In an ongoing search for new ways to deal with depression, researchers have compared psilocybin, the active compound in magic mushrooms, with a well-established antidepressant in a small phase II trial.
Promisingly, the results show that psilocybin was at least as effective as the common antidepressant when used in conjunction with psychological therapy.
They are still very early investigations. But previous studies have suggested that psilocybin does not produce as many side effects as antidepressants and its effects are almost immediate.
Trying the most common type of antidepressant, selective serotonin reuptake inhibitors (SSRIs), on the other hand, can be a nauseating experience for many of us, involving brainwashing, lethargy, and emotional turmoil.
Many patients end up feeling worse before it can finally be established if the drug even works, which can take up to six weeks.
After that, ongoing side effects of antidepressants can include fatigue or insomnia, dizziness, weight gain, and libido loss, among a long list.
The positive effects of the drug can wear off for some people over time, leaving the frustrating side effects to face a new wave of deteriorating mental health. For other people, SSRIs never work to begin with.
But there could be other options on the horizon.
Well guided by mental health professionals, 59 volunteers with depression were divided into two groups. One group was given the antidepressant escitalopram (often sold under the Lexapro, Cipralex, and other brands) daily, with extremely low doses of psilocybin provided twice, three weeks apart.
For the second group, psilocybin doses were much stronger and placebos were administered instead of escitalopram. Both groups also received psychological support throughout 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 depression scores suggest that the magic ingredient in the mushroom was as effective as the antidepressant. Although the psilocybin group reported a slightly higher improvement than the escitalopram group, the researchers noted that it was not at a statistically significant level.
They also suspect that because the SSRI has a delayed effect, if the trial had been extended for longer, they may have seen an even greater improvement in escitalopram depression scores.
Before anyone rushes into self-medication, Carhart-Harris warns that the volunteers had also guided psychotherapy to help them experience hallucinations.
“We firmly believe that the component of psychotherapy is as important as the action of drugs,” he said The guardian.
“With a psychedelic it is more of a release of thoughts and feelings that, when guided with psychotherapy, produces positive results.”
Although five patients taking SSRIs reduced or stopped their doses completely due to the negative effects they experienced, none of the psilocybin group did. But, due to the hallucinogenic effects of psilocybin, volunteers with a family history of psychosis were excluded from the trial, which probably skewed the trial sample toward those who would have no significant side effects.
“The percentages of patients who had anxiety, dry mouth, sexual dysfunction, or reduced emotional response capacity were higher in the escitalopram group than in the psilocybin group,” the team wrote in their work.
The most common side effect experienced by those taking psilocybin was a transient headache after receiving active doses. This was also observed in a pilot study in which some of the same researchers worked in 2016.
In a New England Journal of Medicine the comment accompanying the paper, Columbia University psychiatrist Jeffrey Lieberman warns that while this “is a test milestone in the development of psychedelic drugs” there are still many things we don’t know yet, such as what it does exactly psilocybin in our physiology.
Like regular antidepressants, the active substance in magic mushrooms works 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 chain of biochemical reactions involved in depression.
Although SSRIs lead to a kind of emotional dullness, psilocybin seems to do the opposite: fMRI scans have supported patient reports that the magic mushroom compound appears to increase emotional connections, but it’s still unclear how this happens .
However, we still don’t fully understand how SSRIs make changes to our brain’s serotonin levels to relieve depression or anxiety.
Although the results call for more research, we need to be careful when reading too much, given the small sample size and the fact that many of the participants belonged to the same population of highly educated white males. The results were also reported on their own, meaning that they are difficult to compare objectively.
And given the controversial history of magic mushrooms, Lieberman is wary of the resources the drug has attracted and how this distorts the usual procedures for drug development. It also raises valid concerns about the mind-boggling effects of the drug.
“How do we tell mystical, ineffable, and potentially transformative experiences to patients, especially if they are in a vulnerable mood?” he asks.
However, another recent study suggests that this aspect of the effects of psilocybin is not necessary for its antidepressant benefits, and other researchers have been studying the synthesis of 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 for our brain chemistry look forward to more research in hopes of having easier treatment options.
The new research was published in The New England Journal of Medicine.