Activation of serotonin 2A (5-HT2A) receptors is thought to underly the long-lasting antidepressant effects of psychedelics such as psilocybin, but beyond that, the molecular and cellular mechanisms involved are not well understood. Recent preclinical studies using mice have primarily examined relatively short time points after psychedelic administration, which does not address the long-lasting...
High Resolution Image Download MS PowerPoint Slide Recent patents unveil a new wave of psychedelic analogs optimized for 5-HT 2 A receptor modulation, reduced adverse effects, and tunable duration of action. By refining DMT and psilocin scaffolds through prodrug design, fluorination, and structure–activity exploration, these innovations promise safer, shorter-acting psychedelic medicines that...
Serotonergic psychedelics and 3,4-methylendioxtmethamphetamine (MDMA) are promising treatments for mental disorders with a continuously evolving evidence base. We searched Pubmed/Scopus/clinical trial registries up to 08july2025 for double-blind randomized controlled trials (RCTs) testing MDMA or serotonergic psychedelics in patients with mental disorders. Primary outcomes were change in...
Abstract Various ring-substituted α-methylphenethylamines (i.e., amphetamines) produce psychedelic-like effects that are primarily mediated by activity at 5-hydroxytryptamine 2A (5-HT 2A ) receptors. Small lipophilic substituents at the 4-position of the 2,5-dimethoxyamphetamine core structure can greatly enhance the clinical potency of such derivatives. Here, we studied the effects of various...
Background: Psilocybin, a serotonergic psychedelic compound, has demonstrated long-term antidepressant effects, yet its underlying mechanisms remain unclear. Emerging evidence suggests that epigenetic modifications, particularly 5-methylcytosine (5mC) and 5-hydroxymethylcytosine (5hmC), may play a role in its therapeutic action. Unlike passive demethylation, which requires cell division and...
PsychoactivesNovember 2, 2025Faith Ekoh, Shanice Rerrie, James Angud et al.2 citations
Today’s research highlights the therapeutic potential of the hallucinogen psilocybin in the treatment of pathologies associated with mood, cognitive, and affective dysregulation. These domains of function are regulated by the serotonergic system, which can be influenced by sex hormones, like estrogen and testosterone, and psychedelic compounds including psilocybin. Current evidence supports a...
Neuro-OncologyNovember 1, 2025Richard Drexler, Belgin Yalçın, Rebecca Mancusi et al.
Abstract High-grade gliomas are the most aggressive form of brain tumors, and neuronal activity has emerged as a driver of glioma pathophysiology. Activity-dependent glioma growth results from paracrine factor signaling and bona fide neuron-to-glioma synapses that integrate glioma cells into brain-wide neuronal circuits. Here, we report how glioma cells integrate into serotonergic (5-HT)...
Psilocybin is a serotonergic psychedelic with growing evidence for efficacy in mood disorders, and its therapeutic potential in obsessive—compulsive disorder (OCD) and related conditions is increasingly recognised but remains understudied. We systematically evaluated clinical and preclinical evidence on psilocybin's effects on obsessive and compulsive behaviours with attention to translational...
High Resolution Image Download MS PowerPoint Slide Provided herein are novel psilocin derivatives as serotonergic psychedelic agents, pharmaceutical compositions, use of such compounds in treating central nervous system (CNS) disorders, and processes for preparing such compounds.
Current first-line antidepressants, such as selective serotonin reuptake inhibitors (SSRI), often present a delayed onset of action and fail to effectively treat a large proportion of patients, leaving a gap in the treatment of mood disorders. Psychedelics have recently emerged as promising alternatives due to their ability to produce fast-acting antidepressant effects through neuroplastic...
Regular recreational use of 3,4-methylenedioxymethamphetamine (MDMA, "Ecstasy") has been consistently linked to verbal memory dysfunctions, whose neurobiological origins remain unclear. Although neurochemical, structural, and functional alterations resulting from repeated MDMA intake have been identified in user populations, only limited knowledge exists regarding potential interrelationships...
Background: The treatment of major depressive disorder (MDD) with available antidepressant drugs is characterized by considerable ineffectiveness. Classical psychedelics such as psilocybin and N,N-dimethyltryptamine (DMT), which act primarily as 5-hydroxytryptamine 2A (5-HT 2A ) receptor agonists, have shown preliminary efficacy for inducing long-term remission in MDD after one or two doses....
Background: Results from contemporary clinical trials of serotonergic psychedelic therapies have led to an increasing focus on their potential clinical use across mental disorders. However, studies examining mechanisms of clinical response to psychedelic therapy in psychiatric populations are limited. This review aimed to synthesize evidence from studies examining biomarkers of clinical...
method was developed for the analysis of serotonin in Caenorhabditis elegans. Samples were subjected to solvent-solvent extraction from basic conditions into n-heptanol. The serotonin was then back-extracted into acetic acid, the solution diluted into basic buffer, and labelled with 3-(2-furoyl) quinoline-2-carboxaldehyde in the presence of cyanide. The sample was analyzed by capillary...
Psychedelic compounds have the ability to generate altered states of consciousness and profoundly distort perception, often resulting in visual hallucinations. While psychedelics have recently regained attention for their potential cognitive and therapeutic effects, how these drugs affect visual processing to generate visual distortions and hallucinations is not as well characterized....
Depression is primarily treated with selective serotonin reuptake inhibitors (SSRIs), which are limited by delayed onset of effects and low rates of remission. Recent studies showed that serotonergic psychedelics such as psilocybin can reduce depressive symptoms both rapidly and enduringly. Such effects have been associated with the activation of the serotonin 2A (5-HT2A) receptor in the...
Abstract Background and Purpose Given the increase in recreational psychedelic use and ongoing efforts to explore psychedelics as therapeutic agents for mental health disorders, there is an urgent need to understand the effect of psychedelics such as psilocybin and N,N-dimethyltryptamine (DMT) on sleep-wake states, which share a bidirectional relationship with mental health. Here, we...
Human neuroimaging studies report that psychedelics induce serotonin-2A receptor-dependent changes in functional brain reorganization, presumably reflecting neuromodulation. However, these studies often overlook the potent vasoactive effects of serotonin. Here we identified psilocybin-induced alterations in hemodynamic response functions during human functional magnetic resonance imaging,...
Major depressive disorder (MDD) is one of the most prevalent psychiatric conditions worldwide, affecting over 350 million people. Standard treatments, primarily antidepressants targeting serotonin, noradrenaline, and/or dopamine, are based on the monoamine hypothesis, which links depression to imbalances in these neurotransmitters. A sizable fraction of patients, however, does not get enough...
A meta‐analysis comprising 17 randomized trials has found that rates of control group improvement in depression studies were lower in psilocybin trials than in studies of esketamine or a selective serotonin reuptake inhibitor (SSRI). The results suggest that psilocybin's overall efficacy in the treatment of depression might be overestimated.