Abstract Repeated mild traumatic brain injury (RmTBI) can produce lasting cognitive, emotional, and social deficits (e.g., persistent post-concussion symptoms; PPCS). Despite the prevalence of RmTBI in sports, military, and domestic violence settings, effective treatments to alleviate the neurological consequences of RmTBI remain limited. Psilocybin, a serot...
Abstract Rapid-acting antidepressants like ketamine and serotonergic psychedelics show promise for treatment-resistant depression (TRD), but the molecular mechanisms that contribute to their therapeutic effects remain unclear. Induced pluripotent stem cells (iPSCs) offer a platform to model human cortical neurons and investigate drug effects in a human-relev...
Introduction: Cognitive flexibility is essential for behavioral adaptation in response to environmental changes and is impaired in various neuropsychiatric disorders. The serotonergic psychedelic psilocybin has shown potential in enhancing cognitive flexibility, although with mixed results. In this study, we investigated the effects of psilocybin on cognitiv...
As psychedelic-assisted psychotherapy gains momentum, clinical investigation of next-generation psychedelics may lead to novel compounds tailored for specific populations. 2,5-dimethoxy-4-bromophenethylamine (2C-B) is a psychedelic phenethylamine reported to produce less dysphoria and subjective impairment than the psychedelic tryptamine psilocybin. Despite ...
Psilocybin-assisted interventions have shown rapid reductions in depressive symptoms in controlled clinical settings, raising questions about biological mechanisms supporting durability beyond the acute drug effect. [5,7] Mechanistic accounts increasingly focus on neuroplasticity as a candidate pathway linking transient serotonergic receptor activation to lo...
Psilocybin is a psychoactive chemical compound that exerts its effects through the activation of serotonergic receptors. It occurs naturally in mushrooms of the genus Psilocybe. Despite its potential medical applications, this substance is regarded as a drug with no recognized medical use. Depression constitutes a psychiatric disorder of substantial global b...
Psilocybin is a psychoactive tryptamine produced by a phylogenetically discontinuous yet ecologically diverse subset of fungi. Despite decades of chemical, pharmacological, and ethnobiological research, the evolutionary forces driving the emergence and persistence of this compound remain insufficiently explained. Recent hypotheses proposing that psilocybin e...
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 -...
The escalating global burden of mental health disorders, coupled with the stagnation of innovation in traditional monoaminergic pharmacotherapy (e.g., SSRIs), has precipitated a critical need for novel therapeutic paradigms. This article presents a comprehensive systematic review of the so-called "Psychedelic Renaissance," focusing on the clinical resurgence...
Psilocybin is a naturally occurring psychedelic compound with potential antidepressant effects. Although it has long been used by humans, primarily for recreational purposes, the molecular mechanisms underlying its actions remain incompletely understood. Here, we examined the acute effects of psilocin, the active metabolite of psilocybin, on excitatory neuro...
The serotonergic psychedelic, psilocybin, shows potential for rapid and sustained antidepressant effects but the underlying mechanisms remain unknown. Using a chronic interferon-alpha-induced rat model of depression, we show acute psilocybin (0.3 mg/kg) reverses impaired reward-induced biases within 24hrs, with effects enduring for at least 7 days. This sugg...
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...
Psilocybe cubensis mushrooms are typically not consumed for their nutritional value. The main reason people ingest these mushrooms is for their psychoactive effects. Recently, there has been growing interest in the potential therapeutic applications of psilocybin-containing mushrooms in a range of psychiatric conditions, including depression, anxiety disorde...
Humans have long used classical serotonergic psychedelics, such as psilocybin, for a variety of purposes. Entactogens, such as methylenedioxymethamphetamine (MDMA), emerged during the twentieth century and have likewise seen use in a broad range of settings. Interest has arisen in the use of classical psychedelics and entactogens, together termed "psychedeli...
Psychotic symptoms are uncommon and non-specific adverse effects of classic (serotonergic) psychedelics such as lysergic acid diethylamide (LSD), psilocybin, and mescaline. They can emerge during the acute phase of psychedelic drug effects, persist into the subacute ("afterglow") period, or, in rare cases, develop into long-term psychotic illness. Across all...
Major depressive disorder (MDD), including treatment-resistant depression (TRD), is a highly prevalent psychiatric disorder. MDD is associated with severe suffering, burden and large economical costs. Although various conventional antidepressant treatments are available, a large portion of depressed people does not or not adequately respond to the first-line...
Approximately 15% of pregnant women experience postpartum depression (PPD). Even with currently available antidepressant treatments, many women will continue to be impaired by symptoms. Psychedelic therapy offers a promising transdiagnostic therapeutic strategy for several mental health disorders, and early results from current trials suggest that serotonerg...
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...
