New Drugs Relieve Anxiety and Depression in Mice Without Psychedelic Trip

A team of researchers has created two new drugs based on psychedelics that seem to relieve anxiety and depression in mice without causing hallucinogenic effects. The researchers involved in the study, which was published by the journal Nature in September, determined that two molecules activated the same receptor in the brain as lysergic acid diethylamide (LSD) without producing the psychedelic trip commonly associated with the drug.

“We found our compounds had essentially the same antidepressant activity as psychedelic drugs,” Dr. Bryan Roth, an author of the study and a professor of pharmacology at UNC Chapel Hill School of Medicine, said in a report from NPR. But, he added, “they had no psychedelic drug-like actions at all.”

Psychedelics, Depression And Mental Health

The new study builds on previous research that has shown that psychedelic drugs such as LSD and psilocybin (the psychoactive compound in magic mushrooms) show potential as treatments for mental health conditions including depression and anxiety. In one study conducted by researchers at Johns Hopkins University, researchers found that only two doses of psilocybin relieved symptoms of major depression for at least a month. Another study showed that a substantial majority of people using psilocybin to treat anxiety brought on by a life-threatening cancer diagnosis found considerable relief from the drug.

However, David E. Olson, a chemical neuroscientist at the University of California, Davis who was not involved in the new study, said that the hallucinogenic effects of the drugs, which can last for hours, make using psychedelic compounds for therapeutic use problematic.

“While psychedelics have the potential for treating disorders like depression, their hallucinogenic effects necessitate in-clinic administration, which drastically increases the cost and complexity of the treatment,” Olson told Medical News Today. “Non-hallucinogenic compounds that produce psychedelic-like antidepressant effects could potentially be administered at home, thus reducing costs and increasing patient access.”

He also noted that the researchers represent the “third independent group to develop a non-hallucinogenic antidepressant compound inspired by psychedelics, which is a nice confirmation that this approach has potential.”

“It’s very encouraging to see multiple groups approach this problem in different ways and come up with very similar solutions,” he added in the report from NPR.

Two Promising Psychedelic Drugs for Depression Among Millions of Compounds

To conduct the study, the researchers assembled a virtual library of 75 million molecules that include an unusual structure found in several different psychedelic medicines, including the psychedelics psilocybin and LSD, a migraine drug (ergotamine), and cancer drugs including vincristine. Although they were not specifically looking for an antidepressant, the researchers focused their efforts on compounds that affect the serotonin system in the brain, which is involved in regulating mood. As they continued their research, they learned of other studies showing that people with depression were being helped by psilocybin, with long-lasting effects of up to a year or more.

“There [were] really interesting reports about people getting great results out of this after just a few doses,” said Brian Shoichet, an author of the study and a professor in the pharmaceutical chemistry department at the University of California, San Francisco.

Mouse Study Reveals No Psychedelic Effect

The research team then refined the search to find molecules in the virtual library that might have the same effect. They determined that two molecules were strong possibilities. After synthesizing the drugs, the compounds showed antidepressant and anti-anxiety effects in mouse studies at lower doses than the commonly prescribed antidepressant Prozac.

“They had the best properties,” said Shoichet. “They were the most potent, and when you gave them to a mouse, they got into the brain at the highest concentrations.”

The mice did not exhibit signs of a psychedelic experience, which typically causes a mouse to twitch its nose in a distinctive way. After further study, the researchers determined that the two molecules were also “extremely effective” at relieving symptoms of depression in mice, according to Roth.

The researchers believe the new study could lead to novel drugs that provide the benefits of LSD and psilocybin without the psychedelic trip, a possibility that would make therapy with the class of drugs more practical, by reducing cost and time associated with providing psychedelic medical care.

“Society would like a molecule that you can get prescribed and just take and you don't need a guided tour for your trip,” said Shoichet.