Doctors have reported five new cases of a mysterious memory syndrome in opioid drug users, adding to 14 others reported last year. Although scientists still don’t understand the link, the new reports point to a possible culprit: the synthetic opioid fentanyl.
The New England Journal of Medicine last week described four patients ages 28 to 37 who showed up in emergency rooms in Boston, Massachusetts, in 2017 unable to form new memories. All of them had a history of heroin use, and they all tested positive for fentanyl, a deadly opioid that is increasingly tainting the US heroin supply. In two of the patients, fentanyl was the only drug found in their systems.
Another case report, published in late January, described a 30-year-old man in West Virginia who had severe memory impairment and tested positive for fentanyl and cocaine.
Massachusetts public health officials have been on the lookout for this syndrome because of 14 high-profile cases reported there between 2012 and 2016. Researchers suspect that many other cases of opioid users with amnesia have gone under the radar because most doctors aren’t looking for them.
In the first set of Massachusetts cases, brain scans showed that all 14 people had damage to the hippocampus, the seahorse-shaped region of the brain that is responsible for encoding new memories, and 12 had a history of opioid use.
Because standard toxicology screens don’t test specifically for synthetic opioids, none of these cases were tested for fentanyl. But researchers say it was likely a factor.
“We have to be pretty careful about assigning cause,” said Jed Barash, medical director of Lawrence F. Quigley Memorial Hospital in Massachusetts, who reported the first cases of the amnesic syndrome and led the new New England Journal report. “But it’s becoming increasingly suspicious that fentanyl is the culprit.”
Opioid overdoses have quadrupled in the last 15 years, and fentanyl — a potent opioid 50 times more powerful than heroin — is now the leading cause of US overdose deaths. In Massachusetts, 75% of people who died of an overdose in 2016 had traces of fentanyl in their systems.
Because the initial amnesia cases were so unusual and paralleled the rise in fentanyl in the state’s drug supply, Massachusetts public health officials required that doctors start reporting such cases directly to the state, and encouraged them to screen for fentanyl when possible.
The jury is still out on whether fentanyl is especially toxic to the hippocampus, or if the memory problems are simply the result of the sudden loss of oxygen that comes with any opioid overdose.
The parts of the brain that are most sensitive to oxygen — including the hippocampi — are particularly affected during an overdose, said Gary Franklin, a research professor in neurology at the University of Washington. “I still think the primary hypothesis here is overdose,” Franklin told BuzzFeed News, adding that he didn’t think the new cases offered compelling evidence that fentanyl is specifically to blame.
But others say the particularly sudden oxygen cutoff caused by fentanyl may be behind the brain damage seen in these patients — and could explain the rare finding that many of the patients have fairly isolated brain damage in just their hippocampi.
“Fentanyl results in a very, very profound high, so it’s very quick-acting,” said Chun Lim, a neurologist at Beth Israel Deaconess Medical Center in Boston who reported one such amnesia case in his practice last year. That brief window could be enough time to damage the hippocampus, but not enough time for other regions to be affected.
Or it could be the combination of oxygen deprivation and a specific toxic effect of fentanyl. Studies in rats, for example, have shown that fentanyl can cause over-activation of cells in the hippocampus and other brain regions, damaging the cells, Barash said. “You’re burning both ends of the candle, because the amount of oxygen you’re taking in during an overdose isn’t enough to sustain the metabolism of the hippocampus when it gets ramped up on fentanyl, so it results in damage.”
All of the experts agree that the 19 cases discovered so far aren’t sufficient to determine the cause of the disorder. To better understand what’s happening, emergency room specialists should be aware of possible memory problems after overdoses, and test for fentanyl specifically.
“Some people go to the ER and they write off this amnestic behavior as weird or addicted behavior,” Marc Haut, a professor of behavioral medicine and psychiatry at West Virginia University who reported the first case in his state, told BuzzFeed News.
“Most people, when you talk about the opioid epidemic, they talk about the deaths,” Haut added. “Those are important, but we have to focus on the survivors too if we’re going to have an impact on the opioid crisis. If you have a dense amnesia, it’s really hard to learn a different way to live your life.”