Psychedelics are all the rage – not just in North America, but all over the world. Over the past few years, there has been a spotlight on psychedelics in general because of its proven as well as promising therapeutic applications.
Psychedelics have been shown to be effective in treating so many common ailments that we just can’t seem to treat as well with pharmaceutical drugs. These include PTSD, OCD, depression, anxiety, and addiction to name a few. That said, there’s still so little we know about psychedelics and how they work in the human body; there are many different psychedelics out there to study, too.
So researchers decided to get fish high on psychedelics to help us understand a little more.
In a recent study, whose results were published in Molecular Psychiatry, Dr. Takashi Kawashima led a team of researchers at the Weizmann Institute of Science to understand the behavior of psychedelics in the human body by exposing larval zebrafish to it, and how they influence different cells in the brain to provide its therapeutic benefits. The researchers utilized various scientific tools such as image analysis, optical microscopy, and even artificial intelligence.
Dr. Kawashima, who is a neuroscience researcher as well as a medical doctor, was particularly interested in understanding how psychedelics affect psychiatric or mental health conditions. It’s afflictions of the mind, after all, that psychedelics has been shown to be extremely effective in treating – and where conventional pharmaceutical drugs have failed. In particular, would psychedelics be able to replace selective serotonin reuptake inhibitors (SSRI’s) or even work better than them, but without the side effects?
With the findings, he hopes to contribute to treatments of mood-related disorders.
He adds that it isn’t ideal to experiment with psychedelics on humans because of the drug’s hallucinogenic properties. In addition, he acknowledges the challenges of doing so; it may be futile since psychedelics work with such deep-seated circuits in the brain, making it hard to analyze. “Zebrafish larvae, on the other hand, are transparent, making it possible to monitor drugs’ impact on specific brain cells and to correlate this with behavior,” Dr. Kawashima said. Zebrafish are also excellent test subjects since they share approximately 70% of their DNA with humans, and because of their social nature.
For the trials, the zebrafish were soaked in a psilocybin solution for four hours. Afterwards, they were made to participate in a series of behavioral experiment designed by Kawashima, which started off with the fish diving into a pool of water with vibrant patterns on the glass bottom. The fish were then exposed to a sudden decrease in water temperature, meant to incite stress on purpose so that the scientists could compare the behaviors to fish who weren’t exposed to psychedelics. “We wanted to see how psychedelics affect the fish’s stress response,” said Kawashima. “We found that, similar to what can be true to humans, when you’re heading into a stressful situation, taking a long bath can help.”
They found that the fish soaked in psilocybin were more likely to venture into the water tank’s darker areas even after being exposed to stress, compared to the fish who weren’t exposed to psilocybin. They even swam around faster than the sober fish, suggesting that psilocybin may act as a stimulant. Furthermore, they found that the psilocybin reduced anxiety after exposure to stress.
“SSRIs elevate serotonin levels throughout the brain,” explains Dr. Dotan Braun, a scientist and psychiatrist who worked with Dr. Kawashima’s laboratory. “Psychedelics, in contrast, affect serotonin receptors via a different, much faster mechanism and they appear to act on brain areas in a more targeted manner. A better understanding of their mechanism of action and a mapping of their influence on the brain may lead to more efficient drugs, with fewer side effects.”
Kawashima also explained that through optical imaging, they were able to observe neural activity in the drugged fish which were similar to the activity seen in other laboratories when studying mammalian brains that have been exposed to psychedelic drugs. “This indicates that psilocybin exerts its influence on behavior through neural mechanisms in deep areas of the brain that have been conserved in evolution and are also found in mammals, including humans,” Kawashima said.
Other Fish Studies
Back in 2022, researchers also exposed zebrafish to psychedelics for a study; this time, it was used to understand how microdosing benefits humans.
The study’s author, Trevor James Hamilton of MacEwan University, writes about the study and shares that while it’s common to expose zebrafish to chronic administration of drugs, which entails putting them in a drug solution for long periods of time, they attempted to do things differently for this study by dosing the fish accurately on a regular basis to mimic exact exposure times. They accomplished this by adding a tool into the tank which moved fish from their housing into the dosing tank, enabling them more accurate dosing.
The zebrafish were either given moderate doses of ethanol daily or binge doses for 3 weeks. They followed it up with another experiment of lower doses, then again used the same testing model and nicotine. They found that acute dosing reduced anxiety-like behavior, while repeated dosing resulted in more anxiety-like behaviors especially during withdrawals. According to Hamilton, this can also be observed in humans, such as those who use a cigarette or one alcoholic drink to address anxiety. Meanwhile, taking excessive amounts of either results in behavior that is exhibited during withdrawals.
Afterwards, they repeated the study using LSD on the zebrafish then utilized behavioral neuroscience tests to study behavior. They found that there was no change on behavior after 10 days of repeated exposure, which suggests the lack of addictive potential. This validates the lack of addictive qualities of psychedelics especially LSD, which means that there is no reason for them to be restricted by the government.
Conclusion
While we need more information and studies on the impact of psychedelics on humans, fish studies provide terrific insight on how psychedelics can affect or physiology. These studies are fantastic tools that can help us have a deeper understanding of how hallucinogenic drugs help us.