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Fentanyl was involved in nearly half of New York’s overdose deaths in 2016. In Baltimore, fentanyl was involved in closer to three-quarters of the 574 overdose deaths in the first nine months of 2017.

Annals article with cocaine and fentanyl induced amnesia

An Unusual Amnestic Syndrome Associated With Combined Fentanyl and Cocaine Use

Uzoma B. Duru, MD; Gauri Pawar, MD; Jed A. Barash, MD; Liv E. Miller, PsyD; Indrani K. Thiruselvam, PhD; Marc W. Haut, PhD

Background: Between 2012 and 2016, a total of 14 persons in Massachusetts with a history of substance use developed an unusual amnestic syndrome that included acute, complete, and bilateral hippocampal lesions on magnetic resonance imaging (1).
Objective: To describe an additional patient whose characteristics may extend our understanding of this syndrome.
Case Report: In May 2017, a 30-year-old man was transferred from a local hospital in his native Maryland to a tertiary medical center in West Virginia for persistent memory impairment. According to family members, the patient had a history of heroin use, was recently discharged from a residential addiction treatment program, and had been abstinent from drugs for more than a month. Now back home, he returned late 1 evening and was difficult to arouse the next morning when his family found him in his room with drug paraphernalia. Because the patient was asking repetitive questions as he became more alert, he was taken to the local hospital.
A serum toxicology screen identified cocaine, but results of a urine toxicology screen were negative. Computed tomography of the brain revealed bilateral, symmetrical hypodensities in the hippocampi and basal ganglia. Serum aspartate and alanine aminotransferase levels were minimally elevated (42 and 50 U/L, respectively). The patient was transferred to the tertiary medical center, where his amnesia was characterized as anterograde. Magnetic resonance imaging of the brain found diffusion-weighted hyperintensities involving all of both hippocampi as well as the fornices, mamillary bodies, and globus pallidus (Figure). Cerebrospinal fluid findings and results of an assay for carbon monoxide in the blood were unrevealing.

Trace diffusion-weighted imaging findings on brain magnetic resonance imaging. Axial trace diffusion-weighted imaging shows bright signal involving the bilateral hippocampi (panels A through C, arrows), fornices and mamillary bodies (panel B, arrowheads), and globus pallidus (panel C, arrowheads).

Image: L170575ff1_Figure_Trace_diffusion-weighted_imaging_findings_on_brain_magnetic_resonance_imaging

Approximately 80 hours after presumed exposure, confirmatory urine testing was negative for fentanyl but revealed the presence of its metabolite norfentanyl (3.8 ng/mL). The patient had no known history of fentanyl use. Results of serum tests to detect designer opioids and synthetic cannabinoids and urine tests for buprenorphine, tramadol, and the metabolites of synthetic cannabinoids were negative.
Discussion: A man from Virginia who presented with a similar syndrome was evaluated at the same tertiary hospital in September 2015 (2). To our knowledge, these 2 patients constitute the first cluster of this amnestic syndrome to be documented outside of Massachusetts. This wider distribution implies that physicians in other states should be aware of this syndrome when evaluating patients with new-onset amnesia, particularly those with a history of substance use.
The identity of the offending agent is uncertain. Of the 16 patients with this syndrome, 15 had previously used or tested positive for opioids (12). However, none was tested specifically for fentanyl even though this drug is frequently mixed with other opioids and is not usually detected on routine screening (3). Therefore, to our knowledge this report is the first to associate fentanyl with this amnestic syndrome. Although isolated cocaine use has been associated with a similar presentation (4), the history and toxicology results in 8 of the 16 reported patients showed no evidence of cocaine use (12).
When administered to rats, fentanyl may cause acute neuronal degeneration in the hippocampus and affiliated limbic structures in association with hippocampal hypermetabolism (5). These observations suggest that fentanyl and cocaine together potentiate the underlying mechanism of injury, including the potential for both excitotoxic and hypoxic–ischemic processes; such an interaction may also explain some of the lesions identified outside the hippocampus (for example, those in the globus pallidus) in this patient and others.
We believe that clinicians who encounter patients with new-onset amnesia, particularly in the setting of substance use, should consider including in their evaluation diffusion-weighted magnetic resonance imaging of the head, routine toxicology screening, and neurologic consultation. When circumstances are consistent with this syndrome, we also suggest performing toxicology studies that are specific for fentanyl, its metabolites, and its analogues.


  1. Barash JA Somerville N DeMaria A Jr Cluster of an unusual amnestic syndrome—Massachusetts, 2012-2016 MMWR Morb Mortal Wkly Rep2017 66 76 9
  2. Massachusetts Department of Public Health. Data brief: an assessment of opioid-related deaths in Massachusetts (2013-2014). Accessed at on 10 September 2017.
  3. 83

    Test strips could help people who use drugs avoid fentanyl

    Baltimore Sun article regarding Fentanyl test strips

    People who buy heroin on the street don’t get warned that it may contain fentanyl, the potent opioid responsible for most overdose deaths in Maryland and nationwide.

    But a thin strip, akin to a pregnancy test, could quickly and reliably tell them.

    Those are the findings of researchers at Johns Hopkins and Brown universities, who went looking for a scientifically sound way to spot fentanyl in powder or pills so people could protect themselves by avoiding batches or reducing amounts they use. The researchers used a strip meant to test people’s urine for fentanyl.

    “They don’t want to die,” said Susan Sherman, associate professor in the health, behavior and society department at Hopkins’ Bloomberg School of Public Health.

    Public health officials prefer that everyone with a substance use problem get treatment but have pursued stopgap measures such as distribution of the overdose remedy naloxone to stem a growing tide of deaths. In Maryland, 1,705 people who overdosed and died in the first nine months of 2017 had fentanyl in their systems, up 56 percent from a year earlier.

    While the research shows the strips could work, it’s not clear whether they’ll prove useful. Drug users may not embrace them, they might cost too much or fail to identify fentanyl all the time, researchers and advocates say.

    The message from public health departments from Baltimore to New York is that it’s safest to assume every batch contains fentanyl.

    But some advocates already are handing out the strips through official and unofficial channels. The California Department of Public Health distributes them through almost a dozen needle exchange programs across the state. Advocates in New York give them out, while the New York City health department does not but said it was interested in the Hopkins-Brown research.

    For now, Stephanie Buhle, a department spokeswoman, said, “We encourage people who use drugs to take precautions to reduce their risk of overdose, including: carrying naloxone, using with another person, using a small amount to test potency first and not mixing drugs.”

    Fentanyl was involved in nearly half of New York’s overdose deaths in 2016. In Baltimore, fentanyl was involved in closer to three-quarters of the 574 overdose deaths in the first nine months of 2017.

    Baltimore’s health department aggressively distributes naloxone and developed a text system to alert users to places where fentanyl is likely being sold so they could avoid it. Dr. Leana S. Wen, health commissioner, sees potential in deploying strips.

    “In principle we support the idea of drug checking, but in practice it’s a complex issue and the last thing we want is people thinking testing is the answer,” Wen said. “We really need to assume it’s fentanyl. … But testing could amplify the message to take precautions.”

    The department plans to use the strips as they were intended, for urine tests, in a pilot at Mercy Medical Center and the University of Maryland Medical Center Midtown Campus. The department bought 3,500 strips, costing $1 each, to test overdose survivors with strips in the emergency room. It wants to gauge changes in providers’ and users’ behavior if they learn fentanyl was indeed responsible.

    The idea for checking drugs with strips came from a so-called safe injection site in Vancouver, Canada, researchers and advocates believe.

    The Hopkins-Brown study is probably the first to check the strips’ accuracy and adoptability, said the researchers, who partnered with the Bloomberg American Health Initiative’s public health solutions program.

    There are still barriers. This is an “off-label” use of the strips — one not approved by the U.S. Food and Drug Administration. To test a drug for fentanyl, a sample would be mixed with water and the strip would display two stripes for fentanyl and one stripe for none.

    Public health officials could be put in legal jeopardy if users rely on inaccurate results. They also could be handling illegal drugs that they help test.

    Researchers said the strips do appear reliable, outperforming electronic versions by accurately detecting even tiny amounts of the drug, according to the study, which has not yet been submitted for publication in a scientific journal.

    There also seemed to be interest when researchers asked hundreds of users about using strips. Few said they would abandon drugs with fentanyl, but three-quarters said they would change their behavior, such as using less initially.

    Another drawback is that the strips only detect fentanyl and three chemical variations, while law enforcement officials say illegal labs constantly churn out new formulations. Strips also can’t detect other dangerous substances.

    The researchers hope to spur some pilot projects in cities around the country to assess the strips’ usefulness.

    Tino Fuentes, a former heroin users turned advocate and consultant, believes they will become widely used. After he began buying strips about a year ago and handing them out in the New York area, he began getting calls from people requesting more.

    He said people tell him they are fearful of fentanyl, though he said a small number seek it for a stronger high. He does bring up treatment with those who are receptive but said for now most just want to avoid overdose.

    “This is not a solution to the problem and will not stop drug use, but what they will do is help change user patterns and keep people alive,” Fuentes said. “Overdoses are getting more frequent, so we need new thinking of ways to stop them. Anything to keep them alive.”

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