A new study published in the peer-reviewed journal Nature explored the effects of giving psilocybin, the psychoactive compound found in magic mushrooms, to zebrafish.
Interest has developed in recent years in using zebrafish for psychedelic research. Zebrafish are a small, striped fish that belong to the minnow family. According to a 2013 study of the zebrafish genome also published in Nature, we share about 70% of our genes with these funny little creatures. They’re also considered to be very social as far as fish go, making them good subjects for study on psychedelics in particular and how they might affect human behavior.
The most recent study, published Wednesday, used machine tracking to analyze how psilocybin affects the swimming patterns of zebra fish.
“Here, we developed a wide-field behavioral tracking system for larval zebrafish and investigated the effects of psilocybin, a psychedelic serotonin receptor agonist,” the study said. “Machine learning analyses of precise body kinematics identified latent behavioral states reflecting spontaneous exploration, visually-driven rapid swimming, and irregular swim patterns following stress exposure.”
The study found two distinct patterns in how psilocybin affected their aquatic test subjects. They categorized the responses into “stimulatory” meaning to excite and “anxiolytic” which is a term assigned to anti-anxiety medications. The researchers also found that the effects on the psilocybin were very similar to what we know about how zebrafish (and humans) react to ketamine.
“Using this method, we found that acute psilocybin treatment has two behavioral effects: facilitation of spontaneous exploration (“stimulatory”) and prevention of irregular swim patterns following stress exposure (“anxiolytic”). These effects differed from the effect of acute SSRI treatment and were rather similar to the effect of ketamine treatment,” the study said.
The language of the study clarified exactly how the behavior of the fish differed with regard to the two major effects they found psilocybin to have. As far as the stimulatory effects, the researchers explained that the fish explored more of an area than they ordinarily would while sober.
“We found that acute, short bath pretreatment with psilocybin (2.5 μM, 4 h) in larval zebrafish had stimulatory effects on spontaneous exploration. We determined this pretreatment protocol after testing dosages between 1 μM and 50 μM and durations between 30 min to 24 h,” the study said. “Zebrafish typically swam near the wall in the small arena due to their innate preference called thigmotaxis In our large arena, on the contrary, they explored widely and swam longer distances.”
With regard to the anxiolytic effects of psilocybin on zebrafish, the researchers studied this response by dosing the fish and then exposing them to stress including rapid temperature changes, changes in the pH of the water, physically disturbing them and social isolation. When stressed, sober zebrafish tend to swim in a “zig-zag” pattern but the researchers found that the fish dosed with psilocybin did not respond this way.
“We pre-treated fish with psilocybin with the most effective concentration for enhancing spontaneous exploration, exposed them to stressors for five min, recovered them at a normal temperature, and tested their spontaneous exploration and optomotor response,” the study said. “Importantly, pre-treatment with psilocybin prevented stress-induced changes in swim patterns. Psilocybin-pretreated fish exhibited straight swim patterns even after the stress exposure.”
This is not the first study of psychedelics on zebrafish. A 2022 study by researchers at MacEwan University studied the effects of giving zebrafish microdoses of Lysergic Acid Diethlyamide, more commonly known as LSD or “acid.” They actually found that small doses of LSD barely seemed to affect the zebrafish based on the parameters they were looking at, which they surmised may point to a lack of addictive potential of LSD in humans.
“In our first study, we repeatedly microdosed our zebrafish with LSD. Using behavioural neuroscience tests to quantify locomotion, boldness and anxiety-like behaviour, we observed no impact on behaviour after 10 days of repeated dosing,” said a summary of the study published in The Conversation. “Like with terpenes, this may suggest a lack of withdrawal symptoms or addictive potential, which is encouraging for clinically viability for use in humans.”
Interest in zebrafish for clinical psychedelic research is growing, as a 2021 study published in the National Library of Medicine put it: “the utility of zebrafish (Danio rerio) in neuroscience research is rapidly growing due to their high physiological and genetic homology to humans, ease of genetic manipulation, robust behaviors, and cost effectiveness.”
