The Science of Addiction

Addictions are chronic, relapsing brain diseases that manifest themselves in three distinct phases: craving for the object of addiction, loss of control over its use and continued involvement with it despite harmful consequences. Over time, addiction can change both brain structure and function. Just as diabetes impairs the pancreas and cardiovascular disease damages the heart, addiction ‘hijacks’ the brain and even destroys key brain regions that are meant to help us survive. Similar to other chronic diseases, addiction cannot be cured. However, its severity can be reduced and/or controlled with appropriate medical treatment.

Describing Addiction

A healthy brain rewards healthy behaviors – such as exercising, eating, or bonding with loved ones – by switching on brain circuits that make us feel wonderful, further motivating us to repeat those behaviors. In contrast, when we are in danger, a healthy brain pushes the body to react quickly with fear and move out of harm’s way. If we are tempted by something questionable – such as gambling with money we don’t have or buying things we can’t afford – the front regions of the brain help us decide if the consequences are worth the actions.

But when we are becoming addicted to a substance, that normal hardwiring of helpful brain processes can begin to work against us. Drugs or alcohol can ‘hijack’ the pleasure/reward circuits in the brain and hook us into wanting more and more. Addiction can also send the emotional danger-sensing circuits into overdrive, making us feel anxious and stressed when we’re not using the drugs or consuming alcohol. At this stage, we often use drugs or alcohol to keep from feeling bad rather than for their pleasurable effects.

To compound that, repeated use of drugs can damage the essential decision-making center at the front of the brain. This area, known as the prefrontal cortex, is the very region that should help us recognize the harms of using addictive substances.

“Brain imaging studies of people addicted to drugs or alcohol show decreased activity in this frontal cortex,” says Dr. Nora Volkow, director of NIH’s National Institute on Drug Abuse. “When the frontal cortex isn’t working properly, people can’t make the decision to stop taking the drug – even if they realize the price of taking that drug may be extremely high, and they might lose custody of their children or end up in jail. Nonetheless, they take it.”

The National Institute on Drug Abuse (NIDA) describes addiction as the most severe form of a Substance Use Disorder (SUD).

I tell my family’s story because far too many are facing the same worries for their loved ones. We all ask the same question: How can I contribute to ending the opioid crisis and helping those suffering with addiction? The first step is understanding that opioid use disorder is a chronic but treatable brain disease, and not a moral failing or character flaw. Like many other chronic medical conditions, opioid use disorder is both treatable, and in many cases, preventable.”

Jerome Adams, MD, MPH (Surgeon General)

Addiction and the Brain

Addictive substances (and activities) all produce pleasurable or rewarding effects which are highly reinforcing and increase the likelihood of repeated use. These effects activate the brain’s dopamine and endogenous opioid signaling systems. When activated at normal levels, these systems reward our natural behaviors, such as the enjoyment felt after having a good meal or following a run.

Multiple studies have demonstrated that neurons signaling through dopamine (often referred to as the brain’s pleasure transmitter) and the brain’s endogenous opioids (endorphins) are activated by addictive substances. The brain’s opioid signaling system is especially important in mediating the rewarding effects of alcohol and opioid drugs such as oxycodone, heroin, and fentanyl. 

Illustration of how opioids affect the brain

In the illustration, dopamine neurons originating in the ventral tegmental area (VTA) project to the nucleus accumbens (NAc), forming part of the brain’s reward circuitry. Naturally occurring opioid peptides activate opioid receptors in both the VTA and NAc, enhancing dopamine’s actions. These opioid peptides act directly on receptors in the NAc and indirectly, through opioid receptors located on γ-aminobutyric acid (GABA) containing neurons in the VTA and other brain regions. Despite their structural diversity, addictive substances activate this reward circuitry by either mimicking (opioid analgesics such as morphine and hydrocodone; abused opioids such as heroin) or releasing (alcohol) endogenous opioids.

All drugs of abuse, from nicotine to heroin, cause a particularly powerful surge of dopamine in the NAc. The likelihood that the use of a drug or participation in a rewarding activity will lead to addiction is directly linked to the speed with which it promotes dopamine release, the intensity of that release, and the reliability of that release. Even taking the same drug through different methods of administration can influence how likely it is to lead to addiction. Smoking a drug or injecting it intravenously, as opposed to swallowing it as a pill, for example, generally produces a faster, stronger dopamine signal and is more likely to lead to drug misuse.

Addictive drugs, for example, can release two to ten times the amount of dopamine that natural rewards do, and they do it more quickly and more reliably. In a person who becomes addicted, brain receptors become overwhelmed. The brain responds by producing less dopamine or eliminating dopamine receptors – an adaptation similar to turning the volume down on a loudspeaker when noise becomes too loud.

As a result of these adaptations, dopamine has less impact on the brain’s reward center. People who develop an addiction typically find that, in time, the desired substance no longer gives them as much pleasure. They have to take more of it to obtain the same dopamine “high” because their brains have adapted – an effect known as tolerance. Addictions, then, arise from overactivity in the midbrain. People don’t have control over this region, which is why they can’t “choose” to become addicted.

At this point, compulsion takes over. The pleasure associated with an addictive drug or behavior subsides – and yet the memory of the desired effect and the need to recreate it (the wanting) persists. It’s as though the normal machinery of motivation is no longer functioning.

Opiant uses opioid antagonists to address addictions, with a focus on nasal delivery technology to allow rapid absorption and enable symptom-driven treatment approach.  

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