background Psychedelics have a strong therapeutic potential for the treatment of biomedical disorders, but the working mechanisms underlying psychedelics are only poorly understood.
aim To discuss different mechanisms underlying the therapeutic effects of classic psychedelics.
method To make a distinction between different levels of explanation: the pharmacological, the neurocognitive and the psychological level.
results At the pharmacological level, classic psychedelics affect via the serotonin-receptor, the production of glutamate and brain-derived neurotrophic factor (bdnf), which stimulate neurogenesis. Psychedelics also have anti-flammatory properties and thereby have a protective effect on the brain. At the neurocognitive level, psychedelics have been associated with a reduced activation of the default mode network, which has been implicated in self-referential processing and rumination. At the same time, the brain’s entropy increases, reflected in an increased connectivity between different brain areas. At the psychological level, the therapeutic efficacy of psychedelics has been attributed to the mystical experience, as well as to its awe-inducing potential, the feelings of connectedness and an enhanced awareness of emotions.
conclusion Psycholytic and psychedelic therapy act at different levels, but ultimately the combination of different mechanisms will help us to understand how psychedelics – in the right set and setting – can be used successfully in therapeutic practice.