Magic Mushrooms: From Psychedelic Trip to Therapy?

Whether LSD, ketamine or magic mushrooms: For some years now, psychedelics have increasingly been treated as medical beacons of hope in the therapy of mentally ill people - also because, in contrast to the usual antidepressants, they work faster.

In particular, the active ingredient psilocybin contained in "magic mushrooms" has been the subject of numerous studies;

It is a natural alkaloid from the group of tryptamines, which the Swiss chemist and LSD discoverer Albert Hofmann first succeeded in synthesizing in 1958.

Accordingly, a multi-centre phase II study recently published in the "New England Journal of Medicine" is fueling interest: In this clinical study, the effectiveness of the psychedelic drug was tested on 233 patients at 22 clinics in Europe and North America, funded by the British Company Compass Pathways.

Eighty-six percent of the subjects had a depressive episode that lasted at least a year, and all had had between two and four antidepressant treatments that had been unsuccessful.

Previous psilocybin studies were tested with significantly fewer patients, which meant that the meaningfulness of the results was very limited.

Improvement, but partly with side effects

Before the subjects received the drug once, they had not taken antidepressants or other drugs that affect the central nervous system for at least two weeks.

The doctors involved in the study administered three different strength doses once: either 1 milligram, 10 milligrams or 25 milligrams, whereby neither they nor the patients knew who was receiving which dose.

They then observed the patients over a period of twelve weeks by conducting regular surveys of depressive symptoms.

After three weeks, the high-dose group (25 milligrams) showed a significant improvement compared to the other two groups.

However, not without side effects, as Kevin McConway, Emeritus Professor of Statistics at the Open University, emphasizes when asked: “There were significantly more serious side effects in the participants in the 25 and 10 milligram groups than in the participants in the 1 milligram control group .” In addition to slight symptoms such as headaches and nausea after taking the active substance, there were also thoughts of suicide, suicidal and self-injurious behavior.

Such risks compared to the chances of this therapy were also discussed at the annual meeting of the American Psychiatric Association, where the results were presented for the first time at the end of May.

"The results were positive but not spectacular," says Ravi Das, associate professor at the Institute for Mental Health at University College London.

"The effect wears off after just twelve weeks." Only 20 percent of the patients in the high-dose group reported a sustained effect of the therapy, compared to ten percent in the 1-milligram group.

In addition, from week three through the end of the observation period, over a third of patients in the 25 mg group were taking additional antidepressant treatment, compared to 24 percent in the 10 mg group and 20 percent in the 1 mg group -Group.

"Clearly when people initiate such treatment, their depression is not in remission," Das says, also noting that

that the number of severely depressed patients in the 25 mg group was lower than in the other two groups.

"Major depression is harder to treat, which may explain why the maximum dose of psilocybin was more effective."

And there's something else to consider: "Participants weren't asked if they could guess what dose of the psychedelic they were receiving," says Andrew MacIntosh, head of the Department of Psychiatry at the University of Edinburgh.

This is important, however, as psilocybin can cause euphoria and changes in perception.

"People who believe they are in a higher-dose treatment group may be more likely to report treatment benefits, regardless of whether the treatment is working."

More tightly controlled than previous studies

The results of this study are less impressive than previous ones, which were smaller in scale and less tightly controlled.

According to Matthias Liechti, deputy chief physician at the University Hospital Basel, this allows for a more realistic assessment of the effectiveness of psilocybin.

And Gerhard Gründer, Head of the Department of Molecular Neuroimaging at the Central Institute for Mental Health in Mannheim, states: "The study dampens the euphoria that is often fueled in the lay press in particular." However, there are important findings that can be derived from it, among other things, that many patients would need further doses of the active substance in order to achieve a lasting improvement in their symptoms.

The founder himself is the head of a psilocybin study in cooperation with the Charité Berlin (EPIsoDE study) as well as co-founder and managing director of the company "OVID Health Systems", which is already developing a health infrastructure for psychedelics-supported psychotherapy.

According to McIntosh, the study is "the strongest evidence yet that further larger and longer randomized trials of psychedelics are warranted and that psilocybin may one day represent a potential alternative to the antidepressants that have been prescribed for decades."

Until then, it's just a matter of waiting.

But according to the company Compass Pathways, which has its headquarters in London, a phase III approval study is to start despite the rather sobering results.

The form of therapy is also being tested in a phase II study for the treatment of patients with post-traumatic stress disorders.