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...
Depression, a global health concern with significant implications for suicide rates, remains challenging to treat effectively with conventional pharmacological options. The existing pharmaceutical interventions for these illnesses need daily dosing, are accompanied by various adverse effects, and may exhibit limited efficacy in certain cases. However, hope e...
Psychedelic fungi have experienced a surge in interest in recent years. Most notably, the fungal secondary metabolite psilocybin has shown tremendous promise in the treatment of various psychiatric disorders. The mushroom species that produce this molecule are poorly understood. Here we sought to examine for the first time, the response of a psilocybin-produ...
Treatment-resistant depression (TRD) is a subgroup of major depressive disorder in which the use of classical antidepressant treatments fails to achieve satisfactory treatment results. Although there are various definitions and grading models for TRD, common criteria for assessing TRD have still not been established. However, a common feature of any TRD mode...
Psilocybin is the main psychoactive compound found in hallucinogenic/magic mushrooms and can bind to both serotonergic and tropomyosin receptor kinase b (TrkB) receptors. Psilocybin has begun to show efficacy for a range of neuropsychiatric conditions, including treatment-resistant depression and anxiety disorders; however, neurobiological mechanisms are sti...
Classical serotonergic psychedelics such as lysergic acid diethylamide or the naturally occurring compounds psilocybin and mescaline produce profound changes in mood, thought, intuition, sensory perception, the experience of time and space, and even the experience of self. Research examining psychedelic compounds has had a complex and turbulent evolution. Ma...
Ethnopharmacology relevanceCentral nervous system (CNS) diseases can be diverse and usually present with comorbidity, as in the case of depression and anxiety. Despite alternatives like Psilocybe mushrooms for mental health there is no basic research to evidence their CNS benefits.Aim of the studyTo evaluate the anxiolytic- and antidepressant-like effects, a...
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...
R) agonist, are reported as effective rapid-acting antidepressants. Both compounds increase glutamate signalling and evoke cortical hyperexcitation. S-ketamine induces neurotoxicity especially in the retrosplenial cortex (Olney's lesions). Whether psilocybin produces similar neurotoxic effects has so far not been investigated. We performed an immunohistochem...
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: In clinical studies, psychedelics including psilocybin and D-lysergic acid diethylamide (LSD) demonstrate rapid and persistent antidepressant effects. Since the effective treatment with psychedelics is usually provided with psychotherapy, it is debatable whether their prolonged efficacy can be observed in infrahuman species. Preclinical reports o...
GABAB receptors are the metabotropic GABA neurotransmitter receptors in the central nervous system constituting a fundamental part of the inhibitory modulation mechanism.These receptors are heterodimers composed of GABAB1 and GABAB2 which function is modulated by the potassium channel tetramerization domain proteins (KCTD) from clade F (KCTD16; KCTD12 and KC...
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...
ABSTRACT Intracellular calcium (Ca 2+ ) is ubiquitous to cell signaling across all biology. While existing fluorescent sensors and reporters can detect activated cells with elevated Ca 2+ levels, these approaches require implants to deliver light to deep tissue, precluding their noninvasive use in freely-behaving animals. Here we engineered an enzyme-catalyz...
In this review, we discuss the possible utility of zebrafish in research on psilocybin, a psychedelic drug whose recreational use as well as possible clinical application are gaining increasing interest. First, we review behavioral tests with zebrafish, focussing on anxiety and social behavior, which have particular relevance in the context of psilocybin res...
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...
Evidence suggests that psilocybin has therapeutic benefit for treating depression. However, there is little consensus regarding the mechanism by which psilocybin elicits antidepressant effects. This systematic review summarizes existing evidence. Ovid MEDLINE, EMBASE, psychINFO, and Web of Science were searched, for both human and animal studies, using a com...
Background: Ketamine and psychedelics have abuse liability. They can also induce "transformative experiences" where individuals experience enhanced states of awareness. This enhanced awareness can lead to changes in preexisting behavioral patterns which could be beneficial in the treatment of substance use disorders (SUDs). Preclinical and clinical studies s...
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 ...
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