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Could very small doses of the active ingredient in so-called magic mushrooms help treat mental health conditions? Image credit: Wirestock/Getty Images.
  • Although there are many treatment options, mental health disorders can be difficult to treat sometimes.
  • For this reason, researchers have been looking at potential alternative treatments, including as psychedelic drugs such as psilocybin.
  • A new study in rats from the University of Southern Denmark has found that microdosing on psilocybin may have a beneficial effect in treating mental health disorders.

About 1 billion people around the world live with a mental health disorder. Examples of mental health disorders include depression, anxiety, bipolar disorder, eating disorders, and post-traumatic stress disorder (PTSD).

A study published in September 2023 estimates that approximately half the world’s population can expect to develop one or more mental health disorders by age 75.

While there are treatment options like psychotherapy, medications, and lifestyle changes that can help lessen mental health disorder symptoms, these are not equally effective for everyone.

For this reason, researchers have also been looking at alternative treatments that could help. One of these potential alternative treatments involved the use of psychedelic drugs, such as psilocybin.

Now, a study from the University of Southern Denmark has found that microdosing on — or taking very small doses of — psilocybin may have a beneficial effect on mental health disorders. The researchers conducted their study in rat models.

This recently appeared in the journal Nature – Molecular Psychiatry.

For this study — which was led by Kat Kiilerich, a doctoral researcher at the University of Southern Denmark — the researchers gave rats microdoses of psilocybin for 21 days.

After that time period, researchers discovered the rats tolerated the repeated microdoses of psilocybin well. They also did not show any signs of reduced pleasure, anxiety, or altered locomotor activity, which involves movement from one location to another.

Dr. Mikael Palner, associate professor, and head of the preclinical imaging core facility in the Research Unit for Clinical Physiology and Nuclear Medicine at the University of Southern Denmark, last author of this study, explained that the research team opted for microdoses of psilocybin because higher doses were likely to have the opposite effect, and to worsen mental health symptoms.

“It’s been shown that high doses [do] all of this, and that these [ill] effects mimic schizophrenia phenotypes [traits],” he told Medical News Today.

“Animals who are dosed with high chronic doses of LSD have even been used as models of schizophrenia. So yes, we were a bit happy that this was not the case for chronic low doses of psilocybin,” he said.

The scientists found that the repeated microdosing of psilocybin increased the rats’ stress resiliency, and they displayed fewer compulsive behaviors.

“From Reddit and other forums, we knew that people microdosed for obsessive-compulsive disorder (OCD), so the reduction in compulsive behaviors was our working hypothesis all the way,” Dr. Palner explained.

“It wasn’t until peer review that a clever reviewer assisted in redesigning the sucrose preference test, we had previously done that we noticed the resilience to stress. Compulsive actions and stress are tightly linked, and many psychiatric diseases are also worse in periods of high stress,” he added.

Researchers also noticed an increase in the amount of connections to the thalamus region of the brain. Past studies have linked thalamus connection deficits to mental health issues.

Psilocybin refers to the hallucinogenic chemical found in certain types of Psilocybe mushrooms, colloquially referred to as “magic mushrooms” or “shrooms.”

Psilocybin as a recreational drug is illegal in most places, including the United States. However, the states of Oregon and Colorado have recently passed measures to legalize the use of psilocybin in certain capacities.

Despite its legal status, researchers are studying it as a potential therapy for mental health conditions, as well as addiction and substance misuse disorders.

Psilocybin could help treat certain mental health conditions by stimulating serotonin receptors in the central nervous system. Because serotonin is the body’s “feel good” chemical, this can lead to changes in a person’s mood, how they think, and how they feel.

A study published in December 2016 found that psilocybin helped decrease depression and anxiety in people with life-threatening cancer. And research published in November 2022 discovered that the hallucinogenic chemical may help improve the symptoms of some psychiatric conditions.

Dr. Palner defined “microdosing” as “a term that is used to describe the practice of taking small doses of psychedelic drugs like LSD and psilocybin on a semi-regular basis.”

“There are many anecdotal reports and user services that describe the benefits of this practice, but it has always been very hard to distinguish the effects from placebo effects,” Dr. Palner said.

How much is a “microdose”? According to a paper published in July 2019, there is no agreed scientific consensus yet on what a microdose amounts to. The writers note that some guidelines define a “microdose” as 1% of a pharmacologically active drug dose. They suggest that a microdose of a psychedelic drug would be between 5–10% of the typical psychoactive dose.

Because microdoses are so small, the thought is that people receive the benefits the psychedelic drug offers without the hallucinogenic effects.

Research published in March 2023 found microdosing psychedelic drugs could have beneficial effects on mental health, as well as cognitive, physical, and social changes.

Another study, published in November 2021, reported that adults who microdosed psychedelics had lower levels of anxiety and depression than those who did not.

MNT also spoke with Dr. Keith Heinzerling, internist, addiction medicine specialist, and director of The Pacific Treatment & Research in Psychedelics (TRIP) Program for the Pacific Neuroscience Institute in Santa Monica, California, not involved in the current research, about this study.

He said he was excited to see research regarding microdosing going back to more basic science.

“Psychedelics are so interesting, it’s really hard to get them into a box — every time you think you have them figured out, they defy expectations,” he explained. “The majority of the recent modern research with psychedelics for therapeutic purposes has been with a dose of the psychedelic that produces a full psychedelic experience. And microdosing is a term that has got some traction at this point.”

“Microdosing has potentially a lot of really exciting applications, but there has not been much well-controlled modern scientific studies in humans with microdoses. The ones that have been done, it’s been hard to know whether the effects that some people experience or perceive from microdoses such as feeling healthier, feeling calmer, feeling more creative, whether those are from the drug or perhaps a placebo effect.”
— Dr. Keith Heinzerling

“So when you are able to go back to basic science studies, whether it’s in the lab or in rodents, and identify something biologically that’s happening in the brain of the nervous system that seems like it could align with some of the clinical effects you see in humans, that does provide very good support for [there] being something real happening there with the drug at the dose that’s being tested,” he told MNT.

Dr. Heinzerling said that, in the future, scientists and pharmaceutical companies may develop new antidepressant and anti-anxiety medications mimicking the same serotonin effect as microses of psilocybin.

“Perhaps that specificity might lead to an antidepressant medicine with fewer side effects and more effectiveness — that’s to be determined. And people are working on that, so that could be a good outcome from this,” he suggested.

“I think that psychedelics won’t be used one way — there will be a variety of different ways to use them and different applications at different doses in different settings in healthy people and people with mental health conditions,” added Dr. Heinzerling.

“But in all those cases, we should be excited, enthusiastic, and curious, but move in a measured way with intentionality and respect for the power that these medicines can have,” he cautioned.