A not-so-trippy ‘magic mushroom’-derived compound may offer a way of treating certain neuropsychiatric conditions, without hallucinatory side effects. Scientists from the University of Padova (Italy) have synthesized a modified version of psilocin, the active form of psilocybin, which maintains the drug’s therapeutic promise while minimizing the hallucinogenic effects with which it is usually associated. In a study in mice, they report the design, synthesis and evaluation of a library of compounds that may open up new psychedelic treatment options. A growing body of evidence suggests a key role of serotonin signaling pathways in modulating neuroplasticity – a process with therapeutic implications for a range of neuropsychiatric conditions, including depression, anxiety, substance use disorders and neurodegenerative diseases. For decades, researchers have been studying how psychedelics, like psilocybin, affect these pathways in rodents and whether they could be used to treat the aforementioned conditions in humans. However, their potential medical benefits are offset by acute psychoactive effects. To try and circumvent this roadblock, the team engineered five fluorinated reversible N-alkyl carbamate derivatives of psilocin with limited hallucinogenic-like effects. By varying the number and positioning of fluorine atoms on the alkyl promoiety, they were able to alter carbamate bond stability. How does cocaine rewire the brain? A study in mouse models demonstrates how cocaine alters hippocampal function, driving relapse, and identifies a possible therapeutic target. The resulting substances, compounds 4a–e, were then tested in in vitro models that reproduced the pH conditions of the gastrointestinal tract. During these experiments, compound 4e stood out,…
