Medications such as magic mushrooms and LSD can act as powerful and long-lasting antidepressants. But they also tend to cause mind-altering side effects that limit their use. Yet there is hope on the horizon.
Scientists report in the journal Nature that they have created drugs based on LSD that seem to relieve anxiety and depression in mice without triggering the usual hallucinations.
LSD but different
“We found that our compounds had essentially the same antidepressant activity as psychedelic drugs,” said Dr. Bryan Roth, an author of the study and a professor of pharmacology at the UNC Chapel Hill School of Medicine. “Without the psychedelic side effects.”
The discovery could eventually lead to drugs for depression and anxiety that work better, faster, have fewer side effects and last longer. There is a lot of research on psychedelics and their effects, but research into hallucination-free, similar products is still scarce. In a previous attempt, a variant of ibogaine was made without the hallucinatory effect. The product is made from the root bark of a plant native to Central Africa. Better known as the iboga tree.
The new drug comes from a large team of scientists. They had built a virtual library of 75 million molecules that contain an unusual structure found in a number of drugs, including the psychedelics psilocybin and LSD, a migraine drug (ergotamine) and cancer drugs, including vincristine.
The team decided to focus on molecules that affect the brain's serotonin system, which is involved in regulating a person's mood. but they weren't looking for an antidepressant. However, as their work progressed, the team realized that other researchers showed that the psychedelic drug psilocybin could relieve depression in humans. In addition, the drug's effects could last for a long time.
Psilocybin as base
“There were really interesting reports of people getting great results with this after just a few doses,” said Brian Shoichet, an author of the study and a professor in the department of pharmaceutical chemistry at the University of California, San Francisco. So the team began to refine their search to find molecules in their library that might work in the same way.
Two molecules were found to be extremely active in alleviating symptoms of depression in mice. Scientists have shown that a depressed mouse tends to give up quickly when placed in an awkward situation, such as dangling by its tail. But the same mouse will continue to struggle if given an antidepressant such as Prozac, ketamine or psilocybin. Mice also continued to struggle when they were given the experimental molecules.
But they showed no signs of a psychedelic experience, which usually causes a mouse to pull its nose in a distinctive way. “We were surprised to see that,” Roth says. The team says it needs to refine these new molecules before they can be tried in humans. One reason is that they seem to mimic LSD's ability to increase heart rate and raise blood pressure.
Too much guidance
In addition to these side effects, psychedelic treatment now requires medical supervision and a therapist to guide a patient through the hallucinatory experience. Without these effects, many more patients could be treated.
Another advantage of the new approach is that the antidepressant effects start within hours of taking the drug and can last for a year or more. Drugs such as Prozac and Zoloft often take weeks to work and must be taken every day.
Source: npr.org (EN)