In an ongoing search for new ways to tackle depression, researchers compared psilocybin, the active compound of magic pills, to an established antidepressant in a small phase II trial.
The results show that psilocybin was at least as effective as the usual antidepressant when used in conjunction with psychological therapy.
This was investigated very early on. But previous studies have suggested that psilocybin does not produce nearly as many side effects as antidepressants, and the effects are almost immediate.
Selective serotonin reuptake inhibitors (SSRIs), on the other hand, can be a nagging experience for many of us, with brain sacs, lethargy and emotional turmoil.
Many patients eventually feel worse before it can finally be determined if the remedy even works, which can take up to six weeks.
Thereafter, persistent side effects of antidepressants may include a long list: fatigue or insomnia, dizziness, weight gain and loss of libido.
The positive effects of the drug can then wear off over time for some people, counteracting the frustrating side effects, in addition to a new wave of deteriorating mental health. For other people, SSRIs never work to begin with.
But there may be other options.
Carefully led by mental health workers, 59 volunteers with depression were divided into two groups. One group administered the antidepressant escitalopram (regularly sold under the brand names Lexapro, Cipralex and others) daily, with extremely weak doses of psilocybin twice, three weeks apart.
For the second group, the doses of psilocybin were much stronger, and placebos were given in place 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 counts of depression reported by the volunteer himself indicate that the ingredient of the magic mushroom was just as effective as the antidepressant. While the psilocybin group did report a slightly greater improvement than the escitalopram group, the researchers point out that it was not at a statistically significant level.
They also suspect that the SSRIs have a delayed effect, and that increasing escitalopram might be even better if the trial takes longer.
Before anyone rushes self-medication, Carhart-Harris warns that the volunteers also provided psychotherapy to help them with any hallucination experiences.
“We believe that the … psychotherapy component is just as important as the drug action,” he said The guardian.
“With a psychedelic remedy, it’s more about freeing thoughts and feeling positive outcomes than being guided with psychotherapy.”
While five patients who used the SSRI reduced or discontinued their doses due to the negative effects they experienced, no one in the psilocibin group did so. However, due to the hallucinogenic effects of psilocybin, volunteers with a family history of psychosis were excluded from the trial, who probably favored the trial sample over those who would not have significant side effects.
“The percentage of patients who had anxiety, dry mouth, sexual dysfunction, or decreased emotional responsiveness 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 dose. This was also observed in a pilot study that the same researchers worked on in 2016.
In a New England Journal of Medicine Columbia University psychiatrist Jeffrey Lieberman warns that while it’s an ‘evidence milestone in the development of psychedelic drugs,’ there is still much we do not yet know, as psilocybin does exactly to our physiology.
Like regular antidepressants, the active ingredient 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.
While SSRIs lead to a kind of emotional blunting, psilocybin seems to do the opposite – fMRI scans have supported patients’ reports that the magic mushroom compound looks like emotional compounds, but exactly how it happens is still unclear.
However, we do not yet fully understand how the changes that SSRIs make to the serotonin levels in our brain can relieve depression or anxiety.
Although the results require further investigation, we must be careful not to read too much into it, given the small sample size and the fact that many of the participants belong to the same demographic of highly educated white men. The results are also self-reported, which means that it is difficult to compare objectively.
And given the controversial history of magic mushrooms, Lieberman is wary of the resources that attracted the drug and how it distorts the usual procedures for drug development. He also gives valid concern about the hallucinatory effects of the drug.
“How can we explain mystical, ineffective, 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 the effects of psilocybin is not necessary for the antidepressants, and other researchers have investigated the synthesis of psychedelics for mental health treatments without causing hallucinations.
With nearly 800 million people with mental disorders worldwide, those of us are waiting for external help with our brain chemistry and are waiting for more research in hopes of easier treatment options.
The new research was published in The New England Journal of Medicine.