This May Indiana University researchers Michaela Dvorakova and Alex Straiker published their findings in Cell Reports Medicine.
Dvorakova said their findings are surprising because acetaminophen may do the opposite of what painkillers are expected to do.
“So normally, how we look at pain in the field, is that increased levels of endocannabinoids mean less pain,” she said. “But in our study, we found out that actually might be the opposite in, in the case of 2-AG, which is one of the two endocannabinoids.”
Endocannabinoids are neurotransmitters with many important roles including relaying pain between nerve cells.
Instead of increasing these neurotransmitters, the drug seems to reduce them.
“The researchers found that acetaminophen inhibits an enzyme that makes one of the endogenous cannabinoids, 2-arachidonoyl glycerol, or 2-AG. Endocannabinoids are produced by the body to activate CB1 receptors, the same receptor that produces the psychoactive effects of cannabis” — Indiana University news release
This could be useful in developing painkillers that are less toxic to the liver as acetaminophen.
“Acetaminophen has a good safety profile, but it's just used so much. … when it's not used as directed, there is this liver toxicity risk,” said Straiker. Dvorakova said their finding opens a new way to look at treating pain.
“… by connecting with this enzyme that we see acetaminophen inhibiting, it's a new, completely new approach that we can make use of.”
It’s too soon to say when such research might begin.
Dvorakova said how the drug works, may include several mechanisms. Another hypothesis involves other enzymes which are affected by traditional nonsteroidal anti-inflammatory drugs.
Dvorakova said this was discovered by using a “neat” model, taking a neuron and making it synapse on itself, making a functional circuit.
“And then we use electrophysiology to measure electrical responses of that neuron. So it's a very precise method on a very simplified model. So then we just apply drugs and measure the response. So then we tried acetaminophen, and we saw some changes that were unexpected at first.”
Striker said during the experiment, they were actually testing a different hypothesis at the time.
“Then we realized that that acetaminophen was actually inhibiting the production of one of these endocannabinoids, and that was how it started,” he said. “We just kind of lucked into it.”
Michaela Dvorakova is a postdoctoral researcher at IU’s Gill Institute for Neuroscience and the College of Arts and Sciences’ Department of Psychological and Brain Sciences, and Alex Straiker is a Gill Institute research scientist.
Learn more about the experiment here
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