Journal of Psychopharmacology最新文献

{"title":"Are the LSD-analogs lisuride and ergotamine examples of non-hallucinogenic serotonin 5-HT2A receptor agonists?","authors":"Jan Kehler, Morten Skøtt Thomsen Lindskov","doi":"10.1177/02698811251330741","DOIUrl":"https://doi.org/10.1177/02698811251330741","url":null,"abstract":"<p><p>The recent resurgence of classical psychedelic compounds, specifically 5-HT_2A receptor agonists, as potential therapeutics has led to numerous initiatives aimed at better understanding the mechanisms underlying their effects. Psychedelic compounds are commonly known as hallucinogens. One of the major outstanding questions in the field is whether altered states of consciousness-the hallucinogenic or psychedelic experience-is a prerequisite for the therapeutic effect. As a result, several academic and commercial efforts are focused on developing 5-HT_2A receptor agonists that are speculated not to have these consciousness-altering effects. However, these efforts largely rely on chemical analogs of supposedly non-hallucinogenic 5-HT_2A receptor agonists, such as lisuride and ergotamine. Our review of the literature indicates that there is no basis for claiming that lisuride or ergotamine are non-hallucinogenic at relevant concentrations in the brain. This does not invalidate current efforts to produce non-hallucinogenic 5-HT_2A receptor agonists for the potential benefit of patients, but it calls for caution in the reliance on animal data in the pursuit of such compounds and highlights the need for rigorous determination of target engagement in humans before claiming that 5-HT_2A receptor agonists are non-hallucinogenic.</p>","PeriodicalId":16892,"journal":{"name":"Journal of Psychopharmacology","volume":" ","pages":"2698811251330741"},"PeriodicalIF":4.5,"publicationDate":"2025-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144020705","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Psilocybin and ketamine affect novel neuropeptides gene expression in the rat hypothalamus.","authors":"Artur Pałasz, Marta Pukowiec, Katarzyna Bogus, Aleksandra Suszka-Świtek, Łukasz Filipczyk, Kinga Mordecka-Chamera, John J Worthington, Maria Sygidus, Adam Wojtas, Agnieszka Bysiek, Krystyna Gołembiowska","doi":"10.1177/02698811251330783","DOIUrl":"10.1177/02698811251330783","url":null,"abstract":"<p><strong>Objective: </strong>Psychedelics are able to trigger highly intense and profound alterations in self-consciousness, perception, affective, and cognitive processes. Indeed, recent studies show that ketamine and psilocybin could be used as fast-acting antidepressants. However, the molecular and neurochemical mechanisms of these psychedelics and their actions at the level of diverse brain structures remains so far unclear. Hypothalamic neuropeptides are involved in a wide spectrum of neuronal activities being responsible for the central control of all fundamental autonomic functions.</p><p><strong>Methods: </strong>The purpose of this exploratory pilot study was to assess the gene expression of both classical and novel neuropeptides, including nesfatin-1, phoenixin (PNX), spexin (SPX), neuromedin U (NMU), neuropeptide S (NPS), and their known receptors in the hypothalamus of male Wistar-Han rats subjected to single injections of psilocybin (dose 2 or 10 mg/kg) and ketamine (dose10 mg/kg). Total mRNA was isolated from homogenized tissue and real-time PCR was used for estimation of related gene expression.</p><p><strong>Results: </strong>It was found that a single administration of the higher dose of psilocybin increased the mRNA expression of most noncanonical neuropeptides examined in the study, with only the case of NMU there with a decrease in gene expression. Interestingly, psilocybin administration also increased mRNA expression of the serotonin receptors: 5-HT1A, 5-HT2A, and 5-HT2B, but not 5HT-2C. In contrast, the effect of ketamine on the expression of neuropeptides was much more limited compared to psilocybin, only increasing transcripts of NUCB2, GPR173, and POMC were demonstrated.</p><p><strong>Conclusions: </strong>These results suggest for the first time that selected psychedelics may enhance the signaling of 5-HT2A receptors or inhibit NMDA receptor activity, affecting neuropeptide signaling and serotonin transmission in the rat hypothalamus, which may contribute to a better understanding of psychedelic action in the brain.</p>","PeriodicalId":16892,"journal":{"name":"Journal of Psychopharmacology","volume":" ","pages":"499-508"},"PeriodicalIF":4.5,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144041303","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Commentary: A framework for assessment of adverse events in psychedelic research.","authors":"Katherine Cheung, Rebecca Ehrenkranz, Jared T Hinkle, David B Yaden","doi":"10.1177/02698811241309623","DOIUrl":"https://doi.org/10.1177/02698811241309623","url":null,"abstract":"<p><p>Recent discussions about the methodological rigor of psychedelic clinical trials have focused on potential underreporting or misreporting of adverse events (AEs), with many calling for their systematic assessment to help mitigate these issues. In their recent paper, Palitsky et al. offer a comprehensive framework for the assessment of AEs in psychedelic-assisted therapies, with consideration of the spiritual, existential, religious, and theological impacts that psychedelics can have. In this commentary, we respond to Palitsky et al.'s proposal, discussing the framework, its feasibility, and various assessment methods. We emphasize the need to ensure that AE assessment in psychedelic clinical trials is held to the same rigor and standard as research in other areas, in addition to maintaining and improving transparency and accessibility in AE reporting.</p>","PeriodicalId":16892,"journal":{"name":"Journal of Psychopharmacology","volume":"39 5","pages":"431-433"},"PeriodicalIF":4.5,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144136284","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Co-use of psychedelics with other substances: Findings from the global psychedelic survey.","authors":"Stephanie Lake, Philippe Lucas","doi":"10.1177/02698811241292956","DOIUrl":"10.1177/02698811241292956","url":null,"abstract":"<p><strong>Background/aims: </strong>While most psychedelic substances are considered to carry a relatively low risk of acute or long-term harm, co-use with other psychoactive substances may increase health and social harm. Using a large international survey of adults who use psychedelics, we sought to comprehensively characterize psychedelic co-use.</p><p><strong>Methods: </strong>We used data from the 2023 Global Psychedelic Survey, a web-based survey of adults ⩾21 with lifetime use of psychedelics. We explored patterns of co-use (prevalence, secondary substances used, timing, and motives of co-use) and examined sociodemographic and psychedelic use-related characteristics associated with co-use overall and by specific psychedelics.</p><p><strong>Results: </strong>In total, 5370 respondents were included in this analysis, of whom 3228 (56.3%) reported typically co-using at least one of the 11 psychedelic substances of interest, with co-use lowest for ayahuasca (14.8%) and highest for nitrous oxide (54.5%). Cannabis and alcohol were the most common secondary substances. Depressants were the only secondary substance class that increased in use following psychedelic experiences. Greater experience with psychedelics was significantly associated with co-use, as was using for recreational purposes or to reduce/substitute the use of other substances. Personal exploration and therapeutic purposes for psychedelic use were negatively associated with co-use.</p><p><strong>Conclusions: </strong>In this detailed analysis of psychedelic co-use, we observed high rates of co-use with certain psychedelics, specifically when used recreationally. Our findings highlight psychedelic-specific consumers for whom harm reduction messaging around co-use practices may be best tailored. Further research is justified to assess whether specific patterns of co-use might reduce or increase potential harms.</p>","PeriodicalId":16892,"journal":{"name":"Journal of Psychopharmacology","volume":" ","pages":"453-462"},"PeriodicalIF":4.5,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142522211","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Psychedelic risks and benefits: A cross-sectional survey study.","authors":"Sean P Goldy, Benjamin A Du, Julia S Rohde, Sandeep M Nayak, Justin C Strickland, Rebecca Ehrenkranz, Michael Levine, Frederick S Barrett, David B Yaden","doi":"10.1177/02698811241292951","DOIUrl":"10.1177/02698811241292951","url":null,"abstract":"<p><strong>Background: </strong>As classic psychedelics' therapeutic potential is studied and their popularity continues to rise, it is important to establish their relative risks and benefits. Previous surveys have tended to use convenience sampling on social media, select participants who have had either extremely positive or negative effects, and have not compared the risk/benefit profile of psychedelics to other substances.</p><p><strong>Aims: </strong>To address these limitations, we gathered samples from an opt-in panel service using quota-based sampling to approximate demographics representing US Census data, did not pre-specify positive or negative experiences, and compared experiences with psychedelics to those with cannabis.</p><p><strong>Methods: </strong>We conducted two studies, one using a between-subjects design (<i>n</i> = 743) and one using a within-subjects design (<i>n</i> = 514), in which participants recruited from an opt-in panel service reflected on prior experience with psychedelics or cannabis and indicated self-reported risks and benefits associated with their experience.</p><p><strong>Results: </strong>Results indicated that first or most memorable psychedelic experiences were associated with greater acute challenging effects and persisting negative effects than first or most memorable cannabis experiences, but psychedelic experiences were also associated with greater positive acute and persisting effects. Common predictors of negative and positive acute and persisting effects with psychedelics included various experience qualities (e.g., dose level, presence of others) and individual differences (e.g., religiosity, personality), though only to a small degree.</p><p><strong>Conclusions: </strong>These findings on psychedelic experiences provide a more nuanced characterization of risks and benefits and their predictors.</p>","PeriodicalId":16892,"journal":{"name":"Journal of Psychopharmacology","volume":" ","pages":"436-452"},"PeriodicalIF":4.5,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142750957","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Into the wild frontier: Mapping the terrain of adverse events in psychedelic-assisted therapies.","authors":"Otto Simonsson, Simon B Goldberg, Peter S Hendricks","doi":"10.1177/02698811241292944","DOIUrl":"10.1177/02698811241292944","url":null,"abstract":"","PeriodicalId":16892,"journal":{"name":"Journal of Psychopharmacology","volume":" ","pages":"434-435"},"PeriodicalIF":4.5,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12037866/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142546096","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Hemispheric annealing and lateralization under psychedelics (HEALS): A novel hypothesis of psychedelic action in the brain.","authors":"Adam W Levin","doi":"10.1177/02698811241303599","DOIUrl":"10.1177/02698811241303599","url":null,"abstract":"<p><p>Current models of psychedelic action in the brain propose changes along the dorsal-ventral and anterior-posterior axes but neglect to address the lateral axis. This article proposes a novel model of psychedelic action called HEALS (Hemispheric Annealing and Lateralization Under Psychedelics) which involves the reversal of the typical hierarchical relationship between the two hemispheres of the brain. In typical modes of consciousness, the hemispheres act in parallel process with the left predominating. Under psychedelics, as well as in other altered states of consciousness (ASCs), this hierarchy is reversed, with the right hemisphere released from inhibition by the left. In support of this model, the available neuroimaging evidence for lateralization under psychedelics is reviewed. Then, various cognitive and emotional changes observed under psychedelics are contrasted with those same functions in each hemisphere. These include attention; social and emotional intelligence; creativity and insight; and language. The article concludes with a review of laterality in other ASCs, such as meditative and trance states, and suggests that many phenomena associated with psychedelics, and other ASCs, might be explained by an atypical annealing between the hemispheres toward right hemisphere predominance.</p>","PeriodicalId":16892,"journal":{"name":"Journal of Psychopharmacology","volume":" ","pages":"416-430"},"PeriodicalIF":4.5,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142864044","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Catalyst for change: Psilocybin's antidepressant mechanisms-A systematic review.","authors":"Joshua Liebnau, Felix Betzler, André Kerber","doi":"10.1177/02698811241312866","DOIUrl":"10.1177/02698811241312866","url":null,"abstract":"<p><strong>Background: </strong>Recent clinical trials suggest promising antidepressant effects of psilocybin, despite methodological challenges. While various studies have investigated distinct mechanisms and proposed theoretical opinions, a comprehensive understanding of psilocybin's neurobiological and psychological antidepressant mechanisms is lacking.</p><p><strong>Aims: </strong>Systematically review potential antidepressant neurobiological and psychological mechanisms of psilocybin.</p><p><strong>Methods: </strong>Search terms were generated based on existing evidence of psilocybin's effects related to antidepressant mechanisms. Following Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines, 15 studies were systematically reviewed, exploring various therapeutic change principles such as brain dynamics, emotion regulation, cognition, self-referential processing, connectedness, and interpersonal functioning.</p><p><strong>Results: </strong>Within a supportive setting, psilocybin promoted openness, cognitive and neural flexibility, and greater ability and acceptance of emotional experiences. A renewed sense of connectedness to the self, others, and the world emerged as a key experience. Imaging studies consistently found altered brain dynamics, characterized by reduced global and within default mode network connectivity, alongside increased between-network connectivity.</p><p><strong>Conclusions: </strong>Together, these changes may create a fertile yet vulnerable window for change, emphasizing the importance of a supportive set, setting, and therapeutic guidance. The results suggest that psilocybin, within a supportive context, may induce antidepressant effects by leveraging the interplay between neurobiological mechanisms and common psychotherapeutic factors. This complements the view of purely pharmacological effects, supporting a multileveled approach that reflects various relevant dimensions of therapeutic change, including neurobiological, psychological, and environmental factors.</p>","PeriodicalId":16892,"journal":{"name":"Journal of Psychopharmacology","volume":" ","pages":"397-415"},"PeriodicalIF":4.5,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12099018/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143007079","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Afterglow Inventory (AGI): Validation of a new instrument for measuring subacute effects of classic serotonergic psychedelics.","authors":"Tomislav Majić, Timo Torsten Schmidt, Anna Gröticke, Peter Gasser, William A Richards, Thomas G Riemer, Ricarda Evens","doi":"10.1177/02698811251326937","DOIUrl":"10.1177/02698811251326937","url":null,"abstract":"<p><strong>Background: </strong>Classic psychedelics such as psilocybin and lysergic acid diethylamide are anecdotally associated with the phenomenon of \"psychedelic afterglow,\" a set of predominantly pleasant, temporary psychological effects reported after the acute effects have subsided. Since post-acute effects are crucial for the therapeutic use of psychedelics, an instrument to systematically assess subacute \"afterglow\" effects is needed.</p><p><strong>Aims: </strong>To create and validate a questionnaire to quantify the subacute \"afterglow\" effects of psychedelics.</p><p><strong>Methods: </strong>An international online survey was conducted in English and German. Participants who had consumed a psychedelic (<i>N</i> = 1323) or another non-psychedelic substance (control group, <i>N</i> = 157) within the past 4 weeks were included. An initial list of 97 items was progressively reduced to 24 items.</p><p><strong>Results: </strong>A 5-factor structure best fit the data and showed high internal consistency. The factors included (1) vitality, (2) transpersonal aspects, (3) inspiration/creativity, (4) interpersonal relationships, and (5) relationship to nature. The final 24-item version of the Afterglow Inventory (AGI) effectively differentiated between the psychedelic group and the control group. The overall AGI score positively correlated with the intensity (<i>r</i> = 0.165; <i>p</i> < 0.001) and positive valence (<i>r</i> = 0.251; <i>p</i> < 0.001) of the acute psychedelic effects.</p><p><strong>Conclusions: </strong>The AGI is a novel scale for quantifying positive subacute (\"afterglow\") effects of psychedelics. The use of the AGI could lead to a better understanding of the interplay between acute, subacute, and long-term effects of psychedelics. Insights could also be gained into how different substances, dosages, and extra-pharmacological factors, such as psychotherapy, might influence outcomes.</p>","PeriodicalId":16892,"journal":{"name":"Journal of Psychopharmacology","volume":" ","pages":"474-488"},"PeriodicalIF":4.5,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12099019/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143753253","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Corrigendum: Is psychedelic use associated with cancer? Interrogating a half-century-old claim using contemporary population-level data.","authors":"","doi":"10.1177/02698811241286656","DOIUrl":"10.1177/02698811241286656","url":null,"abstract":"","PeriodicalId":16892,"journal":{"name":"Journal of Psychopharmacology","volume":" ","pages":"509"},"PeriodicalIF":4.5,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144078634","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}