Classical psychedelics are a group of hallucinogens which trigger non-ordinary states of consciousness through activation of the 5-HT2A receptor (5-HT2A R) in the brain. However, the exact mechanism of how 5-HT2A R agonism alters perception remains elusive. When studying receptor signaling, tools which work at the same spatiotemporal resolution as the receptor are exceptionally useful. To...
Background: Depression is a psychiatric disorder with limited therapy options. Psychedelics are new antidepressant candidates, being the ayahuasca one of the most promising ones. A synergistic combination of N,N-dimethyltryptamine (DMT) and β-carbolines allows ayahuasca antidepressant properties. Another psychedelic and DMT-containing beverage is the jurema wine used religiously by indigenous...
There is a growing interest in the medical use of psychedelic substances as preliminary studies using them for psychiatric disorders have shown positive results. In particularly, one of these substances is N,N-dimethyltryptamine (DMT) an agonist serotonergic psychedelic that can induce profound alterations in state of consciousness. In this work, we propose a computational method based on...
Hallucinogenic drugs potently affect brain and behavior and have also recently emerged as potentially promising agents in pharmacotherapy. Complementing laboratory rodents, the zebrafish (Danio rerio) is a powerful animal model organism for screening neuroactive drugs, including hallucinogens. Here, we test a battery of ten novel N-benzyl-2-phenylethylamine (NBPEA) derivatives with the 2,4- and...
Abstract3,4-Methylenedioxymethamphetamine (MDMA, “Ecstasy”) use has been linked to persistent alterations of the brain serotonergic (5-HT) system in animal and human studies, but the molecular underpinnings are still unclear. Cytoskeletal structures such as neurofilament light chain (NfL) are promising markers of drug-induced brain toxicity and may be involved in MDMA neurotoxicity. The...
Schizophrenia is a serious mental disorder that affects 1% of the world’s population. Although various therapeutic tools have been developed since the appearance of the first generation of antipsychotics, the effect of these agents does not manage to attenuate a significant part of psychotic symptoms. Ketamine is an anesthetic agent able to produce psychotic-like symptoms through the antagonism...
Psychedelic-assisted psychotherapy gained considerable interest as a novel treatment strategy for fear-related mental disorders but the underlying mechanism remains poorly understood. The serotonin 2A (5-HT2A) receptor is a key target underlying the effects of psychedelics on emotional arousal but its role in fear processing remains controversial. Using the psychedelic 5-HT2A/5-HT2C receptor...
European PsychiatryJune 1, 2022Jaime Rodrigues, O. Nombora, Luiz Vicente Ribeiro1 citation
Introduction Obsessive Compulsive Disorder (OCD) is a psychiatric disorder associated with suffering and disability. The serotoninergic system is implicated in the neurobiological processes of OCD and serotonin reuptake inhibitors (SRIs) are the first-line treatment. However, clinical improvement after starting SRIs can take long and patients may not fully recover. Meanwhile, recent data...
There has been a substantial growth in private clinics and registered clinical trials employing serotonergic psychedelics for various psychiatric illnesses, including substance use disorder[1][1],[2][2] and major depressive disorder.[3][3]–[6][4] Classical psychedelics include lysergic acid
Clinical studies suggest that psychedelics exert robust therapeutic benefits in a number of psychiatric conditions including substance use disorder. Preclinical studies focused on safety and efficacy of these compounds are necessary to determine the full range of psychedelics' effects. The present study explores the behavioral pharmacology of structurally distinct psychedelics in paradigms...
Psychedelics such as lysergic acid diethylamide (LSD), psilocybin (magic mushrooms), and mescaline exhibit intense effects on the human brain and behaviour. In recent years, there has been a surge in studies investigating these drugs because clinical studies have shown that these once banned drugs are well tolerated and efficacious in medically supervised low doses called microdosing....
Background There are currently relatively few effective pharmacological treatments for obesity, and existing ones may be associated with limiting side-effects. In the search for novel anti-obesity agents, drugs that modify central serotonergic systems have historically proven to be effective in promoting weight loss. Psilocin, which is rapidly metabolized from psilocybin, is an agonist at...
May 12, 2022Jianhao Deng, Jiaxing Zhang, QingXia Zhang et al.
Review question / Objective: To assess the evidence for serotonin syndrome occurring in the context of dextromethorphan administration. To assess concurrent medication to see if there are associations with 1) other serotonergic medication. Condition being studied: It is uncertain whether use of dextromethorphan alone or in therapeutic doses can cause Serotonin syndrome (SS). Also, SS by...
The active hallucinogen of magic mushrooms, psilocin, is being repurposed to treat nicotine addiction and treatment-resistant depression. Psilocin belongs to the tryptamine class of psychedelic compounds which include the hormone serotonin. It is believed that psilocin exerts its effect by binding to the serotonin 5-HT2A receptor. However, recent in-vivo evidence suggests that psilocin may...
Despite the recent promising results of MDMA (3,4-methylenedioxy-methamphetamine) as a psychotherapeutic agent and its history of misuse, little is known about its molecular mode of action. MDMA enhances monoaminergic neurotransmission in the brain and its valuable psychoactive effects are associated to a dual action on the 5-HT transporter (SERT). This drug inhibits the reuptake of 5-HT...
The monoamine oxidases (MAOs) are flavin-containing amine oxidoreductases responsible for metabolism of many biogenic amine molecules in the brain and peripheral tissues. Whereas serotonin is the preferred substrate of MAO-A, phenylethylamine is metabolized by MAO-B, and dopamine and tyramine are nearly ambivalent with respect to the two isozymes. β-Carboline alkaloids such as harmine,...
The use of 3,4‐methylenedioxymethamphetamine (MDMA) has recently gained interest as a potential therapeutic tool for the treatment of post‐traumatic stress disorder (PTSD). However, the mechanism of action of this drug has not yet been fully elucidated. Here we demonstrate that MDMA acts by targeting the trace amine associated receptor 1 (TAAR1), an intracellular G‐protein coupled receptor...
Background Various ring‐substituted phenethylamines and amphetamines are used recreationally due to their mind‐altering effects. Furthermore, such psychedelic substances have recently gained increased interest as prospective therapeutics. Here, we studied the pharmacological properties of 4‐alkylated 2,5‐dimethoxyamphetamines in vitro. Specifically, we assessed the effect of the 4‐alkyl chain...
Lysergic acid diethylamide (LSD) and psilocybin are serotonergic psychedelic compounds with potential in the treatment of mental health disorders. Past neuroimaging investigations have revealed that both compounds can elicit significant changes to whole-brain functional organization and dynamics. A recent proposal linked past findings into a unified model and hypothesized reduced whole-brain...
Letheby’s "Philosophy of Psychedelics" relies on Predictive Processing to try and find unifying explanations relevant to understanding how serotonergic psychedelics work in psychiatric therapy, what subjective experiences are associated with their use and whether such experiences are epistemically defective. But if Predictive Processing lacks genuinely explanatory unifying power, Letheby’s...