By Sara Miller, NoCamels -
A far cry from the pop culture depiction as the sole domain of barefoot hippies seeking enlightenment in a woody glade, scientists are exploring the use of psychedelic drugs as a potential treatment for depression, anxiety and post-traumatic stress disorder.
One such investigation is being carried out at Weizmann Institute of Science, Israel’s respected public research university.
A team at Weizmann’s Brain Sciences Department, led by research neuroscientist Dr. Takashi Kawashima and visiting psychiatrist Dr. Dotan Braun, is working to determine psychedelics’ impact on behavior and individual brain cells – with the aim of helping people with mental health disorders.
“Some types of psychedelic drugs, such as psilocybin [aka magic mushrooms] and MDMA [aka ecstasy], have shown promise as therapies for treatment-resistant depression and post-traumatic stress disorder,” wrote the US Department of Health just last year.
And it is psilocybin that is the focus of Kawashima and Dotan’s research, tying it to the effect of serotonin, a chemical in the brain that has many functions – including acting as a mood stabilizer.
“I have been studying how serotonin works in the brain for 14 years,” Kawashima, who is also a qualified medical doctor, tells NoCamels.
“And the psychedelic boom came and [we understood] psilocybin works as a serotonin mimic in the brain.”
The team’s objective is to determine whether it is possible to develop psychedelic alternatives to the most commonly prescribed antidepressants, known as serotonin-selective reuptake inhibitors (SSRIs).
These SSRIs, which include Prozac and Cipralex, prevent the reabsorption of serotonin, leaving more of it in the brain and potentially reducing the negativity of various forms of stress.
“SSRIs elevate serotonin levels throughout the brain,” according to Braun.
“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,” he said.
“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.”
Braun explains that while such therapies will not become the de facto standard for mental health, they could provide a lifeline for the significant number of patients who do not respond to current treatments.
“No one said that it’s going to be the first line of treatment for everything,” he tells NoCamels. “But [for] people with treatment resistant depression – about 30 to 40 percent of the patients – we did not have anything to offer to them.”
Kawashima also highlights that SSRIs have unwelcome side effects, including insomnia and sexual dysfunction, as well as the limited effectiveness. But, he says, until now the field of psychiatry had been “stuck” for decades on this kind of therapy.
Exploring just how psilocybin has a positive effect on mood, the team is using immature, larval zebrafish – which are completely transparent – to measure the effects of the psychedelic on the brain.
Kawashima also says the serotonin system in fish and humans is “very similar,” making zebrafish the ideal model to understand how serotonin controls behavior.
The fish were placed in a psilocybin “bath” and their behavior monitored and compared to the actions of fish who had not been exposed to the psychedelic.
The team found that the fish who had been exposed to psilocybin displayed less stress-related behavior than their “sober” counterparts when experiencing a sudden, temporary drop in water temperature.
They were more likely to explore their environment, even in the darker recesses of their tank, and also moved more quickly.
These two differences led the team to conclude that the psychedelic reduced stress and even acted as a stimulant.
Using a combination of AI, advanced image analysis and optical microscopy, the researchers also examined the brain activity of the zebrafish in relation to serotonin.
“You can see individual neurons at single cell resolution while the fish is alive,” Kawashima explains. “So we can see the entire serotonin system in action.”
The research is very much still in the early stages, but the team is already working with Yeda, Weizmann’s technology transfer, to help current work in the pharmaceutical industry with psychedelic treatments.
Kawashima believes that these researchers could use their method to test new drug compounds or compare the relative usefulness of the serotonin-targeting drugs already in use.
“I think our job is to find what the psilocybin is doing in the brain,” he says. “Because the entire field doesn’t know how the psychedelic is working, especially how and where it’s acting on to improve depression symptoms.”
This, he posits, could help make discoveries about the mechanics of serotonin-related disorders, and from there possibly generate completely new approaches to the treatment of disorders such as depression, PTSD and even addiction.
For Braun the psychiatrist, whose own patients include some people suffering from severe trauma, psychedelics could work where traditional therapies were not as effective as had been hoped.
“I think it’s for the best to try to offer them something,” he says. “Sometimes it could be much better than very, very high doses of conservative drugs.”
