Drugs that target the human serotonin 2A receptor (5-HT 2A R) are used to treat neuropsychiatric diseases; however, many have hallucinogenic effects, hampering their use. Here, we present structures of 5-HT 2A R complexed with the psychedelic drugs psilocin (the active metabolite of psilocybin) and d -lysergic acid diethylamide (LSD), as well as the endogenous neurotransmitter serotonin and the nonhallucinogenic psychedelic analog lisuride. Serotonin and psilocin display a second binding mode in addition to the canonical mode, which enabled the design of the psychedelic IHCH-7113 (a substructure of antipsychotic lumateperone) and several 5-HT 2A R β-arrestin–biased agonists that displayed antidepressant-like activity in mice but without hallucinogenic effects. The 5-HT 2A R complex structures presented herein and the resulting insights provide a solid foundation for the structure-based design of safe and effective nonhallucinogenic psychedelic analogs with therapeutic effects.

The ionic conductivity of the polycrystalline La0.52_~0.o1Lio,35• has been measured as a function of hydrostatic pressure up to 1.2 GPa in the temperature range between 238 and 294 K. The conductivity decreased with an increase in pressure. The value of activation volume for ionic motion derived from the data is positive and almost invariable, between 1.6 _+ 0.2 and 1.7 _+ 0.2 cmS/mol, in the temperature range measured. This implies that a dilatation of the lattice occurs during the transport process. The activation energy of the ionic conductivity slightly increased with an increase in pressure. The mechanism of the ionic conduction is discussed on the basis of these results.

A perovskite La0.59•}0.01Li0.27•}0.01TiO3.02•}0.02 single crystal was grown by the floating zone method and its lithi um ion conductivity was measured. The conductivity was found to be predominantly ionic. The ionic conduc tivities at 333333arallel and perpendicular to the c-axis are 5.8•~10-4 and 6.8•~10-4S•Ecm-1, respectively. The anisotropy of the ionic conductivity corresponds to that of the structure, i.e., of the distribution of La ions. Furthermore, the ionic conductivity and activation energy for ion conduction are almost the same as those of a grain in polycrystalline samples, indicating that the evaluation of the ionic conductivity of poly crystalline samples was appropriate.

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