Natural Psychoplastogens As Antidepressant Agents

Major depressive disorder is increasingly prevalent and burdensome, posing a challenge for psychiatry. Existing antidepressants take weeks to work, have serious side effects, and fail in one-third of patients. Recent advances have identified psychoplastogens—compounds that rapidly restructure neural networks by targeting mechanisms linked to depression. Evidence suggests they produce both acute and long-term positive effects that extend beyond psychiatric diseases. Several are naturally occurring, including psilocybin, N,N-dimethyltryptamine, and 7,8-dihydroxyflavone. This article discusses their pharmacology and effects in animal and human studies.

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Abstract

Increasing prevalence and burden of major depressive disorder presents an unavoidable problem for psychiatry. Existing antidepressants exert their effect only after several weeks of continuous treatment. In addition, their serious side effects and ineffectiveness in one-third of patients call for urgent action. Recent advances have given rise to the concept of psychoplastogens. These compounds are capable of fast structural and functional rearrangement of neural networks by targeting mechanisms previously implicated in the development of depression. Furthermore, evidence shows that they exert a potent acute and long-term positive effects, reaching beyond the treatment of psychiatric diseases. Several of them are naturally occurring compounds, such as psilocybin, N,N-dimethyltryptamine, and 7,8-dihydroxyflavone. Their pharmacology and effects in animal and human studies were discussed in this article.