Striking long-term beneficial effects of single dose psilocybin and psychedelic mushroom extract in the SAPAP3 rodent model of OCD-like excessive self-grooming.

Obsessive compulsive disorder (OCD) is a highly prevalent disorder that causes serious disability. Available treatments leave 40% or more of people with OCD significantly symptomatic. There is an urgent need for novel therapeutic approaches.

Striking Long Term Beneficial Effects of Single Dose Psilocybin and Psychedelic Mushroom Extract in the SAPAP3 Rodent Model of OCD-Like Excessive Self-Grooming.

Obsessive compulsive disorder (OCD) is a highly prevalent disorder that causes serious disability. Available treatments leave 40% or more of people with OCD significantly symptomatic. There is an urgent need for novel therapeutic approaches.

Effects of psilocybin, psychedelic mushroom extract and 5-hydroxytryptophan on brain immediate early gene expression: Interaction with serotonergic receptor modulators.

Immediate early genes (IEGs) are rapidly activated and initiate diverse cellular processes including neuroplasticity. We report the effect of psilocybin (PSIL), PSIL-containing psychedelic mushroom extract (PME) and 5-hydroxytryptophan (5-HTP) on expression of the IEGs, , and in mouse somatosensory cortex (SSC). In our initial experiment, male C57Bl/6j mice were injected with PSIL 4.

Effect of chemically synthesized psilocybin and psychedelic mushroom extract on molecular and metabolic profiles in mouse brain.

Psilocybin, a naturally occurring, tryptamine alkaloid prodrug, is currently being investigated for the treatment of a range of psychiatric disorders. Preclinical reports suggest that the biological effects of psilocybin-containing mushroom extract or "full spectrum" (psychedelic) mushroom extract (PME), may differ from those of chemically synthesized psilocybin (PSIL). We compared the effects of PME to those of PSIL on the head twitch response (HTR), neuroplasticity-related synaptic proteins and frontal cortex metabolomic profiles in male C57Bl/6j mice.

Synergistic psychedelic - NMDAR modulator treatment for neuropsychiatric disorders.

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 involving the ionotropic glutamate receptors, tropomyosin receptor kinase B (TrkB) and the mammalian target of rapamycin (mTOR). N-methyl-d-aspartate receptors (NMDAR) channel antagonists, i.

Effect of psilocybin on marble burying in ICR mice: role of 5-HT1A receptors and implications for the treatment of obsessive-compulsive disorder.

Preliminary clinical findings, supported by preclinical studies employing behavioral paradigms such as marble burying, suggest that psilocybin may be effective in treating obsessive-compulsive disorder. However, the receptor mechanisms implicated in the putative anti-obsessional effect are not clear. On this background, we set out to explore (1) the role of serotonin 2A (5-HT2A) and serotonin 1A (5-HT1A) receptors in the effect of psilocybin on marble burying; (2) the effect of staggered versus bolus psilocybin administration and persistence of the effect; (3) the effect of the 5-HT1A partial agonist, buspirone, on marble-burying and the head twitch response (HTR) induced by psilocybin, a rodent correlate of psychedelic effects.

Role of 5-HT2A, 5-HT2C, 5-HT1A and TAAR1 Receptors in the Head Twitch Response Induced by 5-Hydroxytryptophan and Psilocybin: Translational Implications.

There is increasing interest in the therapeutic potential of psilocybin. In rodents, the serotonin precursor, 5-hydroxytryptophan (5-HTP) and psilocybin induce a characteristic 5-HT2A receptor (5-HT2AR)-mediated head twitch response (HTR), which is correlated with the human psychedelic trip. We examined the role of other serotonergic receptors and the trace amine -associated receptor 1 (TAAR1) in modulating 5-HTP- and psilocybin-induced HTR.

Could psychedelic drugs have a role in the treatment of schizophrenia? Rationale and strategy for safe implementation.

Schizophrenia is a widespread psychiatric disorder that affects 0.5-1.0% of the world's population and induces significant, long-term disability that exacts high personal and societal cost.

Expert consensus recommendations on the use of randomized clinical trials for drug approval in psychiatry- comparing trial designs.

The use of randomized clinical trials, in particular placebo-controlled trials, for drug approval, is the subject of long-standing debate in the scientific community and beyond. This study offers consensus recommendations from clinical and academic experts to guide the selection of clinical trial design in psychiatry. Forty-one highly cited clinical psychiatrists and/or researchers participated in a Delphi survey.

Psychedelic Mushrooms in the USA: Knowledge, Patterns of Use, and Association With Health Outcomes.

Popular media coverage of psychedelics use, growing research into this class of compounds for psychiatry and decriminalization initiatives, are transforming the public perception of psychedelics. However, little is known about levels of knowledge and psychedelic mushroom (PM) use among American adults. We examined PM use and various measures of health status, quality of life, and self-reported mental health outcome measures obtained through a national on-line, cross-sectional survey of adults with a demographic composition representative of the US adult population by region, gender, age, and race (weighted = 251,297,495) from November 2020-March 2021.

The benefit of diagnostic whole genome sequencing in schizophrenia and other psychotic disorders.

Schizophrenia has a multifactorial etiology, involving a polygenic architecture. The potential benefit of whole genome sequencing (WGS) in schizophrenia and other psychotic disorders is not well studied. We investigated the yield of clinical WGS analysis in 251 families with a proband diagnosed with schizophrenia (N = 190), schizoaffective disorder (N = 49), or other conditions involving psychosis (N = 48).

Targeting the DIO3 enzyme using first-in-class inhibitors effectively suppresses tumor growth: a new paradigm in ovarian cancer treatment.

The enzyme iodothyronine deiodinase type 3 (DIO3) contributes to cancer proliferation by inactivating the tumor-suppressive actions of thyroid hormone (T3). We recently established DIO3 involvement in the progression of high-grade serous ovarian cancer (HGSOC). Here we provide a link between high DIO3 expression and lower survival in patients, similar to common disease markers such as Ki67, PAX8, CA-125, and CCNE1.

Optimizing prediction of response to antidepressant medications using machine learning and integrated genetic, clinical, and demographic data.

Major depressive disorder (MDD) is complex and multifactorial, posing a major challenge of tailoring the optimal medication for each patient. Current practice for MDD treatment mainly relies on trial and error, with an estimated 42-53% response rates for antidepressant use. Here, we sought to generate an accurate predictor of response to a panel of antidepressants and optimize treatment selection using a data-driven approach analyzing combinations of genetic, clinical, and demographic factors.

DIO3, the thyroid hormone inactivating enzyme, promotes tumorigenesis and metabolic reprogramming in high grade serous ovarian cancer.

High grade serous ovarian cancer (HGSOC) is the most lethal gynecologic malignancy with a need for better understanding the disease pathogenesis. The biologically active thyroid hormone, T3, is considered a tumor suppressor by promoting cell differentiation and mitochondrial respiration. Tumors evolved a strategy to avoid these anticancer actions by expressing the T3 catabolizing enzyme, Deiodinase type 3 (DIO3).

Placebo-To be or not to be? Are there really alternatives to placebo-controlled trials?

Recent success of established treatment has driven concerns about the ethics of using placebo-controlled trials in psychiatry. Active-controlled (superiority or non-inferiority) trials do not include a placebo-arm and thus avoid the associated ethical concerns but show disadvantages in other respects. The aim of this paper is to review the available literature and critically discuss the evidence regarding the use of placebo-controlled- versus active-controlled trials.

New insights into tardive dyskinesia genetics: Implementation of whole-exome sequencing approach.

Tardive dyskinesia (TD) is an adverse movement disorder induced by chronic treatment with antipsychotics drugs. The contribution of common genetic variants to TD susceptibility has been investigated in recent years, but with limited success. The aim of the current study was to investigate the potential contribution of rare variants to TD vulnerability.

White matter lesions, cerebral inflammation and cognitive function in a mouse model of cerebral hypoperfusion.

Development of specific treatments for vascular dementia requires appropriate animal models. Bilateral carotid artery stenosis (BCAS) employs metal coils wrapped around both common carotid arteries to induce cerebral hypoperfusion, white matter lesions and memory impairment in mice. We focused on the relationship of memory impairment induced by BCAS to white matter lesions demonstrated by ex vivo magnetic resonance imaging (MRI).

Investigation of the Gene in Tardive Dyskinesia - New Data and Meta-Analysis.

Tardive dyskinesia (TD) is a movement disorder that may occur after extended use of antipsychotic medications. The etiopathophysiology is unclear; however, genetic factors play an important role. The Perlecan () gene was found to be significantly associated with TD in Japanese schizophrenia patients, and this association was subsequently replicated by an independent research group.

Effect of chronic unpredictable stress on mice with developmental under-expression of the Ahi1 gene: behavioral manifestations and neurobiological correlates.

The Abelson helper integration site 1 (Ahi1) gene plays a pivotal role in brain development and is associated with genetic susceptibility to schizophrenia, and other neuropsychiatric disorders. Translational research in genetically modified mice may reveal the neurobiological mechanisms of such associations. Previous studies of mice heterozygous for Ahi1 knockout (Ahi1+/-) revealed an attenuated anxiety response on various relevant paradigms, in the context of a normal glucocorticoid response to caffeine and pentylenetetrazole.

Anorexia Nervosa, Selflessness, and Gender-role Identity: A Study of Daughters and Parents.

Background: This study examines the relationship between anorexia nervosa (AN), selflessness, and genderrole identity in young Israeli women and explores their parents' gender-role identity.

Method: Forty-seven AN women and 50 non-clinical controls completed the Eating Attitudes Test (EAT26), Eating Disorder Inventory (EDI-2), Bem Sex-Role Inventory (BSRI), and Selflessness Scale. Twenty-four parents from the AN group, and 41 mothers and 38 fathers from the control group also completed the BSRI.

One year double blind study of high vs low frequency subcallosal cingulate stimulation for depression.

Subcallosal Brodmann's Area 25 (Cg25) Deep Brain Stimulation (DBS) is a new promising therapy for treatment resistant major depressive disorder (TR-MDD). While different DBS stimulating parameters may have an impact on the efficacy and safety of the therapy, there is no data to support a protocol for optimal stimulation parameters for depression. Here we present a prospective multi-center double-blind randomized crossed-over 13-month study that evaluated the effects of High (130 Hz) vs Low (20 Hz) frequency Cg25 stimulation for nine patients with TR-MDD.