Years ago, when Dr. Alan Leshner was the Director of NIDA and gave talks about addiction, he used the metaphor of a switch in the brain to describe the process of becoming addicted to a drug. While members of congress appreciated the simplicity of the metaphor, many dumped on his switch because in fact, the process of addiction does not occur in the flip of a switch. People wanted him to say it was more like a whirlpool, quicksand, rollercoaster, water lock, or slide, because the process of developing an addiction occurs in stages and involves multiple regions of the brain.
Not long after I heard Dr. Leshner use the switch metaphor, I learned about the work of Dr. Eric Nestler, who presently is the Director of the Friedman Brain Institute at Icahn School of Medicine at Mount Sinai. As a renowned neuroscientist studying addiction, he discovered what essentially is a molecular switch called Delta FosB that helps explain how loss of control happens with addiction.
The switch is a protein (chemical) that accumulates in the nucleus accumbens when you engage in addictive behavior. As levels of Delta FosB increase in the brain, specific genes involved in addiction become activated, leading to cravings which continue to fuel the addiction cycle. Unlike Dr. Leshner’s switch metaphor, this switch is more like a dimmer that is slowly turned on over time, physically rewiring the brain. Since most start down the path to addiction prior to the age of 15, Delta FosB can accumulate over many years. At the same time, evidence suggests it can remain in the brain for some, contributing to cravings and relapse months or even years after addiction ceases. This is another reason why many refer to addiction as a chronic relapsing brain disorder.
Years after I first learned about Delta FosB, I was making regular trips to New York City and was fortunate to connect with Dr. Nestler on multiple occasions to learn more about his latest findings on addiction. Four things from our meetings really stood out.
- First, since discovering Delta FosB, he and his colleagues have identified other molecular switches involved in addiction that adds credence to it being anything but a simple problem. This added complexity has hampered the search for biological treatments, including new addiction medicines.
- Second, he confirmed that research solidly supports addiction involving both substances and behaviors. While it can be challenging getting mice to gamble, watch porn or shop excessively, some creative lab studies have shown that the various molecular switches involved in addiction impact substances and behaviors in the same way. It’s why treatment needs to target all addictions as a package of behavior, because focusing on one addiction while ignoring or not identifying others, leaves the brain vulnerable to relapse and rarely leads to positive outcomes.
- Third, as his work has expanded into mental health disorders, studies confirm that different mental health disorders are more alike than different, and involve similar brain regions and processes. Even more, there is a complex and intermixed relationship between mood disorders and addiction (co-occurring disorders), which suggests that our treatments also need to be integrated. Sadly, our present diagnostic system fragments behavioral health disorders, perpetuating a search for specific treatments for specific problems. Outcomes are optimized when we focus on treating you holistically as a person, and not on specific disorders.
- Lastly, the environment matters. Similar to Dr. Alexander’s findings with Rat Park, his lab has done extensive research on stress and how different levels interact with genes to produce various outcomes, both positive and negative. For example, when mice are exposed to high levels of stress similar to humans being exposed to 4 or more ACEs, there is evidence that when bred, their offspring are more vulnerable to stress. At the same time, when mice are exposed to less stress, say 1 or 2 ACEs, evidence suggests that offspring actually become more resilient to stress. The take home here is similar to Rat Park. Too much stress in your life complicates your ability to overcome addiction.