Work package leader: Patrick Fisher, NRU

Serotonin 2A receptor (5-HT2AR) agonists, which have hallucinogenic properties, have emerged as an intriguing novel treatment for MDD and other mood and anxiety disorders. 5-HT2AR agonists such as psilocybin result in both acute and lasting improvements in well-being. Psilocybin has been found to produce sustained antidepressant-like effects in patients and well-being in healthy volunteers and changes in brain activity that are consistent with effective antidepressant interventions. Thus, a better understanding of psilocybin’s brain effects with PET and MRI will advance our understanding of serotonergic mechanisms implicated in depression and treatment. Comparing 5- HT2AR agonist effects against drugs with opposing pharmacological actions (e.g., ketanserin, a 5- HT2AR antagonist) would further elucidate the role 5-HT2AR in these processes.

In this work package, we will with PET (11C-Cimbi36) and rs-fMRI investigate healthy individuals to establish dose-dependent drug effects of psilocybin and pimavanserin on cerebral 5-HT2AR binding and determine if psilocybin and ketanserin have opposing effects on brain connectivity. Also, we will determine the neurobiological effects of the interventions and relate those to effects on cognition and mood. This will generate important insights into aspects of the neuromodulatory effects of 5-HT2AR on cognition and mood and will provide a direction for the development of this and other potential future treatments.

More information (in Danish) in this article on about the project.