In recent years, psychedelic research has gone through a renaissance. Experiments on substances like LSD, ecstasy and psilocybin — one of the primary psychoactive ingredients in psychedelic mushrooms — have shown promising results for treating mental health disorders, like post-traumatic stress disorder, depression and even end-of-life anxiety for cancer patients. This year, Oregon became the first state to widely legalize psilocybin and more states are considering legislation that would follow in Oregon’s footsteps.
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In particular, psilocybin has attracted interest from scientists and the public alike as a potential treatment for depression. Over the last couple months, two teams found that single-dose psilocybin treatments significantly decrease depressive symptoms. Despite these recent rigorous projects, concerns about pseudoscience in psychedelics research still loom large over the field.
Psilocybin for Depression
The first placebo-controlled trial of psilocybin’s antidepressant effects came from a group at the University of Zurich and another study from pharmaceutical company COMPASS Pathways.
In both studies, participants with depression who had a moderate dose of psilocybin (25 mg for one study and roughly 15 mg for the other) reported significantly less severe depressive symptoms. The two studies also suggested that these effects may endure for around 2 to 3 weeks, but beyond that, the data was murky.
These trials build on previous research suggesting that psilocybin may have antidepressant effects, so the results weren’t particularly surprising, says Manoj Doss, postdoctoral researcher at Johns Hopkins University.
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“The COMPASS trial, however, did move the needle a bit more than most trials because it's the largest study to date across multiple sites, so it's unlikely that all of those sites have the same types of biases and hype as those at places like [Johns] Hopkins,” says Doss.
Now that researchers have a better understanding of what doses of psilocybin are necessary and sufficient for depression treatments, they’re moving onto other questions about these therapies.
“We still need to find out why these substances are helping patients. I.e., the clinical mechanism of action is still unknown,” says study author Katrin Preller, group leader at the University of Zurich. “In addition, we need larger trials. Furthermore, we need to find out what the optimal way is to conduct the non-pharmacological part of psychedelic-assisted therapy.”
Psilocybin Enhances Cognitive Flexibility
Previous studies suggest that psilocybin may have antidepressant effects because it increases certain types of cognitive flexibility that are linked to depression. Cognitive flexibility is the ability to switch between different ways of thinking, depending on changes in your environment.
In experimental settings, participants are tasked with choosing which item doesn’t belong in a set. But every few trials, the rule for not-belonging changes.
Doss and his team investigated the broad effects of psilocybin on cognitive flexibility in people with depression in a 2021 study published in Translational Psychiatry. They found that one week after two high doses of psilocybin spaced one to two weeks apart, patients with depression showed improved cognitive flexibility, measured by performance on that complicated rule-changing game.
As with many attention-grabbing fields of study, psychedelics research tends to prompt premature excitement. But jumping to conclusions too quickly could lead to dangerous outcomes.
“We need to be honest that these drugs do have risks,” says Doss. He notes that the COMPASS study reported that 8.6 percent of participants experienced severe adverse events, ranging from headaches to panic attacks to suicidal ideation. More research needs to be done to figure out how to curb these negative effects. To avoid over-hyping psychedelics research, be wary of bold and surprising claims.