Promising results from a novel psychedelic compound

Early in 2025, the Psychiatry team completed a first-in-human study with a new psychedelic drug, the 5-HT2A agonist and 5-HT releaser bretisilocin. Dr Gabriel Jacobs, Research Director Psychiatry: ‘As we previously did an in-depth characterisation of the 5-HT2A agonist DMT, we were able to thoroughly characterise the pharmacodynamics of bretisilocin. Based on the results from the first-in-human study, the optimal dose range for a meaningful and safe psychedelic experience was estimated to be between 10 and 15 milligrams. A dosage of 10 milligrams has now also been tested in patients.’ The manufacturer, Gilgamesh Pharmaceuticals, investigated the drug in a Phase 2 study in patients with major depressive disorder in 2025. This study showed that a single dose of 10 mg achieves a noticeable reduction in depressive symptoms as measured by the Montgomery-Åsberg Depression Rating Scale (MADRS). Shortly after the publication of these results, bretisilocin was acquired by AbbVie for 1.2 billion dollars.

Jacobs: ‘One of the interesting properties of bretisilocin is that in terms of duration of action and intensity of the psychedelic experience, it falls between psilocybin and DMT.’ Various 5-HT2A agonists are currently being investigated for their potential effectiveness in treating depression, often in combination with psychotherapy. The altered state of consciousness (‘psychedelic experience’) induced by psilocybin emerges gradually and lasts four to six hours, offering an opportunity to be combined with psychotherapy. However, the relatively long duration of action makes this approach labour-intensive and limits scalability in clinical practice. On the other hand, the psychedelic experience induced by DMT is much shorter due to its rapid clearance, lasting no longer than 30 minutes after a single dose, and is often overwhelming, making DMT less suitable to combine with psychotherapy.

Based on the measurements taken by Jacobs' team, bretisilocin may find itself at a “sweet spot” between these extremes. Although the psychedelic experience was less overwhelming than with DMT, it was nonetheless robust and meaningful, and the effects disappeared within an hour. A session with this drug would therefore not need to last much longer than a regular psychotherapy session. Jacobs: ‘Further research will be needed to determine how to apply this drug in psychiatric practice. But the recent acquisition by AbbVie shows this drug is considered promising. We are pleased to have been able to contribute to the first steps in its clinical development.’