Psychedelic effects of psilocin at the molecular level

Breaking new ground 22. jun 2023 2 min Associate Professor Himanshu Khandelia Written by Kristian Sjøgren

Researchers have determined how the active compound of magic mushrooms, psilocin, affects the brain at the molecular level and causes hallucinations and feelings of well-being and happiness. A researcher says that the discovery could be used to make new drugs to combat anxiety, depression and post-traumatic stress disorder.

Within the past decade, researchers all over the world have begun to examine the therapeutic potential of magic mushrooms. They have been shown to have great potential for treating people with anxiety, depression and post-traumatic stress disorder and may even help in smoking cessation.

A new study shows what happens in the brain when people eat magic mushrooms.

The results may pave the way for understanding how to develop drugs with the same effect in the brain as magic mushrooms and how these can be used for treating people.

“Magic mushrooms have great therapeutic potential, but getting them approved for pharmaceutical use can be difficult. Developing and producing drugs with the same effect under controlled conditions is therefore required so that various regulatory agencies approve the drugs. However, developing drugs with effects similar to those of magic mushrooms requires that researchers know how the compounds exert their effect at the molecular level in the brain, and this is exactly what we have revealed in this study,” explains a researcher behind the study, Ali Zanjani, Postdoctoral Fellow, Department of Physics, Chemistry and Pharmacy, University of Southern Denmark, Odense.

The research, which was carried out in collaboration with Himanshu Khandelia, Associate Professor and others at the same department, has been published in Biochimica et Biophysica Acta (BBA) – Proteins and Proteomics.

Regulatory ban halted research on psychedelics

About 200 mushroom species contain the active hallucinogen psilocybin, which has been known and used both medicinally and ritually by peoples all over the world for millennia.

This was also the case in high-income countries until the 1970s, but that was stopped when regulatory agencies banned the use of and research on psilocybin and other psychedelic compounds.

However, the rules have since been relaxed, and several interesting research results within the past decade have shown that psilocybin can be beneficial for treating people with depression in connection with cancer.

“Psilocybin can help people cope with their condition and not live the last part of their lives in depression and anxiety. Acknowledging this therapeutic potential has led to increased interest in developing drugs with the same effect as magic mushrooms,” says Ali Zanjani.

Investigated the chemistry using computer models

The researchers from the University of Southern Denmark investigated how psilocin, the bioactive form of psilocybin, affects the brain at the molecular level.

The researchers created computer-based mathematical models of the physical and chemical characteristics of specific compounds. This enabled them to investigate very precisely how the compounds interact with each other or with, for example, membranes and proteins in the brain.

“In the computer model, we can explore all the processes around every single atom and every single molecule. We can see where they can bind to each other and how much energy this requires,” explains Ali Zanjani.

How psilocin affects the brain

The results show that the psychedelic compounds can bind to both cell membranes in the brain and to the serotonin receptor, which is deeply involved in our feelings of well-being and happiness.

In fact, the study shows that psilocin binds more strongly than serotonin to the serotonin receptor, which may help explain the hallucinogenic effects of eating magic mushrooms.

The study also shows that psilocin binds very differently to the cell membrane and to the serotonin receptor and that very small changes in the atoms in the molecular structure greatly alter psilocin's properties as a psychedelic compound.

Finally, the study also shows how the bond between psilocin and the serotonin receptors in the brain causes the serotonin receptors to change structure and thereby send signals into the brain.

“Using the computer models, we can now understand the interaction between psilocin and the brain at a fundamental level, which is important to be able to develop drugs with a similar effect,” says Ali Zanjani.

“In the future, people can use the knowledge we presented to develop a new class of drugs for treating many conditions that are very difficult to treat today,” concludes Ali Zanjani.

The molecular basis of the antidepressant action of the magic mushroom extract, psilocin” has been published in Biochimica et Biophysica Acta (BBA) – Proteins and Proteomics. The Lundbeck Foundation and Novo Nordisk Foundation funded the project.

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