Post-stroke rehabilitation primarily relies on physiotherapy, yet functional gains plateau in many survivors. Classical “psychoplastogens” such as Psilocybin and N,N-dimethyltryptamine (DMT) are high-affinity 5-HT2A agonists, promoting dendritic spine density and synaptogenesis and therefore support reorganisation after ischemic insults. In a mouse model, we...
Serotonin receptors, also known as 5-hydroxytryptamine (5-HT) receptors, are a diverse family of G protein-coupled and ligand-gated ion channel receptors that mediate the physiological effects of the neurotransmitter serotonin. These receptors are widely distributed throughout the central and peripheral nervous systems, where they regulate numerous processes...
Psychedelics are psychoactive substances that cause changes in perception, state of consciousness, mood and numerous cognitive processes. The best known are lysergic acid diethylamide (LSD), N,N-dimethyltryptamine (DMT), psilocybin and mescaline. The main mechanism of action of psychedelics is agonism towards serotonin 5-HT2A receptors. In the middle of the ...
The investigators wish to investigate neurobiological effects of serotonin 2A receptor modulation in healthy volunteers, contrasting effects of an agonist (psilocybin) and an antagonist (ketanserin). Magnetic resonance imaging (MRI) and positron emission tomography (PET) will be used as neuroimaging tools. This project applies an experimental medicine strate...
Serotonergic psychedelics induce altered states of consciousness and have shown potential for treating a variety of neuropsychiatric disorders, including depression and addiction. Yet their modes of action are not fully understood. Here, we provide a novel, synergistic understanding of psychedelics arising from systematic reviews and meta-analyses of three h...
Serotonergic psychedelics induce their characteristic subjective effects via activation of the serotonin 2A receptor (5-HT2AR). This structurally diverse class of drugs includes ergolines (e.g., LSD), phenethylamines (e.g., mescaline), and tryptamines (e.g., psilocin), all of which have NPS analogues that have emerged on recreational drug markets. Importantl...
Understanding neuromodulatory effects of serotonin 2A receptor (5-HT2A R) agonists with diverse pharmacological profiles is relevant to advancing psychedelic-related drug applications. We performed simultaneous positron emission tomography (PET) and pharmacological magnetic resonance imaging (phMRI) in anesthetized nonhuman primates (NHP; N = 3) to examine p...
Recent advancements in the study of mushroom-derived tryptamines, particularly psilocybin and its metabolite psilocin, highlight their unique psychedelic properties and potential therapeutic applications, especially for mental health conditions like depression. This study examines how the position of the hydroxyl group on the indole ring affects the 5-HT2A r...
Psilocybin has been shown to induce fast and sustained improvements in mental well-being across various populations, yet its long-term mechanisms of action are not fully understood. Initial evidence suggests that longitudinal functional and structural brain changes implicate fronto-striatal-thalamic (FST) circuitry, a broad system involved in goal-directed b...
"Iracema comes with the pot full of the green liquor. The shaman decrees the dreams to each warrior and distributes the wine of jurema, which carries the brave Tabajara to heaven." José de Alencar, in his poetic novel “Iracema” (1865)1. IntroductionThe "wine of jurema", used in ancient Brazilian shamanic rituals, is rich in N,N-dimethyltryptamine (DMT), a na...
The purpose of this study is to assess the impact of psilocybin on cognitive inflexibility and neural plasticity in a cohort of people with obsessive-compulsive disorder (OCD). This mechanistic study will utilise a within-subjects design, administering up to 10mg of psilocybin to participants with OCD (DSM-5 criteria) on two separate instances spaced four we...
Psilocybin is a serotonergic psychedelic with therapeutic potential for treating mental illnesses 1-4. At the cellular level, psychedelics induce structural neural plasticity 5,6, exemplified by the drug-evoked growth and remodeling of dendritic spines in cortical pyramidal cells 7-9. A key question is how these cellular modifications map onto cell type-spec...
As psychedelic-assisted psychotherapy gains momentum, clinical investigation of next-generation psychedelics may lead to novel compounds tailored for specific populations. 2,5-dimethoxy-4-bromophenethylamine (2C-B) is a psychedelic phenethylamine reported to produce less dysphoria and subjective impairment than the psychedelic tryptamine psilocybin. Despite ...
In recent decades, psilocybin has gained attention as a potential drug for several mental disorders. Clinical and preclinical studies have provided evidence that psilocybin can be used as a fast-acting antidepressant. However, the exact mechanisms of action of psilocybin have not been clearly defined. Data show that psilocybin as an agonist of 5-HT2A recepto...
The distinct subjective effects that define psychedelics such as LSD, psilocybin or DOI as drug class are causally linked to activation of the serotonin 2A receptor (5-HT2A R). However, some aspects of 5-HT2A R pharmacology remain elusive, such as what molecular drivers differentiate psychedelic from non-psychedelic 5-HT2A R agonists. We developed an ex vivo...
Abstract Psychedelic drugs have profound effects on perception, cognition and mood. How psychedelics affect neural signaling to produce these effects remains poorly understood. We investigated the effect of the classic psychedelic psilocybin on neural activity patterns and spatial encoding in the retrosplenial cortex of head-fixed mice navigating on a treadm...
Background & aimTreatment of Parkinson's disease (PD) has remained largely unchanged and focuses primarily on symptomatic relief through activation of dopaminergic pathways. Currently, there are no proven prophylactic approaches to the prevention of PD. This systematic review seeks to compare two separate compounds, metformin (MTF) and psilocybin, as potenti...
For 3000 years, psychedelics have been used in religious contexts to enhance spiritual thinking, well-being, and a sense of community. In the last few years, a renaissance in the use of psychedelic drugs for mental disorders has occurred in Western society; consequently, a pressing scientific need to elucidate the intricate mechanisms underlying their action...
Psilocybin is a classic psychedelic and a novel treatment for mood disorders. Psilocybin induces dose-dependent transient (4-6 hours) usually pleasant changes in perception, cognition, and emotion by non-selectively agonizing the 5-HT2A receptors and negatively regulating serotonin reuptake, and long-term positive antidepressant effect on mood and well-being...
In the contemporary landscape of psychiatric medicine, critical advancements have been noted in the utilization of psychoactive substances such as hallucinogens, 3,4-methylenedioxymethamphetamine (MDMA), and ketamine for the treatment of severe mental health disorders. This review provides a detailed evaluation of these substances, focusing on their mechanis...
