Current topics in behavioral neurosciences最新文献

{"title":"Chemical Probes for Investigating the Endocannabinoid System.","authors":"Annaleah Hanske, Marc Nazaré, Uwe Grether","doi":"10.1007/7854_2024_563","DOIUrl":"10.1007/7854_2024_563","url":null,"abstract":"<p><p>Cannabis sativa has been used therapeutically since early civilizations, with key cannabinoids Δ<sup>9</sup>-tetrahydrocannabinol (THC) 3.1 and cannabidiol characterized in the 1960s, leading to the discovery of cannabinoid receptors type 1 (CB<sub>1</sub>R) and type 2 (CB<sub>2</sub>R) and the endocannabinoid system (ECS) in the 1990s. The ECS, involving endogenous ligands like 2-arachidonoylglycerol (2-AG) 1.1, anandamide (N-arachidonoylethanolamine (AEA)) 1.2, and various proteins, regulates vital processes such as sleep, appetite, and memory, and holds significant therapeutic potential, especially for neurological disorders. Small molecule-derived pharmacological tools, or chemical probes, target key components of the ECS and are crucial for target validation, mechanistic studies, pathway elucidation, phenotypic screening, and drug discovery. These probes selectively interact with specific proteins or pathways, enabling researchers to modulate target activity and observe biological effects. When they carry an additional reporter group, they are referred to as labeled chemical probes. Developed through medicinal chemistry, structural biology, and high-throughput screening, effective chemical probes must be selective, potent, and depending on their purpose meet additional criteria such as cell permeability and metabolic stability.This chapter describes high-quality labeled and unlabeled chemical probes targeting ECS constituents that have been successfully applied for various research purposes. CB<sub>1</sub>R and CB<sub>2</sub>R, class A G protein-coupled receptors, are activated by 2-AG 1.1, AEA 1.2, and THC 3.1, with numerous ligands developed for these receptors. Imaging techniques like single-photon emission computed tomography, positron emission tomography, and fluorescently labeled CB<sub>1</sub>R and CB<sub>2</sub>R probes have enhanced CB receptor studies. CB<sub>2</sub>R activation generally results in immunosuppressive effects, limiting tissue injury. AEA 1.2 is mainly degraded by fatty acid amide hydrolase (FAAH) or N-acylethanolamine acid amidase (NAAA) into ethanolamine and arachidonic acid (AA) 1.3. FAAH inhibitors increase endogenous fatty acid amides, providing analgesic effects without adverse effects. NAAA inhibitors reduce inflammation and pain in animal models. Diacylglycerol lipase (DAGL) is essential for 2-AG 1.1 biosynthesis, while monoacylglycerol lipase (MAGL) degrades 2-AG 1.1 into AA 1.3, thus regulating cannabinoid signaling. Multiple inhibitors targeting FAAH and MAGL have been generated, though NAAA and DAGL probe development lags behind. Similarly, advancements in inhibitors targeting endocannabinoid (eCB) cellular uptake or trafficking proteins like fatty acid-binding proteins have been slower. The endocannabinoidome (eCBome) includes the ECS and related molecules and receptors, offering therapeutic opportunities from non-THC cannabinoids and eCBome mediators. Ongoing research aims to refine chemical tools","PeriodicalId":11257,"journal":{"name":"Current topics in behavioral neurosciences","volume":" ","pages":"69-144"},"PeriodicalIF":0.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142921266","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Canonical Cannabinoid Receptors.","authors":"Beth Ehrlich, Monica Patel, Xiaoxi Zheng, Michelle Glass","doi":"10.1007/7854_2024_556","DOIUrl":"10.1007/7854_2024_556","url":null,"abstract":"<p><p>This chapter will review the basic pharmacology of the canonical cannabinoid receptors. The endocannabinoid system is a complex signalling network involved in a wide range of physiological processes, including pain modulation, appetite regulation, and synaptic plasticity. The canonical cannabinoid receptors, CB₁ and CB₂, are central in orchestrating this system. CB₁ is highly enriched in the central nervous system (CNS), where it plays a crucial role in modulating neurotransmitter release and synaptic plasticity. In contrast, CB₂ is predominantly expressed in peripheral tissues and immune cells, participating in anti-inflammatory processes. Here, we focus on cannabinoid receptor distribution, intracellular signalling, and receptor regulation. We describe the intracellular signalling pathways activated by CB₁, including the modulation of ion channels, second messengers, and protein kinases. Overall, this chapter provides an overview of the canonical cannabinoid receptors and their role in the regulation of neuronal signalling and plasticity, highlighting the molecular and cellular mechanisms underlying their effects in the CNS.</p>","PeriodicalId":11257,"journal":{"name":"Current topics in behavioral neurosciences","volume":" ","pages":"37-68"},"PeriodicalIF":0.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143572454","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Psychedelic Harm Reduction and Integration: A Transtheoretical Model for Clinical Practice.","authors":"Xiaojue Hu, Ingmar Gorman, Elizabeth Nielson","doi":"10.1007/7854_2024_529","DOIUrl":"10.1007/7854_2024_529","url":null,"abstract":"<p><p>Psychedelic Harm Reduction and Integration (PHRI) is a transtheoretical clinical model for working with psychedelic experiences in therapeutic settings. Drawing from harm reduction psychotherapy, psychedelic-assisted therapy, mindfulness-based modalities, and psychodynamic therapy, PHRI offers a framework for clinicians to assist clients in preparing for and integrating psychedelic experiences without directly administering psychedelics. This approach emphasizes non-pathologizing, client-empowering strategies to address both challenging and positive psychedelic experiences. PHRI incorporates principles such as non-directive and inner-directed approaches, somatic awareness, and psychological flexibility. The model addresses common integration challenges including fear, ego dissolution, and increased emotional sensitivity. By bridging various therapeutic modalities, PHRI aims to support clients in translating psychedelic experiences into enduring positive changes while decreasing potential harms. This chapter outlines the theoretical foundations of PHRI, distinguishes it from existing approaches, and explores its application in clinical practice, with a focus on the integration phase of psychedelic experiences.</p>","PeriodicalId":11257,"journal":{"name":"Current topics in behavioral neurosciences","volume":" ","pages":"397-416"},"PeriodicalIF":0.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142799737","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Phenomenology of Psychedelic Experiences and Psychedelic-Associated Distressing Effects: Quantifying Subjective Experiences.","authors":"Cyril Costines, Timo Torsten Schmidt","doi":"10.1007/7854_2024_562","DOIUrl":"10.1007/7854_2024_562","url":null,"abstract":"<p><p>The range of phenomena that can be induced by psychedelic substances is broad and variable, including effects on perception, cognition, and emotion. The umbrella term \"psychedelic phenomenology\" is used to refer to a combination of altered experiential features, such as hallucinations or ego dissolution, which together constitute a psychedelic experience. However, there is no consensus on the set of alterations of consciousness that qualifies an altered state to be a \"psychedelic state.\" In this chapter we summarize the most commonly discussed changes in subjective experiences which could be seen as \"core features\" of psychedelic experiences. While acknowledging the rich history of pioneering phenomenological work of the last century, this chapter focuses on more recent developments in the quantitative work on the assessment of these phenomena. We also address the under-researched phenomenology of distressing effects, often referred to as \"challenging experiences\" or \"bad trips,\" and point to their importance in understanding the therapeutic potential and risks associated with psychedelic phenomenology. Historically, one can find many links between psychedelic phenomenology and the phenomenology of psychopathology. We stress the importance to refine the assessment and description also of distressing effects, to identify factors that promote acute experiences which are beneficial and limit those which can have potentially harmful long-term effects.</p>","PeriodicalId":11257,"journal":{"name":"Current topics in behavioral neurosciences","volume":" ","pages":"63-85"},"PeriodicalIF":0.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142909594","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Traumatic Psychedelic Experiences.","authors":"Abigail E Calder, Vincent J Diehl, Gregor Hasler","doi":"10.1007/7854_2025_579","DOIUrl":"10.1007/7854_2025_579","url":null,"abstract":"<p><p>Psychedelic experiences involving extreme feelings of horror, helplessness, and perceived threats can be traumatizing. Traumatic psychedelic experiences are a rare, extreme, and largely preventable form of challenging experience which can arise due to frightening psychedelic drug effects, unsafe settings, and emergence of pre-existing trauma. Some people recover quickly, but others develop prolonged anxiety, sleep disturbances, derealization, or other potentially trauma-related symptoms. This chapter discusses the causes, phenomenology, and potential outcomes of traumatic psychedelic experiences, as well as how to prevent them and minimize their negative impact.</p>","PeriodicalId":11257,"journal":{"name":"Current topics in behavioral neurosciences","volume":" ","pages":"271-296"},"PeriodicalIF":0.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143968643","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Psychedelic-Associated Depersonalization-Derealization Disorder.","authors":"Matthias Michal","doi":"10.1007/7854_2025_599","DOIUrl":"10.1007/7854_2025_599","url":null,"abstract":"<p><p>Depersonalization (DP) and Derealization (DR) refer to perceptual changes of \"as-if-character\" where the self (→DP) or the surroundings (→DR) are experienced as unreal. These symptoms are highly prevalent in individuals with mental disorders. If these symptoms persist most of the day for months, the diagnosis of depersonalization-derealization-disorder (DDD) is likely. DDD is a common disorder with a high comorbidity with depression, anxiety disorders, and personality disorders.The intake of classic psychedelic drugs often elicits DP/DR symptoms, which cease in most cases when the drug is eliminated. DDD is frequently precipitated by drug intoxication (cannabis and classic psychedelics). Patients and some researchers assume, therefore, that drug intoxication is the cause of DDD and frame it as a \"never-ending trip.\" Researchers base their assumption on the potential of psychedelics to elicit DP/DR symptoms and on case series of individuals reporting long-lasting uncomfortable symptoms after drug intake. Arguments are presented that demonstrate this is a reductionist conclusion and that this assertion may lead to false illness perceptions, hinder awareness of emotional conflicts, and erode patients' self-efficacy. The main arguments are that, first, DDD is a mental disorder resulting from the avoidance of aversive emotional states. DDD is related to functional alterations of brain networks rather than organic brain damage. Second, psychedelics act as a catalyst that accelerates the onset of DDD in vulnerable individuals by mobilizing complex anxiety-laden unconscious emotions from early attachment traumas.The treatment of DDD encompasses psychoeducation about the nature of the disorder, challenging false causal attributions to external causes (such as drug intake) and helping the patient experience and process their emotions adaptively. To achieve remission, patients usually need long-term psychotherapy of 50-100 sessions.</p>","PeriodicalId":11257,"journal":{"name":"Current topics in behavioral neurosciences","volume":" ","pages":"217-239"},"PeriodicalIF":0.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145063616","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Acute Effects and Long-Term Neuropsychological Consequences of Classic Psychedelics Use.","authors":"Lukas Andreas Basedow, Thomas Günther Riemer","doi":"10.1007/7854_2025_600","DOIUrl":"10.1007/7854_2025_600","url":null,"abstract":"<p><p>Psychedelics are gaining attention for their potential as therapeutic adjuncts for the treatment of psychological disorders. Additionally, the recreational use of these substances has been rising for the past years. In the context of a comprehensive analysis of potential harms induced by these substances, concerns regarding the cognitive and neuropsychological impact of their use remain. This chapter explores the acute, subacute, and long-term neuropsychological consequences of psychedelic use. Studies show that neuropsychological performance, especially attention and working memory, is reduced under the influence of a psychedelic. While not harmful in itself, this effect poses potential risks when combined with high-risk environments, such as road traffic. While these acute impairments seem to disappear on the day after psychedelic use, there is limited evidence that some impairments in executive functioning can persist for up to 24 h. Thus, caution is not only warranted during psychedelic use but also for the following day. In contrast, psychedelics do not seem to induce persistent changes in neuropsychological performance through repeated use, indicating no direct neuropsychological harms. However, further research is required to clarify the differential effects of various psychedelic substances and to assess the impact of chronic use across different contexts.</p>","PeriodicalId":11257,"journal":{"name":"Current topics in behavioral neurosciences","volume":" ","pages":"107-124"},"PeriodicalIF":0.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144946643","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Correction to: Psychedelic Drug Checking: Analytical and Strategic Challenges in Harm Reduction for Classic Psychedelics.","authors":"Tim Hirschfeld, Felix Blei, Lavinia Stegemann, Daan van der Gouwe, Laura Smit-Rigter","doi":"10.1007/7854_2025_611","DOIUrl":"10.1007/7854_2025_611","url":null,"abstract":"","PeriodicalId":11257,"journal":{"name":"Current topics in behavioral neurosciences","volume":" ","pages":"567-568"},"PeriodicalIF":0.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145667513","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Pharmacological Profile of Plant-Derived Cannabinoids In Vitro.","authors":"Stephen P H Alexander","doi":"10.1007/7854_2025_605","DOIUrl":"10.1007/7854_2025_605","url":null,"abstract":"<p><p>With over 100 apparently unique metabolites in the Cannabis plant, there are a plethora of potential molecular targets. The molecular actions of Δ⁹-tetrahydrocannabinol are the best-investigated, which have centred mostly on a relatively high-potency, low-efficacy action at the CB₁ cannabinoid receptor. By contrast, cannabidiol has a multitude of lower potency molecular targets identified in vitro, but with limited clarity about their relevance for the effects of cannabidiol in humans. This review highlights the incomplete nature of studies of the major phytocannabinoids, particularly the acid phytocannabinoids.</p>","PeriodicalId":11257,"journal":{"name":"Current topics in behavioral neurosciences","volume":" ","pages":"1-36"},"PeriodicalIF":0.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145257746","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Neurobiological Correlates of Psychedelic Experiences and Psychedelic-Associated Adverse Effects.","authors":"Nathalie M Rieser, Timo T Schmidt, Katrin H Preller","doi":"10.1007/7854_2024_507","DOIUrl":"10.1007/7854_2024_507","url":null,"abstract":"<p><p>This chapter offers a comprehensive overview of our current understanding of the neural mechanisms underlying the effects of psychedelic drugs, with a primary focus on human neuroimaging studies. Whenever possible, we explore the neurobiological mechanisms that may underly acute and subacute adverse effects and describe hypotheses on how these results may inform on the pathophysiology of psychiatric illnesses. We delve into the general effects of psychedelics on EEG, fMRI, and PET measurements, drawing insights from experiments that have assessed their acute biological mechanisms. Additionally, we review the relatively limited literature exploring pre- to postdrug changes. Throughout this chapter, we explore the prevailing models of psychedelic drug actions, including the Cortico-Striato-Thalamo-Cortical (CSTC) feedback loop model, the entropic brain hypothesis, the REBUS principle (an extension of predictive brain theories), and the claustrum hypothesis. Finally, we delve into the neural correlates of distinct features of the psychedelic experience, encompassing visual effects, social and emotional impacts, and the phenomenon of ego dissolution. We offer speculations on how our current understanding of acute drug effects might relate to the rarely occurring long-term adverse effects. It is important to note that due to the scarcity of data, these speculations remain tentative.</p>","PeriodicalId":11257,"journal":{"name":"Current topics in behavioral neurosciences","volume":" ","pages":"87-106"},"PeriodicalIF":0.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141855127","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}