Fruit Fly Study Shows Psilocybin Produces Long-Lasting Antidepressant-Like Effect

A recently published study has found that psilocybin can have a long-lasting effect similar to antidepressants in fruit flies, bolstering evidence that the psychoactive compound found in magic mushrooms may one day be used to treat serious mental health conditions in humans.

Charles D. Nichols, a professor of pharmacology at the Louisiana State University Health Sciences Center in New Orleans and one of the study’s authors, said that research with fruit flies can support investigations into other animal organisms including mammals.

“I have been studying fruit flies since my Ph.D. dissertation work, and have looked at the effects of psychedelics and serotonin receptor drugs in them as part of my overall research program ever since,” Nichols told PsyPost.

“Serotonins and their receptors in flies are involved in several key behaviors shared with mammals and humans, including many aspects of social interaction, and learning and memory,” Nichols added. “Fruit flies represent a powerful genetic model to elucidate mechanisms of drug effects and behaviors at the cellular level, and allow for more rapid discovery than in mammalian systems.”

Previous research has shown that psilocybin seems to have an antidepressant effect. A study published in 2020 showed that psilocybin can be an effective and quick-acting treatment for major depressive disorder. Most participants showed a substantial decrease in depression after treatment, and more than half were considered to be in remission from depression four weeks after treatment. Among the 24 patients, 67% showed a more than 50% reduction in depression symptoms after one week, and 71% showed similar progress at four weeks.

“The magnitude of the effect we saw was about four times larger than what clinical trials have shown for traditional antidepressants on the market,” said study co-author Alan Davis of Johns Hopkins University.

No, Fruit Flies Don’t Get Depressed

To conduct the new study, the researchers employed the forced swim test, a commonly used animal model to assess antidepressant effects by recording the behavior of rodents facing inescapable adversity. The scientists adapted the test for use with Drosophila melanogaster, the common fruit fly, which have neurotransmitter systems similar to mammals and have been widely used for genetic research. Although fruit flies and humans are very different, the research could be relevant to humans.

“Fruit flies likely don’t get ‘depressed’ (for that matter mice or rats don’t either — depression is a human disorder),” Nichols explained. “We are limited to studying how a drug alters neural physiology relevant to a specific behavior, not a psychiatric condition. For example, the forced swim test in and of itself does not measure a specific behavior seen in humans, but the forced swim test in rodents is highly predictive of antidepressant efficacy in humans. Nevertheless, fundamental processes are conserved, and the study of fruit flies has led to insights into human biology in several areas.”

Nichols’ team found that repeated doses of the antidepressant drug citalopram reduced immobility in fruit flies during the forced swim test.

“This is similar to SSRI effects in humans, where chronic dosing is necessary to produce an antidepressant effect,” the researchers noted.

Psilocybin Had Antidepressant Effect

Psilocybin was found to have an antidepressant effect on fruit flies during the forced swim test. Just a single dose of psilocybin administered several days before the swim test reduced immobility in fruit flies.

“The ability of a single exposure to psilocybin to alter neural biology and behavior long-term in a similar manner to SSRI antidepressants indicates that the effects of psilocybin (and likely other psychedelics) are highly evolutionarily conserved,” said Nichols. “This means that we can perhaps use fruit flies in rapid and powerful genetic experiments to identify key mechanisms underlying how psilocybin alters behaviors similar to antidepressants. Knowing how psilocybin alters neurobiology at the molecular and genetic level will hopefully lead to development and refinement of the use of psychedelics to treat psychiatric disorders.”

Nichols noted that using fruit flies can help speed research because they have short life spans and reproduce rapidly. In contrast, studies that use mammals for research can take considerably longer.

“We previously developed rat models where just one dose of psilocybin has very long-lasting antidepressant-like effects,” Nichols said. “These models are laborious and take several months from start to finish.”

“The first author on the study, Dr. Meghan Hibicke, designed and ran the experiments and leveraged her expertise in rodent behavioral pharmacology and models of depression to make this study a success,” Nichols added.

The researchers called for continued research with fruit flies to help determine how psilocybin might one day be used to treat depression in humans.

“Open areas for further research include determining which neurotransmitter receptor(s) are mediating the effects of psilocybin, and if other receptors that activate this target have similar effects, identifying other behaviors in the fly relevant to antidepressant effects in humans that may respond to psychedelics, and finally determining the molecular and genetic mechanisms underlying the effects of psilocybin to alter behaviors relevant to the study of depression in humans,” said Nichols.

The study, “Validation of the forced swim test in Drosophila, and its use to demonstrate psilocybin has long-lasting antidepressant-like effects in flies“, was published last month by the journal Scientific Reports.

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