Natural Psychoplastogens As Antidepressant Agents

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.

Mini-review: The neurobiology of treating substance use disorders with classical psychedelics

“…Agonism at the 5-HT-2A receptor (5HT2AR) is thought to be the most relevant mechanism of serotonergic hallucinogens for eliciting psychoactive effects and lasting behavioral changes ( Benko and Vrankova, 2020 ; DiVito and Leger, 2020 ; Pędzich et al, 2022 ). 5HT2ARs are abundantly expressed at dendrites of glutamatergic PFC pyramidal neurons in layer V, projecting to regions such as the amygdala, VTA, or NAc ( Mocci et al, 2014 ; de Veen et al, 2017 ; Nichols and Hendricks, 2020 ).…”

Traditional Chinese Medicine for Coronary Artery Disease Treatment: Clinical Evidence From Randomized Controlled Trials

“…Moreover, Huoxin Formula delayed the increase of intima-media thicknesses of the internal carotid artery and common carotid artery, as well as the increase in cardio-ankle vascular index (34). Most patients with SCAD have depression or anxiety symptoms, and this is associated with increased mortality (42,43). Xinkeshu Tablet (心可舒片) can effectively address anxiety and depression symptoms of patients with SCAD via balancing the inflammatory environment-results from a double-blinded, randomized, placebo-controlled, clinical trial (35).…”

Pharmacologic Similarities and Differences Among Hallucinogens

“…Psilocybin, the psychedelic component of “magic mushrooms” is a compound derived from several mushroom‐forming fungi species including the potent Psilocybe genus 27,28 . Psilocybin is a prodrug and undergoes rapid dephosphorylation in the digestive tract and kidney to form its most prominent active metabolite, psilocin (4‐hydroxy‐ N,N ‐dimethyltryptamine) 2,27,28 . Psilocybin has been ingested for centuries in sacred rituals in areas including South America, Mexico, India, Japan, and New Guinea 28 .…”

“…Psilocybin can be ingested in the raw mushroom form or steeped in water to create a tea 2,27 . Following first‐pass metabolism, the psychoactive psilocin is able to cross the blood‐brain barrier.…”