Psilocybin causes sex, time, and dose dependent alterations in brain signaling pathways DOI
J. Hudson Barnett, Kennedi T. Todd, Joseph Benetatos

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: Dec. 17, 2024

Abstract Psilocybin is a psychedelic tryptamine that has emerged as potential candidate for the treatment of variety conditions, including resistant depression and post-traumatic stress disorder. Clinical trials which have assessed efficacy psilocybin these conditions report rapid sustained improvement in patient- clinician-rated scores. The established mechanism action psychedelics such agonism serotonin 2A receptor (5HT R), however, downstream events mediate their therapeutic effects remain uncertain. As high doses are known to induce strong perceptual alterations, an additional outstanding question whether subperceptual similar molecular psychoactive dosages. Here, we first analysis dose- sex-dependent transcriptional changes forebrains female male mice at 3 timepoints (8 hours, 24 7 days) following single administration low (0.25 mg/kg) or (1 doses. Grouped both sexes reveals time-dependent transcriptomic alterations. We more attenuation females low-dose relative males treated identically. Females also responded robustly high-dose 8 with signal by days. A notable observation was persistent effect days, outlasted changes, suggests may prolonged biological effects. myriad pathways were altered depending on sex timepoint, but common features included functions related neuronal differentiation, neurogenesis, signaling. These data reveal support previous studies demonstrating its dendritogenesis. Given ongoing clinical interest treating mental health disorders, our results suggest sexually divergent should be considered when weighing strategies. Additional consideration given temporal vs dosages gene transcription, especially timing adjuvant cognitive behavioral therapy.

Language: Английский

Are “mystical experiences” essential for antidepressant actions of ketamine and the classic psychedelics? DOI Creative Commons
Kenji Hashimoto

European Archives of Psychiatry and Clinical Neuroscience, Journal Year: 2024, Volume and Issue: unknown

Published: Feb. 27, 2024

The growing interest in the rapid and sustained antidepressant effects of dissociative anesthetic ketamine classic psychedelics, such as psilocybin, is remarkable. However, both psychedelics are known to induce acute mystical experiences; can cause symptoms out-of-body experience, while typically bring about hallucinogenic experiences, like a profound sense unity with universe or nature. role these experiences enhancing outcomes for patients depression currently an area ongoing investigation debate. Clinical studies have shown that following administration (S)-ketamine (esketamine) not directly linked their properties. In contrast, potential (R)-ketamine (arketamine), thought lack side effects, has yet be conclusively proven large-scale clinical trials. Moreover, although activation serotonin 5-HT

Language: Английский

Citations

29
Molecular basis of opioid receptor signaling DOI Creative Commons
Tao Che, Bryan L. Roth

Cell, Journal Year: 2023, Volume and Issue: 186(24), P. 5203 - 5219

Published: Nov. 1, 2023

Language: Английский

Citations

41
1-(2,5-Dimethoxy-4-iodophenyl)-2-aminopropane (DOI): From an Obscure to Pivotal Member of the DOX Family of Serotonergic Psychedelic Agents – A Review DOI Creative Commons
Richard A. Glennon, Małgorzata Dukat

ACS Pharmacology & Translational Science, Journal Year: 2024, Volume and Issue: 7(6), P. 1722 - 1745

Published: May 8, 2024

1-(2,5-Dimethoxy-4-iodophenyl)-2-aminopropane (DOI, or DOX where X = −I) was first synthesized in 1973 a structure–activity study to explore the effect of various aryl substituents on then newly identified, and subsequently controlled, hallucinogenic agent 1-(2,5-dimethoxy-4-methylphenyl)-2-aminopropane (DOM, −CH3). Over time, DOI found be serotonin (5-HT) receptor agonist using peripheral 5-HT tissue assays later, following identification multiple families central receptors, an at 5-HT2 receptors rat and, then, human brain. Today, classical hallucinogens, currently referred as serotonergic psychedelic agents, are receiving considerable attention for their potential therapeutic application neuropsychiatric disorders including treatment-resistant depression. Here, we review, historical current developments that led becoming unique, perhaps landmark, research.

Language: Английский

Citations

10
Novel rapid treatment options for adolescent depression DOI Creative Commons
Sandra Ledesma‐Corvi, Jordi Jornet-Plaza, Laura Gálvez‐Melero

et al.

Pharmacological Research, Journal Year: 2024, Volume and Issue: 201, P. 107085 - 107085

Published: Feb. 2, 2024

There is an urgent need for novel fast-acting antidepressants adolescent treatment-resistant depression and/or suicidal risk, since the selective serotonin reuptake inhibitors that are clinically approved age (i.e., fluoxetine or escitalopram) take weeks to work. In this context, one of main research lines our group characterize at preclinical level approaches rapid-acting adolescence. The present review summarizes potential use in adolescence non-pharmacological options, such as neuromodulators (electroconvulsive therapy and other innovative types brain stimulation), well pharmacological including consciousness-altering drugs (mainly ketamine but also classical psychedelics) cannabinoids cannabidiol), with promising responses. Following a brief analytical explanation depression, we general introduction each therapeutical approach together clinical evidence supporting its beneficial extrapolated from prior successful examples adults), then report recent ongoing studies will aid improving inclusion these therapies clinic, by considering sex-, age-, dose-related differences, factors might affect efficacy long-term safety. Finally, conclude providing future avenues maximize treatment response, more importance designing testing options safe depression.

Language: Английский

Citations

9
A Brief Historical Overview of Psychedelic Research DOI
Mark A. Geyer

Biological Psychiatry Cognitive Neuroscience and Neuroimaging, Journal Year: 2023, Volume and Issue: 9(5), P. 464 - 471

Published: Nov. 23, 2023

Language: Английский

Citations

17
Psilocybin for the treatment of Alzheimer’s disease DOI Creative Commons
Siyi Zheng,

Rong Ma,

Yang Yang

et al.

Frontiers in Neuroscience, Journal Year: 2024, Volume and Issue: 18

Published: July 10, 2024

Alzheimer’s disease (AD) stands as a formidable neurodegenerative ailment and prominent contributor to dementia. The scarcity of available therapies for AD accentuates the exigency innovative treatment modalities. Psilocybin, psychoactive alkaloid intrinsic hallucinogenic mushrooms, has garnered attention within neuropsychiatric realm due its established safety efficacy in treating depression. Nonetheless, potential therapeutic avenue remains largely uncharted. This comprehensive review endeavors encapsulate pharmacological effects psilocybin while elucidating existing evidence concerning mechanisms contributing positive impact on AD. Specifically, active metabolite psilocybin, psilocin, elicits through modulation 5-hydroxytryptamine 2A receptor (5-HT2A receptor). causes heightened neural plasticity, diminished inflammation, improvements cognitive functions such creativity, flexibility, emotional facial recognition. Noteworthy is psilocybin’s promising role mitigating anxiety depression symptoms patients. Acknowledging attendant adverse reactions, we proffer strategies aimed at tempering or effects. Moreover, broach ethical legal dimensions inherent exploration treatment. By traversing these avenues, We propose nuanced management disease.

Language: Английский

Citations

7
Isolation of psychedelic-responsive neurons underlying anxiolytic behavioral states DOI
Jessie Muir,

Shengyin Lin,

Isak K. Aarrestad

et al.

Science, Journal Year: 2024, Volume and Issue: 386(6723), P. 802 - 810

Published: Nov. 14, 2024

Psychedelics hold promise as alternate treatments for neuropsychiatric disorders. However, the neural mechanisms by which they drive adaptive behavioral effects remain unclear. We isolated specific neurons modulated a psychedelic to determine their role in driving behavior. Using light- and calcium-dependent activity integrator, we genetically tagged psychedelic-responsive medial prefrontal cortex (mPFC) of mice. Single-nucleus RNA sequencing revealed that drove network-level activation multiple cell types beyond just those expressing 5-hydroxytryptamine 2A receptors. labeled mPFC with an excitatory channelrhodopsin enable targeted manipulation. found reactivation these cells recapitulated anxiolytic without its hallucinogenic-like effects. These findings reveal essential insight into cell-type-specific underlying psychedelic-induced states.

Language: Английский

Citations

7
Stimulant and hallucinogenic novel psychoactive substances; an update DOI Creative Commons
Fabrizio Schifano, Alessandro Vento, Norbert Scherbaum

et al.

Expert Review of Clinical Pharmacology, Journal Year: 2023, Volume and Issue: 16(11), P. 1109 - 1123

Published: Nov. 2, 2023

Introduction The renewed interest in considering a range of stimulants, psychedelics and dissociatives as therapeutics emphasizes the need to draft an updated overview these drugs' clinical pharmacological issues.

Language: Английский

Citations

14
Making Sense of Psychedelics in the CNS DOI Creative Commons

Blake A. Fordyce,

Bryan L. Roth

The International Journal of Neuropsychopharmacology, Journal Year: 2024, Volume and Issue: 27(2)

Published: Jan. 30, 2024

For centuries, ancient lineages have consumed psychedelic compounds from natural sources. In the modern era, scientists since harnessed power of computational tools, cellular assays, and behavioral metrics to study how these instigate changes on molecular, cellular, circuit-wide, system levels. Here, we provide a brief history psychedelics their use in science, medicine, culture. We then outline current techniques for studying pharmacological perspective. Finally, address known gaps field potential avenues further research broaden our collective understanding physiological induced by psychedelics, limits therapeutic capabilities, researchers can improve inform treatments that are rapidly becoming accessible worldwide.

Language: Английский

Citations

4
Clinical and preclinical evidence of psilocybin as antidepressant. A narrative review DOI Creative Commons
I. Erkizia-Santamaría, Igor Horrillo, J. Javier Meana

et al.

Progress in Neuro-Psychopharmacology and Biological Psychiatry, Journal Year: 2025, Volume and Issue: unknown, P. 111249 - 111249

Published: Jan. 1, 2025

Language: Английский

Citations

0