The serotonergic psychedelic psilocybin shows efficacy in treating neuropsychiatric disorders, though the mechanism(s) underlying its therapeutic effects remain unclear. We show that a similar psychedelic tryptamine, N,N-dipropyltryptamine (DPT), completely prevents audiogenic seizures (AGS) in an Fmr1 knockout mouse model of fragile X syndrome at a 10 mg/kg...
Interest in the use of serotonergic agonists such as psilocybin in treatment-resistant depression (TRD) has grown more quickly than the evidence on which to base a final opinion, as emphasized by McIntyre et al1 in their review. Psilocybin, once metabolized to psilocin, activates 5-HT2A receptors, enhancing GABA function in local circuits in the cortex and i...
Psychedelic indolethylamines have emerged as potential medicines to treat several psychiatric pathologies. Natural sources of these compounds include ‘magic mushrooms' ( Psilocybe spp.), plants used to prepare ayahuasca, and toads. The skin and parotid glands of certain toads accumulate a variety of specialized metabolites including toxic guanidine alkaloids...
Intestinal inflammation and dysbiosis can lead to inflammatory bowel diseases (IBD) and systemic inflammation, affecting multiple organs. Developing novel anti-inflammatory therapeutics is crucial for preventing IBD progression. Serotonin receptor type 2A (5-HT2A) ligands, including psilocybin (Psi), 4-Acetoxy-N,N-dimethyltryptamine (4-AcO-DMT), and ketanser...
Psychedelic microdosing is the practice of taking very low doses of psychedelic substances, typically over a longer period of time. The long-term safety of chronic microdosing is relatively uncharacterized, but valvular heart disease (VHD) has been proposed as a potential risk due to activation of the serotonin 5-HT2B receptor. However, this risk has not yet...
High Resolution Image Download MS PowerPoint Slide While correlations between drug-induced cortisol elevation, self-reported anxiety, and treatment outcomes have been reported for human studies during psilocybin-assisted psychotherapy, the mechanistic relationship between psychedelic-associated alterations in plasma glucocorticoid responses and the time cour...
Serotonergic psychedelics such as psilocybin, lysergic acid diethylamide, and DOI exert a hallucinatory effect through serotonin 5-HT2A receptor (5-HT2A) activation. Recent studies have revealed that serotonergic psychedelics have therapeutic potential for neuropsychiatric disorders, including major depressive and anxiety-related disorders. However, the invo...
BACKGROUND: Randomised controlled trials (RCTs) of psilocybin have reported large antidepressant effects in adults with major depressive disorder and treatment-resistant depression (TRD). Given psilocybin's psychedelic effects, all published studies have included psychological support. These effects depend on serotonin 2A (5-HT2A) receptor activation, which ...
Major depressive disorder (MDD) is a chronic relapsing psychiatric disorder. Conventional antidepressants usually require several weeks of continuous administration to exert clinically significant therapeutic effects, while about two-thirds of the patients are prone to relapse of symptoms or are completely ineffective in antidepressant treatment. The recent ...
Introduction Psilocybin is one of the most extensively studied psychedelic drugs with a broad therapeutic potential. Despite the fact that its psychoactivity is mainly attributed to the agonism at 5-HT2A receptors, it has high binding affinity also to 5-HT2C and 5-HT1A receptors and indirectly modulates the dopaminergic system. Psilocybin and its active meta...
The COVID-19 pandemic has resulted in a surge in depression cases, a pervasive and debilitating mental illness1. This trend is evident in the increased prescriptions for antidepressants. Depression is a chronic condition that affects a significant proportion of the global population, with ~280 million people, or about 3.8%, suffering from it. As a result, it...
Abstract Psychedelics produce fast and persistent antidepressant effects and induce neuroplasticity resembling the effects of clinically approved antidepressants. We recently reported that pharmacologically diverse antidepressants, including fluoxetine and ketamine, act by binding to TrkB, the receptor for BDNF. Here we show that lysergic acid diethylamide (...
The psychedelic compound psilocybin has shown therapeutic benefit in the treatment of numerous psychiatric diseases. A recent randomized clinical trial conducted at Johns Hopkins Bayview Medical Center demonstrated the efficacy of psilocybin-assisted therapy in the treatment of Major Depressive Disorder (MDD). Similarly, a phase IIb study evaluating psilocyb...
Mescaline (the active substance in Peyote and San Pedro cacti) is a classic and long known serotonergic psychedelic substance (hallucinogen) that is widely used for recreational, spiritual, and/or ethno medical purposes. Despite its long history, modern data on the acute effects of mescaline on human is lacking. Mescaline produces prototypical psychedelic ef...
Major depressive disorder presents a substantial global health burden, and at least 30-40% of patients exhibit treatment resistance to antidepressants. Ketamine, an NMDA receptor antagonist, is used as an anesthetic agent. In 2019, the U.S. Food and Drug Administration (FDA) approved esketamine (the S-enantiomer of ketamine) as a therapeutic agent for treatm...
Analogues of 4-phosphoryloxy- N,N -dimethyltryptamine (psilocybin) are being sold on recreational drug markets and developed as potential medications for psychedelic-assisted therapies. Many of these tryptamine-based psilocybin analogues produce psychedelic-like effects in rodents and humans primarily by agonist activity at serotonin 2A receptors (5-HT2A ). ...
The clinical evaluation of hallucinogens and other small molecules, conventionally termed psychedelics, has seen a dramatic increase in the past 5 years. Several key clinical trials recently demonstrated the potential efficacy of these compounds in treating a variety of mental health conditions including depression, anxiety, and substance use disorders. Conc...
Psychedelics belong to a group of compounds called psychoplastogens, which can promote neuronal growth and restore atrophied connections in the brain. This ability makes the molecules promising as potential treatments for neuropsychiatric diseases such as chronic depression and addiction. In a new study, scientists have untangled the mechanism of how these c...
Introduction Curiosity toward the effects of psychedelic drugs on neural activation has increased due to their potential therapeutic benefits, particularly serotonergic psychedelics that act as 5-HT2A receptor agonists such as LSD, psilocybin, and MDMA. However, the pattern of their effects on neural activity in various brain regions in both clinical and hea...
