Psilocin (4-hydroxy-N, N-dimethyltryptamine) is a substituted tryptamine alkaloid and a nonselective serotonergic agonist acting predominantly at 5-HT2A/C receptors, with substantial binding to 5-HT1A and 5-HT2B receptors. Microdosing is the practice of taking a very small, sub-perceptual dose, typically 5% to 10% of a full recreational dose, to improve mood...
BACKGROUND: Major depressive disorder is one of the most debilitating psychiatric disorders worldwide. First-line treatments such as selective serotonin reuptake inhibitors have significant limitations, including delayed onset of therapeutic effects and treatment resistance in about 30% of patients. Increasing evidence suggests that acute administration of s...
Background: Psilocybin, the main psychoactive compound found in Psilocybe mushrooms, has gained increasing attention due to its potential therapeutic effects in neuropsychiatric disorders [1]. Beyond its central effects, increasing evidence highlights the relevance of the gut-brain axis, suggesting that psychedelics may also influence intestinal microbiota c...
Background: Psilocybin, a key psychoactive compound found in Psilocybe mushrooms, has gained increasing attention due to its therapeutic potential in neuropsychiatric disorders [1]. However, comparative preclinical data between isolated psilocybin and whole mushroom extracts remain scarce, particularly regarding behavioural reinforcement and peripheral toxic...
Auditory steady-state responses (ASSRs), particularly at 40 Hz, are promising biomarkers for psychiatric disorders involving dysregulated neural synchronization. Although most ASSR studies have focused on the glutamatergic system, the serotonergic system, specifically 5-HT2A receptor signaling, has received limited attention. Psilocin, the active metabolite ...
Psychedelics have emerged as potential therapeutics for substance use disorders, yet preclinical data validating their efficacy remain limited. Here, we investigated the effects of a clinically inspired dose-escalation protocol of psilocybin and ibogaine on extinction and cue-induced reinstatement in Wistar male rats following intravenous cocaine self-admini...
BACKGROUND: The claustrum, a subcortical structure densely expressing 5-hydroxytryptamine 2 A (5-HT2A) receptors, has been implicated in sensory integration, emotional regulation, salience, and attention. Despite its hypothesized involvement in the effects of serotonergic psychedelics, the neurochemical impact of these substances on claustral neurotransmissi...
Psilocybin-containing mushrooms, commonly known as magic mushrooms, strongly affect mood, cognition, and behavior. Psilocybe azurescens is a species of psilocybin mushrooms that contains the main active compounds psilocybin and psilocin. Psilocybin mushrooms have been used since ancient times to improve the quality of life. However, their adverse effects hav...
OBJECTIVE: Psychedelics such as psilocybin are known for their hallucinogenic properties and have also been reported to produce long-lasting therapeutic effects in depression and possibly also other psychiatric disorders. Several lines of evidence suggest that psilocybin exerts its effects through activation of 5-HT2A receptors located postsynaptically to se...
Introduction:Psilocybin, a classical psychedelic, has shown to produce persistent antidepressant effects, including in patients with treatment-resistant depression. In clinical practice, it is common to coprescribe benzodiazepines (BZDs) alongside antidepressants. However, our preliminary study indicated that preadministration of lorazepam diminished the ant...
BackgroundRecent evidence suggests that psychedelics can induce rapid and long-lasting antidepressant effects. The generally acknowledged explanation for these traits is the phenomenon of neuroplasticity, although the exact underlying molecular mechanisms remain unclear.AimsThis study investigates the effects of psilocin, lysergic acid diethylamide (LSD) and...
Abstract Major depressive disorder (MDD) is a leading cause of disability that affects over 300 million people globally. Despite multiple antidepressant trials, approximately one-third of MDD patients remain symptomatic, progressing to treatment-resistant depression (TRD). This persistence possibly is due to the multifaceted etiology of TRD, encompassing bio...
OBJECTIVE: Psychedelics are able to trigger highly intense and profound alterations in self-consciousness, perception, affective, and cognitive processes. Indeed, recent studies show that ketamine and psilocybin could be used as fast-acting antidepressants. However, the molecular and neurochemical mechanisms of these psychedelics and their actions at the lev...
Chronic stress exerts profound effects on mental health, contributing to disorders such as depression, anxiety, and cognitive impairment. This study examines the potential of psilocybin to alleviate behavioral despair and cognitive deficits in a rodent model of chronic stress, focusing on the interplay between the Hypothalamic-Pituitary-Adrenal (HPA) axis an...
RATIONALE: Our study aimed to unravel the unknown mechanisms behind the exceptional efficacy of Psilocybin (PSI) in treating treatment-resistant depression (TRD). Focusing on Wistar-Kyoto (WKY) rats with a TRD phenotype and Wistar (WIS) rats as a normative comparison, we investigated behavioral and neuroplasticity-related responses to PSI, striving to shed l...
ABSTRACT Psychedelic-assisted psychotherapy has over the last decade emerged as a promising treatment strategy for mental health disease, and the therapeutic potential in classical psychedelics such as psilocybin, LSD and 5-MeO-DMT is presently being pursued in a plethora of clinical trials. However, the resurgent interest in the drugs as therapeutics has al...
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...
Abstract Background Psilocybin-containing mushrooms induce antidepressant and momentary increase in blood pressure (BP) with potential risk to users with cardiovascular diseases. Irregularities in nitric oxide (NO) levels play a key role in endothelial dysfunctions leading to increases in BP. Mushrooms species show large variation in potency which may potent...
