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

Towards an understanding of psychedelic-induced neuroplasticity DOI Creative Commons
Abigail E. Calder, Gregor Hasler

Neuropsychopharmacology, Journal Year: 2022, Volume and Issue: 48(1), P. 104 - 112

Published: Sept. 19, 2022

Classic psychedelics, such as LSD, psilocybin, and the DMT-containing beverage ayahuasca, show some potential to treat depression, anxiety, addiction. Importantly, clinical improvements can last for months or years after treatment. It has been theorized that these long-term arise because psychedelics rapidly lastingly stimulate neuroplasticity. The focus of this review is on answering specific questions about effects Firstly, we evidence promote neuroplasticity examine cellular molecular mechanisms behind different aspects neuroplasticity, including dendritogenesis, synaptogenesis, neurogenesis, expression plasticity-related genes (e.g., brain-derived neurotrophic factor immediate early genes). We then where in brain particularly discussing prefrontal cortex hippocampus. also what doses are required produce effect hallucinogenic vs. "microdoses"), how long purported changes last. Finally, discuss likely consequences psychedelics' both patients healthy people, identify important research would further scientific understanding its applications.

Language: Английский

Citations

188
Drugs of abuse hijack a mesolimbic pathway that processes homeostatic need DOI
Bowen Tan, Caleb J. Browne, Tobias Nöbauer

et al.

Science, Journal Year: 2024, Volume and Issue: 384(6693)

Published: April 18, 2024

Drugs of abuse are thought to promote addiction in part by “hijacking” brain reward systems, but the underlying mechanisms remain undefined. Using whole-brain FOS mapping and vivo single-neuron calcium imaging, we found that drugs augment dopaminoceptive ensemble activity nucleus accumbens (NAc) disorganize overlapping responses natural rewards a cell type–specific manner. Combining FOS-Seq, CRISPR-perturbation, single-nucleus RNA sequencing, identified Rheb as molecular substrate regulates signal transduction NAc while enabling suppress consumption. Mapping NAc-projecting regions activated revealed input-specific effects on These findings characterize dynamic, circuit basis common pathway, wherein interfere with fulfillment innate needs.

Language: Английский

Citations

29
TrkB transmembrane domain: bridging structural understanding with therapeutic strategy DOI Creative Commons
Giray Enkavi, Mykhailo Girych, Rafael Moliner

et al.

Trends in Biochemical Sciences, Journal Year: 2024, Volume and Issue: 49(5), P. 445 - 456

Published: March 2, 2024

TrkB (neuronal receptor tyrosine kinase-2, NTRK2) is the for brain-derived neurotrophic factor (BDNF) and a critical regulator of activity-dependent neuronal plasticity. The past few years have witnessed an increasing understanding structure function TrkB, including its transmembrane domain (TMD). interacts with membrane cholesterol, which bidirectionally regulates signaling. Additionally, has recently been recognized as binding target antidepressant drugs. A variety different antidepressants, typical rapid-acting well psychedelic compounds, act allosteric potentiators BDNF signaling through TrkB. This suggests that common compounds. Although more research needed, current knowledge promising further drug development.

Language: Английский

Citations

18
Psychedelic-Induced Neural Plasticity: A Comprehensive Review and a Discussion of Clinical Implications DOI Creative Commons
Francesco Weiss, Anna Magnesa,

Matteo Gambini

et al.

Brain Sciences, Journal Year: 2025, Volume and Issue: 15(2), P. 117 - 117

Published: Jan. 25, 2025

Background: Psychedelics are increasingly recognized as a promising and innovative treatment strategy for several mental disorders. However, there is still lively controversy in the medical community regards rationale of their employment, specifically indications potential dangers. Methods: A comprehensive literature search on “MEDLINE/PubMed” “Web Science” was performed from inception to 26 June 2024, cross-checking obtained references. We included all studies, i.e., both clinical preclinical, that supplied original data. Results: initially total 1083 entries, 813 MEDLINE/PubMed 270 Web Science. After duplicate elimination, 903 underwent systematic selection. Primary abstract screening yielded 572 candidates eligibility assessment excluded 331 entries formal grounds. Eligibility led exclusion 501 titles. Finally, 70 articles were this review. Discussion: Preclinical evidence genetic expression, histology behavioral studies soundly consistent with psychedelics possessing neuroplasticity-inducing properties. Despite methodological difficulties, seems be inferentially agreement preclinical findings. it unclear whether “neuroplastic boost” induced by classic might dissociable psychodysleptic effects, thereby reducing psychopathological hazards implied these compounds. Moreover, fact so-called “relaxation priors” should unconditionally beneficial appears debatable, further research clarify possible contraindications psychedelic psychoplastogens within precision medicine perspective.

Language: Английский

Citations

9
Psychedelics and Neural Plasticity: Therapeutic Implications DOI Creative Commons
Steven F. Grieco, Eero Ċastrén, Gitte M. Knudsen

et al.

Journal of Neuroscience, Journal Year: 2022, Volume and Issue: 42(45), P. 8439 - 8449

Published: Nov. 9, 2022

Psychedelic drugs have reemerged as tools to treat several brain disorders. Cultural attitudes toward them are changing, and scientists once again investigating the neural mechanisms through which these impact function. The significance of this research direction is reflected by recent work, including work presented authors at 2022 meeting Society for Neuroscience. As 2022, there were hundreds clinical trials recruiting participants testing therapeutic effects psychedelics. Emerging evidence suggests that psychedelic may exert some their long-lasting inducing structural functional plasticity. Herein, basic attempting elucidate compounds showcased. Topics covered include receptor binding sites, psychedelics on gene expression, dendrites, microcircuitry brain-wide circuits. We describe unmet needs current state translation clinic psychedelics, well other unanswered neuroscience questions addressable with future studies.

Language: Английский

Citations

45
Acute psilocybin enhances cognitive flexibility in rats DOI Creative Commons
Alejandro Torrado Pacheco, Randall J. Olson, Gabriela Garza

et al.

Neuropsychopharmacology, Journal Year: 2023, Volume and Issue: 48(7), P. 1011 - 1020

Published: Feb. 20, 2023

Psilocybin has been shown to improve symptoms of depression and anxiety when combined with psychotherapy or other clinician-guided interventions. To understand the neural basis for this pattern clinical efficacy, experimental conceptual approaches that are different than traditional laboratory models needed. A potential novel mechanism is acute psilocybin improves cognitive flexibility, which then enhances impact clinician-assisted Consistent idea, we find robustly flexibility in male female rats using a task where animals switched between previously learned strategies response uncued changes environment. did not influence Pavlovian reversal learning, suggesting its effects selective enhanced switching behavioral strategies. The serotonin (5HT) 2 receptor antagonist ketanserin blocked psilocybin's effect on set-shifting, while 5HT2C-selective not. Ketanserin alone also improved set-shifting performance, complex relationship pharmacology flexibility. Further, psychedelic drug 2,5-Dimethoxy-4-iodoamphetamine (DOI) impaired same task, does generalize all serotonergic psychedelics. We conclude provides useful model investigate neuronal relevant positive outcome.

Language: Английский

Citations

41
Ketamine and the neurobiology of depression: Toward next-generation rapid-acting antidepressant treatments DOI Creative Commons
John H. Krystal, Alfred P. Kaye, Sarah Jefferson

et al.

Proceedings of the National Academy of Sciences, Journal Year: 2023, Volume and Issue: 120(49)

Published: Nov. 27, 2023

Ketamine has emerged as a transformative and mechanistically novel pharmacotherapy for depression. Its rapid onset of action, efficacy treatment-resistant symptoms, protection against relapse distinguish it from prior antidepressants. discovery reconceptualization the neurobiology depression and, in turn, insights elaboration its mechanisms action inform studies pathophysiology related disorders. It been 25 y since we first presented our ketamine findings Thus, is timely this review to consider what have learned suggest future directions optimization rapid-acting antidepressant treatment.

Language: Английский

Citations

35
5-MeO-DMT modifies innate behaviors and promotes structural neural plasticity in mice DOI
Sarah J. Jefferson, Ian Gregg, Mark Dibbs

et al.

Neuropsychopharmacology, Journal Year: 2023, Volume and Issue: 48(9), P. 1257 - 1266

Published: April 4, 2023

Language: Английский

Citations

31
UNRAVELing the synergistic effects of psilocybin and environment on brain-wide immediate early gene expression in mice DOI
Daniel Ryskamp Rijsketic, Austen B. Casey, Daniel A. N. Barbosa

et al.

Neuropsychopharmacology, Journal Year: 2023, Volume and Issue: 48(12), P. 1798 - 1807

Published: May 29, 2023

Language: Английский

Citations

30
Therapeutic mechanisms of psychedelics and entactogens DOI
Boris D. Heifets, David E. Olson

Neuropsychopharmacology, Journal Year: 2023, Volume and Issue: 49(1), P. 104 - 118

Published: July 24, 2023

Language: Английский

Citations

30