Psilocybin for Depression Treatment – a Miracle Cure?

Psilocybin therapy is a current topic in medicine. Especially in cases of depression and anxiety, therapists are hoping for breakthroughs in treatment-resistant conditions where conventional therapy approaches only yield moderate success. Although the study situation indicates great potential, the legal situation with the non-marketable active ingredient currently makes widespread application impossible.

Only for study purposes and in justified individual cases is psilocybin therapy permitted. Even analogues like 4‑PrO‑MET are not used due to the unclear legal situation. Nevertheless, it is a promising future prospect that we would like to present to you in detail in this article. Since the topic of psilocybin therapy is complex both in content and legally, we have divided this article into several sections. This will give you a practical overview and allow you to quickly find the information you are looking for:

Psilocybin is of interest for therapy because it has potent effects, mostly seen with the use of magic mushrooms. Possible effects include the well-known visual hallucinations, which can range from more intense color perception and geometric patterns to synesthesia.

The reason is that the active ingredient, an indole alkaloid belonging to the group of tryptamines, is structurally similar to the body's own neurotransmitter serotonin and interacts with its receptors. The so-called "happiness hormone" is responsible for coordinating inner contentment, the day-night rhythm, and appetite.

This interaction with the central nervous system therefore causes effects in a person's emotional and sensory world. Reports from experience and research speak of greater satisfaction and emotional openness. Precisely because of this effect, psilocybin therapy for depression is promising.

After early research into psilocybin-assisted therapies largely ceased due to the strict US anti-drug policy of the 1970s, it has been pursued with renewed enthusiasm since the 1990s and 2000s. And rightly so, because the number of antidepressant prescriptions has more than doubled since 1990, with common medications often having only moderate effects.

Study results show that psilocybin can support the treatment of depression and help where conventional therapeutic approaches fail. This is indicated by the EPIsoDE study (Efficacy and safety of Psilocybin In treatment-resistant major Depression) conducted from 2021 to 2023. In this study, conducted by the ZI (Central Institute of Mental Health) in Mannheim, 144 participants received two six-to-eight-hour therapy sessions every six weeks with the help of psilocybin.

One group of participants received a high dose, the second group a small amount corresponding to that of microdosing mushrooms, and the third group received a placebo. To ensure robust results, it was ensured that each participant was treated once with high-dose psilocybin during one of the two six-week sessions.

The study results are still being evaluated, but older studies from the 1960s and 1970s indicate promising potential, as an improvement in depressive symptoms was observed in the majority of participants.

The course of a therapy using psilocybin is structured similarly to a classic psychotherapeutic session. The goal for conditions such as depression or other anxiety disorders is to break rigid thought patterns and get to the core of the problem so that it can be worked through in a therapeutic conversation. A similar process and objective apply to the treatment of post-traumatic stress disorder (PTSD).

It is important to create a pleasant setting that makes it easier for the patient to relax. Then, a single, controlled dose of psilocybin is given, which increases the patient's well-being and makes it easier to overcome entrenched thought and feeling patterns, to re-perspective and categorize them. All of this happens under the constant guidance and supervision of an experienced psychotherapist.

The conducted studies primarily tested psilocybin as an adjunct to therapies for the treatment of depression and other anxiety disorders. However, the studies were only conducted for the aforementioned conditions. Therefore, it is reasonable to assume that psilocybin therapy could also be successfully used for other mental illnesses.

For example, in post-traumatic stress disorder (PTSD). For the treatment of this condition, it is also important to help the patient bring out the trauma hidden within them in a positive context in order to process it sustainably. The stimulating, opening effect of the active ingredient could therefore also pave the way for the treatment of this condition.

Basically, the active ingredient falls under the German Narcotics Act (BtMG), which means it is not marketable and is classified as illegal. For a long time, it was only permitted for research purposes. However, after the conclusive study results, the situation was relaxed somewhat. It is now possible for the ZI to carry out psilocybin therapy in Germany in justified individual cases.

These include treatment-resistant conditions where conventional approaches fail. Therefore, it is possible to undergo treatment in individual cases at the ZI in Mannheim. This therapeutic approach can also be pursued at the OVID Clinic in Berlin.

Further study series on psilocybin therapy, which rely on participants, are taking place in Berlin, Stuttgart, and Cologne. However, the ZI emphasizes that the hardship clause and the isolated chance of participating in a study will not meet the demand and are no substitute for official approval of the active ingredient as a medicine.

In addition to the natural active ingredient, synthetic analogues such as 4‑PrO‑MET are also being developed. These derivatives operate in a legal grey area, as they have a similar, but not identical, chemical structure to the natural active ingredient.

Therefore, they do not fall under the BtMG (German Narcotics Act), though this may change if the legal text is amended. Due to this legal grey area, this alternative option is not utilized in medicine and research. Instead, therapy has so far only involved the actual active ingredient, psilocybin.

According to numerous studies, psilocybin therapy offers great potential for the treatment of treatment-resistant depression. Nevertheless, in Germany, the active ingredient falls under the BtMG and is therefore not marketable - not even for medical purposes. Currently, it is primarily possible to qualify for therapy with psilocybin or mushrooms as part of microdosing within the framework of medical studies.

However, it has recently become permissible to use psilocybin for therapy in severe, justified exceptional cases of treatment-resistant depression. It remains to be seen whether the legal situation will be further liberalized thanks to the tireless work of many researchers, so that psilocybin therapy can be widely used in Germany.

If you still have questions about the exciting topic of psilocybin therapy, you've come to the right place. We have collected the most common questions from other interested parties and answered them clearly for you:

In Germany, psilocybin therapy can only be received in exceptional cases for treatment-resistant conditions. Another option is to apply as a subject for a study.

Currently, psilocybin therapy can be received at the ZI in Mannheim and at the OVID Clinic in Berlin.

No, synthetic analogues such as 4‑PrO‑MET are not used for treatment in Germany.