Speaker Bio
Matthias E. Liechti is the head of the Clinical Pharmacology Division and a professor for clinical pharmacology and internal medicine at the University Hospital Basel. With his psychopharmacology research group at the Departments of Biomedicine and Clinical Research, Matthias Liechti investigates the pharmacology of psychoactive substances both in vitro and in humans. The group is best known for the work on the acute effects of MDMA (ecstasy) and psychedelics including LSD, psilocybin, DMT, and mescaline in humans. The team also characterizes the pharmacology of the constantly emerging novel psychoactive substances (designer drugs) using in vitro methods. In experimental clinical studies, the team investigates the clinical pharmacology of psychedelics and MDMA. The team also conducted Pharmaco-fMRI studies and phase 2 studies with LSD in patients with anxiety disorder, major depression, cluster headache, and ADHD in collaboration with the respective disease specialists. The group closely collaborates with other academic researchers in Switzerland and with pharmaceutical companies.
ICPR 2024 Abstract
Estimating potential therapeutic effects of classic serotonergic psychedelics by profiling different serotonin receptor subtypes
Depression and anxiety disorders, affecting around 10% of the population, lead to substantial health, social, and ecological consequences. Recent studies have shown that psychedelics may be promising in the treatment of various neuropsychiatric and neurologic disorders. Interactions of psychedelics with the serotonin 2A receptor (5-HT2AR) predict their psychedelic properties and clinical potency. Assessing potency at the 5-HT receptor subtypes 2B, 2C, and 1A allows estimating potential therapeutic effects, interferences, or side effects.
We investigated the activation potency of various serotonergic psychedelics at the 5-HT receptor subtypes 5-HT2AR, 5-HT2BR, 5-HT2CR, and 5-HT1AR. We used stably transduced cells to assess the activation potency at the different 5-HT receptors by phospholipase C (PLC) activation quantifying the accumulation of inositol monophosphate 1.
Across all 5-HT receptor subtypes, LSD emerged as the most potent, while MDA and mescaline were the least potent of all tested serotonergic psychedelics. Notably, all psychedelics demonstrated greater selectivity for the 5-HT2AR over the 5-HT2BR, indicating a low risk for cardiac valvopathy. Most psychedelics displayed high 5-HT2CR selectivity, suggesting a low abuse liability. Additionally, psilocin exhibited the strongest 5-HT1AR selectivity, indicative of anxiolytic properties.
The tested classic psychedelics displayed a favorable 5-HT receptor profile including an overall low 5-HT2BR selectivity alongside high 5-HT2CR and 5-HT1AR selectivity for certain tested psychedelics. Hence, a comprehensive investigation of serotonergic psychedelics, considering potency across various 5-HT receptor subtypes, is essential for estimating therapeutic potential and assessing the risk for certain side effects.