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Genes Jan 2024Serotonin emerges as a pivotal factor influencing the growth and functionality of β-cells. Psilocybin, a natural compound derived from mushrooms of the genus, exerts...
Serotonin emerges as a pivotal factor influencing the growth and functionality of β-cells. Psilocybin, a natural compound derived from mushrooms of the genus, exerts agonistic effects on the serotonin 5-HT2A and 5-HT2B receptors, thereby mimicking serotonin's behavior. This study investigates the potential impacts of psilocybin on β-cell viability, dedifferentiation, and function using an in vitro system. The INS-1 832/13 Rat Insulinoma cell line underwent psilocybin pretreatment, followed by exposure to high glucose-high lipid (HG-HL) conditions for specific time periods. After being harvested from treated cells, total transcript and cellular protein were utilized for further investigation. Our findings implied that psilocybin administration effectively mitigates HG-HL-stimulated β-cell loss, potentially mediated through the modulation of apoptotic biomarkers, which is possibly related to the mitigation of TXNIP, STAT-1, and STAT-3 phosphorylation. Furthermore, psilocybin exhibits the capacity to modulate the expression of key genes associated with β-cell dedifferentiation, including and , indicating its potential in attenuating β-cell dedifferentiation. This research lays the groundwork for further exploration into the therapeutic potential of psilocybin in Type II diabetes intervention.
Topics: Animals; Rats; Psilocybin; Cell Survival; Serotonin; Diabetes Mellitus, Type 2; Glucose; Lipids; Cell Cycle Proteins
PubMed: 38397173
DOI: 10.3390/genes15020183 -
Frontiers in Psychiatry 2024The practice of taking small, sub-hallucinogenic doses of psychedelics, known as microdosing, has exploded in popularity over the last decade. Users claim benefits...
INTRODUCTION
The practice of taking small, sub-hallucinogenic doses of psychedelics, known as microdosing, has exploded in popularity over the last decade. Users claim benefits ranging from improved mood and enhanced creativity to an increased sense of meaning and connectedness in life. While research on microdosing is still lagging behind the shift in public opinion, several papers have been published in the last five years which attempted to assess the effects of microdosing.
METHODS
This review paper aimed to critically analyze the research practices used in the recent wave of microdosing research: We reviewed 15 papers published before the closing date of this review in March 2022.
RESULTS
Our review concludes that it is premature to draw any conclusions about the efficacy or safety of microdosing since the research quality cannot be considered confirmatory.
DISCUSSION
We propose some potential causes for the current state of the literature and some suggestions for how these causes may be ameliorated.
PubMed: 38374976
DOI: 10.3389/fpsyt.2024.1217102 -
Scientific Reports Feb 2024Psychedelic substances induce profound alterations in consciousness. Careful preparation is therefore essential to limit adverse reactions, enhance therapeutic benefits,...
Psychedelic substances induce profound alterations in consciousness. Careful preparation is therefore essential to limit adverse reactions, enhance therapeutic benefits, and maintain user safety. This paper describes the development of a self-directed, digital intervention for psychedelic preparation. Drawing on elements from the UK Medical Research Council (MRC) framework for developing complex interventions, the design was informed by a four-factor model of psychedelic preparedness, using a person-centred approach. Our mixed-methods investigation consisted of two studies. The first involved interviews with 19 participants who had previously attended a 'high-dose' psilocybin retreat, systematically exploring their preparation behaviours and perspectives on the proposed intervention. The second study engaged 28 attendees of an ongoing psilocybin retreat in co-design workshops, refining the intervention protocol using insights from the initial interviews. The outcome is a co-produced 21-day digital course (Digital Intervention for Psychedelic Preparation (DIPP)), that is organised into four modules: Knowledge-Expectation, Psychophysical-Readiness, Safety-Planning, and Intention-Preparation. Fundamental components of the course include daily meditation practice, supplementary exercises tied to the weekly modules, and mood tracking. DIPP provides a comprehensive and scalable solution to enhance psychedelic preparedness, aligning with the broader shift towards digital mental health interventions.
Topics: Humans; Hallucinogens; Psilocybin; Mental Health; Consciousness; Pentamidine
PubMed: 38374177
DOI: 10.1038/s41598-024-54642-4 -
Frontiers in Pharmacology 2024Hallucinogenic drugs are used because they have effects on the central nervous system. Their hallucinogenic effects probably occur via stimulation of serotonin... (Review)
Review
Hallucinogenic drugs are used because they have effects on the central nervous system. Their hallucinogenic effects probably occur via stimulation of serotonin receptors, namely, 5-HT-serotonin receptors in the brain. However, a close study reveals that they also act on the heart, possibly increasing the force of contraction and beating rate and may lead to arrhythmias. Here, we will review the inotropic and chronotropic actions of bufotenin, psilocin, psilocybin, lysergic acid diethylamide (LSD), ergotamine, ergometrine, N,N-dimethyltryptamine, and 5-methoxy-N,N-dimethyltryptamine in the human heart.
PubMed: 38370480
DOI: 10.3389/fphar.2024.1334218 -
Frontiers in Psychiatry 2024
PubMed: 38356910
DOI: 10.3389/fpsyt.2024.1279072 -
BioRxiv : the Preprint Server For... May 2024The serotonin 2 receptor (5HT2R) agonist psilocybin displays rapid and persistent therapeutic efficacy across neuropsychiatric disorders characterized by cognitive...
The serotonin 2 receptor (5HT2R) agonist psilocybin displays rapid and persistent therapeutic efficacy across neuropsychiatric disorders characterized by cognitive inflexibility. However, the impact of psilocybin on patterns of neural activity underlying sustained changes in behavioral flexibility has not been characterized. To test the hypothesis that psilocybin enhances behavioral flexibility by altering activity in cortical neural ensembles, we performed longitudinal single-cell calcium imaging in the retrosplenial cortex across a five-day trace fear learning and extinction assay. A single dose of psilocybin induced ensemble turnover between fear learning and extinction days while oppositely modulating activity in fear- and extinction- active neurons. The acute suppression of fear-active neurons and delayed recruitment of extinction-active neurons were predictive of psilocybin-enhanced fear extinction. A computational model revealed that acute inhibition of fear-active neurons by psilocybin is sufficient to explain its neural and behavioral effects days later. These results align with our hypothesis and introduce a new mechanism involving the suppression of fear-active populations in the retrosplenial cortex.
PubMed: 38352491
DOI: 10.1101/2024.02.04.578811 -
Translational Psychiatry Feb 2024Recent studies have implicated the endogenous opioid system in the antidepressant actions of ketamine, but the underlying mechanisms remain unclear. We used a...
Recent studies have implicated the endogenous opioid system in the antidepressant actions of ketamine, but the underlying mechanisms remain unclear. We used a combination of pharmacological, behavioral, and molecular approaches in rats to test the contribution of the prefrontal endogenous opioid system to the antidepressant-like effects of a single dose of ketamine. Both the behavioral actions of ketamine and their molecular correlates in the medial prefrontal cortex (mPFC) are blocked by acute systemic administration of naltrexone, a competitive opioid receptor antagonist. Naltrexone delivered directly into the mPFC similarly disrupts the behavioral effects of ketamine. Ketamine treatment rapidly increases levels of β-endorphin and the expression of the μ-opioid receptor gene (Oprm1) in the mPFC, and the expression of gene that encodes proopiomelanocortin, the precursor of β-endorphin, in the hypothalamus, in vivo. Finally, neutralization of β-endorphin in the mPFC using a specific antibody prior to ketamine treatment abolishes both behavioral and molecular effects. Together, these findings indicate that presence of β-endorphin and activation of opioid receptors in the mPFC are required for the antidepressant-like actions of ketamine.
Topics: Rats; Animals; Ketamine; Analgesics, Opioid; beta-Endorphin; Naltrexone; Antidepressive Agents; Prefrontal Cortex
PubMed: 38346984
DOI: 10.1038/s41398-024-02796-0 -
Biological Psychiatry. Cognitive... May 2024There has been renewed interest in the use of 3,4-methylenedioxy-methamphetamine (MDMA) and serotonergic psychedelics in the treatment of multiple psychiatric disorders.... (Review)
Review
There has been renewed interest in the use of 3,4-methylenedioxy-methamphetamine (MDMA) and serotonergic psychedelics in the treatment of multiple psychiatric disorders. Many of these compounds are known to produce prosocial effects, but how these effects relate to therapeutic efficacy and the extent to which prosocial effects are unique to a particular drug class is unknown. In this article, we present a narrative overview and compare evidence for the prosocial effects of MDMA and serotonergic psychedelics to elucidate shared mechanisms that may underlie the therapeutic process. We discuss 4 categories of prosocial effects: altered self-image, responses to social reward, responses to negative social input, and social neuroplasticity. While both categories of drugs alter self-perception, MDMA may do so in a way that is less related to the experience of mystical-type states than serotonergic psychedelics. In the case of social reward, evidence supports the ability of MDMA to enhance responses and suggests that serotonergic psychedelics may also do so, but more research is needed in this area. Both drug classes consistently dampen reactivity to negative social stimuli. Finally, preclinical evidence supports the ability of both drug classes to induce social neuroplasticity, promoting adaptive rewiring of neural circuits, which may be helpful in trauma processing. While both MDMA and serotonergic psychedelics produce prosocial effects, they differ in the mechanisms through which they do this. These differences affect the types of psychosocial interventions that may work best with each compound.
Topics: Humans; N-Methyl-3,4-methylenedioxyamphetamine; Hallucinogens; Social Behavior; Serotonin Agents; Reward; Neuronal Plasticity; Self Concept; Animals
PubMed: 38341085
DOI: 10.1016/j.bpsc.2024.02.001 -
Scientific Reports Feb 2024Preparing participants for psychedelic experiences is crucial for ensuring these experiences are safe and, potentially beneficial. However, there is currently no...
Preparing participants for psychedelic experiences is crucial for ensuring these experiences are safe and, potentially beneficial. However, there is currently no validated measure to assess the extent to which participants are well-prepared for such experiences. Our study aimed to address this gap by developing, validating, and testing the Psychedelic Preparedness Scale (PPS). Using a novel iterative Delphi-focus group methodology ('DelFo'), followed by qualitative pre-test interviews, we incorporated the perspectives of expert clinicians/researchers and of psychedelic users to generate items for the scale. Psychometric validation of the PPS was carried out in two large online samples of psychedelic users (N = 516; N = 716), and the scale was also administered to a group of participants before and after a 5-7-day psilocybin retreat (N = 46). Exploratory and confirmatory factor analysis identified four factors from the 20-item PPS: Knowledge-Expectations, Intention-Preparation, Psychophysical-Readiness, and Support-Planning. The PPS demonstrated excellent reliability (ω = 0.954) and evidence supporting convergent, divergent and discriminant validity was also obtained. Significant differences between those scoring high and low (on psychedelic preparedness) before the psychedelic experience were found on measures of mental health/wellbeing outcomes assessed after the experience, suggesting that the scale has predictive utility. By prospectively measuring modifiable pre-treatment preparatory behaviours and attitudes using the PPS, it may be possible to determine whether a participant has generated the appropriate mental 'set' and is therefore likely to benefit from a psychedelic experience, or at least, less likely to be harmed.
Topics: Humans; Hallucinogens; Psychometrics; Reproducibility of Results; Psilocybin; Surveys and Questionnaires
PubMed: 38332334
DOI: 10.1038/s41598-024-53829-z -
Trends in Molecular Medicine Apr 2024In anorexia nervosa (AN), measurable biological parameters can inform the process of treating patients. Such biomarkers include established laboratory parameters as well... (Review)
Review
In anorexia nervosa (AN), measurable biological parameters can inform the process of treating patients. Such biomarkers include established laboratory parameters as well as a range of potential future biomarkers, including genetic, metabolomic, microbiomic, endocrine, immunological, hematological, electrophysiological, and neuroimaging parameters. In this opinion article we discuss how these biomarkers can support diagnosic and therapeutic processes at specific steps during the AN treatment cycle, that is, the diagnosis, diagnostic specification, risk management, choice of therapy, therapy monitoring, and treatment review. History-taking, physical and neuropsychological examination, clinical observation, and judgment about treatment success by the patient, their carers, and members of the multidisciplinary team are essential to interpret laboratory and imaging data appropriately and to assess the full clinical picture.
Topics: Humans; Anorexia Nervosa; Treatment Outcome
PubMed: 38331700
DOI: 10.1016/j.molmed.2024.01.002