Psychotropic drugs (here: prescription drugs) represent a mainstay in the treatment of many psychiatric disorders since the 1950s, and they have profoundly changed the practice of psychiatry worldwide. While their molecular mechanisms of action are understood in detail, it is still largely unclear, however, how the binding to a certain molecular target in the brain translates into changes in mood, emotions or behavior. The main paradigm dominating psychiatry and psychopharmacology for decades is that specific molecular defects underlie psychiatric disorders, and that these defects have to and can be treated with continuous drug treatment – analogous to e.g. type 1 diabetes (“metabolic brain disorder”). This traditional view is too narrow and has to be challenged, not only because it might have led the development of new psychotropic drugs into a wrong direction. A large proportion of patients treated with the currently available drugs does not adequately respond to treatment, and an even larger proportion does not reach remission, i.e. a state of complete and enduring wellbeing. Many patients with psychiatric disorders are being treated long-term despite insufficient control of their symptoms, persisting suffering, and debilitating side-effects especially with continuous treatment. There are even indications that drug treatment actually facilitates treatment resistance in some patients. – Psychedelic drugs also have a defined molecular target, the 5-HT2A serotonin receptor, and at least for psilocybin it has been shown that the binding of its active metabolite to this target directly correlates with the intensity of the psychedelic state. But here again, it is completely mysterious how agonism at a neurotransmitter receptor leads to profound changes in perception of oneself, time and space. It is equally unclear, how psychedelics exert their therapeutic effects in psychiatric disorders, which seem to be surprisingly long-lasting at least in some patients. – Psychedelics challenge our current thinking of the neurobiology of psychiatric disorders, the prevailing biological treatment approaches in psychiatry and the relationship between brain function and psyche in general. This presentation will summarize the current thinking in academic psychiatry and will try to provide some future perspectives for research and clinical practice.