Promising clinical trials of the hallucinogen psilocybin show that it may be an effective treatment for depression, but it’s too early to know for certain.
Interest in using hallucinogens, such as magic mushrooms, to treat depression is on the rise, fueled by the results of early clinical trials in people with cancer.
Researchers caution it will be several years before data is available from the first randomized trials of psilocybin — the hallucinogenic compound in magic mushrooms — for depression in those without cancer.
But advocates say psilocybin could provide an effective treatment for depression with fewer side effects than current antidepressants, which leave many people emotionally “blunted.”
“The work is very promising, with large effects shown for depression in the two largest studies in cancer patients, and large effects in the single published study outside of cancer,” said Matthew W. Johnson, PhD, associate professor of psychiatry and behavioral sciences at Johns Hopkins Medicine.
One of these studies — conducted in 2016 by researchers at Imperial College London and other institutions — found that a single dose of psilocybin had a long-lasting effect on people with moderate to severe major depression.
“This study showed an antidepressant effect after a week and enduring for a couple of months,” said Dr. Stephen Ross, co-director of the NYU Psychedelic Research Group in New York City.
However, he points out the study didn’t compare people taking psilocybin to people not taking the drug — the control group. So, the study results don’t necessarily show that psilocybin works for depression.
The strongest psilocybin data so far is for treating anxiety and depression in people with cancer, carried out in two clinical trials by Ross and other researchers at NYU and by Johnson and others at Johns Hopkins University.
These studies, which included 80 participants combined, showed that psilocybin worked better than a non-hallucinogenic placebo for treating cancer-related depression.
“Our group found that psilocybin was a rapidly acting antidepressant,” Ross said. “And the effects lasted at least seven weeks, but maybe as long as six months. The Hopkins group found a similar thing.”
While these are some promising results, this is pretty much it for data on the use of psilocybin for the treatment of depression.
That hasn’t stopped people from promoting the drug’s potential.
“We’re at this interesting inflection point, where people have a lot of strong opinions with very little data. But wait a couple of years and we’ll have a decent amount of data,” said Dr. David Hellerstein, professor of clinical psychiatry at the Columbia University Irving Medical Center in New York City.
Johnson says much larger randomized studies are needed before we’ll know the true potential of psilocybin for the treatment of depression.
Some of this work is already underway.
ClinicalTrials.gov, a database of medical research studies in the United States and other countries, lists 12 current studies for psilocybin treatment of depression.
In addition to research being done at NYU, Johns Hopkins, and other universities, two pharmalike companies are also doing psilocybin research.
Usona Institute in Madison, Wisconsin, is planning a multisite phase II study of psilocybin for major depression. This kind of early clinical trial focuses on determining the best dose of psilocybin to use and its safety.
Ross will be the lead investigator for the NYU site. He says the hope is that this research, once completed, will go on to a full randomized clinical trial, also known as phase III.
The other company is U.K.-based COMPASS Pathways. It’s beginning a randomized clinical trial looking at psilocybin therapy for treatment-resistant depression.
In 2018, the company received breakthrough therapy designation from the Food and Drug Administration (FDA) for this therapy.
This shows that even the FDA thinks the research is promising. In spite of that, it’s still difficult for researchers to find money to pay for psilocybin clinical trials.
“The largest obstacle for this research field is obtaining funding,” said Johnson. “There has yet to be public funding in the U.S. for therapeutic trials with psychedelics, despite promising initial evidence.”
Hellerstein says researchers also have to deal with people joining clinical trials thinking they’ll be radically changed by psilocybin.
“People come in with such profound expectations for a life-transforming effect based on the cancer studies that have been done,” he said.
When analyzing the data, researchers have to tease apart the health effects caused by these expectations from the real effects of psilocybin.
Even with a limited amount of data, it’s clear that psilocybin stands apart from current antidepressants.
Psilocybin acts quickly, whereas antidepressants can take weeks to work. Also, the effects of a single dose of psilocybin appear to last for weeks to months.
Ross says if these effects are confirmed by randomized clinical trials, it could lead to a major change in the treatment of depression.
“Rather than a pill every day, it’s one treatment or maybe a couple treatments with enduring effects,” Ross said. “And because you wouldn’t have to keep taking the medication, it minimizes side effects compared to antidepressants.”
Hellerstein says psilocybin also stands out in how it’s given to patients.
In current clinical trials, participants are given a single dose of psilocybin and monitored by a specially trained psychotherapist, who stays in the room for the entire six- to eight-hour hallucinogenic “trip.”
Participants are also prepared for their experience beforehand. They meet with the therapist several times afterward to help them process what they went through.
“This is not just a medication effect,” Hellerstein said. “It’s a medication interwoven with interpersonal experience.”
Ross says the approach they use at NYU for psilocybin is as a medication-assisted psychotherapy.
“We don’t think this is a pharmacologic-only intervention,” he said. “This is used in the hands of skilled psychotherapists to inform the psychotherapy and to deepen it.”
This approach means it’s harder to test psilocybin than other medications; you can’t just give people a pill and send them on their way.
Researchers also have to consider the effect that therapy and the psychotherapist have on a patient’s depression, not just the effects of the psilocybin.
In addition, if clinical trials show that psilocybin is effective for treating depression, doctors will need to contend with other issues related to this type of medication-assisted psychotherapy.
“It makes it much more challenging to provide widespread psilocybin treatment,” Hellerstein said. “How do you set up a clinic where people have to come in for eight hours every time they need a treatment?”
Will psilocybin one day replace current antidepressants?
Ross says psilocybin research is still in the very early stages, so it’s too soon to know.
“We first have to establish that it works,” he said. “Then the only way to compare it to other treatments would be to do a comparison trial.”
The Imperial College London group is recruiting people for just such a clinical trial, one that compares psilocybin to the antidepressant escitalopram (Lexapro) for the treatment of major depression.
“That head-to-head comparison will help answer the question of how psilocybin works compared to other antidepressants,” Ross said.
Hellerstein said it will take at least five years before we see results from phase III clinical trials, which are needed for FDA approval of psilocybin as a treatment for depression. These studies have not been started yet.
In the meantime, he cautions people against using psilocybin to self-treat their depression.
If you take psilocybin at home, you don’t get the guidance of a trained psychotherapist like in the clinical trials. Psilocybin taken in medical studies is also synthetic, so physicians know the exact dosage.
Additionally, if some people have an underlying condition, such as schizophrenia, physicians would likely not recommend giving them psilocybin even if they have depression.
There are also dangers that come from trying to treat your own mental illness.
“These clinical trials are different from grow-your-own psilocybin mushrooms from a bunch of spores and take the mushroom at home or at a concert,” Hellerstein said. “People with depression might be suicidal or might have other medical or psychiatric problems. So, it’s a safety issue.”