Journal of Psychopharmacology (Oxford, England)最新文献

{"title":"Activation of the aryl hydrocarbon receptor by clozapine induces preadipocyte differentiation and contributes to endothelial dysfunction.","authors":"K Fehsel,&nbsp;K Schwanke,&nbsp;B A Kappel,&nbsp;E Fahimi,&nbsp;E Meisenzahl-Lechner,&nbsp;C Esser,&nbsp;K Hemmrich,&nbsp;T Haarmann-Stemmann,&nbsp;G Kojda,&nbsp;C Lange-Asschenfeldt","doi":"10.1177/02698811211055811","DOIUrl":"https://doi.org/10.1177/02698811211055811","url":null,"abstract":"<p><strong>Background: </strong>The superior therapeutic benefit of clozapine is often associated with metabolic disruptions as obesity, insulin resistance, tachycardia, higher blood pressure, and even hypertension.</p><p><strong>Aims: </strong>These adverse vascular/ metabolic events under clozapine are similar to those caused by polycyclic aromatic hydrocarbons (PAHs), and clozapine shows structural similarity to well-known ligands of the aryl hydrocarbon receptor (AhR). Therefore, we speculated that the side effects caused by clozapine might rely on AhR signaling.</p><p><strong>Methods: </strong>We examined clozapine-induced AhR activation by luciferase reporter assays in hepatoma HepG2 cells and we proved upregulation of the prototypical AhR target gene Cyp1A1 by realtime-PCR (RT-PCR) analysis and enzyme activity. Next we studied the physiological role of AhR in clozapine's effects on human preadipocyte differentiation and on vasodilatation by myography in wild-type and AhR-/- mice.</p><p><strong>Results: </strong>In contrast to other antipsychotic drugs (APDs), clozapine triggered AhR activation and Cyp1A1 expression in HepG2 cells and adipocytes. Clozapine induced adipogenesis via AhR signaling. After PGF2α-induced constriction of mouse aortic rings, clozapine strongly reduced the maximal vasorelaxation under acetylcholine in rings from wild-type mice, but only slightly in rings from AhR-/- mice. The reduction was also prevented by pretreatment with the AhR antagonist CH-223191.</p><p><strong>Conclusion: </strong>Identification of clozapine as a ligand for the AhR opens new perspectives to explain common clozapine therapy-associated adverse effects at the molecular level.</p>","PeriodicalId":156490,"journal":{"name":"Journal of Psychopharmacology (Oxford, England)","volume":" ","pages":"191-201"},"PeriodicalIF":4.1,"publicationDate":"2022-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8847763/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39782724","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":"Subchronic PCP effects on DNA methylation and protein expression of NMDA receptor subunit genes in the prefrontal cortex and hippocampus of female rats.","authors":"Camila M Loureiro,&nbsp;Helene A Fachim,&nbsp;Michael K Harte,&nbsp;Caroline F Dalton,&nbsp;Gavin P Reynolds","doi":"10.1177/02698811211069109","DOIUrl":"https://doi.org/10.1177/02698811211069109","url":null,"abstract":"<p><strong>Background: </strong>N-methyl-d-aspartate receptor (NMDAR) dysfunction is implicated in schizophrenia, and NMDAR antagonists, such as phencyclidine (PCP), can induce behaviours that mimic aspects of the disorder.</p><p><strong>Aims: </strong>We investigated DNA methylation of <i>Grin1, Grin2a</i> and <i>Grin2b</i> promoter region and NR1 and NR2 protein expression in the prefrontal cortex (PFC) and hippocampus of adult female Lister-hooded rats following subchronic PCP (scPCP) administration. We also determined whether any alterations were tissue-specific.</p><p><strong>Methods: </strong>Rats were divided into two groups that received vehicle (0.9% saline) or 2 mg/kg PCP twice a day for 7 days (n = 10 per group). After behavioural testing (novel object recognition), to confirm a cognitive deficit, brains were dissected and NMDAR subunit DNA methylation and protein expression were analysed by pyrosequencing and ELISA. <i>Line-1</i> methylation was determined as a measure of global methylation. Data were analysed using Student's <i>t</i>-test and Pearson correlation.</p><p><strong>Results: </strong>The scPCP administration led to <i>Grin1</i> and <i>Grin2b</i> hypermethylation and reduction in NR1 protein in both PFC and hippocampus. No significant differences were observed in <i>Line-1</i> or <i>Grin2a</i> methylation and NR2 protein.</p><p><strong>Conclusions: </strong>The scPCP treatment resulted in increased DNA methylation at promoter sites of <i>Grin1</i> and <i>Grin2b</i> NMDAR subunits in two brain areas implicated in schizophrenia, independent of any global change in DNA methylation, and are similar to our observations in a neurodevelopmental animal model of schizophrenia - social isolation rearing post-weaning. Moreover, these alterations may contribute to the changes in protein expression for NMDAR subunits demonstrating the potential importance of epigenetic mechanisms in schizophrenia.</p>","PeriodicalId":156490,"journal":{"name":"Journal of Psychopharmacology (Oxford, England)","volume":" ","pages":"238-244"},"PeriodicalIF":4.1,"publicationDate":"2022-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39577682","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":"Refractory delirium tremens treated with ketamine.","authors":"Alessio Cittadini,&nbsp;Etrusca Brogi,&nbsp;Emiliano Gamberini,&nbsp;Andrea Sica,&nbsp;Luca Bissoni,&nbsp;Emanuele Russo,&nbsp;Vanni Agnoletti","doi":"10.1177/02698811211069112","DOIUrl":"https://doi.org/10.1177/02698811211069112","url":null,"abstract":"Dear Editor, Delirium tremens (DT) is a severe form of alcohol withdrawal syndrome (AWS). DT presents commonly on the third to fifth day after alcohol abstinence and lasts about 24 h to 6 days. DT requires high level of monitoring and intensive care unit (ICU) treatment. From a pathophysiological point of view, alcohol’s inhibitory effects in the brain are primarily achieved through the γ-aminobutyric acid (GABA) neurotransmitter, resulting in a global slowing of neurotransmission with consequent anxiolysis, sedation, and anticonvulsant activity (Schmidt et al., 2016). In addition, alcohol also produces physiological changes in excitatory neurotransmission. Alcohol competitively inhibits the binding of glycine to the N-methyl-d-aspartate (NMDA) receptors in the brain, consequently preventing the action of the major excitatory neurotransmitter glutamate on the NMDA receptors. The human brain undergoes functional adaptations that eventually result in tolerance in the presence of chronic alcohol ingestion. There is a progressively higher expression of excitatory NMDA receptors and a compensatory downregulation of GABAA receptors (Schmidt et al., 2016). DT needs to be managed as medical emergency. The goal of treatment of alcohol withdrawal is to ameliorate agitation and other symptoms of delirium, recognition and treatment of underlying medical co-morbidities, and of course prompt, adequate, and protocol-driven treatment of alcohol withdrawal. Standard management for any patient with suspected alcohol withdrawal is initial resuscitation and rehydration. Benzodiazepines remain the cornerstone of therapy in the treatment of alcohol withdrawal. Benzodiazepines act on the same GABAA receptors as alcohol, thereby mimicking the inhibitory effects. However, the superiority of one benzodiazepine over another remains unclear in the literature (Schmidt et al., 2016). Benzodiazepine refractory delirium is defined as, “frank delirium or inability to control symptoms despite medication” and/or “requirement of 200 mg in the initial 3 h or 400 mg of diazepam in the first 8 h or 30 mg in the initial 3 h or 60 mg of lorazepam in the initial 8 h.” Several other drugs can be used for the treatment of refractory DT. Propofol potentiates GABA receptor activity and can also inhibit NMDA receptors, thus acting at several receptors to decrease withdrawal effects (Schmidt et al., 2016). Case series and trials have supported the use of propofol in refractory DT and withdrawal. However, patients on propofol frequently experienced more days of mechanical ventilation and length of stay, which may be due to more refractory cases of alcohol withdrawal (Brotherton et al., 2016). A great deal of controversy surrounds the use of dexmedetomidine in alcohol withdrawal and DT. Ketamine is an enantiomeric, lipid-soluble phencyclidine derivative and, like ethanol, ketamine is a nonselective NMDA receptor antagonist. Unfortunately, ketamine has largely remained unstudied for the treatment","PeriodicalId":156490,"journal":{"name":"Journal of Psychopharmacology (Oxford, England)","volume":" ","pages":"245-246"},"PeriodicalIF":4.1,"publicationDate":"2022-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39809784","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":"Evaluation of the effectiveness and acceptability of the long-acting oral antipsychotic penfluridol: Illustrative case series.","authors":"Danielle Dunnett, Ebenezer Oloyede, Oluwakemi Oduniyi, Barbara Arroyo, Olubanke Dzahini, David Taylor, Sukhi S Shergill, Eromona Whiskey","doi":"10.1177/02698811211050561","DOIUrl":"10.1177/02698811211050561","url":null,"abstract":"<p><strong>Aim: </strong>In this study, we sought to determine clinical outcomes at 1 year for patients prescribed penfluridol in an inner London National Health Service Trust. Using noninterventional data, we describe the use, effectiveness and safety of this treatment modality.</p><p><strong>Results: </strong>We retrospectively followed up 17 patients prescribed penfluridol as part of routine clinical practice. All patients took penfluridol once weekly. Of these patients, 12 (70.6%) were considered treatment resistant. The average duration of illness for this cohort was 10 years (SD = 6.7). At 1 year, nine (53%) patients remained on treatment. Median survival time was not reached at 1-year follow-up; mean time on penfluridol was 251 days (95% confidence interval (CI), 184-318). The mean number of admissions to hospital in the year following penfluridol initiation was 0.6 compared with 0.8, 1 year before initiation (<i>p</i> = 0.465). The median number of bed days 1 year before penfluridol initiation was 24, whereas in the year following penfluridol initiation, it was 0 (<i>p</i> = 0.514).</p><p><strong>Clinical implications: </strong>Although penfluridol is unlicensed in the United Kingdom, limited data suggest that this long-acting oral therapy has the potential to be used safely and effectively for the treatment of psychotic disorders. However, more data are required to establish the place of penfluridol and other potential long-acting oral antipsychotic formulations in the treatment of psychotic disorders.</p>","PeriodicalId":156490,"journal":{"name":"Journal of Psychopharmacology (Oxford, England)","volume":" ","pages":"223-231"},"PeriodicalIF":0.0,"publicationDate":"2022-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39559427","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 neuropeptide cycloprolylglycine produces antidepressant-like effect and enhances <i>BDNF</i> gene expression in the mice cortex.","authors":"Aliya A Abdullina,&nbsp;Ekaterina V Vasileva,&nbsp;Elizabeth A Kulikova,&nbsp;Vladimir S Naumenko,&nbsp;Alexandra V Plyusnina,&nbsp;Tatyana A Gudasheva,&nbsp;Georgy I Kovalev,&nbsp;Sergei B Seredenin","doi":"10.1177/02698811211069101","DOIUrl":"https://doi.org/10.1177/02698811211069101","url":null,"abstract":"<p><strong>Background: </strong>Cycloprolylglycine (CPG) is an endogenous dipeptide with a wide range of psychotropic activity and putative therapeutic potential for depression. A small but growing body of data suggests that antidepressant-like effect of CPG is associated with neuroplastic changes in the brain or 5-HT system modulation. However, the mechanisms of the dipeptide action remain elusive.</p><p><strong>Aims: </strong>Here, we characterize the effects of chronic CPG administration on behavior and genes expression of antidepressants sensitive catalepsy (ASC) mice strain, characterized by depressive-like behavior.</p><p><strong>Methods: </strong>ASC mice were injected with saline, fluoxetine (10 mg/kg/day), or CPG (1 and 2 mg/kg/day) during 2 weeks. Behavior was studied using the open field test, novel object test, elevated plus maze test, forced swim test, and tail suspension test (TST). The expressions of genes coding BDNF, CREB, 5-HT_1A and 5-HT_2A receptors, TPH2, and SERT in the brain were measured with quantitative real-time reverse transcription polymerase chain reaction (RT-PCR).</p><p><strong>Results: </strong>Chronic intraperitoneal administration of 1 and 2 mg/kg of CPG revealed the significant antidepressant-like effect by decreasing immobility time in the TST. At the same time, CPG did not negatively affect locomotor activity, cognition, or anxiety. In the real-time quantitative polymerase chain reaction (PCR) assay, chronic CPG treatment (2 mg/kg for 14 days) increased <i>Bdnf</i> mRNA level in the frontal cortex.</p><p><strong>Conclusions: </strong>Our findings extend the evidence for the effectiveness of CPG to reduce depressive-like behaviors. The antidepressant-like effect of CPG is mediated, as least in part, by BDNF-dependent mechanism. The exact mechanism remains to be elucidated, and further studies are warranted.</p>","PeriodicalId":156490,"journal":{"name":"Journal of Psychopharmacology (Oxford, England)","volume":" ","pages":"214-222"},"PeriodicalIF":4.1,"publicationDate":"2022-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39577684","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":"Impact of drug-induced Parkinsonism and tardive dyskinesia on health-related quality of life in schizophrenia.","authors":"Gurpreet Rekhi,&nbsp;Jenny Tay,&nbsp;Jimmy Lee","doi":"10.1177/02698811211055812","DOIUrl":"https://doi.org/10.1177/02698811211055812","url":null,"abstract":"<p><strong>Background: </strong>Both drug-induced Parkinsonism (DIP) and tardive dyskinesia (TD) have been shown to be associated with lower health-related quality of life (HRQOL) in schizophrenia, but few studies have examined their relative impact.</p><p><strong>Aims: </strong>This study aimed to examine and compare the association of DIP and TD with HRQOL in schizophrenia.</p><p><strong>Methods: </strong>In total, 903 patients with schizophrenia were assessed on the Positive and Negative Syndrome Scale (PANSS), Simpson-Angus Scale (SAS), and Abnormal Involuntary Movement Scale (AIMS). EuroQoL five-dimensional (EQ-5D-5L) utility scores were derived from PANSS scores via a previously validated algorithm and used as a measure of HRQOL.</p><p><strong>Results: </strong>In total, 160 (17.7%) participants had only DIP, 119 (13.2%) had only TD, and 123 (13.6%) had both DIP and TD. HRQOL was lowest for participants with both DIP and TD, followed by only DIP group, only TD group, and highest in the group with neither condition. HRQOL scores differed significantly between the four groups, <i>F</i>(3, 892) = 13.724, <i>p</i> < 0.001, <math><mrow><msubsup><mi>η</mi><mi>p</mi><mn>2</mn></msubsup></mrow></math> = 0.044). HRQOL of participants having only DIP or both DIP and TD was significantly lower than those having neither condition. There was no significant interaction between the presence of DIP and TD on the association with HRQOL.</p><p><strong>Conclusions: </strong>DIP was the main antipsychotic-induced movement disorder associated with a poorer HRQOL in patients with schizophrenia. Therefore, clinicians should focus on prevention, detection, and effective management of DIP to optimize HRQOL in patients with schizophrenia.</p>","PeriodicalId":156490,"journal":{"name":"Journal of Psychopharmacology (Oxford, England)","volume":" ","pages":"183-190"},"PeriodicalIF":4.1,"publicationDate":"2022-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39782717","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":"Bench, bedside, and balance.","authors":"Sameer Jauhar,&nbsp;Allan H Young","doi":"10.1177/02698811221078894","DOIUrl":"https://doi.org/10.1177/02698811221078894","url":null,"abstract":"Citing this paper Please note that where the full-text provided on King's Research Portal is the Author Accepted Manuscript or Post-Print version this may differ from the final Published version. If citing, it is advised that you check and use the publisher's definitive version for pagination, volume/issue, and date of publication details. And where the final published version is provided on the Research Portal, if citing you are again advised to check the publisher's website for any subsequent corrections.","PeriodicalId":156490,"journal":{"name":"Journal of Psychopharmacology (Oxford, England)","volume":" ","pages":"129-130"},"PeriodicalIF":4.1,"publicationDate":"2022-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39632088","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":"Efficacy and safety of psilocybin-assisted treatment for major depressive disorder: Prospective 12-month follow-up.","authors":"Natalie Gukasyan,&nbsp;Alan K Davis,&nbsp;Frederick S Barrett,&nbsp;Mary P Cosimano,&nbsp;Nathan D Sepeda,&nbsp;Matthew W Johnson,&nbsp;Roland R Griffiths","doi":"10.1177/02698811211073759","DOIUrl":"https://doi.org/10.1177/02698811211073759","url":null,"abstract":"<p><strong>Background: </strong>Preliminary data suggest that psilocybin-assisted treatment produces substantial and rapid antidepressant effects in patients with major depressive disorder (MDD), but little is known about long-term outcomes.</p><p><strong>Aims: </strong>This study sought to examine the efficacy and safety of psilocybin through 12 months in participants with moderate to severe MDD who received psilocybin.</p><p><strong>Methods: </strong>This randomized, waiting-list controlled study enrolled 27 patients aged 21-75 with moderate to severe unipolar depression (GRID-Hamilton Depression Rating Scale (GRID-HAMD) ⩾ 17). Participants were randomized to an immediate or delayed (8 weeks) treatment condition in which they received two doses of psilocybin with supportive psychotherapy. Twenty-four participants completed both psilocybin sessions and were followed through 12 months following their second dose.</p><p><strong>Results: </strong>All 24 participants attended all follow-up visits through the 12-month timepoint. Large decreases from baseline in GRID-HAMD scores were observed at 1-, 3-, 6-, and 12-month follow-up (Cohen <i>d</i> = 2.3, 2.0, 2.6, and 2.4, respectively). Treatment response (⩾50% reduction in GRID-HAMD score from baseline) and remission were 75% and 58%, respectively, at 12 months. There were no serious adverse events judged to be related to psilocybin in the long-term follow-up period, and no participants reported psilocybin use outside of the context of the study. Participant ratings of personal meaning, spiritual experience, and mystical experience after sessions predicted increased well-being at 12 months, but did not predict improvement in depression.</p><p><strong>Conclusions: </strong>These findings demonstrate that the substantial antidepressant effects of psilocybin-assisted therapy may be durable at least through 12 months following acute intervention in some patients.</p>","PeriodicalId":156490,"journal":{"name":"Journal of Psychopharmacology (Oxford, England)","volume":" ","pages":"151-158"},"PeriodicalIF":4.1,"publicationDate":"2022-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/b8/57/10.1177_02698811211073759.PMC8864328.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39632089","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":"Can pragmatic research, real-world data and digital technologies aid the development of psychedelic medicine?","authors":"Robin L Carhart-Harris,&nbsp;Anne C Wagner,&nbsp;Manish Agrawal,&nbsp;Hannes Kettner,&nbsp;Jerold F Rosenbaum,&nbsp;Adam Gazzaley,&nbsp;David J Nutt,&nbsp;David Erritzoe","doi":"10.1177/02698811211008567","DOIUrl":"https://doi.org/10.1177/02698811211008567","url":null,"abstract":"<p><p>Favourable regulatory assessments, liberal policy changes, new research centres and substantial commercial investment signal that psychedelic therapy is making a major comeback. Positive findings from modern trials are catalysing developments, but it is questionable whether current confirmatory trials are sufficient for advancing our understanding of safety and best practice. Here we suggest supplementing traditional confirmatory trials with pragmatic trials, real-world data initiatives and digital health solutions to better support the discovery of optimal and personalised treatment protocols and parameters. These recommendations are intended to help support the development of safe, effective and cost-efficient psychedelic therapy, which, given its history, is vulnerable to excesses of hype and regulation.</p>","PeriodicalId":156490,"journal":{"name":"Journal of Psychopharmacology (Oxford, England)","volume":" ","pages":"6-11"},"PeriodicalIF":4.1,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1177/02698811211008567","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38899607","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":"Lifetime use of MDMA/ecstasy and psilocybin is associated with reduced odds of major depressive episodes.","authors":"Grant M Jones,&nbsp;Matthew K Nock","doi":"10.1177/02698811211066714","DOIUrl":"https://doi.org/10.1177/02698811211066714","url":null,"abstract":"<p><strong>Background: </strong>Depression is a major mental health issue worldwide, with high rates of chronicity and non-recovery associated with the condition. Existing treatments such as antidepressant medication and psychological treatments have modest effectiveness, suggesting the need for alternative interventions.</p><p><strong>Aim: </strong>The aim of this study was to examine the relationships between MDMA (3,4-methylenedioxymethamphetamine)/ecstasy and psilocybin use and major depressive episodes (MDEs).</p><p><strong>Methods: </strong>This observational study used data from a large (<i>N</i> = 213,437) nationally representative sample of US adults to test the association of lifetime use of MDMA/ecstasy, psilocybin and other classic psychedelics (lysergic acid diethylamide (LSD), peyote, mescaline), other illegal substances (e.g. cocaine, phencyclidine (PCP)), and legal/medicinal substances of misuse (e.g. pain relievers, tranquilizers) with lifetime, past year, and past year severe MDEs.</p><p><strong>Results: </strong>Results revealed that lifetime MDMA/ecstasy use was associated with significantly lowered odds of a lifetime MDE (adjusted odds ratio (aOR) = 0.84; <i>p</i> < 0.001), past year MDE (aOR = 0.84; <i>p</i> < 0.001), and past year severe MDE (aOR = 0.82; <i>p</i> < 0.001). Psilocybin was associated with significantly lowered odds of a past year MDE (aOR = 0.90; <i>p</i> < 0.05) and past year severe MDE (aOR = 0.87; <i>p</i> < 0.05). All other substances either shared no relationship with a MDE or conferred increased odds of an MDE.</p><p><strong>Conclusions: </strong>These results suggest that MDMA/ecstasy and psilocybin use is associated with lower risk of depression. Experimental studies are needed to test whether there is a causal association between use of these compounds and the alleviation of depressive symptoms.</p>","PeriodicalId":156490,"journal":{"name":"Journal of Psychopharmacology (Oxford, England)","volume":" ","pages":"57-65"},"PeriodicalIF":4.1,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39784647","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}