Understanding Adolescent Addiction with Dr. Shahrdad Lotfipour

Dr. Lotfipour is an Assistant Professor in the Departments of Emergency Medicine, Pharmaceutical Sciences, Pathology and Laboratory Medicine at the University of California, Irvine. He directs the Translational Addiction Biology Lab, where his research focuses on adolescent drug use, maternal nicotine exposure, gut-brain interactions in opioid use, the genetic and epigenetic mechanisms underlying substance use, and potential therapeutic interventions.

He also leads the UCI Neuroscience Behavioral Testing Core, a state-of-the-art facility for rodent behavioral analysis equipped with video monitoring and recording systems. The core was established through a $1.667 million grant awarded in 2019. Scan the QR Code to take a virtual visit.

Adolescence is a time of change, socially, emotionally, and neurologically. It’s also when many people first encounter substances like nicotine or opioids, often without understanding their long-term effects. I (Ananya Devkirti) spoke with Dr. Shahrdad Lotfipour, a researcher at UC Irvine, about how early exposure can shape the brain, why adolescence is such a critical window, and how his journey from pediatric drama therapy to neuroscience has shaped the way he views addiction.

How did you initially become interested in adolescent addiction science?

My journey began with my own experience around cigarettes. When I was growing up, tobacco use was everywhere. My father smoked, and being exposed to secondhand smoke was just part of daily life. I never became addicted myself but it did worsen my asthma symptoms, and I found the experience unpleasant. But I later learned how early exposure like that is a strong predictor of future addiction, and I was lucky to be among the small percentage who don’t go down that path.

In college at UC Irvine, I majored in both biology and drama. I started using improvisational theater techniques with children in the pediatric ward, many of whom were stuck in bed or constantly being told what to do. The goal was to give them back a sense of control and let them imagine other environments to reduce their psychosocial pain. That experience made me wonder about the actual mechanisms behind pain and relief. I wanted to understand them scientifically.

That curiosity led me to apply for a Fulbright Fellowship to Australia, which allows you to participate in cultural exchange with almost any country in the world. At the time, I also had a dream of attending the 2000 Sydney Olympics. I had originally hoped to attend as an athlete, but when that didn’t pan out, Fulbright offered another path. I ended up studying opioid receptors at the University of Queensland’s School of Pharmacy, focusing on morphine and oxycodone’s role in treating diabetic neuropathy and cancer pain. This was during the early 2000s, right as the opioid epidemic was beginning to surge, and I was struck by how commonly such addictive drugs were being prescribed, especially at a time when people were breaking into pharmacies for OxyContin. This led me to become more interested in the mechanisms behind addiction.

I returned to UC Irvine for my PhD, where I joined a lab with deep expertise in opioid research. My advisor had trained under Hans Kosterlitz, one of the pioneers in discovering endogenous opioids like enkephalins. He also led the Translational Tobacco Use Research Center, which studied why people, especially adolescents, become addicted to tobacco products during the developmental period of adolescence.

That was my first real exposure to how adolescence shapes vulnerability to addiction. The adolescent brain is still maturing, and substances like nicotine or opioids can have long-lasting effects on its development. That realization became the foundation for everything I’ve done since.

Adolescence is a critical time in brain development. Can you explain how addiction during this period can impact mental health, both in the short and long term?

One of the areas we’ve focused on is how nicotine affects the brain differently during adolescence compared to adulthood. What we’ve found is that nicotine exposure during adolescence but not adulthood is sufficient to potentiate the effects of other substances. In other words, adolescent nicotine use acts as a gateway, enhancing the brain’s response to other drugs of abuse.

This effect has been observed with substances like alcohol, cocaine, methamphetamine, and even fentanyl. But when nicotine is given to adults in our models, those same reinforcing effects just aren’t there. Most of the drugs show no impact at all from prior nicotine exposure in adults with the one exception being methamphetamine, which shows some effects in adult females.

What this tells us is that nicotine has age-dependent effects on the brain, and adolescence is a particularly vulnerable period. The developing brain seems especially sensitive to nicotine’s ability to increase the rewarding effects of other drugs. Thich is why early exposure can have such long-term mental health consequences and lead to future addiction.

In your opinion, what are some of the biggest failures in how we currently address addiction in adolescents and what needs to change?

One of the major issues we’ve seen is the rise of nicotine exposure through vaping. A lot of companies have deliberately marketed these products to adolescents, and many of them have faced (and lost) lawsuits for these predatory marketing practices.

By 2019, right before the pandemic, vaping among adolescents had surged dramatically. If you look at the data, nearly one in four high school seniors had experimented with e-cigarettes by 12th grade. That’s deeply concerning, especially in light of our findings that exposure to nicotine during adolescence increases susceptibility to other drugs of abuse. It’s not just about vaping but about the long-term neurological consequences.

There’s been some public health progress, like raising the legal age to purchase e-cigarettes from 18 to 21. But we know the brain continues to mature, particularly the prefrontal cortex, until around age 25. If we could delay exposure to addictive substances until after that point, we’d see huge improvements in public health outcomes.

Cigarette smoking, for example, tends to peak around age 18. After age 25, only about 3–5% of people begin smoking for the first time. So, the earlier someone starts, the more likely they are to become addicted. If we can prevent or delay that initial exposure to drugs for as long as possible, especially during adolescence, we can make a major difference in reducing addiction risk across the lifespan.

Why do you think most people begin using or becoming addicted to substances before age 25? Is it primarily because of marketing practices targeting youth, or are there other contributing factors?

There’s definitely more to it than marketing. There are strong biological reasons why adolescents and young adults are more vulnerable to addiction. The brain isn’t fully mature during this period, especially in regions like the prefrontal cortex and the reward circuitry. These areas continue developing into the mid-20s.

Nicotine, for example, binds to specific receptors in the brain: nicotinic acetylcholine receptors, which are highly expressed in those reward pathways during adolescence. That heightened expression makes the brain more sensitive to nicotine’s effects at this age, increasing the risk of reinforcing behaviors and addiction.

This developmental vulnerability aligns with what we see behaviorally, too. Adolescents are at a stage of life when they’re beginning to assert independence, move away from home, explore new environments, and engage more with peers. It’s also a time of increased risk-taking and thrill-seeking, behaviors that parallel what we see in adolescent rodents, who start engaging in rough-and-tumble play, leaving the nest to forage for their own food. And it just so happens that the period where they are beginning to explore these alternative activities is the period that makes them most susceptible to the reinforcing rewarding effects of drugs of abuse.

If adolescents don’t use substances during this time, their risk of addiction later in life drops significantly. But if they do, the brain is especially primed to internalize those rewarding effects, making long-term addiction more likely. It’s a uniquely sensitive window, and one that really underscores the importance of early prevention.

View article in our magazine.

Are there any major misconceptions about adolescent addiction that you wish more people understood?

Absolutely. I was just talking to a high school student recently, and one common misconception is that vaping products either don’t contain nicotine or that the nicotine they do contain isn’t harmful, especially compared to traditional cigarettes. Many teens view vaping as relatively safe, almost like caffeine. That perception has led to a huge rise in experimentation with vaping among adolescents.

But what we’ve found is that nicotine alone, even at low doses, can have serious neurological effects. Just the equivalent of one to two cigarettes worth of nicotine over four days is enough to enhance the brain’s response to other drugs of abuse. You don’t need a lot of nicotine exposure for it to alter how the brain processes rewards, especially during adolescence.

In fact, nicotine can be reinforcing on its own during this stage of development. We see this in studies using a method called conditioned place preference, where animals are given nicotine in a specific environment. Adolescent rodents will spend more time in the environment paired with nicotine, showing that even a single low dose can be rewarding. But when we run the same experiment with adults, that effect disappears: they spend equal time in both environments.

So it’s clear that the adolescent brain is uniquely sensitive to nicotine’s reinforcing properties. And beyond that, chronic exposure can lead to withdrawal, dependence, and long-term changes in brain chemistry. That’s why the idea that nicotine, especially in vaping products, is somehow “safer” is so dangerous. In my view, no amount of nicotine exposure is safe during critical developmental periods, from maternal exposure all the way through adolescence.

What do you think schools, communities, or even parents can do to help prevent adolescents from being exposed to drugs or to support those who have already been exposed?

Open dialogue is really important. Teens are already being exposed to vaping and other substances in their environments, sometimes even in middle school. In my conversations with students, they’ve told me about vaping happening in school bathrooms and how some schools have started stationing staff outside restrooms to try to reduce use.

The reality is that not talking about it doesn’t make the problem go away. Parents, teachers, and community members need to be having honest, nonjudgmental conversations with young people about what they’re seeing, what they’re experiencing, and how it affects them. The earlier someone is exposed to nicotine, the more likely they are to develop dependence, and nicotine can act as a gateway drug, enhancing the rewarding effects of alcohol, cocaine, methamphetamine, and more.

So prevention really starts with listening. It means understanding what teens are going through in their environments and working with them to reduce or delay exposure. The adolescent brain is incredibly sensitive during this period, so even short-term experimentation can have lasting consequences.

Limiting exposure is clearly important. But what about teens who have already used substances? Are there interventions that can help reverse or reduce the long-term effects?

That’s actually a major focus of our research: figuring out how to reduce the brain’s long-term susceptibility to addiction after early exposure. One promising direction involves targeting inflammation in the brain. For example, nicotine exposure during adolescence increases the activity of microglia (immune cells in the brain) which contributes to this heightened vulnerability.

In our studies, we’ve found that if we inhibit microglial activation, we can block the effect nicotine has on enhancing the brain’s response to later drug exposure. The goal is to bring the brain back to a “baseline,” essentially undoing the priming effect that nicotine creates.

There are also medications already approved by the FDA for nicotine addiction, such as varenicline (known as Chantix), which acts as a partial agonist on nicotinic acetylcholine receptors. It can reduce cravings and cigarette intake, but its effectiveness tends to drop off after three to six months. So while it can help in the short term, it’s not a long-term solution.

That’s why we’re also looking at combinatorial therapies, which use multiple drugs together to improve outcomes. One option is combining varenicline with bupropion (Wellbutrin), which blocks the reuptake of dopamine and norepinephrine, neurotransmitters involved in addiction and mood regulation. This combination could potentially reduce cravings more effectively and for a longer duration, though we still need more research to test safety and efficacy.

In short, there’s progress but no silver bullet yet. We need more time, more research, and more innovation to build sustainable, long-term interventions that can truly reverse or reduce the impact of early exposure to substances like nicotine.