A supposed "brain-boosting" drug that the FDA previously rejected as a supplement can easily be bought online, and can deliver doses far above normal, researchers found.
Although piracetam is approved in Europe to treat cognitive impairment, it was never okayed by the FDA, neither as a drug nor as a supplement. Still, it's readily available online and is part of a rising tide of "nootropic" or cognition-enhancing drugs that are growing in popularity, according to a research letter appearing in JAMA Internal Medicine, with the U.S. market estimated at $640 million annually.
"The FDA has yet to warn consumers about piracetam," lead author Pieter Cohen, MD, of Cambridge Health Alliance in Massachusetts, told MedPage Today. "This drug is just the tip of the iceberg of how companies introduce a variety of unapproved drugs in 'cognitive enhancement' supplements."
Cohen said he can't keep track of how often over the past few years he's been asked about nootropics by patients: "It seems as if the idea of improving concentration and memory by taking a supplement has really captured consumers' imagination."
He and colleagues previously investigated two pharmaceutical-grade drugs passing as cognitive enhancement supplements in the U.S., vinpocetine and picamilon. The FDA subsequently determined that vinpocetine didn't meet the definition of a supplement, and recently warned against its use by women of childbearing age.
Though piracetam is approved in Europe, a Cochrane Review found its use is backed by just a few studies, all of poor quality. It was never approved in the U.S., and the only drug in its class that is on the American market is levetiracetam, an antiepileptic.
When a company applied to sell piracetam as a dietary supplement in 2004, the FDA rejected the request, telling the owner it was concerned "about the evidence on which you rely to support your conclusion that a dietary supplement containing piracetam will reasonably be expected to be safe."
Although Cohen said he hasn't yet seen patients who have been harmed by piracetam supplements, "I worry that these dosages could cause anxiety, depression, or unpredictable reactions in consumers given what we know about the drug's adverse effects," he said. So he and his team decided to take a closer look at piracetam, which some have described as the "original" nootropic drug.
They searched online for piracetam dietary supplements and analyzed 10 samples from 5 brands. They found that 8 samples from 4 brands contained piracetam, at a quantity ranging from 831 mg to 1,542 mg, which varied from 85% to 118% of the labeled amount.
In Europe, a typical daily dose is 2,400 mg to 4,800 mg, depending on renal function. But if one of the supplements is taken as labeled, a user could ingest more than 11,000 mg daily, they reported.
"This investigational drug that has never been approved by the FDA is readily available in over-the-counter supplements at supratherapeutic dosages," Cohen said.
Adverse effects that can occur when the drug is taken at normal doses include anxiety, insomnia, agitation, depression, drowsiness, and weight gain -- and the risks when taken at supratherapeutic doses aren't known, Cohen said.
He and his team cautioned that the sample size in their study was small and not necessarily representative because it only analyzed products marketed as dietary supplements. Still, they raised concerns that despite FDA warnings, pharmaceutical-grade brain-boosting supplements remain on the market.
For instance, even after FDA determined in 2016 that vinpocetine supplements couldn't be sold, "the agency has yet to actually follow up and remove it from the market," Cohen said, hence the recent warning for women of childbearing age.
Joshua Sharfstein, MD, of Johns Hopkins Bloomberg School of Public Health in Baltimore and a former FDA deputy commissioner, told MedPage Today that it's "nearly impossible for FDA to keep these [drugs and supplements] off the market with current laws."
"A critical step is mandatory registration, so FDA can immediately remove products that are not registered lawfully," said Sharfstein, who wasn't involved in the study.
Until laws governing supplements are reformed, Cohen and colleagues wrote, "clinicians should advise patients that supplements marketed as cognitive enhancers may contain prohibited drugs at supratherapeutic doses."
Last Updated November 25, 2019