Potentially devastating effects in the central nervous system, such as neuronal hyperexcitability, seizures, memory deficits, and increased anxiety (MacLennan et al., 2001; Akahoshi et al., 2011), suggested by observations with S1P2 knockout mice or JTE-013 treatment, must be avoided by appropriate chemical–pharmaceutical engineering, i.e., by designing compounds that do not cross the blood brain barrier. Here, S1PR2 is linked to Anxiety.