ABSTRACT Psychedelics such as psilocybin and lysergic acid diethylamide (LSD) exert hallucinogenic effects through stimulation of serotonin 5-HT2A receptors (5-HT2ARs) in the cerebral cortex. In recent years, numerous reports have demonstrated that psychedelics are effective in treating various psychiatric disorders such as major depressive disorder (MDD), t...
Interest has grown in the effects of psilocybin on mental health, but little is known about its naturalistic use alongside alcohol and its relationship to depression and/or anxiety symptoms. Data from the nationally-representative 2024 National Survey Investigating Hallucinogenic Trends of participants who did ( n = 1234) or did not ( n = 1607) report past-y...
Psychedelic drugs such as LSD and psilocin were once relegated to the fringes of medical research because of their association with counterculture movements and a perceived concern about harm through recreational use, and their consequent legal prohibition in the early 1970s. However, these drugs are now experiencing a renaissance in the field of psychiatry ...
Currently, the most actively investigated rapidly acting antidepressants, anxiolytics and/or anti PTSD agents, include psychedelics e.g. psilocybin, LSD, N,N-dimethyltryptamine, ayahuasca; non-hallucinogenic entactogens, e.g. MDMA; psychoplastogens which rapidly promote neuroplasticity, e.g. ibogaine, ketamine and esketamine; and other atypicals e.g. dextrom...
Fragile X Syndrome (FXS) is the most common inherited intellectual disability and a leading monogenic cause of autism spectrum disorder (ASD). As a synaptic disorder, FXS involves the loss of Fragile X messenger ribonucleoprotein 1 (FMRP), leading to abnormal dendrite development and immature dendritic spines. Serotonergic signaling, essential for neuronal d...
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...
Psilocin is a psychedelic indole alkaloid and one of the major human metabolites of its phosphorylated precursor, psilocybin. Psilocin binds to the serotonin receptor, 5-HT2A, and dose-dependently induces hallucinogenic effects stronger than psilocybin. As a result, psilocin has been a drug of interest in the analytical toxicology community for years. In viv...
Reliable documentation of the traditional use of serotonergic psychedelics has long been confined to the Americas. Prevailing narratives often overstate the global prevalence and uniformity of traditional psychedelic use, extrapolating from a limited set of well-documented cases. Here, we report evidence of psilocybin mushroom use among Basotho traditional h...
It is unclear how serotonin 2A receptors (5-HT2A Rs) in cortical layer 5 pyramidal neurons (L5 PyrNs) differentially contribute to psilocybin-induced hallucinations versus neuroplasticity. Here we show that psilocybin promotes synapse formation and maturation while accelerating the elimination of pre-existing synapses. Cell type-specific manipulation further...
Serotonergic psychedelics have attracted considerable interest as promising therapeutic agents. However, the molecular mechanisms linking their acute hallucinogenic-like effects to longer-lasting neuroplastic responses remain incompletely understood, partly because of the scarcity of native neural models suitable for mechanistic studies. Here, we developed a...
This open-label pilot study examines whether the hallucinogenic drug, psilocybin, given under supportive conditions, is safe and effective for depression in people with Mild Cognitive Impairment (MCI) or early Alzheimer's Disease (AD). This study will also assess whether psilocybin may improve quality of life in those individuals. This is a pilot study evalu...
The purpose of this study is to determine whether psilocybin, a hallucinogenic drug, is effective in reducing depressive symptoms and amount of drinking in patients with co-occurring Major Depressive Disorder (MDD) and Alcohol Use Disorder (AUD). The objectives of this double-blind, placebo-controlled study are to test the hypotheses that a single high (25 m...
The purpose of the present study is to evaluate the feasibility, initial signals of efficacy, and potential mechanisms of action of "microdoses" of psilocybin (i.e., low doses of psilocybin that are not believed to produce mystical-type, transcendent, hallucinogenic, or other overtly salient subjective effects that limit functionality) in the treatment of mo...
Neuroplasticity refers to the ability of the brain to modify synaptic connections and reorganize neural circuits, underpinning cognitive function, emotional regulation, and recovery from injury. Recent advances have redefined adult neuroplasticity as more dynamic and therapeutically accessible than previously thought, spurring investigation into pharmacologi...
Background: Psilocybin is a psychoactive compound found in hallucinogenic mushrooms and is rapidly dephosphorylated in vivo to psilocin, its pharmacologically active metabolite. Despite the growing clinical and scientific interest in these substances, information regarding their interaction with cytochrome P450 (CYP450) enzymes remains scarce, raising concer...
Psilocin, a naturally occurring hallucinogenic component of magic mushrooms, exerts notable psychoactive effects in both humans and rodents. However, the underlying mechanisms remain not fully understood. Blood-oxygenation level-dependent (BOLD) functional magnetic resonance imaging (fMRI) is a valuable tool in many preclinical and clinical trials for invest...
About 30-50% of patients with advanced illness experience depression, anxiety, or decreased sense of purpose and autonomy. Together, these are called psychological distress. Treatment options such as medication and therapy are available; however, they do not always work and can be time-consuming and expensive. We need treatments that work well, quickly, and ...
High Resolution Image Download MS PowerPoint Slide Psilocybin, the phosphorylated prodrug of psilocin, holds therapeutic promise across a range of neuropsychiatric conditions, yet its clinical utility is constrained by acute psychoactive effects. Here, we report the rational design, synthesis, and evaluation of a focused library of fluorinated reversible N -...
Panaeolus sensu lato is a group of hallucinogenic mushrooms commonly found on dung, in pasture areas, grasslands, and forests. Previous studies indicated that the Panaeolus s.l. clade (panaeo-clade) could be ranked as a family ( Galeropsidaceae ), pending further evidence. In this study, based on phylogenomic, multigene phylogenetic, molecular clock, and mor...
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...
