Peptide could allow medical marijuana to relieve pain without side effects — ScienceDaily

Many people live with chronic pain, and in some cases cannabis can provide relief. However, the drug can also significantly affect memory and other cognitive functions. Now researchers, who report in the ACS Journal of Medicinal Chemistry, have developed a peptide that uses ∆9-tetrahydrocannabinol (THC), the main component of Cannabis sativa, to relieve pain without side effects in mice.

According to the U.S. Centers for Disease Control and Prevention, around 20% of adults in the U.S. had chronic pain in 2019. Opioids, the mainstay in the management of severe pain, are effective, but patients can easily become dependent on them. In some studies, medical marijuana has been helpful in relieving pain associated with migraines, neuropathy, cancer, and other conditions, but the side effects pose barriers to widespread therapeutic use. Previously, the researchers identified two peptides that cause an interaction between a receptor that the target of THC and disrupt another receptor that binds serotonin, a neurotransmitter that regulates learning, memory, and other cognitive functions. When the researchers injected the peptides into the brains of mice, the mice had fewer memory problems caused by THC. This team, led by Rafael Maldonado, David Andreu, and colleagues, wanted to improve these peptides to make them smaller, more stable, orally active, and able to cross the blood-brain barrier.

Based on data from molecular dynamics simulations, the researchers designed two peptides that were less than half the length of the original ones, but retained their receptor binding and other functions. They also optimized the peptide sequences for improved cell entry, stability, and the ability to cross the blood-brain barrier. Then the researchers gave mice orally the most promising peptide along with an injection of THC and tested the pain threshold and memory of the mice. Mice treated with both THC and the optimized peptide reaped the pain relieving benefits of THC and also showed improved memory compared to mice treated with THC only. It is important that multiple treatments with the peptide did not elicit an immune response. These results suggest that the optimized peptide is an ideal drug candidate for reducing cognitive side effects through cannabis-based pain management, say the researchers.

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