Probing the Biological Roots of Drug Addiction

Probing the Biological Roots of Drug Addiction
Researcher on a quest to understand addictive behaviors and design interventions.

In an effort to uncover alternative treatments for pain management beyond opioids, researchers at Vanderbilt University Medical Center are developing drugs and other therapies that treat pain, but have no addictive potential. A breakthrough would go a long way toward addressing the larger drug addiction crisis, says Erin Calipari, Ph.D., assistant professor of pharmacology at Vanderbilt.

Calipari uses preclinical models to better understand addictive behavior. She hopes her studies of the neural characteristics that drive addictive behavior, and her findings on sex differences in drug addiction vulnerability, will inform human studies and lead to long-overdue pharmacologic solutions.

“We have methadone as replacement therapy, but we really don’t have effective pharmocotherapies for treating addictive behavior,” Calipari said. “We don’t yet have a cure.”

Assessing Pharmacologic Solutions

The focus of Calipari’s research on addictive behavior is to answer the fundamental question of what drives people to use drugs. Answering this question, she explains, will not only enable the development of drugs that modify addictive behavior, but also promote an understanding of how to better utilize existing drugs to treat underlying mental health disorders.

“I think the biggest thing is understanding the differences in why people are taking a drug in the first place so that we can intervene in specific ways,” Calipari said. “If it is to minimize anxiety – we can treat the anxiety. If we understand the triggers that drive drug use, we can focus on drugs that inhibit those neurological cues and help avoid relapse.”

“If we understand the triggers that drive drug use, we can focus on drugs that inhibit those neurological cues and help avoid relapse.”

She also acknowledges the benefits of counseling people in how to lead more fulfilling lives. “In an ideal world, environmental enrichment – a deterrent to addictive behaviors – would be doled out instead of drugs,” Calipari said. “What helps the most is that enrichment, simply put, involves fun experiences. These experiences help produce chemicals that bind to the opioid receptors that are activated to seek reward.”

Sex-Specific Differences

Calipari also leads studies to examine why certain populations are more vulnerable to addiction. While traditional addiction research has been based on a male animal models, findings from her research team show that female mice are more biologically vulnerable – they transition much faster from first use to addiction.

In one study, Calipari found that when choosing between a reward and avoiding a negative outcome, male mice were more motivated by the reward, while females were more motivated to avoid negative consequences. “These sex-specific differences have implications for why people take drugs in the first place,” Calipari said. “Data from studies involving humans support this, meaning that treatments for men and women warrant different approaches.”

In another study, Calipari showed that when ovarian hormone levels were high, female rats made stronger associations between drugs and certain cues in the environment that can trigger drug-seeking and relapse. Related research has shown that the menstrual cycle affects levels of craving.

Consequences of Social Isolation

The challenge of addressing substance use disorder is now exacerbated by a year-long pandemic. In the twelve months ending in May 2020, over 81,000 drug overdose deaths occurred in the U.S. According to the CDC, this is the highest number of overdose deaths ever recorded in a 12-month period, and the numbers suggest that part of the acceleration was spurred by the pandemic.

“If we take the time now to really examine how characteristics of these equally deadly epidemics meet and converge, we have the chance to solve not just one, but two public health crises.”

“Social isolation, a reduced access to enriching experiences, and the stress of health concerns and school closures have been a perfect storm in increasing drug use and vulnerability to addiction,” Calipari said.

“We will see the aftermath of this for years to come. But if we take the time now to really examine how characteristics of these equally deadly epidemics meet and converge, we have the chance to solve not just one, but two public health crises.”