The astrocytes in the prefrontal cortex contribute to the rapid antidepressant-like effects of psilocybin in the chronic restraint stress mouse model.

Psilocybin showed a rapid antidepressant response in several clinical trials, which offers new hope for treating depression. Astrocytes were associated with the etiology of depression and might contribute to the onset of psilocybin. In this study, we investigated the fast antidepressant effect of psilocybin and tested variations of GFAP (astrocytic markers) ...

Observing the mind under psychedelics: conceptual metaphors used following four once-weekly macrodoses of psilocybin

Psilocybin elicits a conserved glucocorticoid-responsive gene signature across five 5-HT2A receptor-rich brain regions in rat.

ObjectivePsychedelics 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 sero...

Sex-specific increased reactivity of the PVT and prolonged PVT→CeA circuit engagement following psilocin administration.

The psychedelic psilocybin has shown therapeutic potential, yet underlying neural mechanisms remain poorly understood. We investigated the impact of psilocin-the active metabolite of psilocybin-on basal activity and reactivity within the paraventricular nucleus of the thalamus (PVT) and PVT projections to central amygdala (CeA) in rats. Psilocin administrati...

Evaluation of a facilitator training program in a randomized controlled trial of psilocybin treatment for depression.

BackgroundMajor depression is a prevalent condition among patients with life-threatening illnesses, such as cancer, and recent findings suggest that psilocybin may hold promising treatment potential. Contemporary trials of psilocybin generally employ a model that includes psychotherapeutic support consisting of preparation and integration sessions surroundin...

Severe Illness Associated with Eating Mushroom-Containing Chocolate Products - United States, January-October 2024.

In late spring 2024, CDC was alerted to an outbreak of poisoning potentially associated with eating Diamond Shruumz microdosing chocolate bars. Diamond Shruumz microdosing chocolate bars are edible products designed so that small doses of mushroom-derived psychoactive compounds and other psychoactive ingredients can be eaten in a presectioned serving. In res...

Dissociating the Hallucinogenic and Neuroplastic Effects of Psilocybin

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...

Safety Profile of 25 mg Psilocybin in Individuals With Cocaine Use Disorder

The purpose of this study is to establish the safe administration of psilocybin in individuals with cocaine use disorder in terms of cardiovascular (e.g., heart rate) and subjective (e.g., mood) effects. The study's subject population consists of men and women between the ages of 21 and 55 from the Los Angeles area that meet criteria for cocaine use disorder...

Altered States of Consciousness and the Subconscious Mind: A Comprehensive Comparative Review of Disciplines, Neurobiological Mechanisms, Clinical Applications, and Philosophical Frameworks - Including Life Between Lives and Transpersonal Hypnotherapy

Altered states of consciousness (ASC) represent a universal human capacity for accessing and transforming the subconscious mind, employed across cultures and millennia through diverse contemplative, somatic, pharmacological, ritual, and technological modalities. This comprehensive review synthesizes evidence from over 25 distinct disciplines spanning five cl...

Psychedelic-assisted pharmacotherapy: clinical applications and regulatory considerations.

IntroductionAfter decades of regulatory marginalization, psychedelic compounds have reemerged as promising therapeutic tools in psychiatry, driven by unmet clinical needs in treatment-resistant mental disorders and by growing evidence of rapid and sustained effects on mood, cognition, and behavior.Areas coveredThis narrative review critically examined the cu...

A living systematic review, meta-analysis and open-data resource of randomized controlled trials of psilocybin treatment for symptoms of depression

An international mega-analysis of psychedelic drug effects on brain circuit function.

Psychedelic drugs are re-emerging as promising scientific and clinical tools. However, despite a rapidly expanding literature on their therapeutic value, the neural mechanisms underlying psychedelic effects remain unclear. Resting-state functional magnetic resonance imaging studies of acute psychedelic effects, conducted independently by several research gro...

Catatonia Associated With First-Time Psilocybin Exposure: A Case Report.

In this case report, we highlight a 28-year-old male patient with predominantly retarded type of catatonia following a single incidence of psilocybin ingestion. This patient presented with a history of six months of mutism and inability to feed himself after consuming psilocybin for the first time. He did not have any history of psychiatric illness or substa...

Role of Experience, Conscious Awareness, and Plasticity in Psilocybin's Behavioral Effects - Follow-Up Study (The RECAP 2 Study)

The goal of this clinical trial is to learn about the role that inducing neuroplasticity (the brain's ability to adapt and change) plays in the behavioral effects of psilocybin in people who have experienced a mild decline in emotional wellbeing. Researchers will compare different doses of psilocybin combined with midazolam or placebo to see what dose induce...

Activating Neuroplasticity to ENHANCE the Perception Box Expanding Effects of Psilocybin

This study will examine whether combining a single dose of psilocybin with non-invasive transcutaneous auricular vagus nerve stimulation (taVNS), a potential inducer of neuroplasticity and enhanced memory formation, will enhance the long-term beneficial behavioral effects of psilocybin when compared to sham taVNS or no VNS by allowing memory for insights gai...

Psilocybin and human longevity.

Psilocybin extends lifespan in aged mice, and this has prompted extensive media speculation about possible human longevity benefits. We examined mortality among prominent psychedelic personalities, researchers, and advocates who claimed psychedelic use (n = 11) and compared them with cancer (n = 12) and aging researchers (n = 5). All groups exceeded populati...

Acute Analgesic Effects of DMT on Experimentally Induced Acute Nociceptive Pain, Hyperalgesia and Allodynia in Healthy Participants

N,N-dimethyltryptamine (DMT) is a classical psychedelic with similar effects like LSD or psilocybin. Preliminary evidence from case series and small open-label trials suggests that psychedelics may be promising candidates for the treatment of several pain-related diseases such as chronic pain, migraine, cluster headache or phantom limb pain. However, data fr...

Effects of Psilocybin in Obsessive Compulsive Disorder

This study will test the feasibility, safety, and evidence for efficacy of psilocybin administration in participants with obsessive compulsive disorder (OCD). This will serve as a preliminary proof of concept study for future larger studies aimed to investigate the utility, cognitive mechanisms, and neural correlates of this intervention. Participants in thi...

265 Self-reported rates of psilocybin use in North Florida, 2012 to present

Objectives/Goals: Mainstream interest in psilocybin (“shrooms”) has grown over the past several years as two US states have “legalized” psilocybin and clinical trials are underway for use in multiple mental health conditions. We evaluated self-reported use of psilocybin among community members in North Florida and trends in use from 2012 to the present. Meth...

361 Effect of intravenous psilocybin on mechanical hypersensitivity in a rat model of reserpine-induced chronic centralized pain

Objectives/Goals: We recently showed that a single dose of psilocybin, a serotonergic psychedelic, attenuated mechanical hypersensitivity for up to 28 days in a rat model of formalin-induced chronic centralized pain. The goal of this study is to determine whether psilocybin can alleviate chronic pain in a rat model of reserpine-induced chronic centralized pa...