement therapies. “We don’t have a drug for every single addictive substance, but there’s lot of exciting work in this space,” Dr. Lembke says.

“In terms of psychological intervention,” adds Dr. Lembke, “individual and group psychotherapy have been shown to be effective. In terms of social interventions, peer recovery groups like Alcoholic Anonymous and other 12 step groups are effective for those who actively participate, and may be even better than individual psychotherapy over the long term. Social interventions also include improving family systems, providing access to jobs, and creating a healthy living environment where people can rest, recreate, and reflect.”

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Last Updated: Jul 8, 2020