Study: Microdosing Psilocybin May Help Treat Compulsive Behaviors, Anhedonia

A recent study looking at the effects of psilocybin microdosing observed a number of potential mental health benefits in rats, notably a reduction in stress-induced compulsive behaviors and anhedonia.

Microdosing, a once somewhat niche practice, is slowly gaining momentum in the mainstream as the psychedelic renaissance continues to take shape. It’s often associated with psychedelics like LSD and psilocybin, involving a regular dose of very small amounts of a substance to reap the benefits without the effects of a standard dose that may interfere with daily life.

As research around psychedelics as a whole continues to expand, so too does the research surrounding microdosing. A recent study from researchers at the University of Denmark looked at psilocybin, or the compound in magic mushrooms, and microdosing in rats. 

Ultimately the study, published in the journal Molecular Psychiatry, found that microdosing psilocybin could offer a number of therapeutic benefits, specifically reducing stress-induced compulsive behaviors and anhedonia, the inability to feel pleasure, interest or enjoyment in life experiences.

Creating a Microdose Model in Rats

It’s no secret by now that psilocybin has been scientifically shown to carry potential in treating a number of mental health symptoms and conditions, some of which are considered treatment resistant under traditional medicine. 

In the study abstract, researchers note that low-dose psychedelic use is still a lesser explored topic, especially as it pertains to its therapeutic potential — most psychedelic-assisted therapies being explored today involve larger doses with prominent effects.

They also note the anecdotal evidence around the wellness benefits of microdosing psilocybin, though they say these accounts tend to be “highly biased and vulnerable to placebo effects.”

To examine the effects of psilocybin microdosing, researchers housed 78 Long Evan rats in a number of experimental setups along with a proper “microdose” fit for rat brains. For the study, a dose occupying less than 20% of the rats’ 5-HT2A serotonin receptors in the brain without inducing overt behavioral changes was considered a microdose.

Researchers administered a microdose on rats every other day for 24 days, examining their behaviors including anxiety levels, reaction to stress and compulsive actions in familiar and novel environments.

Microdosing Psilocybin and Potential Mental Health Benefits

The study found that microdosed rats in controlled studies did not exhibit increased anxiety or symptoms related to schizophrenia, and they also showed a reduction in compulsive self-grooming behavior. Researchers said this suggested a possible impact on stress-related or compulsive behaviors. Researchers also noticed similar results for rats in new environments, showing no significant increase in anxiety.

Relating to stress-based anhedonia, researchers also noted that microdosed rats maintained a preference for sucrose, which showed that they hadn’t lost the ability to feel pleasure. The study also noted a lack of behavioral desensitization to psilocybin, meaning that rats’ responses to the substance was consistent over the treatment period. This is especially relevant as it relates to humans and microdosing long term for therapeutic reasons.

The study also showed the microdosed rats had an increased 5-HT7 receptor expression and synaptic vesicle protein 2A levels in the brain. Researchers said this could indicate that microdosing created changes in synaptic connections and receptor expressions, meaning that low-dose psilocybin was potentially responsible for these behavioral shifts.

Like any study, this one was not without its limitations. Rats are commonly used in studies as a lens to understand humans, though it’s difficult to determine how some of these findings may translate to human brains and behaviors in actuality. While the study did show a consistent response to microdosing over the research period, there’s also a remaining question surrounding a long-term psilocybin microdosing regimen and how long the effects of psilocybin would remain consistent in humans over months or even years.

“These results establish a well-validated regimen for further experiments probing the effects of repeated low doses of psilocybin,” researchers said. “Results further substantiate anecdotal reports of the benefits of psilocybin microdosing as a therapeutic intervention, while pointing to a possible physiological mechanism.”

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