Chronic pain,characterized by pain lasting for more than three months,is a debilitating condition frequently caused by conditions such as fibromyalgia,arthritis,neuropathy,and migraine[1-3].
Depression is a common mental disorder and one of the leading causes of disability around the world.Monoaminergic antidepressants often take weeks to months to work and are not effective for all patients.This has led ...Depression is a common mental disorder and one of the leading causes of disability around the world.Monoaminergic antidepressants often take weeks to months to work and are not effective for all patients.This has led to a search for a better understanding of the pathogenesis of depression as well as to the development of novel antidepressants.One such novel antidepressant is ketamine,which has demonstrated both clinically promising results and contributed to new explanatory models of depression,including the potential role of neuroplasticity in depression.Early clinical trials are now showing promising results of serotonergic psychedelics for depression;however,their mechanism of action remains poorly understood.This paper seeks to review the effect of depression,classic antidepressants,ketamine,and serotonergic psychedelics on markers of neuroplasticity at a cellular,molecular,electrophysiological,functional,structural,and psychological level to explore the potential role that neuroplasticity plays in the treatment response of serotonergic psychedelics.展开更多
A recent study published in Neuron by Tiwari et al.identified the critical role of 5-HT2A receptor in ventral hippocampal parvalbumin(PV)interneurons(INs)in mediating the acute anxiolytic effects of the serotonergic p...A recent study published in Neuron by Tiwari et al.identified the critical role of 5-HT2A receptor in ventral hippocampal parvalbumin(PV)interneurons(INs)in mediating the acute anxiolytic effects of the serotonergic psychedelic 2,5-dimethoxy-4-iodoamphetamine(DOI).This study not only advances psychedelic neuropharmacology but also provides a robust framework for developing novel rapid-acting therapeutics for anxiety disorders[1].展开更多
Psychedelics have long been recognized not only for their profound impact on human consciousness but also for their potential therapeutic applications.This perspective explores the multifaceted relationship between ps...Psychedelics have long been recognized not only for their profound impact on human consciousness but also for their potential therapeutic applications.This perspective explores the multifaceted relationship between psychedelics and consciousness,emphasizing their capacity to alter sensory perceptions,disrupt selfreferential thought processes,and catalyze profound spiritual and existential experiences.As research advances,psychedelics are being integrated into therapeutic settings,challenging existing psychiatric models and offering new insights into the complex nature of consciousness and mental health.This emerging paradigm marks the need for careful regulation and ethical considerations in the therapeutic use of psychedelics,promising a more holistic approach to mental health disorders.展开更多
Psychedelics,encompassing both classical and non-classical categories,are psychoactive substances known for inducing hallucinations as well as a range of cognitive and emotional effects[1].Archeological studies have d...Psychedelics,encompassing both classical and non-classical categories,are psychoactive substances known for inducing hallucinations as well as a range of cognitive and emotional effects[1].Archeological studies have demonstrated that both classical psychedelics and non-classical psychedelics have been used for medical purposes for centuries.Moreover,accumulating evidence supports the idea that psychedelics can regulate mood disturbances and psychiatric disorders.展开更多
The United States Food and Drug Administration's(FDA's)August 2024 determination that an additional phase Ⅱ study will be required to consider the approval of midomafetamine for the treatment of posttraumatic...The United States Food and Drug Administration's(FDA's)August 2024 determination that an additional phase Ⅱ study will be required to consider the approval of midomafetamine for the treatment of posttraumatic stress disorder(PTSD)could delay the potential approval of this promising treatment by several years.展开更多
This article explores the intersection of the Eight-Circuit Model of Consciousness (ECM), initially conceptualized by Timothy Leary and expanded by Robert Anton Wilson, and its implications for mind-body health. By an...This article explores the intersection of the Eight-Circuit Model of Consciousness (ECM), initially conceptualized by Timothy Leary and expanded by Robert Anton Wilson, and its implications for mind-body health. By analyzing each circuit’s role in human consciousness, we discuss how activating and balancing these circuits can lead to enhanced psychological well-being, stress reduction, and overall physical health. Recent research is integrated to provide a contemporary understanding of how the ECM can be applied to modern mind-body therapies, with a focus on both theoretical implications and practical applications.展开更多
Objective:This study investigated trends in the study of phytochemical treatment of post-traumatic stress disorder(PTSD).Methods:The Web of Science database(2007-2022)was searched using the search terms“phytochemical...Objective:This study investigated trends in the study of phytochemical treatment of post-traumatic stress disorder(PTSD).Methods:The Web of Science database(2007-2022)was searched using the search terms“phytochemicals”and“PTSD,”and relevant literature was compiled.Network clustering co-occurrence analysis and qualitative narrative review were conducted.Results:Three hundred and one articles were included in the analysis of published research,which has surged since 2015 with nearly half of all relevant articles coming from North America.The category is dominated by neuroscience and neurology,with two journals,Addictive Behaviors and Drug and Alcohol Dependence,publishing the greatest number of papers on these topics.Most studies focused on psychedelic intervention for PTSD.Three timelines show an“ebb and flow”phenomenon between“substance use/marijuana abuse”and“psychedelic medicine/medicinal cannabis.”Other phytochemicals account for a small proportion of the research and focus on topics like neurosteroid turnover,serotonin levels,and brain-derived neurotrophic factor expression.Conclusion:Research on phytochemicals and PTSD is unevenly distributed across countries/regions,disciplines,and journals.Since 2015,the research paradigm shifted to constitute the mainstream of psychedelic research thus far,leading to the exploration of botanical active ingredients and molecular mechanisms.Other studies focus on anti-oxidative stress and anti-inflammation.展开更多
Psychedelic is one of psychoac⁃tive drug substances which leads to abnormali⁃ties in thinking,mood and sensory perception via the subtype of 5-HT receptor(5-HT2A receptor).Psychedelic is known to cause schizophrenia-l...Psychedelic is one of psychoac⁃tive drug substances which leads to abnormali⁃ties in thinking,mood and sensory perception via the subtype of 5-HT receptor(5-HT2A receptor).Psychedelic is known to cause schizophrenia-like symptoms or worsen schizophrenia.Mean⁃while it causes abnormalities in neural synchroni⁃zation and oscillations.In recent years,with the prevalence of various new psychedelic drugs and the rising population of young addicts,the clinical effects of psychedelic have been highly concerned.Adolescence is an important period for the formation of neuroplasticity,and it is an important stage in the functional development and maturation of the central nervous system.However,it is currently unclear about the endur⁃ing effects of juvenile exposure to psychedelic on social behavior,and neural network function.OBJECTIVE The chronic exposure model of psy⁃chedelic(2CC-NBOMe,2CC)in rats was used to reveal the enduring effects on social behavior and neural network function in adulthood,which is intended to provide important reference infor⁃mation about the potential enduring effects and clinical applicability of psychedelic.METHODS Repeated exposure of normal saline in adoles⁃cence group(0.1 mL·kg-1,for 14 d),repeated exposure of 2CC group(0.1 mg·kg-1,for 14 d).The duration of adolescent administration was 35-48 d after birth.Adulthood means 9 weeks after birth.Behavioral and somatic neuroelectro⁃physiological experiments were performed 9-12 weeks after birth in the adolescent drug exposure group.RESULTS Psychedelic-exposed animals during adolescence showed a significant decline in social rank and an increase in social willingness.Coherence of theta waves(6-10 Hz)from the hippocampal CA1 to the orbital frontal cortex(Orb)was significantly reduced in the psy⁃chedelic-exposed animals compared to the con⁃trol animals.During the social task,the coher⁃ence of theta waves between CA1 and Orb was significantly reduced in the control animals,but not in the psychedelic-exposed animals.CON⁃CLUSION The altered social function caused by chronic psychedelic exposure during adoles⁃cence is associated with abnormal CA1-Orb theta wave coherence.展开更多
Objective: Psychedelic drug therapy is banned in all countries of the world except Australia, where the government regulatory watchdog, the Therapeutic Goods Administration, is planning to allow approved psychiatrists...Objective: Psychedelic drug therapy is banned in all countries of the world except Australia, where the government regulatory watchdog, the Therapeutic Goods Administration, is planning to allow approved psychiatrists, as of July 1, 2023, to prescribe psilocybin to treat depression and MDMA to treat post-traumatic stress disorder, a move precipitated by the U.S. Food and Drug Administration’s designation of these two drugs as “breakthrough therapy”. The objective of the present article is to demonstrate that the evidence on which the FDA and then the TGA relied is irretrievably flawed and should be dismissed. Method: Expert review of psychedelic therapy clinical trials and specifically of the methodology and measures used. Results: The present review demonstrates that the studies the U.S. FDA and the Australian TGA relied on to approve these two psychedelic drugs for therapy are irretrievably flawed. All future trials will follow the same procedure and are therefore bound to be flawed as well. Conclusions: Psychedelic drug studies have so far provided no trustworthy evidence of their effectiveness for treating mental disorders and are not likely to produce this evidence in the future. Psychedelic drug therapy is in any event impractical because of its specialized training requirements and very high treatment costs. It is also dangerous because false publicity about its effectiveness will almost certainly lead to unsupervised self-dosing with drugs that not only are illegal but have an unacceptably high addiction rate.展开更多
After having laid down the Axiom of Algebra, bringing the creation of the square root of -1 by Euler to the entire circle and thus authorizing a simple notation of the nth roots of unity, the author uses it to organiz...After having laid down the Axiom of Algebra, bringing the creation of the square root of -1 by Euler to the entire circle and thus authorizing a simple notation of the nth roots of unity, the author uses it to organize homogeneous divisions of the limited development of the exponential function, that is opening the way to the use of a whole bunch of new primary functions in Differential Calculus. He then shows how new supercomplex products in dimension 3 make it possible to calculate fractals whose connexity depends on the product considered. We recall the geometry of convex polygons and regular polygons.展开更多
G protein-coupled receptors(GPCRs)represent key drug targets,with approximately 30%-40%of all medications acting on these receptors.Recent advancements have uncovered the complexity of GPCR signaling,including biased ...G protein-coupled receptors(GPCRs)represent key drug targets,with approximately 30%-40%of all medications acting on these receptors.Recent advancements have uncovered the complexity of GPCR signaling,including biased signaling,which allows selective activation of specific intracellular pathways―primarily mediated by G proteins andß-arrestins.Among aminergic GPCRs,the serotonin 5-HT_(2A)receptor has garnered attention for its potential to generate therapeutic effects without adverse outcomes,such as hallucinations,through biased agonism.This review delivers a comprehensive overview of 5-HT_(2A)receptor-biased signaling and its significance in developing safer mental health therapeutics,particularly for depression and anxiety.We provide a critical evaluation of methodologies for assessing biased signaling,spanning from traditional radioligand binding assays to advanced biosensor technologies.Furthermore,we review structural studies and computational modeling that have identified key receptor residues modulating biased signaling.We also highlight novel biased ligands with selective pathway activation,presenting a promising avenue for developing targeted antidepressant therapies without psychedelic effects.Additionally,we explore the 5-HT_(2A)receptor’s role in memory processes and stress response regulation.Ultimately,advancing our understanding of 5-HT_(2A)receptor-biased signaling could drive the development of next-generation GPCR-targeted therapies,maximizing therapeutic efficacy while minimizing side effects in psychiatric treatment.展开更多
基金supported by the National Natural Science Foundation of China(T2241028)the STI2030-Major Projects[2021ZD0203000(2021ZD0203003)]the Chinese Academy of Sciences Hundred Talents Program.
文摘Chronic pain,characterized by pain lasting for more than three months,is a debilitating condition frequently caused by conditions such as fibromyalgia,arthritis,neuropathy,and migraine[1-3].
文摘Depression is a common mental disorder and one of the leading causes of disability around the world.Monoaminergic antidepressants often take weeks to months to work and are not effective for all patients.This has led to a search for a better understanding of the pathogenesis of depression as well as to the development of novel antidepressants.One such novel antidepressant is ketamine,which has demonstrated both clinically promising results and contributed to new explanatory models of depression,including the potential role of neuroplasticity in depression.Early clinical trials are now showing promising results of serotonergic psychedelics for depression;however,their mechanism of action remains poorly understood.This paper seeks to review the effect of depression,classic antidepressants,ketamine,and serotonergic psychedelics on markers of neuroplasticity at a cellular,molecular,electrophysiological,functional,structural,and psychological level to explore the potential role that neuroplasticity plays in the treatment response of serotonergic psychedelics.
基金supported by the National Natural Science Foundation of China(82204353).
文摘A recent study published in Neuron by Tiwari et al.identified the critical role of 5-HT2A receptor in ventral hippocampal parvalbumin(PV)interneurons(INs)in mediating the acute anxiolytic effects of the serotonergic psychedelic 2,5-dimethoxy-4-iodoamphetamine(DOI).This study not only advances psychedelic neuropharmacology but also provides a robust framework for developing novel rapid-acting therapeutics for anxiety disorders[1].
基金supported by the National Natural Science Foundation of China(T2241028)the STI2030-Major Projects[2021ZD0203000(2021ZD0203003)]+1 种基金the Science and Technology Development Plan Project of Jilin Province(20220402045GH)the Chinese Academy of Sciences(CAS)Hundred Talents Program.
文摘Psychedelics have long been recognized not only for their profound impact on human consciousness but also for their potential therapeutic applications.This perspective explores the multifaceted relationship between psychedelics and consciousness,emphasizing their capacity to alter sensory perceptions,disrupt selfreferential thought processes,and catalyze profound spiritual and existential experiences.As research advances,psychedelics are being integrated into therapeutic settings,challenging existing psychiatric models and offering new insights into the complex nature of consciousness and mental health.This emerging paradigm marks the need for careful regulation and ethical considerations in the therapeutic use of psychedelics,promising a more holistic approach to mental health disorders.
基金supported by the National Natural Science Foundation of China(32192410,32192414,32330043,T2350008,82325019,and 32241015)the Science and Technology Commission of Shanghai Municipality(23XD1423000 and 23ZR1480800)+1 种基金Shanghai Municipal Commission of Health(2022JC016)Shanghai Municipal Education Commission-Gaofeng Clinical Medicine Grant Support(20181715)。
文摘Psychedelics,encompassing both classical and non-classical categories,are psychoactive substances known for inducing hallucinations as well as a range of cognitive and emotional effects[1].Archeological studies have demonstrated that both classical psychedelics and non-classical psychedelics have been used for medical purposes for centuries.Moreover,accumulating evidence supports the idea that psychedelics can regulate mood disturbances and psychiatric disorders.
文摘The United States Food and Drug Administration's(FDA's)August 2024 determination that an additional phase Ⅱ study will be required to consider the approval of midomafetamine for the treatment of posttraumatic stress disorder(PTSD)could delay the potential approval of this promising treatment by several years.
文摘This article explores the intersection of the Eight-Circuit Model of Consciousness (ECM), initially conceptualized by Timothy Leary and expanded by Robert Anton Wilson, and its implications for mind-body health. By analyzing each circuit’s role in human consciousness, we discuss how activating and balancing these circuits can lead to enhanced psychological well-being, stress reduction, and overall physical health. Recent research is integrated to provide a contemporary understanding of how the ECM can be applied to modern mind-body therapies, with a focus on both theoretical implications and practical applications.
基金the National Natural Science Foundation of China(No.81573150)Military Key Discipline Construction Projects of China(No.HL21JD1206).
文摘Objective:This study investigated trends in the study of phytochemical treatment of post-traumatic stress disorder(PTSD).Methods:The Web of Science database(2007-2022)was searched using the search terms“phytochemicals”and“PTSD,”and relevant literature was compiled.Network clustering co-occurrence analysis and qualitative narrative review were conducted.Results:Three hundred and one articles were included in the analysis of published research,which has surged since 2015 with nearly half of all relevant articles coming from North America.The category is dominated by neuroscience and neurology,with two journals,Addictive Behaviors and Drug and Alcohol Dependence,publishing the greatest number of papers on these topics.Most studies focused on psychedelic intervention for PTSD.Three timelines show an“ebb and flow”phenomenon between“substance use/marijuana abuse”and“psychedelic medicine/medicinal cannabis.”Other phytochemicals account for a small proportion of the research and focus on topics like neurosteroid turnover,serotonin levels,and brain-derived neurotrophic factor expression.Conclusion:Research on phytochemicals and PTSD is unevenly distributed across countries/regions,disciplines,and journals.Since 2015,the research paradigm shifted to constitute the mainstream of psychedelic research thus far,leading to the exploration of botanical active ingredients and molecular mechanisms.Other studies focus on anti-oxidative stress and anti-inflammation.
文摘Psychedelic is one of psychoac⁃tive drug substances which leads to abnormali⁃ties in thinking,mood and sensory perception via the subtype of 5-HT receptor(5-HT2A receptor).Psychedelic is known to cause schizophrenia-like symptoms or worsen schizophrenia.Mean⁃while it causes abnormalities in neural synchroni⁃zation and oscillations.In recent years,with the prevalence of various new psychedelic drugs and the rising population of young addicts,the clinical effects of psychedelic have been highly concerned.Adolescence is an important period for the formation of neuroplasticity,and it is an important stage in the functional development and maturation of the central nervous system.However,it is currently unclear about the endur⁃ing effects of juvenile exposure to psychedelic on social behavior,and neural network function.OBJECTIVE The chronic exposure model of psy⁃chedelic(2CC-NBOMe,2CC)in rats was used to reveal the enduring effects on social behavior and neural network function in adulthood,which is intended to provide important reference infor⁃mation about the potential enduring effects and clinical applicability of psychedelic.METHODS Repeated exposure of normal saline in adoles⁃cence group(0.1 mL·kg-1,for 14 d),repeated exposure of 2CC group(0.1 mg·kg-1,for 14 d).The duration of adolescent administration was 35-48 d after birth.Adulthood means 9 weeks after birth.Behavioral and somatic neuroelectro⁃physiological experiments were performed 9-12 weeks after birth in the adolescent drug exposure group.RESULTS Psychedelic-exposed animals during adolescence showed a significant decline in social rank and an increase in social willingness.Coherence of theta waves(6-10 Hz)from the hippocampal CA1 to the orbital frontal cortex(Orb)was significantly reduced in the psy⁃chedelic-exposed animals compared to the con⁃trol animals.During the social task,the coher⁃ence of theta waves between CA1 and Orb was significantly reduced in the control animals,but not in the psychedelic-exposed animals.CON⁃CLUSION The altered social function caused by chronic psychedelic exposure during adoles⁃cence is associated with abnormal CA1-Orb theta wave coherence.
文摘Objective: Psychedelic drug therapy is banned in all countries of the world except Australia, where the government regulatory watchdog, the Therapeutic Goods Administration, is planning to allow approved psychiatrists, as of July 1, 2023, to prescribe psilocybin to treat depression and MDMA to treat post-traumatic stress disorder, a move precipitated by the U.S. Food and Drug Administration’s designation of these two drugs as “breakthrough therapy”. The objective of the present article is to demonstrate that the evidence on which the FDA and then the TGA relied is irretrievably flawed and should be dismissed. Method: Expert review of psychedelic therapy clinical trials and specifically of the methodology and measures used. Results: The present review demonstrates that the studies the U.S. FDA and the Australian TGA relied on to approve these two psychedelic drugs for therapy are irretrievably flawed. All future trials will follow the same procedure and are therefore bound to be flawed as well. Conclusions: Psychedelic drug studies have so far provided no trustworthy evidence of their effectiveness for treating mental disorders and are not likely to produce this evidence in the future. Psychedelic drug therapy is in any event impractical because of its specialized training requirements and very high treatment costs. It is also dangerous because false publicity about its effectiveness will almost certainly lead to unsupervised self-dosing with drugs that not only are illegal but have an unacceptably high addiction rate.
文摘After having laid down the Axiom of Algebra, bringing the creation of the square root of -1 by Euler to the entire circle and thus authorizing a simple notation of the nth roots of unity, the author uses it to organize homogeneous divisions of the limited development of the exponential function, that is opening the way to the use of a whole bunch of new primary functions in Differential Calculus. He then shows how new supercomplex products in dimension 3 make it possible to calculate fractals whose connexity depends on the product considered. We recall the geometry of convex polygons and regular polygons.
基金supported by a statutory funds grant from the Medical University of Lublin,Poland(grant number DS33),to Agnieszka A.Kaczor.
文摘G protein-coupled receptors(GPCRs)represent key drug targets,with approximately 30%-40%of all medications acting on these receptors.Recent advancements have uncovered the complexity of GPCR signaling,including biased signaling,which allows selective activation of specific intracellular pathways―primarily mediated by G proteins andß-arrestins.Among aminergic GPCRs,the serotonin 5-HT_(2A)receptor has garnered attention for its potential to generate therapeutic effects without adverse outcomes,such as hallucinations,through biased agonism.This review delivers a comprehensive overview of 5-HT_(2A)receptor-biased signaling and its significance in developing safer mental health therapeutics,particularly for depression and anxiety.We provide a critical evaluation of methodologies for assessing biased signaling,spanning from traditional radioligand binding assays to advanced biosensor technologies.Furthermore,we review structural studies and computational modeling that have identified key receptor residues modulating biased signaling.We also highlight novel biased ligands with selective pathway activation,presenting a promising avenue for developing targeted antidepressant therapies without psychedelic effects.Additionally,we explore the 5-HT_(2A)receptor’s role in memory processes and stress response regulation.Ultimately,advancing our understanding of 5-HT_(2A)receptor-biased signaling could drive the development of next-generation GPCR-targeted therapies,maximizing therapeutic efficacy while minimizing side effects in psychiatric treatment.
