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May 23, 2021 2 min read

New chemical could put a stop to marijuana memory issues

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by Leo Bear-McGuinness
A woman recalls a pleasant memory

This article was first published on Analytical Cannabis. It is republished here with permission.

Cannabis is used by countless patients all over the world for pain relief. But the medication can come with side effects, such as cognitive issues and memory loss.  

Now, scientists say they have created a molecule that prevents these cognitive effects.

Published in the “Journal of Medicinal Chemistry,” the scientists’ study found that, when given to mice, their molecule allowed the rodents to feel the pain-relieving benefits of THC without any memory impairment. The authors of the study hope the new molecule could one day allow actual cannabis patients to receive the same benefits.

Total recall

Previous research has shown that cannabinoids like THC can elicit pain-relief by bonding with a receptor in the body called CB1. But this bond also incurs other effects of THC, such as memory impairment.

To remove this concern for patients, the researchers – largely from the University of Barcelona and the University of Lisbon – attempted to create a peptide molecule that could inhibit the chemical pathway of memory loss.

They started by studying two existing peptides in the body, which are thought to disrupt communication between the CB1 receptor and another receptor, 5HT2A, that binds to serotonin, a neurotransmitter that regulates learning and memory. With this understanding, the researchers created two synthetic peptides, similar in structure to the organic ones, but optimized for improved passage across the blood-brain barrier.

The team then fed the more promising of the two peptides to mice and injected the animals with THC.

To test the rodents’ memory, the mice were twice placed in a maze. Prior to the second experience, an object in the maze was replaced with a novel substitute. The time the mice spent inspecting the novel object was used to indicate their memory and whether it had been impaired.

A hot plate, set to gradually increase in heat, was used to measure the pain-relieving effects of THC. The time it took for a mouse to jump from the plate was recorded and used to indicate THC’s sedative properties.

After analyzing the results, the researchers found that the mice given both THC and the optimized peptide showed a higher pain threshold and improved memory compared with the mice only given THC.

Crucially, the researchers say, the peptide didn’t appear to abate with further use. Following multiple treatments with the new chemical, the mice still broadly displayed the same responses.

As such, the authors of the study are confident that their optimized peptide would be an ideal drug candidate for reducing the cognitive side effects of medical cannabis in humans.

“Our work has resulted in a novel tool to minimize the most prominent of [cannabis’] adverse outcomes, namely cognitive impairment,” the researchers write in their conclusion.

“We specifically propose a new approach based on the administration of a CB1R cannabinoid agonist (e.g., THC) in combination with a CB1R−5HT2AR altering agent,” they continue. “This compound is a 16-residue peptide that provides a convincing proof of concept that appropriately modified peptides constitute valid therapeutic candidates for treating pain with cannabinoids minimizing their side effects.”

The research was partly funded by Rhodes Pharmaceuticals, a wholly owned subsidiary of Purdue Pharma.

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