Journal of Psychopharmacology (Oxford, England)最新文献

{"title":"Glutamate levels across deep brain structures in patients with a psychotic disorder and its relation to cognitive functioning","authors":"T. Broeders, A. Bhogal, L. Morsinkhof, M. Schoonheim, C. Röder, M. Edens, D. Klomp, J. Wijnen, C. Vinkers","doi":"10.1177/02698811221077199","DOIUrl":"https://doi.org/10.1177/02698811221077199","url":null,"abstract":"Background: Patients with psychotic disorders often show prominent cognitive impairment. Glutamate seems to play a prominent role, but its role in deep gray matter (DGM) regions is unclear. Aims: To evaluate glutamate levels within deep gray matter structures in patients with a psychotic disorder in relation to cognitive functioning, using advanced spectroscopic acquisition, reconstruction, and post-processing techniques. Methods: A 7-Tesla magnetic resonance imaging scanner combined with a lipid suppression coil and subject-specific water suppression pulses was used to acquire high-resolution magnetic resonance spectroscopic imaging data. Tissue fraction correction and registration to a standard brain were performed for group comparison in specifically delineated DGM regions. The brief assessment of cognition in schizophrenia was used to evaluate cognitive status. Results: Average glutamate levels across DGM structures (i.e. caudate, pallidum, putamen, and thalamus) in mostly medicated patients with a psychotic disorder (n = 16, age = 33, 4 females) were lower compared to healthy controls (n = 23, age = 24, 7 females; p = 0.005, d = 1.06). Stratified analyses showed lower glutamate levels in the caudate (p = 0.046, d = 0.76) and putamen p = 0.013, d = 0.94). These findings were largely explained by age differences between groups. DGM glutamate levels were positively correlated with psychomotor speed (r(30) = 0.49, p = 0.028), but not with other cognitive domains. Conclusions: We find reduced glutamate levels across DGM structures including the caudate and putamen in patients with a psychotic disorder that are linked to psychomotor speed. Despite limitations concerning age differences, these results underscore the potential role of detailed in vivo glutamate assessments to understand cognitive deficits in psychotic disorders.","PeriodicalId":156490,"journal":{"name":"Journal of Psychopharmacology (Oxford, England)","volume":"PC-20 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2022-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"126665917","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":"Debunking the myth of 'Blue Mondays': No evidence of affect drop after taking clinical MDMA.","authors":"Ben Sessa,&nbsp;Jacob S Aday,&nbsp;Steve O'Brien,&nbsp;H Valerie Curran,&nbsp;Fiona Measham,&nbsp;Laurie Higbed,&nbsp;David J Nutt","doi":"10.1177/02698811211055809","DOIUrl":"https://doi.org/10.1177/02698811211055809","url":null,"abstract":"<p><strong>Background: </strong>Incorporating 3,4-methylenedioxymethamphetamine (MDMA) as an adjunct to psychotherapy has shown promise in recent years for treating various mental health conditions, particularly those involving trauma. However, concerns about declines in mood and cognition during the days following dosing, also known as 'Blue Mondays', have been raised as limitations to its clinical use. Although these changes have been well-documented among recreational users, there are critical confounds to these reports that limit generalizability to clinically administered MDMA.</p><p><strong>Aims: </strong>Here, we aimed to evaluate the evidence basis for the negative side effects associated with MDMA as well as inform our understanding of the drug's post-acute effects in a clinical context with an open-label study.</p><p><strong>Methods: </strong>The current open-label study examined MDMA therapy for alcohol use disorder (AUD; <i>N</i> = 14) and measured mood, sleep quality, illicit MDMA consumption and anecdotal reports after the acute drug effects had worn off.</p><p><strong>Results: </strong>Participants maintained a positive mood during the week following drug administration in a clinical context. Relative to baseline, self-reported sleep quality improved at the 3- and 6-month follow-ups. Finally, no participants reported using or desiring to use illicit MDMA, and the anecdotal reports indicated that they perceived the treatment favourably.</p><p><strong>Conclusion: </strong>The results support the overall safety and tolerability of clinically administered MDMA and, importantly, suggest that the 'come downs' previously associated with the substance may be explained by confounds in research relating to the illicit sourcing of the drug and specific environmental setting for recreational consumption.</p>","PeriodicalId":156490,"journal":{"name":"Journal of Psychopharmacology (Oxford, England)","volume":" ","pages":"360-367"},"PeriodicalIF":4.1,"publicationDate":"2022-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39805160","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 epidemiology of mescaline use: Pattern of use, motivations for consumption, and perceived consequences, benefits, and acute and enduring subjective effects.","authors":"Malin Vedøy Uthaug,&nbsp;Alan K Davis,&nbsp;Trevor Forrest Haas,&nbsp;Dawn Davis,&nbsp;Sean B Dolan,&nbsp;Rafael Lancelotta,&nbsp;Christopher Timmermann,&nbsp;Johannes G Ramaekers","doi":"10.1177/02698811211013583","DOIUrl":"https://doi.org/10.1177/02698811211013583","url":null,"abstract":"<p><strong>Background: </strong>Mescaline is a naturally occurring psychoactive phenethylamine found in several cacti and historically used ceremonially by Indigenous and Latin American populations. Broader recognition of its possible therapeutic value in Western science began in the 1950s; however, knowledge of the safety profile of mescaline and the extent of its use remains limited. The primary aim of this study is to examine the epidemiology of mescaline use among English-speaking adults.</p><p><strong>Methods: </strong>About 452 respondents completed a web-based survey designed to assess their previous experience with mescaline (subjective effects, outcome measures, and mescaline type used).</p><p><strong>Results: </strong>Most respondents reported that they had consumed mescaline infrequently (⩽once/year), for spiritual exploration or to connect with nature (74%). A small number of respondents reported drug craving/desire (9%), whereas very few reported legal (1%), or psychological problems (1%) related to its use, and none reported seeking any medical attention. Overall, respondents rated the acute mystical-type effects as \"<i>moderate</i>,\" ego-dissolution and psychological insight effects as \"<i>slight</i>,\" and challenging effects as \"<i>very slight</i>.\" Most respondents reported that they used Peyote and San Pedro in their most memorable mescaline experience. Overall, the intensity of acute mescaline effects did not differ between mescaline types. About 50% of the sample reported having a psychiatric condition (i.e. depression, anxiety, etc.), and most (>67%) reported improvements in these conditions following their most memorable experience with mescaline.</p><p><strong>Conclusion: </strong>Findings indicate that the mescaline in any form may produce a psychedelic experience that is associated with the spiritual significance and improvements in the mental health with low potential for abuse.</p>","PeriodicalId":156490,"journal":{"name":"Journal of Psychopharmacology (Oxford, England)","volume":" ","pages":"309-320"},"PeriodicalIF":4.1,"publicationDate":"2022-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1177/02698811211013583","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38950841","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"LSD and creativity: Increased novelty and symbolic thinking, decreased utility and convergent thinking.","authors":"Isabel Wießner,&nbsp;Marcelo Falchi,&nbsp;Lucas Oliveira Maia,&nbsp;Dimitri Daldegan-Bueno,&nbsp;Fernanda Palhano-Fontes,&nbsp;Natasha L Mason,&nbsp;Johannes G Ramaekers,&nbsp;Madeleine E Gross,&nbsp;Jonathan W Schooler,&nbsp;Amanda Feilding,&nbsp;Sidarta Ribeiro,&nbsp;Draulio B Araujo,&nbsp;Luís Fernando Tófoli","doi":"10.1177/02698811211069113","DOIUrl":"https://doi.org/10.1177/02698811211069113","url":null,"abstract":"<p><strong>Background: </strong>Controversy surrounds psychedelics and their potential to boost creativity. To date, psychedelic studies lack a uniform conceptualization of creativity and methodologically rigorous designs.</p><p><strong>Aims: </strong>This study aimed at addressing previous issues by examining the effects of lysergic acid diethylamide (LSD) on creativity using multimodal tasks and multidimensional approaches.</p><p><strong>Methods: </strong>In a randomized, double-blind, placebo-controlled, crossover study, 24 healthy volunteers received 50 μg of LSD or inactive placebo. Near drug peak, a creativity task battery was applied, including pattern meaning task (PMT), alternate uses task (AUT), picture concept task (PCT), creative metaphors task (MET) and figural creativity task (FIG). Creativity was assessed by scoring creativity criteria (novelty, utility, surprise), calculating divergent thinking (fluency, originality, flexibility, elaboration) and convergent thinking, computing semantic distances (semantic spread, semantic steps) and searching for data-driven special features.</p><p><strong>Results: </strong>LSD, compared to placebo, changed several creativity measurements pointing to three overall LSD-induced phenomena: (1) 'pattern break', reflected by increased novelty, surprise, originality and semantic distances; (2) decreased 'organization', reflected by decreased utility, convergent thinking and, marginally, elaboration; and (3) 'meaning', reflected by increased symbolic thinking and ambiguity in the data-driven results.</p><p><strong>Conclusion: </strong>LSD changed creativity across modalities and measurement approaches. Three phenomena of pattern break, disorganization and meaning seemed to fundamentally influence creative cognition and behaviour pointing to a shift of cognitive resources 'away from normal' and 'towards the new'. LSD-induced symbolic thinking might provide a tool to support treatment efficiency in psychedelic-assisted therapy.</p>","PeriodicalId":156490,"journal":{"name":"Journal of Psychopharmacology (Oxford, England)","volume":" ","pages":"348-359"},"PeriodicalIF":4.1,"publicationDate":"2022-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39576467","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":"Development and validation of the Reward Deficiency Syndrome Questionnaire (RDSQ-29).","authors":"Eszter Kótyuk,&nbsp;Róbert Urbán,&nbsp;Borbála Hende,&nbsp;Mara Richman,&nbsp;Anna Magi,&nbsp;Orsolya Király,&nbsp;Csaba Barta,&nbsp;Mark D Griffiths,&nbsp;Marc N Potenza,&nbsp;Rajendra D Badgaiyan,&nbsp;Kenneth Blum,&nbsp;Zsolt Demetrovics","doi":"10.1177/02698811211069102","DOIUrl":"https://doi.org/10.1177/02698811211069102","url":null,"abstract":"<p><strong>Background: </strong>The reward deficiency syndrome (RDS) integrates psychological, neurological, and genetic factors of addictive, impulsive, and compulsive behaviors. However, to date, no instrument has been validated to assess the RDS construct.</p><p><strong>Aims: </strong>The present study developed and tested a tool to assess RDS.</p><p><strong>Methods: </strong>Data were collected on two college and university samples. Exploratory factor analysis (EFA) and confirmatory factor analysis (CFA) were performed on Sample 1 (<i>N</i> = 1726), and confirmatory analysis was conducted on an independent sample (<i>N</i> = 253). Impulsivity and sensation-seeking were assessed.</p><p><strong>Results: </strong>Based on EFAs, a 29-item Reward Deficiency Syndrome Questionnaire (RDSQ-29) was developed, containing four subscales (lack of sexual satisfaction, activity, social concerns, and risk-seeking behavior). CFA indicated good fit (comparative fit index (CFI) = 0.941; Tucker-Lewis index (TLI) = 0.933; root mean square error of approximation (RMSEA) = 0.068). Construct validity analysis showed strong relationship between sensation-seeking and the RDS scale.</p><p><strong>Conclusion: </strong>The RDSQ-29 is an adequate scale assessing psychological and behavioral aspects of RDS. The RDSQ-29 assesses psychological and behavioral characteristics that may contribute to addictions generally.</p>","PeriodicalId":156490,"journal":{"name":"Journal of Psychopharmacology (Oxford, England)","volume":" ","pages":"409-422"},"PeriodicalIF":4.1,"publicationDate":"2022-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39753856","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":"Challenges in translational research: MDMA in the laboratory versus therapeutic settings.","authors":"Harriet de Wit,&nbsp;Anya K Bershad,&nbsp;Charles Grob","doi":"10.1177/02698811211015221","DOIUrl":"https://doi.org/10.1177/02698811211015221","url":null,"abstract":"<p><p>Despite substantial progress in the use of mind-altering drugs to treat psychiatric disorders, the psychological processes through which these drugs change mood or behavior are poorly understood. Controlled laboratory studies with well-defined psychological constructs are valuable to understand how these drugs manifest their therapeutic benefit. However, there are substantial methodological differences between clinical studies investigating therapeutic outcome and laboratory studies investigating the processes that might underlie the therapeutic effects. Here, we examine some of these differences using the example of 3,4-methylenedioxymethamphetamine (MDMA). We review differences in expectancies, social and physical context, participant characteristics, pharmacological factors, and outcome measures in studies with participants who do or do not have psychiatric diagnoses. We describe the challenges and opportunities in translating findings from laboratory studies to the clinic and identify ways to bridge the gap between these approaches.</p>","PeriodicalId":156490,"journal":{"name":"Journal of Psychopharmacology (Oxford, England)","volume":" ","pages":"252-257"},"PeriodicalIF":4.1,"publicationDate":"2022-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1177/02698811211015221","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38866540","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 Acceptance/Avoidance-Promoting Experiences Questionnaire (APEQ): A theory-based approach to psychedelic drugs’ effects on psychological flexibility","authors":"M. Wolff, L. Mertens, M. Walter, S. Enge, R. Evens","doi":"10.1177/02698811211073758","DOIUrl":"https://doi.org/10.1177/02698811211073758","url":null,"abstract":"Background: Many benefits and some harms associated with psychedelic use could be attributable to these drugs’ acceptance/avoidance-promoting effects and corresponding changes in psychological flexibility. Underlying psychological mechanisms are insufficiently understood. Aim: The purpose of this study was the validation of a psychological model of acceptance/avoidance-promoting psychedelic experiences, which included the development of a theory-based self-report instrument: the Acceptance/Avoidance-Promoting Experiences Questionnaire (APEQ). Its two main scales, acceptance-related experience (ACE) and avoidance-related experience (AVE), represent the theorized model’s core constructs. We aimed to test the model’s central assumptions of complementarity (ACE and AVE may occur alternatingly but not simultaneously, and are therefore empirically independent), intertwinedness (subaspects within ACE and AVE are mutually contingent and therefore highly inter-correlated), context-dependence (ACE and AVE depend on context factors) and interaction (longer-term outcomes depend on the interplay between ACE and AVE). Method: A bilingual retrospective online survey including 997 English- and 836 German-speaking participants. Each participant reported on one psychedelic experience occasioned by lysergic acid diethylamide (LSD), psilocybin, mescaline, or ayahuasca. Results: Whereas ACE and AVE were found to be relatively independent aspects of participants’ reported psychedelic experiences (complementarity), their subaspects were mostly distinguishable but strongly correlated among each other (intertwinedness). Therapeutic, escapist, and hedonic use motives were differentially associated with ACE and AVE (context-dependence), which were in turn associated with retrospective changes in psychological flexibility following participants’ reported experiences. The positive association between ACE and increased psychological flexibility was significantly moderated by AVE (interaction). Conclusion: These results provide an initial validation of the APEQ and its underlying theoretical model, suggesting the two can help clarify the psychological mechanisms of psychedelic-induced benefits and harms. Both should be further investigated in prospective-longitudinal and clinical studies.","PeriodicalId":156490,"journal":{"name":"Journal of Psychopharmacology (Oxford, England)","volume":"1199 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2022-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"133403552","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":"Clinical effects of glabellar botulinum toxin injections on borderline personality disorder: A randomized controlled trial.","authors":"M Axel Wollmer,&nbsp;Insa Neumann,&nbsp;Stefanie Jung,&nbsp;Agnès Bechinie,&nbsp;Julian Herrmann,&nbsp;Antje Müller,&nbsp;Peter Wohlmuth,&nbsp;Larissa Fournier-Kaiser,&nbsp;Christian Sperling,&nbsp;Liza Peters,&nbsp;Jonas Kneer,&nbsp;Jannis Engel,&nbsp;Frank Jürgensen,&nbsp;Jara Schulze,&nbsp;Matthias Nagel,&nbsp;Welf Prager,&nbsp;Christopher Sinke,&nbsp;Kai G Kahl,&nbsp;Matthias Karst,&nbsp;Birger Dulz,&nbsp;Tillmann H C Kruger","doi":"10.1177/02698811211069108","DOIUrl":"https://doi.org/10.1177/02698811211069108","url":null,"abstract":"<p><strong>Background: </strong>Inhibition of frowning via injections of botulinum toxin A (BTX) into the glabellar region has shown beneficial effects in the treatment of major depression. Preliminary research suggests that improvements in the affective domain are not depression-specific, but may also translate to other psychiatric disorders.</p><p><strong>Aim: </strong>This 16-week, single-blind, two-center randomized controlled trial investigated the influence of BTX on clinical symptoms of borderline personality disorder (BPD).</p><p><strong>Methods: </strong>Fifty-four patients with BPD were randomly assigned to treatment with BTX <i>(n</i> = 27) or a minimal acupuncture (ACU) control condition (<i>n</i> = 27). Clinical outcomes were followed at 2, 4, 6, 8, 12, and 16 weeks. Primary endpoint was the relative score change on the Zanarini Rating Scale for Borderline Personality Disorder (ZAN-BPD) 8 weeks after baseline relative to the control group and adjusted for treatment center. Secondary and additional outcome variables were self-rated borderline symptoms, comorbid symptoms of depression, psychological distress, and clinical global impression.</p><p><strong>Results: </strong>Participants showed significant improvements at the primary efficacy endpoint in both treatment groups (BTX: <i>M</i> = -0.39, <i>SD</i> = 0.39; ACU: <i>M</i> = -0.35, <i>SD</i> = 0.42), but no superior effect of the BTX condition in comparison with the control intervention was found-<i>F</i>(1,5323) = 0.017, <i>p</i> = 0.68). None of the secondary or additional outcomes yielded significant group differences. Side effects were mild and included headache, transient skin or muscle irritations, and dizziness.</p><p><strong>Conclusion: </strong>Evidence regarding the efficacy of BTX for BDP remains limited, and the design of adequate control conditions presents an opportunity for further research.<i>ClinicalTrials.gov registry</i>: Botulinum Toxin A for Emotional Stabilization in Borderline Personality Disorder (BPD), NCT02728778, https://clinicaltrials.gov/ct2/show/NCT02728778.</p>","PeriodicalId":156490,"journal":{"name":"Journal of Psychopharmacology (Oxford, England)","volume":" ","pages":"159-169"},"PeriodicalIF":4.1,"publicationDate":"2022-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39577683","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":"Incident infection during the first year of treatment - A comparison of clozapine and paliperidone palmitate long-acting injection.","authors":"Shubhra Mace,&nbsp;Olubanke Dzahini,&nbsp;Victoria Cornelius,&nbsp;Hadar Langerman,&nbsp;Ebenezer Oloyede,&nbsp;David Taylor","doi":"10.1177/02698811211058973","DOIUrl":"https://doi.org/10.1177/02698811211058973","url":null,"abstract":"<p><strong>Background: </strong>To examine the risk of infection in patients prescribed clozapine compared with patients prescribed paliperidone palmitate long-acting injection (PPLAI).</p><p><strong>Method: </strong>A retrospective, 1-year, cohort study conducted on events occurring in eligible patients beginning treatment for the first time with clozapine or PPLAI between June 2017 and June 2019 in a UK mental health trust providing in-patient and out-patient services.</p><p><strong>Results: </strong>The study included 64 patients starting clozapine and 120 patients starting PPLAI. Incidence of infection was greater in clozapine starters than in PPLAI starters (28% vs 6%; <i>p</i> = 0.001; adjusted odds ratio 5.82 (95% confidence interval (CI) = 2.15-15.76, <i>p</i> = 0.001). Infectious episodes in clozapine patients were not related to changes in neutrophil counts. Incident infection in the clozapine group was highest in the first 3 months of treatment. The most commonly reported infection in the clozapine group was chest infection; however, the majority of infections were non-chest-related.</p><p><strong>Conclusion: </strong>Patients starting clozapine showed a substantially increased likelihood of infection compared with patients starting PPLAI.</p>","PeriodicalId":156490,"journal":{"name":"Journal of Psychopharmacology (Oxford, England)","volume":" ","pages":"232-237"},"PeriodicalIF":4.1,"publicationDate":"2022-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39791077","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":"Cevimeline co-treatment attenuates olanzapine-induced metabolic disorders via modulating hepatic M3 muscarinic receptor: AMPKα signalling pathway in female rats.","authors":"Mei Han,&nbsp;Jiamei Lian,&nbsp;Yueqing Su,&nbsp;Chao Deng","doi":"10.1177/02698811211050549","DOIUrl":"https://doi.org/10.1177/02698811211050549","url":null,"abstract":"<p><strong>Background: </strong>Olanzapine is one of the most commonly used antipsychotic drugs; however, its metabolic disorders are the main obstacle in the clinic. Olanzapine is a potent antagonist of the M3 acetylcholine muscarinic receptor (M3R), while the downregulated hepatic M3R-AMPKα signalling pathway is involved in metabolic disorders.</p><p><strong>Aim: </strong>This study investigated the effects of chronic co-treatment with cevimeline (an agonist of M3Rs) in attenuating olanzapine-induced metabolic disorders and the underlying mechanisms.</p><p><strong>Methods: </strong>Forty-eight adult female Sprague-Dawley rats were treated orally with olanzapine (2 mg/kg, 3 times/day (t.i.d.)) and/or cevimeline (9 mg/kg, t.i.d.), or control (vehicle) for 9 weeks.</p><p><strong>Results: </strong>Cevimeline co-treatment significantly attenuated olanzapine-induced body weight gain and glucolipid metabolic disorders. Importantly, cevimeline co-treatment attenuated olanzapine-induced upregulation of M3Rs, while the co-treatment improved olanzapine-induced downregulation of AMPKα in the liver. Cevimeline co-treatment attenuated olanzapine-induced dyslipidaemia by modulating the hepatic M3R-AMPKα downstream pathways. Cevimeline co-treatment also improved lower activated AKT-GSK3β signalling to reverse impairment of glucose metabolism and insulin resistance caused by chronic olanzapine treatment.</p><p><strong>Conclusion: </strong>These results not only support the important role of M3R antagonism and its related AMPKα and downstream pathways in antipsychotic-induced metabolic disorders but also indicate that these pathways might be promising targets for pharmacological intervention to control these side effects caused by antipsychotic therapy.</p>","PeriodicalId":156490,"journal":{"name":"Journal of Psychopharmacology (Oxford, England)","volume":" ","pages":"202-213"},"PeriodicalIF":4.1,"publicationDate":"2022-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39554805","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}