Psychoactive substances obtained from botanicals have been applied for a wide variety of purposes in the rituals of different cultures for thousands of years. Classical psychedelics from N,N'-dimethyltryptamine, psilocybin, mescaline and various lysergamides cause specific alterations in perception, emotion and cognition by acting through serotonin 5-HT2A re...
Psychedelic substances such as lysergic acid diethylamide (LSD) and psilocybin show potential for the treatment of various neuropsychiatric disorders1-3. These compounds are thought to mediate their hallucinogenic and therapeutic effects through the serotonin (5-hydroxytryptamine (5-HT)) receptor 5-HT2A (ref. 4). However, 5-HT1A also plays a part in the beha...
ABSTRACT A variety of classic psychedelics and MDMA have been shown to enhance fear extinction in rodent models. This has translational significance because a standard treatment for posttraumatic stress disorder (PTSD) is prolonged exposure therapy. However, few studies have investigated psilocybin’s potential effect in fear learning paradigms. More specific...
Psilocybin has shown promise for alleviating symptoms of depression and is currently in clinical trials for the treatment of anorexia nervosa (AN), a condition that is characterised by persistent cognitive inflexibility. Considering that enhanced cognitive flexibility after psilocybin treatment is reported to occur in individuals with depression, it is plaus...
BACKGROUND: The primary psychoactive drug in magic mushrooms, psilocybin, induces profound alterations in consciousness through the 5-HT2A receptor. This review consolidates current research findings to elucidate the pharmacology, safety profile, and clinical applications of psilocybin. AREAS OF UNCERTAINTY: Despite initial concerns that psilocybin could cau...
The growing interest in the rapid and sustained antidepressant effects of the dissociative anesthetic ketamine and classic psychedelics, such as psilocybin, is remarkable. However, both ketamine and psychedelics are known to induce acute mystical experiences; ketamine can cause dissociative symptoms such as out-of-body experience, while psychedelics typicall...
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 drugs such as psilocybin and ketamine are returning to clinical research and intervention across several disorders including the treatment of depression. This chapter focusses on psychedelics that specifically target the 5-HT2A receptor such as psilocybin and DMT. These produce plasma-concentration related psychological effects such as hallucinat...
Psychedelics belong to the oldest psychoactive drugs. They arouse recent interest due to their therapeutic applications in the treatment of major depressive disorder, substance use disorder, end-of-life anxiety,= and anxiety symptoms, and obsessive-compulsive disorder. In this review, the current state of preclinical research on the mechanism of action, neur...
Inflammation plays a pivotal role in the development and progression of inflammatory bowel disease (IBD), by contributing to tissue damage and exacerbating the immune response. The investigation of serotonin receptor 2A (5-HT2A) ligands and transient receptor potential (TRP) channel ligands is of significant interest due to their potential to modulate key in...
Psilocybin has shown promise for alleviating symptoms of depression and is currently in clinical trials for the treatment of anorexia nervosa (AN), a condition that is characterised by persistent cognitive inflexibility. Considering that enhanced cognitive flexibility after psilocybin treatment is reported to occur in individuals with depression, it is plaus...
Psychedelics make up a group of psychoactive compounds that induce hallucinogenic effects by activating the serotonin 2A receptor (5-HT2AR). Clinical trials have demonstrated the traditional psychedelic substances like psilocybin as a class of rapid-acting and long-lasting antidepressants. However, there is a pressing need for rationally designed 5-HT2AR ago...
Psilocybe mushrooms, otherwise known as “magic” mushrooms, owe their psychedelic effect to psilocin, a serotonin subtype 2A (5-HT2A ) receptor agonist and metabolite of psilocybin, the primary indole alkaloid found in Psilocybe species. Metabolomics is an advanced fingerprinting tool that can be utilized to identify the differences among fungal life stages t...
Since its emergence in the 1960s, the serotonergic theory of depression bore fruit in the discovery of a plethora of antidepressant drugs affecting the lives of millions of patients. While crucial in the history of drug development, recent studies undermine the effectiveness of currently used antidepressant drugs in comparison to placebo, emphasizing the lon...
Serotonergic psychedelics, such as psilocybin and LSD, have garnered significant attention in recent years for their potential therapeutic effects and unique mechanisms of action. These compounds exert their primary effects through activating serotonin 5-HT2A receptors, found predominantly in cortical regions. By interacting with these receptors, serotonergi...
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...
Psychedelics are powerful psychoactive substances that alter perception and mood processes. Their effectiveness in the treatment of psychiatric diseases was known before their prohibition. An increasing number of recent studies, due to the indisputable resurgence of serotonergic hallucinogens, have shown their efficacy in alleviating depression, anxiety, sub...
Psychedelic therapy (PT) is an emerging paradigm with great transdiagnostic potential for treating psychiatric disorders, including depression, addiction, post-traumatic stress disorder, and potentially others. 'Classic' serotonergic psychedelics, such as psilocybin and lysergic acid diethylamide (LSD), which have a key locus of action at the 5-HT2A receptor...
Pathophysiology of depression is related with reduced volume of the hippocampus and amygdala and hypertrophy of the nucleus accumbens. The mechanism of these changes is not well under-stood, but clinical studies have shown that administration of the fast-acting antidepressant keta-mine reversed the decrease in hippocampus and amygdala volume in depressed pat...
Psychedelics hold therapeutic promise for mood disorders due to rapid, sustained results. Human neuroimaging studies have reported dramatic serotonin-2A receptor-(5-HT2AR)-dependent changes in functional brain reorganization that presumably reflect neuromodulation. However, the potent vasoactive effects of serotonin have been overlooked. We found psilocybin-...
