In an ongoing search for new ways to tackle depression, researchers compared psilocybin, the active ingredient in magic mushrooms, with a proven antidepressant in a small phase II study.
It is promising that the results show that psilocybin was at least as effective as the usual antidepressant when used in addition to psychological therapy.
It is still very early research. But previous studies have suggested that psilocybin doesn’t cause nearly as many side effects as antidepressants, and the effects are almost immediate.
On the other hand, testing the most common type of antidepressants, selective serotonin reuptake inhibitors (SSRIs), can be a nauseating experience for many of us, with brain fog, lethargy, and emotional turbulence.
Many patients end up feeling worse before it can finally be determined if the drug is even working, which can take up to six weeks.
After that, persistent side effects of antidepressants can include fatigue or insomnia, dizziness, weight gain, and loss of libido, among a long list.
The drug’s positive effects may wear off over time for some people, causing the frustrating side effects to contend with a new wave of deteriorating mental health. For other people, SSRIs never work to begin with.
But there may be other options on the horizon.
Closely supervised by mental health professionals, 59 volunteers with depression were divided into two groups. One group was given the antidepressant escitalopram (often sold under the brand names Lexapro, Cipralex, and others) daily, with two extremely weak doses of psilocybin, three weeks apart.
For the second group, the doses of psilocybin were much stronger and placebos were given instead of escitalopram. Both groups also received psychological support during the trial.
Neither the volunteers nor the research team, led by Imperial College London neuroscientist Robin Carhart-Harris, knew which group would receive which treatment.
After six weeks, the volunteer’s self-reported scores of depression suggest that the magic mushroom ingredient was just as effective as the antidepressant. Although the psilocybin group reported slightly greater improvement than the escitalopram group, the researchers point out that it was not at a statistically significant level.
They also suspect that because the SSRI has a delayed effect, they may have also seen an even greater improvement in escitalopram depression scores had the trial lasted longer.
Before anyone rushes to self-medicate, Carhart-Harris warns that the volunteers had also counseled psychotherapy to help them through hallucination experiences.
“We strongly believe that the… psychotherapy component is just as important as how drugs work,” he said The Guardian
“A psychedelic is more about letting go of thoughts and feelings that, when accompanied by psychotherapy, produces positive results.”
While five patients taking the SSRI reduced their dose or stopped it altogether because of the negative effects they experienced, none of the patients in the psilocybin group did. But because of psilocybin’s hallucinogenic effects, volunteers with a family history of psychosis were excluded from the study, likely biasing the test lead toward those who would not have significant side effects.
“The percentage of patients with anxiety, dry mouth, sexual dysfunction or decreased emotional response was higher in the escitalopram group than in the psilocybin group,” the team wrote in their paper.
The most common side effect experienced by those taking psilocybin was a transient headache after receiving the active doses. This was also observed in a pilot study that some of the same researchers worked on in 2016.
In a New England Journal of Medicine Commentary accompanying the paper, Columbia University psychiatrist Jeffrey Lieberman warns that while this is “an evidential milestone in the development of psychedelic drugs,” there is still much we don’t yet know, such as what psilocybin does to our physiology.
Like many common antidepressants, the active ingredient in magic mushrooms acts on the serotonin pathways in our brain. Rodent studies have shown that psilocybin binds to a serotonin receptor called 5-hydroxytryptamine type 2A, which is part of a series of biochemical reactions involved in depression.
While SSRIs lead to a kind of emotional blunting, psilocybin appears to do the opposite – fMRI scans have supported patients’ reports that the magic mushroom connection appears to increase emotional connections, but exactly how this happens is still unclear.
However, we still don’t fully understand how the changes SSRIs make to serotonin levels in our brain work to relieve depression or anxiety.
While the results call for further investigation, we must be careful not to read too much into them, given the small sample size and the fact that many of the participants belonged to the same demographics of highly educated white men. The results are also self-reported, which means they are difficult to compare objectively.
And given the controversial history of magic mushrooms, Lieberman is wary of the agents the drug has attracted and how it interferes with common drug development procedures. He also expresses legitimate concerns about the drug’s hallucinogenic effects.
“How do we explain mystical, ineffable and potentially transformative experiences to patients, especially when they are in a vulnerable state of mind?” he asks.
However, another recent study suggests that this aspect of psilocybin’s effects is not required due to its antidepressant action, and other researchers have looked at synthesizing psychedelics for mental health treatments without causing hallucinations.
With nearly 800 million people with mental health disorders worldwide, those of us who rely on outside help with our brain chemistry are eagerly awaiting more research in the hope of easier treatment options.
The new research is published in The New England Journal of Medicine