Psychopharmacology最新文献

{"title":"Comparison of the reinforcing, antinociceptive, and respiratory depressant effects of prototypical and G-protein biased mu-opioid receptor agonists in male and female Sprague-Dawley rats.","authors":"C Austin Zamarripa, Tanya Pareek, Loc M Pham, Bruce E Blough, Hayley M Schrock, Eric J Vallender, Kenneth J Sufka, Kevin B Freeman","doi":"10.1007/s00213-024-06690-x","DOIUrl":"https://doi.org/10.1007/s00213-024-06690-x","url":null,"abstract":"<p><strong>Rationale: </strong>G-protein biased mu-opioid receptor (MOR) agonists have been reported to exhibit superior therapeutic windows compared to prototypical MOR agonists when relating antinociception to respiratory depression. However, there is relatively little research on the abuse potential of G-protein biased MOR agonists in relation to other behavioral endpoints.</p><p><strong>Objectives: </strong>The aim of the present study was to quantitatively compare the reinforcing, antinociceptive, and respiratory-depressant effects of the prototypical MOR agonists, fentanyl and oxycodone, to the G-protein biased MOR agonists, SR14968 and SR17018, in male and female rats.</p><p><strong>Methods: </strong>In the self-administration study, four separate groups of Sprague-Dawley (SD) rats self-administered intravenous (i.v.) fentanyl, oxycodone, SR14968, and SR17018 under a progressive-ratio schedule of reinforcement. Using a within-subjects design, separate cohorts of SD rats were tested with i.v. fentanyl, oxycodone, SR14968, and SR17018 using a hot-plate assay, assays of neuropathic and inflammatory antinociception, and whole-body plethysmography.</p><p><strong>Results: </strong>All MOR agonists functioned as reinforcers, but SR14968 and SR17018 were less efficacious relative to oxycodone and fentanyl. Moreover, all MOR agonists produced dose-dependent and fully efficacious antinociception across all nociception modalities. Oxycodone and fentanyl, but not SR14968 or SR17018, produced respiratory depression in a dose-dependent manner.</p><p><strong>Conclusion: </strong>The present results indicate that the G-protein biased MOR agonists tested herein produce MOR-typical antinociception, exhibit reduced but apparent abuse potential, and do not produce respiratory effects at doses that are above the antinociceptive range. Atypical MOR agonists within the SR series should be further studied as foundational molecules for the development of safter analgesics.</p>","PeriodicalId":20783,"journal":{"name":"Psychopharmacology","volume":null,"pages":null},"PeriodicalIF":3.5,"publicationDate":"2024-09-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142352687","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":"Oxytocin effects on socially transmitted food preferences are moderated by familiarity between rats.","authors":"Irina Noguer-Calabús, Sandra Schäble, José Dören, Tobias Kalenscher","doi":"10.1007/s00213-024-06682-x","DOIUrl":"https://doi.org/10.1007/s00213-024-06682-x","url":null,"abstract":"<p><strong>Rationale: </strong>In the socially transmitted food preference (STFP) paradigm, rats change their preference for food rewards after socially interacting with a conspecific who has been fed with the originally non-preferred food. Here, we asked if oxytocin (OXT), a neuropeptide known for its role in social affiliation and social behavior, plays a role in STFP. Since OXT's influences on social behavior can be familiarity-dependent, we further asked if OXT effects on STFP are moderated by the familiarity between rats.</p><p><strong>Objectives: </strong>Does OXT modulate rats' socially transmitted food choices in a familiarity-dependent way.</p><p><strong>Methods: </strong>We systemically injected either vehicle, low-dose (0.25 mg/kg) of OXT, or large-dose (1.0 mg/kg) of OXT before social interaction with either a familiar cagemate (in-group) or an unfamiliar conspecific from a different cage (out-group).</p><p><strong>Results: </strong>We found an intergroup bias in STFP: vehicle-treated rats showed larger socially transmitted changes in food preference in the out-group than the in-group condition. OXT modulated STFP in a familiarity-dependent way: OXT prevented the increase in the consumption of the non-preferred food in the out-group, and decreased the consumption of the preferred food in the in-group. These effects were dose-dependent and observed under acute OXT action, but also on the subsequent day when acute OXT effects dissipated, suggesting long-lasting social learning effects of OXT. Additional analyses suggest that the familiarity and dose-dependent effects of OXT on STFP cannot be attributed to OXT's anorexic actions or differences in the duration of the social interactions.</p><p><strong>Conclusions: </strong>OXT modulates STFP in a familiarity-dependent way.</p>","PeriodicalId":20783,"journal":{"name":"Psychopharmacology","volume":null,"pages":null},"PeriodicalIF":3.5,"publicationDate":"2024-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142352688","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":"Bioinformatics analysis of the mechanisms of traumatic brain injury-associated dementia based on the competing endogenous RNA.","authors":"Changmeng Cui, Li Zhu, Guangkui Han, Jianping Sun, Liang Zhang, Yujin Guo, Pei Jiang","doi":"10.1007/s00213-024-06691-w","DOIUrl":"https://doi.org/10.1007/s00213-024-06691-w","url":null,"abstract":"<p><strong>Rationale: </strong>Traumatic brain injury (TBI) is a critical condition associated with cognitive impairments, including dementia. This study is aimed to construct a long noncoding RNA (lncRNA)-microRNA (miRNA)-messenger RNA (mRNA) network based on bioinformatics analysis and explore molecular mechanisms underlying post-TBI dementia.</p><p><strong>Methods: </strong>GSE104687 and GSE205661 datasets were downloaded from Gene Expression Omnibus database. Molecular Signatures Database (MSigDB) was used to search oxidative stress-, metabolism- and immune-related genes as the target gene datasets. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes were carried out for functional annotation and enrichment analysis. A TBI mouse model was built to validate the expression of NF2, PLXNA2, NCBP2 and U2SURP in brain tissues.</p><p><strong>Results: </strong>A total of 7 differentially expressed lncRNAs (DElncRNAs) and 191 DEmRNAs were obtained. Subsequent to differential expression (DE) analysis, a lncRNA-miRNA-mRNA network was established. Notably, 13 key DEmRNAs were identified, potentially playing pivotal roles in the pathogenesis of TBI-induced dementia. By comparing the target gene datasets with 13 DEmRNAs, we identified 4 target genes that overlap with the 13 DEGmRNAs, namely NF2, PLXNA2, NCBP2 and U2SURP. Functional enrichment analysis highlighted the involvement of neuronal projections in the dementia-enriched cluster, while the protective cluster showed associations with protein synthesis and ubiquitination pathways. Importantly, we explored potential drug interventions based on interactions with the above 4 target genes. Additionally, drug interaction prediction showed that NF2 could interact with SELUMETINIB, EVEROLIMUS and TEMSIROLIMUS.</p><p><strong>Conclusion: </strong>Our study provides insights into the complex regulatory networks underlying post-TBI dementia and suggests a potential role for three classes of drugs in managing dementia symptoms in TBI-induced dementia.</p>","PeriodicalId":20783,"journal":{"name":"Psychopharmacology","volume":null,"pages":null},"PeriodicalIF":3.5,"publicationDate":"2024-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142352685","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":"Effects of zuranolone on next-day simulated driving in healthy adults.","authors":"Joi Dunbar, Gaetano Morelli, Rakesh Jain, Carrie Vaudreuil, Indrani Nandy, Victor Ona, Margaret K Moseley, Seth Levin, Gary Kay","doi":"10.1007/s00213-024-06687-6","DOIUrl":"https://doi.org/10.1007/s00213-024-06687-6","url":null,"abstract":"<p><strong>Rationale: </strong>Zuranolone is an oral positive allosteric modulator of GABA_A receptors. Due to its central nervous system (CNS) activity, zuranolone may impact activities requiring complex cognition, including driving.</p><p><strong>Objective: </strong>Evaluate the effect of zuranolone on simulated driving performance.</p><p><strong>Methods: </strong>In this randomized, double-blind, active- and placebo-controlled, four-period crossover study, treatments included once-nightly zuranolone 50 mg on days 1-7, zuranolone 50 mg on days 1-6 and zuranolone 100 mg on day 7, zopiclone 7.5 mg on days 1 and 7, and placebo on days 1-7. Driving was assessed using a validated simulator. Primary endpoint was standard deviation of lateral position (SDLP), evaluated 9 h post-dose on days 2 and 8. Secondary endpoints included additional driving assessments, cognitive tests, pharmacokinetics, and safety.</p><p><strong>Results: </strong>Healthy adults (N = 67) enrolled and received ≥ 1 dose. Zuranolone 50 mg increased SDLP versus placebo on days 2 (least squares mean difference [LSMD]: 7.4 cm; p < 0.0001) and 8 (LSMD: 4.6 cm; p = 0.0106). Zuranolone 100 mg evoked a larger increase in SDLP versus placebo on day 8 (LSMD 18.9 cm; p < 0.0001). Reduced performance in other driving assessments and cognition were observed with zuranolone 50 mg on day 2; many resolved by day 8. Despite the SDLP observations, most participants judged themselves capable of driving. Frequent adverse events (≥ 20%) were CNS-related; most were mild/moderate.</p><p><strong>Conclusion: </strong>Zuranolone impaired simulated driving and reduced cognitive function versus placebo 9 h after administration. Although many impairments resolved after 7 days of dosing, driving remained impaired. These results may inform prescriber decision-making.</p>","PeriodicalId":20783,"journal":{"name":"Psychopharmacology","volume":null,"pages":null},"PeriodicalIF":3.5,"publicationDate":"2024-09-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142293958","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":"Exploring the role of orexins in the modulation of social reward.","authors":"Inês M Amaral, Sara Ouaidat, Laura Scheffauer, Anna E Granza, Diogo G Monteiro, Ahmad Salti, Alex Hofer, Rana El Rawas","doi":"10.1007/s00213-024-06688-5","DOIUrl":"https://doi.org/10.1007/s00213-024-06688-5","url":null,"abstract":"<p><strong>Rationale: </strong>positive social interactions are essential for mental health, by offering emotional support, reducing stress levels, and promoting resilience against drugs of abuse effects. However, not all individuals perceive social interaction as rewarding.</p><p><strong>Objectives: </strong>the goal of this study was to investigate whether the modulation of the orexin system can shift passive coping and non-social behavior (vulnerable) to active coping and social behavior (resilient). This knowledge is primordial for stress- and addiction-related disorders, and for other psychiatric disorders involving impairment in social interaction.</p><p><strong>Methods: </strong>male C57/BL6N mice categorized into social and non-social groups, received injections of SB334867, a selective orexin 1 receptor (OX1R) antagonist, before the conditioning sessions with a male conspecific of the same weight and age.</p><p><strong>Results: </strong>our results from the conditioned place preference test (CPP) show that SB334867 has no effect on social preference in non-social mice, but it reduces their stress levels and depression-like behavior. These effects appear to be due to a higher OX1R expression in the basolateral amygdala (BLA), a stress-related brain area, of non-social mice compared to their social counterparts.</p><p><strong>Conclusions: </strong>these data suggest that the orexin system may be a target to alleviate stress and depression-like behavior in non-social individuals rather than to promote social reward.</p>","PeriodicalId":20783,"journal":{"name":"Psychopharmacology","volume":null,"pages":null},"PeriodicalIF":3.5,"publicationDate":"2024-09-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142293970","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":"Effect of chronic delivery of the NOP/MOR partial agonist AT-201 and NOP antagonist J-113397 on heroin relapse in a rat model of opioid maintenance","authors":"Jennifer M. Bossert, Kiera E. Caldwell, Hannah Korah, Ashley Batista, Hannah Bonbrest, Ida Fredriksson, Shelley N. Jackson, Agnieszka Sulima, Kenner C. Rice, Nurulain T. Zaveri, Yavin Shaham","doi":"10.1007/s00213-024-06678-7","DOIUrl":"https://doi.org/10.1007/s00213-024-06678-7","url":null,"abstract":"<h3 data-test=\"abstract-sub-heading\">Rationale</h3><p>The opioid crisis persists despite availability of effective opioid agonist maintenance treatments (methadone and buprenorphine). Thus, there is a need to advance novel medications for the treatment of opioid use and relapse.</p><h3 data-test=\"abstract-sub-heading\">Objectives</h3><p>We recently modeled maintenance treatment in rats and found that chronic delivery of buprenorphine and the mu opioid receptor (MOR) partial agonist TRV130 decreases relapse to oxycodone seeking and taking. In contrast, chronic delivery of the buprenorphine analog BU08028 had mixed effects on different heroin relapse-related measures. Here, we tested the effect of the mixed nociceptin (NOP) receptor/MOR partial agonist AT-201 and the NOP receptor antagonist J-113397 on different heroin relapse-related measures.</p><h3 data-test=\"abstract-sub-heading\">Methods</h3><p>We trained male and female rats to self-administer heroin (6-h/d, 14-d) in context A and then implanted osmotic minipumps containing AT-201 (0, 3.8, or 12 mg/kg/d) or J-113397 (0, 12.6, or 40 mg/kg/d). Next, we tested the effect of chronic delivery of the compounds on (1) incubation of heroin seeking in a non-drug context B, (2) extinction responding reinforced by heroin-associated discrete cues in context B, (3) context A-induced reinstatement of heroin seeking, and (4) reacquisition of heroin self-administration in context A.</p><h3 data-test=\"abstract-sub-heading\">Results</h3><p>In females, AT-201 modestly <i>increased</i> reacquisition of heroin self-administration and J-113397 modestly <i>decreased</i> incubation of heroin seeking. The compounds had no effect on the other relapse-related measures in females, and no effect on any of the measures in males.</p><h3 data-test=\"abstract-sub-heading\">Conclusion</h3><p>The NOP/MOR partial agonist AT-201 and the NOP antagonist J-113397 did not mimic buprenorphine’s inhibitory effects on relapse in a rat model of opioid maintenance treatment.</p>","PeriodicalId":20783,"journal":{"name":"Psychopharmacology","volume":null,"pages":null},"PeriodicalIF":3.4,"publicationDate":"2024-09-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142192898","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":"Emerging roles of cannabinoid receptor CB2 receptor in the central nervous system: therapeutic target for CNS disorders","authors":"Kanchan Bala, Pratyush Porel, Khadga Raj Aran","doi":"10.1007/s00213-024-06683-w","DOIUrl":"https://doi.org/10.1007/s00213-024-06683-w","url":null,"abstract":"<h3 data-test=\"abstract-sub-heading\">Rationale</h3><p>The endocannabinoid system (ECS) belongs to the G protein-coupled receptor family of cell membranes and is associated with neuropsychiatric conditions, and neurodegenerative diseases. Cannabinoid 2 receptors (CB2) are expressed in the central nervous system (CNS) on microglia and subgroups of neurons and are involved in various behavioural processes via immunological and neural regulation.</p><h3 data-test=\"abstract-sub-heading\">Objective</h3><p>The objective of this paper is to summarize and explore the impact of CB2 receptors on neuronal modulation, their involvement in various neurological disorders, and their influence on mood, behavior, and cognitive function.</p><h3 data-test=\"abstract-sub-heading\">Results</h3><p>The activation of CB2 appears to protect the brain and its functions from damage under neuroinflammatory actions, making it an attractive target in a variety of neurological conditions such as Parkinson’s disease (PD), multiple sclerosis (MS), Alzheimer’s disease (AD), and Huntington’s disease (HD). During inflammation, there is an overexpression of CB2 receptors, and CB2 agonists show a strong anti-inflammatory effect. These results have sparked interest in the CB2 receptors as a potential target for neurodegenerative and neuroinflammatory disease treatment.</p><h3 data-test=\"abstract-sub-heading\">Conclusion</h3><p>In conclusion, CB2 receptors signalling shows promise for developing targeted interventions that could positively affect both immune and neuronal functions, ultimately influencing behavioral outcomes in both health and disease.</p>","PeriodicalId":20783,"journal":{"name":"Psychopharmacology","volume":null,"pages":null},"PeriodicalIF":3.4,"publicationDate":"2024-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142192797","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":"Elucidating the molecular symphony: unweaving the transcriptional & epigenetic pathways underlying neuroplasticity in opioid dependence and withdrawal","authors":"Shahid Nazir Wani, Amarjot Kaur Grewal, Heena Khan, Thakur Gurjeet Singh","doi":"10.1007/s00213-024-06684-9","DOIUrl":"https://doi.org/10.1007/s00213-024-06684-9","url":null,"abstract":"<p>The persistent use of opioids leads to profound changes in neuroplasticity of the brain, contributing to the emergence and persistence of addiction. However, chronic opioid use disrupts the delicate balance of the reward system in the brain, leading to neuroadaptations that underlie addiction. Chronic cocaine usage leads to synchronized alterations in gene expression, causing modifications in the Nucleus Accumbens (NAc), a vital part of the reward system of the brain. These modifications assist in the development of maladaptive behaviors that resemble addiction. Neuroplasticity in the context of addiction involves changes in synaptic connectivity, neuronal morphology, and molecular signaling pathways. Drug-evoked neuroplasticity in opioid addiction and withdrawal represents a complicated interaction between environmental, genetic, and epigenetic factors. Identifying specific transcriptional and epigenetic targets that can be modulated to restore normal neuroplasticity without disrupting essential physiological processes is a critical consideration. The discussion in this article focuses on the transcriptional aspects of drug-evoked neuroplasticity, emphasizing the role of key transcription factors, including cAMP response element-binding protein (CREB), ΔFosB, NF-kB, Myocyte-enhancing factor 2 (MEF2), Methyl-CpG binding protein 2 (MeCP2), E2F3a, and FOXO3a. These factors regulate gene expression and lead to the neuroadaptive changes observed in addiction and withdrawal. Epigenetic regulation, which involves modifying gene accessibility by controlling these structures, has been identified as a critical component of addiction development. By unraveling these complex molecular processes, this study provides valuable insights that may pave the way for future therapeutic interventions targeting the mechanisms underlying addiction and withdrawal.</p><h3 data-test=\"abstract-sub-heading\">Graphical abstract</h3>","PeriodicalId":20783,"journal":{"name":"Psychopharmacology","volume":null,"pages":null},"PeriodicalIF":3.4,"publicationDate":"2024-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142192928","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":"Efficacy of agomelatine on sleep disorders and lateral habenula neuronal activity in chronic restraint stress depression model mice.","authors":"Zhuojun Kang, Zhenzhen Zheng, Wenli Guo","doi":"10.1007/s00213-024-06681-y","DOIUrl":"https://doi.org/10.1007/s00213-024-06681-y","url":null,"abstract":"<p><strong>Background: </strong>Sleep disorders (SD) are one of the common manifestations of depression patients. This article aimed to explore the effect of Agomelatine (Ago) on SD in chronic restraint stress (CRS) depression model mice and its effect on the activity of neurons in the lateral habenula (LHb).</p><p><strong>Methods: </strong>30 C57BL/6 J mice were divided into normal (C57BL/6 J) group, CRS group, and Ago group. CRS experiment was used to establish the depression model, and Ago was used to treat CRS mice. Based on behavioral tests in mice and electrophysiology record, SD and LHb neuron activity were assessed. The expression levels of brain-derived neurotrophic factor (BDNF) and nuclear phosphoprotein (c-Fos) in LHb were detected by Western blot (WB).</p><p><strong>Results: </strong>As against the CRS group, the Ago group had a reduction in the immobility time during forced swimming training and an increase in the preference for sucrose in the sucrose preference test; The expression levels of c-Fos and BDNF proteins in the LHb neurons of the Ago group mice were lower than those in the CRS group (P < 0.05), and the values approached the levels of the normal control group. In both dark and light environments, the rapid eye movement (REM) sleep duration of the CRS group mice was significantly longer than that of the normal control group (P < 0.05).</p><p><strong>Conclusion: </strong>It was concluded that Ago may intervene in the depressive-like behavior and overall sleep patterns of CRS depression model mice by regulating the activity of LHb neurons and inhibiting the neuroinflammatory process. This provides a potential drug target for the development of new treatment strategies for depression.</p>","PeriodicalId":20783,"journal":{"name":"Psychopharmacology","volume":null,"pages":null},"PeriodicalIF":3.5,"publicationDate":"2024-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142154819","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":"Multimodal creativity assessments following acute and sustained microdosing of lysergic acid diethylamide.","authors":"Robin J Murphy, Rachael L Sumner, Kate Godfrey, Acima Mabidikama, Reece P Roberts, Frederick Sundram, Suresh Muthukumaraswamy","doi":"10.1007/s00213-024-06680-z","DOIUrl":"https://doi.org/10.1007/s00213-024-06680-z","url":null,"abstract":"<p><strong>Introduction: </strong>Enhanced creativity is often cited as an effect of microdosing (taking repeated low doses of a psychedelic drug). There have been recent efforts to validate the reported effects of microdosing, however creativity remains a difficult construct to quantify.</p><p><strong>Objectives: </strong>The current study aimed to assess microdosing's effects on creativity using a multimodal battery of tests as part of a randomised controlled trial of microdosing lysergic acid diethylamide (LSD).</p><p><strong>Methods: </strong>Eighty healthy adult males were given 10 µg doses of LSD or placebo every third day for six weeks (14 total doses). Creativity tasks were administered at a drug-free baseline session, at a first dosing session during the acute phase of the drug's effects, and in a drug-free final session following the six-week microdosing regimen. Creativity tasks were the Alternate Uses Test (AUT), Remote Associates Task (RAT), Consensual Assessment Technique (CAT), and an Everyday Problem-Solving Questionnaire (EPSQ).</p><p><strong>Results: </strong>No effect of drug by time was found on the AUT, RAT, CAT, or EPSQ. Baseline vocabulary skill had a significant effect on AUT and RAT scores.</p><p><strong>Conclusions: </strong>Despite participants reporting feeling more creative on dose days, objective measurement found no acute or durable effects of the microdosing protocol on creativity. Possible explanations of these null findings are that laboratory testing conditions may negatively affect ability to detect naturalistic differences in creative performance, the tests available do not capture the facets of creativity that are anecdotally affected by microdosing, or that reported enhancements of creativity are placebo effects.</p>","PeriodicalId":20783,"journal":{"name":"Psychopharmacology","volume":null,"pages":null},"PeriodicalIF":3.5,"publicationDate":"2024-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142133525","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}