Psilocybin, the chemical component of "magic mushrooms", has been administered with psychotherapy in several randomized clinical trials (RCTs) showing large and sustained antidepressant effects. In healthy volunteers, the psychedelic effects of psilocybin have been shown to be blocked by administration of serotonin (5HT)2A receptor antagonists such as risper...
Psychedelic drugs are increasingly under investigation as potential therapeutic agents for mental health conditions and are being increasingly used recreationally. Psychedelic use may result in an episode of intense psychological distress, commonly referred to as a "bad trip." Bad trips represent a potentially volatile, erratic, and dangerous situation, whic...
Major depressive disorder (MDD) continues to pose a major therapeutic challenge due to its clinical heterogeneity. This chapter looks at the development of antidepressant treatments, starting with early interventions such as electroconvulsive therapy (ECT), monoamine oxidase inhibitors (MAOIs) and tricyclic antidepressants (TCAs). Although these treatments t...
The psychedelic psilocybin has gained popularity in recent years as a therapy for treatment-resistant depression and has been reported to reduce symptoms of depression and anxiety. Psilocybin's active metabolite, psilocin, possesses a binding affinity for serotonin receptors as well as for the serotonin transporter (5-HTT). We recently reported that in contr...
method was developed for the analysis of serotonin in Caenorhabditis elegans. Samples were subjected to solvent-solvent extraction from basic conditions into n-heptanol. The serotonin was then back-extracted into acetic acid, the solution diluted into basic buffer, and labelled with 3-(2-furoyl) quinoline-2-carboxaldehyde in the presence of cyanide. The samp...
Human neuroimaging studies report that psychedelics induce serotonin-2A receptor-dependent changes in functional brain reorganization, presumably reflecting neuromodulation. However, these studies often overlook the potent vasoactive effects of serotonin. Here we identified psilocybin-induced alterations in hemodynamic response functions during human functio...
Serotonin 5-HT2A receptors were one of the first serotonin receptors to be pharmacologically characterized. In mammals, they are expressed throughout the body in nearly every cell and tissue type, with the highest density in cortical layer V of the brain. They are involved in several aspects of normal physiological processes and behaviors and have been impli...
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...
Background: Psychedelic drugs have recently emerged as plausibly effective pharmacological agents for the management of depression, anxiety, and other neuropsychiatric conditions, including conditions that have not benefited from prior interventions. The latter half of the twentieth century marked a revolution in the treatment of depression, anxiety, and psy...
Background: Psychedelic drugs have recently emerged as plausibly effective pharmacological agents for the management of depression, anxiety, and other neuropsychiatric conditions, including conditions that have not benefited from prior interventions. The latter half of the twentieth century marked a revolution in the treatment of depression, anxiety, and psy...
Modern research data suggest a therapeutic role for serotonergic psychedelics in depression and other neuropsychiatric disorders, although psychotomimetic effects may limit their widespread utilization. Serotonergic psychedelics enhance neuroplasticity via serotonin 2 A receptors (5HT2AR) activation and complex serotonergic-glutamatergic interactions involvi...
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 ...
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...
Pharmacotherapy of depression is characterized by the delayed onset of action, chronic treatment requirements, and insufficient effectiveness. Ketamine, with its rapid action and long-lasting effects, represents a breakthrough in the modern pharmacotherapy of depression. The current review summarizes the latest findings on the mechanism of the antidepressant...
Rationale & objectives ± 3,4-Methylenedioxymethamphetamine (MDMA) and psilocybin are currently moving through the US Food and Drug Administration's phased drug development process for psychiatric treatment indications: posttraumatic stress disorder and depression, respectively. The current standard of care for these disorders involves treatment with psychiat...
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