Major antidepressants for the treatment of depression have several shortcomings such as delayed therapeutic action, limited remission rate and various adverse effects. Psychedelics are a group of psychoactive substances that can improve perception, mood and cognition. An increasing body of evidence shows that psychedelics positively promote individual social functioning and have a rapid and sustained improvement in moderate or severe depression. Therefore, the antidepressant effects of psychedelics have gained increasing attentions in recent years. This review summarizes the progress of research on the antidepressant effects of some representative psychedelics and their potential mechanisms of antidepressant action, and discusses the risks of clinical application of psychedelics.

Major antidepressants for the treatment of depression have several shortcomings such as delayed therapeutic action, limited remission rate and various adverse effects. Psychedelics are a group of psychoactive substances that can improve perception, mood and cognition. An increasing body of evidence shows that psychedelics positively promote individual social functioning and have a rapid and sustained improvement in moderate or severe depression. Therefore, the antidepressant effects of psychedelics have gained increasing attentions in recent years. This review summarizes the progress of research on the antidepressant effects of some representative psychedelics and their potential mechanisms of antidepressant action, and discusses the risks of clinical application of psychedelics.

Basic and cIinicaI studies demonstrate that depression is associated with abnormaI neuraI pIasticity in some brain regions,incIuding the prefrontaI cortex and hippocampus. Brain-derived neurotro-phic factor(BDNF)and its signaIing pathways pIay a cruciaI roIe in reguIating neuraI pIasticity and deveI-opment of depression. Ketamine or scopoIamine can produce a quick and sustained antidepressant effect,and both can quictIy activate BDNF-signaIing pathways reIated to neuraI pIasticity. In order to pro-vide the theoreticaI basis for future researches on new antidepressants,the neuraI pIasticity mechanisms of faster-onset antidepressants are reviewed in this paper.

Objective To investigate the effects of estradiol replacement therapy on novel-object recognition and extinction of conditioned fear memory in ovariectomized (OVX) rats.Methods Sixty sexually mature (＞90 days) female SD rats weighing 250g-300g were used as subjects.The rats were randomly divided into 7groups as following:OVX with low dose of estradiol replacement (OVX + LD,0.1 mg · kg-1),medium dose (OVX + MD,0.3mg · kg-1) and high dose (OVX + HD,0.9mg · kg-1),estradiol replacement with medium dose at 2 weeks after OVX (MD + 2W) and 4 weeks after OVX (MD + 4W),OVX group and Sham group (SH).According to the different dose and time schedules,each group was administrated estradiol or vehicle via subcutaneous injection on the dorsal side of the rat.Estradiol maintained for one month after the surgery,and then the novel-object recognition and extinction of conditioned fear memory were tested.Results (1) The rats after OVX (5.83 ±4.5)s showed access-dependent impairments on novel-object recognition ((5.83 ± 4.5)s vs(27.14 ± 6.6)s,P ＜0.01) and the estradiol replacement therapy can reverse this impairment,but not in the HD group.There was an increase of the ability on novel-object recognition in group LD and MD + 2W as compared with group OVX,but the difference was not statistically significant (P ＞ 0.05).Moreover,group MD (27.86 ± 2.6)s had a significant difference compared with group OVX (P ＜ 0.05).(2) The conditioned fear memory of rats after OVX (21.67 ± 2.0) ％showed significantly lower than group SH (56.81 ± 4.6) ％ (P ＜ 0.01).Chronic administration with estradiol enhanced acquisition of context fear,respectively (P ＜ 0.01),but except group HD and group MD + 4W.The group HD(18.43 ± 1.1)％ was negatively enhanced and the group MD +4W(25.25 ±2.5)％ was no difference compared with group OVX.(3) On extinction of conditioned fear memory,the OVX rats produced significantly less freezing by fear context (F =3.337,P ＜ 0.01),and estradiol treatment (except group MD + 4W)also facilitated the extinction of conditioned fear memory,respectively (P ＜ 0.01).Conclusion These results demonstrate that estradiol may have a beneficial effect on the cognition function,and the improving effect is better when estradiol replacement is given at once depriving of sex hormone.