Research & Development Fentanyl’s dangerous effects potentially reversible by new compound

Fentanyl’s dangerous effects potentially reversible by new compound


The devastation by fentanyl is reflected in the provisional statistics from the CDC (Centers for Disease Control and Prevention). According to the data, synthetic opioid overdose numbers increased by 20% from 2020 to 2021, rising to 71,000 people.

A new drug developed in the University of Maryland lab has shown potential early on against fentanyl’s effects as well as methamphetamine and a few other substances. The lead author of the study on the drug, Lyle Isaacs said that it functions very differently from the current first-line drug for opioid overdose, naloxone, which is thrilling.

Isaacs’ goal was not to develop a treatment when the molecule Pillar[6]MaxQ (or P6AS) was synthesized two years ago in his lab. Isaacs’ team examines the method through which the container molecules attach to smaller molecules. It was later realized that the molecule would probably attach to ammonium ions as well and some experiments were conducted. These ions are usually found on drugs that are commonly abused.

The experiments showed that the molecule indeed does attach to the abused drugs, upon which the researchers decided to dig deeper and see if fentanyl and methamphetamine effects could be reversed. The researchers and Matthew Roesch’s psychology lab teamed up to conduct studies on mice.

High doses of either fentanyl or methamphetamine were given to groups of 8 to 10 mice. They were also given P6AS soon after, at different intervals. The results showed that the effects could be reversed if the molecule was given up to five minutes after methamphetamine, while the time frame was 15 minutes for fentanyl.

When the mice were given methamphetamine or fentanyl they would run around their boxes. Scientists called this hyperlocomotion. They could tell the molecule was working because the mice returned to a normal state after receiving it. They also tested naloxone similarly. Both P6AS and naloxone reduced locomotion levels at the same rate when given 15 minutes after fentanyl.

Isaacs said that the molecule seems to work for the animals that are potentially overdosing, but the molecule’s other possible applications are secondary. Isaacs and Weijian Xue (former post-doc) applied for the patent of the molecule, and the university has shown interest in talking to partners or investors for further development.

National Harm Reduction Coalition (NHRC), a group that supports addiction-struggling people or those who are damaged by racist drug policies, has said that though the advancement in new methods to prevent overdoses is a positive thing, the main issue is that the tools that are already there are inaccessible.

Mary Sylla, NHRC’s director of overdose prevention policy and strategy said, “We’re excited about any opportunities to reduce overdoses. However, naloxone is available and it reverses overdose for opioids and fentanyl. What’s more important is that we get naloxone to people who need it.”

The issue with naloxone is that it is not available as an over-the-counter (OTC) drug and a prescription for generic naloxone is roughly $68 for an uninsured person (2018 figures published in JAMA 2022). The FDA may make naloxone available OTC soon.

Talking about the cost of drugs using P6AS, Sylla said that a lot can be done for the overdose crisis if the cost of the agents can be reduced.

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