Psychedelic-inspired drug may reduce depression without causing hallucinations | Chemistry

Preliminary results from clinical trials suggest that psychedelic drugs, best known for causing hallucinations, can also make users feel better. However, travel-related risks are an obstacle to using this drug as an antidepressant. Hallucinations can cause psychosis in people with certain risk factors, and their unpredictable effects require clinicians to closely monitor drug-taking patients.

Researchers now think hallucinations may be out of the question. Psyrosin, a psychedelic compound found in LSD and magic mushrooms, can induce antidepressant responses in mice by: Molecular mechanisms completely separate from those that cause hallucinations,team is natural neuroscience Paper today. The result, they say, has paved the way for the development of psychedelic-like drugs that can treat depression without hallucinations.

Neuroscientist Levathy Chottekarapanda of Weill Cornell Medical School said the study was rigorous and cautious, and the results were intriguing. But Chottekarapanda and colleagues stress that the path from demonstrating this kind of effect in basic research to developing effective drugs in humans can be perilous.

Research into the effects of hallucinogens has focused on serotonin 2A receptors in the brain. This is because drugs bind to this receptor and cause hallucinations. But psychedelics are “notorious as hyper-promiscuous drugs,” says neuroscience doctor Rafael Molinar. He is a student at the University of Helsinki and the first author of the paper. “They interact with many receptors.”

and Papers for 2021 cell, Moliner et al. showed that classical antidepressants work by binding to receptors for a signaling molecule called brain-derived neurotrophic factor (BDNF). When BDNF binds to this receptor, called TrkB, it initiates cellular processes that promote neuroplasticity: the growth and reorganization of connections between brain cells. The researchers found that antidepressants bind to TrkB and, rather than play a role in BDNF, help with that signaling process and induce neuroplasticity, which is thought to be an important part of the antidepressant response. found to cause

In a new study, researchers show that psychedelic drugs have a similar mechanism. First, we demonstrated that LSD and thyrosine bind to her TrkB in cells in culture dishes, binding him 1000 times stronger than conventional antidepressants. They also found that the drug stimulated increased neural connectivity in rat and mouse neurons, indicating increased neuroplasticity.

These findings suggested that psychedelic drugs may have antidepressant effects by acting on TrkB, even if they do not induce serotonin receptors. So the researchers gave mice LSD along with a compound that blocks the drug from binding to serotonin 2A receptors to see if this reduced depression-like behavior without inducing hallucinations. For humans, it’s easy to ask if someone has experienced hallucinations, but “for mice, it’s not so easy,” Molinar says.

His research team took advantage of the fact that rodents ingested hallucinogens typically jerked their heads as if to shake off flies. Mice treated with LSD and a serotonin 2A blocker did not exhibit head spasm responses. However, there was an improvement in the “crouching” behavior that researchers use as an analogue of depression in humans, suggesting that the drug still has antidepressant effects.

Gabriel Jacobs, a clinical pharmacologist at Leiden University, said these results could prompt further interest in finding drugs that target TrkB alone, and in researching whether hallucinations are necessary for the therapeutic effects of psychedelic drugs in humans. says it has the potential.

Some have warned that animal studies on depression often do not translate well to humans, and that expectations of psychedelics in clinical trials are unclear. Eiko Fried, a clinical psychologist at Leiden University, said that “hundreds of papers” had found promising mechanisms of antidepressant treatment in mice, but “none of them outperformed the gold-standard treatment for depression.” “It didn’t lead to the development of new pharmacological agents that are effective.” Baraz Szigeti, a psychedelics researcher at Imperial College London, says psychedelics can actually make patients feel better, but they can’t hide from patients whether they’ve taken a psychedelic or a placebo. . This obscures evidence from clinical trials.

Helsinki neuroscientist and lead author Eero Castren believes his team’s work could pave the way for promising psychedelic antidepressants. But “it’s going to be a pretty long journey,” Castren says. Even if such drugs appear to be effective in animals, large-scale human trials are needed to confirm that improved psychedelic drugs reduce depression and are not hallucinogenic. will be “It’s not going to happen in the next five years.”