Drugs that target the human serotonin 2A receptor (5-HT2AR) are used to treat neuropsychiatric diseases; however, many have hallucinogenic effects, hampering their use. Here, we present structures of 5-HT2AR complexed with the psychedelic drugs psilocin (the active metabolite of psilocybin) and d-lysergic acid diethylamide (LSD), as well as the endogenous ne...
Various metabolites identified with therapeutic mushrooms have been found from different sources and are known to have antibacterial, antiviral, and anticancer properties. Over thousands soil growth-based mushroom metabolites have been discovered, and utilized worldwide to combat malignancy. In this study, psilocybin-mushroom that contains the psychedelic co...
Antibody engineering is a powerful method used to generate high-affinity antibodies that enables sensitive immunoassays. It is commonly performed with the following steps: First, antibody fragments (e.g., single-chain Fv fragments; scFvs) with various mutations are displayed on the surface of filamentous bacteriophages to generate a diverse scFv-phages libra...
It is well established that a wide range of drugs of abuse acutely boost the signaling of the sympathetic nervous system and the hypothalamic-pituitary-adrenal (HPA) axis, where norepinephrine and epinephrine are major output molecules. This stimulatory effect is accompanied by such symptoms as elevated heart rate and blood pressure, more rapid breathing, in...
There is an increasing interest in the neural effects of psychoactive drugs, in particular tryptamine psychedelics, which has been incremented by the proposal that they have potential therapeutic benefits, based on their molecular mimicry of serotonin. It is widely believed that they act mainly through 5HT2A receptors but their effects on neural activation o...
BackgroundThough drugs binding to serotonergic 5-HT2A receptors have long been claimed to influence human anxiety, it remains unclear if this receptor subtype is best described as anxiety promoting or anxiety dampening. Whereas conditioned fear expressed as freezing in rats is modified by application of 5-HT2A-acting drugs locally into different brain region...
BackgroundPsilocybin is a psychedelic drug that has shown lasting positive effects on clinical symptoms and self-reported well-being following a single dose. There has been little research into the long-term effects of psilocybin on brain connectivity in humans.AimEvaluate changes in resting-state functional connectivity (RSFC) at 1 week and 3 months after o...
Serotonergic hallucinogens psilocybin, and its active metabolite psilocin, have shown promise as rapid-acting antidepressants. The FDA granted breakthrough therapy designation for psilocybin's use as an antidepressant in 2019, and phase II clinical trials are currently ongoing. Psilocybin is converted to psilocin following oral administration, and this metab...
Hallucinogens are a loosely defined group of compounds including LSD, N,N-dimethyltryptamines, mescaline, psilocybin/psilocin, and 2,5-dimethoxy-4-methamphetamine (DOM), which can evoke intense visual and emotional experiences. We are witnessing a renaissance of research interest in hallucinogens, driven by increasing awareness of their psychotherapeutic pot...
ABSTRACT Background Psilocybin is a psychedelic drug that has shown lasting positive effects on clinical symptoms and self-reported well-being following a single dose. There has been little research into the long-term effects of psilocybin on brain connectivity in humans. Aims Evaluate changes in resting-state functional connectivity (RSFC) at one-week and t...
BACKGROUND: Psilocybin is a serotonergic psychedelic with psychoactive effects mediated by serotonin 2A receptor (5-HT2AR) activation. It produces an acute psychedelic altered state of consciousness with a unique phenomenology that can be temporally characterized by three intensity phases: onset of psychoactive effect, a peak plateau and return to normal con...
Psilocin is a molecule found in psilocybin mushrooms, which are typically consumed recreationally for their hallucinogenic effects. Recently, studies have shown that psilocin can have almost immediate antidepressant effects in patients who are treatment-resistant to medications that increase serotonin levels in the synapse. Researchers believe that the molec...
One among four people in the world are affected by mental or neurological illness at some point of their lives. An estimated number of 450 million people suffers from neurological disorders of one or the other type making mental disorders as the leading cause for disability across the globe. Under psychosis and depression maintenance therapy drug acting on D...
Psilocybin and its direct precursor baeocystin are indole alkaloids of psychotropic Psilocybe mushrooms. The pharmaceutical interest in psilocybin as a treatment option against depression and anxiety is currently being investigated in advanced clinical trials. Here, we report a biocatalytic route to synthesize 6-methylated psilocybin and baeocystin from 4-hy...
Aromatic l-amino acid decarboxylases (AAADs) are a phylogenetically diverse group of enzymes responsible for the decarboxylation of aromatic amino acid substrates into their corresponding aromatic arylalkylamines. AAADs have been extensively studied in mammals and plants as they catalyze the first step in the production of neurotransmitters and bioactive phy...
Current understanding of the neurobiology of depression has grown over the past few years beyond the traditional monoamine theory of depression to include chronic stress, inflammation and disrupted synaptic plasticity. Tissue plasminogen activator (tPA) is a key factor that not only promotes fibrinolysis via the activation of plasminogen, but also contribute...
Users of psychedelic drugs often report that their sense of being a self or 'I' distinct from the rest of the world has diminished or altogether dissolved. Neuroscientific study of such 'ego dissolution' experiences offers a window onto the nature of self-awareness. We argue that ego dissolution is best explained by an account that explains self-awareness as...
Serotonergic hallucinogens produce alterations of perceptions, mood, and cognition, and have anxiolytic, antidepressant, and antiaddictive properties. These drugs act as agonists of frontocortical 5-HT2A receptors, but the neural basis of their effects are not well understood. Thus, we conducted a systematic review of neuroimaging studies analyzing the effec...
