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

According to the U.S. Centers for Disease Control and Prevention, about 20% of adults in the U.S. experienced chronic pain in 2019. Opioids, the mainstay for severe pain management, are effective, but patients can easily become addicted to them. In some studies, medical marijuana has been helpful in relieving pain from migraines, neuropathy, cancer and other conditions, but the side effects present hurdles for widespread therapeutic use. Previously, researchers identified two peptides that disrupt an interaction between a receptor that’s the target of THC and 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. Now, 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.

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