New research supports the use of psilocybin—the active compound in mushrooms with psychedelic properties—as a therapeutic tool. It examines the effects of microdosing (small daily doses) of psilocybin on rats, avoiding bias in humans from suggestion and other factors.

Understanding the effects and side effects of lower doses

Psilocybin is being widely investigated for its potential to assist in the treatment of various psychiatric disorders, primarily depression and addiction, through therapy supplemented with a high dose of psilocybin.

Now, research by Associate Professor Mikael Palner and PhD student Kat Kiilerich at the University of Southern Denmark has focused on repeated microdoses of psilocybin, which are significantly lower than the doses typically used in therapeutic settings.

Published in the journal Nature Molecular Psychiatry, the paper focuses on a study of how rats tolerated the repeated low doses of psilocybin (well) and didn’t exhibit signs of reduced pleasure, anxiety, or altered locomotor activity.

New research method

“The increased anxiety and stress in society currently have placed a strong focus on microdosing, leading to a surge in the trade of mushrooms,” said Palner. “Countries such as the Netherlands, Australia, the USA, and Canada have either legalized or are in the process of legalizing psilocybin for therapeutic treatment.”

The researchers say they have established a valid new method that can be used for further research into the effects of repeated low doses of psilocybin. The study also supports the numerous anecdotal reports of the benefits of microdosing as a therapeutic intervention, and suggests new approaches to treating various mental disorders.

Enhanced Understanding

Mikael Palne, an associate professor affiliated with the Research Unit for Clinical Physiology and Nuclear Medicine at SDU and OUH, conducts research on the biological understanding of mental illness and treatment with psychedelic substances.

Palner developed an interest in researching psychedelic substances and psilocybin when he lived in Silicon Valley, California, eleven years ago, where he witnessed the surge of self-improvement practices that garnered significant media attention and prompted more people to experiment with microdosing.

“This motivated me to launch the project I’ve been devoted to for the past six years,” he says.

Psilocybin’s ubiquitous uses

Palner notes that Psilocybin (4-phosphoryloxy-N,N-dimethyltryptamine) is a naturally occurring psychoactive compound found in over 200 different species of mushrooms. It has been used in religious and ceremonial contexts by various cultures for centuries, particularly among Native American tribes.

In the body, psilocybin is converted into psilocin, which is responsible for its psychoactive effects. Psilocin affects serotonin receptors in the brain that can alter mood, perception, and cognition.

Citation: Kiilerich, K.F., Lorenz, J., Scharff, M.B. et al. Repeated low doses of psilocybin increase resilience to stress, lower compulsive actions, and strengthen cortical connections to the paraventricular thalamic nucleus in rats. Mol Psychiatry (2023). https://doi.org/10.1038/s41380-023-02280-z

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