How hallucinogenic substance in psilocybin mushrooms works on the molecular level

Newswise —

Psilocybin is a type of hallucinogenic substance found in approximately 200 mushroom species, such as the liberty cap (Psilocybe semilanceata). This compound has been known and utilized by humans for thousands of years, and recently, it has gained attention from scientists and therapists for research purposes.

Many believe that psilocybin has the potential to revolutionize the treatment of conditions like severe depression and substance addiction. This is also the belief of researchers Himanshu Khandelia and Ali Asghar Hakami Zanjani from the Department of Physics, Chemistry and Pharmacy at the University of Southern Denmark.

The two researchers have recently published the scientific paper The Molecular Basis of the Antidepressant Action of the Magic Mushroom extract, Psilocin. The article is the third in a series on the same topic from the two researchers (Interaction of psychedelic tryptamine derivatives with a lipid bilayer and Magic mushroom extracts in lipid membranes). The newest study's co-authors are Teresa Quynh Tram Nguyen and Luise Jacobsen. The work is supported by the Lundbeck Foundation and the Novo Nordisk Foundation.

Binds stronger than serotonin

Himanshu Khandelia mentioned that his interest in psilocybin was sparked after listening to a podcast about using it to treat smoking addiction. As psilocybin mushrooms are abundant in Denmark, Khandelia was able to collect some from Svanninge Bakker and start his research easily.

Himanshu Khandelia and Ali Asghar Hakami Zanjani are researching the molecular-level changes that occur when psilocybin enters the body, gets converted to psilocin, and reaches the brain.

Ali Asghar Hakami Zanjani stated that previous studies have demonstrated that psilocin binds to serotonin receptors in the brain. Their research showed that psilocin binds more strongly than serotonin to a specific serotonin receptor called 5-HT2AR. This information can be useful in developing drugs that mimic the effects of psilocybin.

The researchers' focus is primarily on fundamental research and understanding the molecular mechanisms of psilocybin's effects. They currently do not have any plans to conduct clinical trials or design new drugs, as their expertise is not in neuroscience or pharmacology. Their aim is to contribute to the scientific community's understanding of the compound's potential uses and effects.

"I would be very happy if society can use our research. Maybe someone will take this further and create a molecule that can be used in medical treatment for conditions like depression," says Himanshu Khandelia.

Continuing their research in this area, Zanjani and Khandelia are currently exploring the mechanism through which the binding of the compounds to the receptor leads to psychoactive effects.

Researchers now have a more favorable environment than ever before to study the potential of psilocybin as a treatment for conditions such as depression, addiction, anorexia, and PTSD.

Since the 1960s, many countries' health authorities have had strict bans on researching hallucinogenic substances like psilocybin and LSD.

In 1959, Swiss chemist Albert Hoffman extracted psilocybin and psilocin from the P. mexicana mushroom. The pharmaceutical company he was employed with marketed and sold pure psilocybin to doctors and therapists who used it to treat their patients.

In the late 1960s, numerous countries, particularly the United States, enacted stricter laws on psychoactive substances, which also impacted research on psilocybin and related compounds. This led to a prolonged period of inactivity in psilocybin research, which lasted until just a few years ago.

Today, countries like the United States, England, and Denmark are again active in the research field - now with a more cautious approach.

Ali Asghar Hakami Zanjani cautions that both eating a psilocybin mushroom to take a trip and taking the substance in a medically prescribed tablet can lead to hallucinations and a feeling of being disconnected from the world, highlighting the need for caution.

Ali Asghar Hakami Zanjani explains that research shows that consuming psilocybin can result in hallucinations and a feeling of detachment from the world. Patients may experience a new perspective on their situation, such as a terminally ill cancer patient losing their fear of death and accepting their life situation. However, Zanjani emphasizes that these sessions should only take place in safe and guided settings under the supervision of trained therapists. He warns against taking psilocybin on one's own at home without proper guidance, as it can be dangerous.

More psychedelic research at University of Southern Denmark: 

Assistant Professor Mikael Palner from the Department of Clinical Research is also involved in research on psychedelic substances. He and his team are conducting experiments on rats to investigate the effects of different psychedelic substances like LSD, psilocybin, and DMT. One area of their research focuses on studying the pharmacokinetics of these substances in rats, while another area aims to examine whether psilocybin can alleviate symptoms of mental disorders like anxiety, compulsive behaviors, and PTSD in rats. More information about their work can be found on their website: https://www.palnerlab.org/.