5HT 2A R is a G-protein-coupled receptor that drives many neuronal functions and is a target for psychedelic drugs. Understanding ligand interactions and conformational transitions is essential for developing effective pharmaceuticals, but mechanistic details of 5HT 2A R activation remain poorly understood. We utilized all-atom molecular dynamics simulations...
Despite enormous interest in psychedelics for psychiatric interventions, potential underlying biological mechanisms remain unclear. Here, we confirm that a single dose of psilocybin increases synaptic transmission in mouse medial prefrontal cortex. Using scRNA-sequencing, we identify cell-type specific mechanisms of sustained neuroplastic effects. We show th...
RATIONALE: Our study aimed to unravel the unknown mechanisms behind the exceptional efficacy of Psilocybin (PSI) in treating treatment-resistant depression (TRD). Focusing on Wistar-Kyoto (WKY) rats with a TRD phenotype and Wistar (WIS) rats as a normative comparison, we investigated behavioral and neuroplasticity-related responses to PSI, striving to shed l...
Preclinical and human studies indicate psilocybin may reduce perseverant maladaptive behaviors, including nicotine and alcohol seeking. Such studies in the opioid field are lacking, though opioids are involved in more >50% of overdose deaths. Psilocybin is an agonist at the serotonin 2A receptor (5-HT2A R), a well-documented target for modulation of drug see...
Psilocybin, an innate compound produced by mushrooms belonging to the Psilocybe genus, is primarily known for its agonistic effects on the serotonin 5-HT2A receptor. This receptor’s functioning is involved in many neurological processes. In the context of this research, our primary aim was to comprehensively investigate the influence of psilocybin as a serot...
Psychedelic substances have gained significant attention in recent years for their potential therapeutic effects on various psychiatric disorders. This review delves into the intricate cellular neurobiology of psychedelics, emphasizing their potential therapeutic applications in addressing the global burden of mental illness. It focuses on contemporary resea...
Alcohol abuse is a leading risk factor for the public health burden worldwide. Approved pharmacotherapies have demonstrated limited effectiveness over the last few decades in treating alcohol use disorders (AUD). New therapeutic approaches are therefore urgently needed. Historical and recent clinical trials using psychedelics in conjunction with psychotherap...
AIM: Psilocin is an active metabolite form of psilocybin and exerts psychoactive effects. Recent studies suggest that psilocin may have regulatory effects on abuse drugs, but the mechanisms remain unclear. In this study, we want to explore the effects of psilocin on methamphetamine (METH)-induced alterations of behavior in mice and its molecular mechanisms. ...
RNA editing is a process by which post-transcriptional changes of mRNA nucleotides alter protein function through modification of the amino acid content. The 5HT2C serotonin receptor, which undergoes 32 distinct RNA-editing events leading to 24 protein isoforms, is a notable example of this process. These 5HT2C isoforms display differences in constitutive ac...
The emerging therapeutic efficacy of ketamine and classical psychedelics for depression has inspired tremendous interest in the underlying neurobiological mechanisms. We review preclinical and clinical evidence supporting neuroplasticity as a convergent downstream mechanism of action for these novel fast-acting antidepressants. Through their primary glutamat...
The heteroreceptor complexes present a novel biological principle for signal integration. These complexes and their allosteric receptor-receptor interactions are bidirectional and novel targets for treatment of CNS diseases including mental diseases. The existence of D2R-5-HT2AR heterocomplexes can help explain the anti-schizophrenic effects of atypical anti...
The concept of self and self-referential processing has a growing explanatory value in psychiatry and neuroscience, referring to the cognitive organization and perceptual differentiation of self-stimuli in health and disease. Conditions in which selfhood loses its natural coherence offer a unique opportunity for elucidating the mechanisms underlying self-dis...
Psychedelic drugs, including the serotonin 2a (5-HT2A) receptor partial agonist psilocybin, are receiving renewed attention for their possible efficacy in treating a variety of neuropsychiatric disorders. Psilocybin induces widespread dysregulation of cortical activity, but circuit-level mechanisms underlying this effect are unclear. The claustrum is a subco...
A unifying mechanism for abused drugs has been proposed previously from the standpoint of electron transfer. Mescaline can be accommodated within the theoretical framework based on redox cycling by the catechol metabolite with its quinone counterpart. Electron transfer may play a role in electrical effects involving the nervous system in the brain. This appr...
Hallucinogens, including mescaline, psilocybin, and lysergic acid diethylamide (LSD), profoundly affect perception, cognition, and mood. All known drugs of this class are 5-HT(2A) receptor (2AR) agonists, yet closely related 2AR agonists such as lisuride lack comparable psychoactive properties. Why only certain 2AR agonists are hallucinogens and which neural...
