- Researchers sought to determine the acute cardiovascular effects of amphetamine-dextroamphetamine use in healthy people free of ADHD.
- Study volunteers showed increases in blood pressure, heart rate, and sympathetic activation after a single dose of 25 mg.
- Study findings may help explain how acute cardiovascular events can be associated with illicit stimulant use among students and recreational users.
A single dose of amphetamine-dextroamphetamine (Adderall) had acute cardiovascular effects for healthy young people not regularly using it, a small controlled study found.
Resting systolic blood pressure (BP) increased significantly, from 116 to 126 mm Hg at 3 hours after a 25-mg dose. Also rising significantly were diastolic BP (from 72 to 78 mm Hg), heart rate (from 60 to 70 beats/min), and plasma norepinephrine (from 215 to 301 pg/mL), reported Anna Svatikova, MD, PhD, of Mayo Clinic in Rochester, Minnesota, and colleagues.
Meanwhile, there were no such changes observed when healthy volunteers were given placebo.
"Healthy Adderall-naive participants consuming a single dose of Adderall manifest striking increases in BP, HR [heart rate], and sympathetic activation, even at rest. These findings may have important mechanistic implications for understanding acute cardiovascular events associated with illicit Adderall use," study authors wrote in Mayo Clinic Proceedings.
Amphetamine-dextroamphetamine is an established prescription medicine for attention deficit-hyperactivity disorder (ADHD) and narcolepsy. It is considered safe and effective when it is prescribed and its use monitored.
Its illicit use is of concern, however, as "an increasing number of high school and college students are taking Adderall without prescription, abusing these drugs for both cognitive enhancement and recreational use to enhance performance in tests and sports, respectively," according to Svatikova's group. "There are a myriad of adverse effects from Adderall consumption ... Sudden cardiac death, cardiomyopathy, stroke, and myocardial infarction due to Adderall consumption have been documented in individual case reports."
The investigators thus designed their study to better understand the mechanistic underpinnings of the acute cardiovascular events and increased emergency room visits associated with illicit amphetamine-dextroamphetamine use.
"The model that we sought to replicate was that of college and graduate students who take Adderall without prescription as a study aid, to increase alertness and maintain wakefulness, and for purposes of social interaction. These data indicate that Adderall induces a marked pressor response and tachycardia at rest, accompanied by increased plasma norepinephrine, indicative of sympathetic activation," they wrote.
"Adderall may likely induce greater pressor and tachycardic responses when combined with energy drinks, as is often done to maintain wakefulness during studying," the authors speculated.
The study ultimately emphasizes that for people who don't have ADHD, a high dose of amphetamine-dextroamphetamine carries certain risks, commented Steven Pliszka, MD, of UT Health San Antonio, in an interview. "You shouldn't do it."
It's a different risk-benefit calculation for patients with ADHD, he cautioned, as they do have clinical benefits from stimulants.
In an accompanying editorial, Bhanu Kolla, MD, and Meghna Mansukhani, MD, both also of Mayo Clinic, also stressed interpreting the observed BP and heart rate increases (and perhaps slight excess risk of systemic hypertension with prolonged use) from stimulant use in the general population in the context of the known benefits of treating ADHD with these medications.
"These patients should continue to be managed with stimulants started at low dose and titrated to maximal efficacy as tolerated. A similar consideration applies to the off-label use of Adderall for depression wherein patients may derive benefit from Adderall, having failed to respond to standard therapy for depression," they advised.
Pliszka made a point that patients and telepsychiatry doctors should be reminded that amphetamine-dextroamphetamine users should at least take BP measurements once a month at home. If BP is consistently elevated for a few days, he emphasized "no need to panic" for patients and to ask the prescribing physician to adjust the dose or switch ADHD medications.
"It's unequivocal, if you have ADHD, you're going to benefit from stimulating treatment and you should seek treatment. If you don't have ADHD and you think, 'Everyone is taking Adderall, I should as well,' don't do it. Because it may not benefit in terms of your learning and may have other effects that you don't know about. Especially if you take a high dose if you've never taken it before," according to Pliszka.
The randomized double-blind crossover trial was conducted from 2018 to 2021. Enrolled were 30 healthy young adults who were free of ADHD and naïve to amphetamine-dextroamphetamine. Each received a total of 25 mg of oral amphetamine-dextroamphetamine or placebo on the first study day. The second study day, spaced a median 10 days later, they received the other pill.
Of the 29 participants who completed the study, 16 were women and the average age was 27 years.
Of note, there was a surprising orthostatic response to amphetamine-dextroamphetamine, with a 7-mm Hg decrease in systolic BP and a heart rate increase of 38 beats/min upon standing.
Svatikova and colleagues warned that the study could not draw conclusions on long-term medication use or use in people with cardiovascular comorbidities.
The 25-mg dose studied is also a bit higher than the usual starting dose of around 10 mg for people with ADHD, according to Pliszka. "That said, people who are diverting Adderall, say using it to take an exam or some illegitimate reason, they might take a higher dose."
He noted that it remains up in the air whether taking a stimulant really leads to any cognitive advantage for students in the first place.
Amphetamine-dextroamphetamine and other prescription stimulants remain under short supply in the U.S.
Disclosures
The study was supported by an institutional award and an NIH grant.
Svatikova and co-authors declared no competing interests.
Kolla, Mansukhani, and Pliszka also declared no competing interests.
