A High Price to Pay for Pills that Promise ‘Focus’: Long-term Fallout from ADHD Drugs

A host of concerns and scholarship have surrounded the increased use – or abuse, as the case may be – of ADHD drugs like Adderall and Ritalin over the last several years. Some have centered squarely on the potential for abuse of drugs that are in the stimulant family, with recent critiques even suggesting that a steady proliferation in prescriptions, off label use, and some users’ pursuit of street drugs to cut costs mimics the trajectory of the opiate explosion. Others have expanded on the potential dangers of pursuing “performance advantages” with pills and the expansion of that trend beyond stressed-out college students into a large segment of adults. Finally, there has been a pretty steady drumbeat of research suggesting that these drugs can have disturbing physical effects – cardiovascular and heart health risks, among them. And, as this blog previously noted, when you combine some of these potential dangers with new packaging that can make these drugs look – and taste – like candy or chewy vitamins, it’s a brave new world that looks a little scary.

The red flags raised not only seem warranted, but a sound basis for the caution that experts now urge must be a critical part of prescribing these kinds of drugs. Now, it seems, there is even more reason to be wary. Recent studies that examined the effects of common ADHD drugs on patients found that repeated use – particularly in higher doses – has long-term implications on the way the brain develops – from possible alterations in personality to the way blood circulates in the brain and the way it responds to dopamine over time.

The latest study, published in the journal Neuroscience, suggests that adolescents who are frequently exposed to high doses of amphetamine, a stimulant that is used to treat attention deficit hyperactivity disorder (ADHD) and narcolepsy, are at risk of developing long-term changes in dopamine signaling. As part of the study, the researchers examined how amphetamines can affect the dopamine system in younger rats as an indicator of how they were likely to impact human adolescents. They found that repeated exposure in rats causes changes in dopamine signals and response. Since dopamine can affect memory, learning, attention span, and reward-motivated behaviors, any changes can negatively impact these functions.

"The dopamine system, which continues to develop throughout adolescence and young adulthood, is a primary target of psycho-stimulant drugs like amphetamine," said Joshua Gulley, a psychology professor at the University of Illinois and the lead investigator of the study. "Changes in dopamine function in response to repeated drug exposure are likely to contribute to the behavioral consequences – addiction and relapse, for example – that abusers experience."

Researchers could not pinpoint specifically how the stimulant was affecting brain function, but they suggest that since the adolescent brain is still developing, early exposure can impact the brain's development process. To understand this link further, the researchers analyzed the effects that amphetamine had on the prefrontal cortex, which is one of the last regions in the brain to fully develop in adolescence. The researchers found that repeated exposure affected how cells responded to dopamine.

"You need cells that are firing and communicating with one another, but you also need cells to stop communicating with one another at certain times and become quiet," Gulley explained. "Our research suggests that a subtype of dopamine receptor, the D1 receptor, is altered following amphetamine exposure. It's either not responding to dopamine or there are not as many of these receptors after exposure as there used to be."

The research team noted that the changes in dopamine signaling lasted for at least 14 weeks. At this point, the rats would resemble people in their 30s.

"This shows pretty clear evidence that drug use during adolescence, a time when the brain is still developing, has extremely long-lasting consequences that go far beyond the last drug exposure," Gulley said.

The study’s authors are careful to acknowledge that since their study was conducted on animal subjects, the findings might not yet be clearly extended to the human population. However, they note that "rats [can] exhibit many of the characteristics that human adolescents do." This is not the first time that leaders of this study have examined the effects of amphetamine abuse. In a 2013 study, Professor Gulley found that frequent amphetamine exposure affected the working memory in rats.

Once again, we may be seeing evidence that the solution to some of our human challenges may not be best met with a fast-acting pharmaceutical solution. There are certainly sound, and highly praised, natural (yet scientific) methods of improving brain balance and focus, including meditative practices and neurofeedback therapy – which trains the brain, over time and through a series of exercises, to be both more calm and attentive. It’s something that we have been incorporating into our practice at BTG for years now and it continues to show efficacy in both research and practice. It’s worth exploring, particularly when the promises of ADHD (and other) meds seem to come with so many pitfalls…