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November 30, 2016

A Johns Hopkins study suggests chemical compound can boost moods quickly and safely.

When people suffering from depression receive a prescription for antidepressants, they often assume they’ll feel better quickly. But in reality, most antidepressants take a month or longer to kick in.

“There’s a lag phase of four to eight weeks before there’s any improvement,” says Solomon Snyder, professor of neuroscience at the Johns Hopkins University School of Medicine. “For anyone who is seriously depressed or suicidal, that’s a very long wait.”

Snyder and other Johns Hopkins neuroscientists may have discovered a quick solution for depression. A chemical compound known as CPG3466B appears to boost the moods of mice in just a few hours, according to a study the team published in Molecular Psychiatry. Research associate Maged Harraz was the lead author; Snyder was a co-author.

CPG3466B mimics some of the effects of ketamine, a powerful tranquilizer that can serve as an antidepressant in small doses. Developed in the 1960s, ketamine was used to anesthetize injured American soldiers during the Vietnam War and is still used to treat pain in emergency rooms and intensive care units.

Ketamine carries many risks—it can be disorienting, causing symptoms similar to schizophrenia. Known as “Special K” on the street, it’s abused by those seeking a dreamlike high and dissociative state. Sexual predators slip the drug to potential victims, taking advantage of its power as a tranquilizer.

But in low doses, ketamine is also an effective—and rapid—antidepressant, elevating a patient’s mood in a matter of minutes. And because it works on a different chemical pathway than most antidepressants, it can bring relief to those who don’t get results from traditional antidepressants. Psychiatrists have experimented with giving intravenous infusions of the drug to those with severe, persistent depression, but they are wary of the risks.

“There’s a need for something similar,” Snyder says.

The Johns Hopkins team studied the effects of ketamine on the brain, isolating the chemical pathway that it alters. They found that CPG3466B acts on a different spot within the same pathway. But unlike ketamine, the compound is safe and nonaddictive. CPG3466B was synthesized by a drug company years ago and tested in clinical trials for Lou Gehrig’s disease and Alzheimer’s. It didn’t help these conditions, but it also did not harm subjects or appear to be addictive.

When school of medicine researchers gave the compound to mice, they found that it improved their performance in two tasks commonly used to measure depression. Compared with a control group, mice that took the compound swam longer after being plopped into a vat of cold water—showing that they were persistent. The compound also appeared to embolden mice to run into an unfamiliar, bright space to snatch a morsel of food. Treated mice hesitated less before running into the space than those in the control group.

Snyder is optimistic that a drug company will seize on his group’s research and begin testing a version of the compound as a treatment for depression. He also hopes this research will lead to the discovery of other drugs that work along the same pathway—producing, one day, an entire class of safe and rapid antidepressants.