Journal of Psychopharmacology (Oxford, England)最新文献

{"title":"Effects of acute lysergic acid diethylamide on intermittent ethanol and sucrose drinking and intracranial self-stimulation in C57BL/6 mice","authors":"L. Elsilä, J. Harkki, Emma Enberg, Alvar Martti, A. Linden, E. Korpi","doi":"10.1177/02698811221104641","DOIUrl":"https://doi.org/10.1177/02698811221104641","url":null,"abstract":"Background: Psychedelics, like lysergic acid diethylamide (LSD), are again being studied as potential therapies for many neuropsychiatric disorders, including addictions. At the same time, the acute effects of psychedelics on rewarding behaviours have been scarcely studied. Aims: The current study aimed to clarify if LSD decreases binge-like ethanol drinking in mice, and whether the observed acute effects on ethanol consumption are generalizable to a natural reinforcer, sucrose, and if the effects resulted from aversive or reward-attenuating effects caused by LSD. Methods: The effects of acute LSD were examined using 2-bottle choice intermittent ethanol (20%) and sucrose drinking (10%), discrete-trial current-intensity threshold method of intracranial self-stimulation and short-term feeding behaviour assay in C57BL/6 male mice. Results: The results showed that acute 0.1 mg/kg, but not 0.05 mg/kg, dose (i.p.) of LSD reduced 2-h intermittent ethanol drinking transiently without any prolonged effects. No effects were seen in intermittent 2-h sucrose drinking. The tested LSD doses had neither effect on the intracranial self-stimulation current-intensity thresholds, nor did LSD affect the threshold-lowering, or rewarding, effects of simultaneous amphetamine treatment. Furthermore, LSD had small, acute diminishing effects on 2-h food and water intake. Conclusions: Based on these results, LSD decreases binge-like ethanol drinking in mice, but only acutely. This effect is not likely to stem from reward-attenuating effects but could be in part due to reduced consummatory behaviour.","PeriodicalId":156490,"journal":{"name":"Journal of Psychopharmacology (Oxford, England)","volume":"75 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2022-06-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"133285270","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":"BAP editorial: Improving the validity and translation of preclinical research","authors":"J. Pratt, E. Robinson, C. Fernandes, D. Heal, S. Stanford","doi":"10.1177/02698811221104064","DOIUrl":"https://doi.org/10.1177/02698811221104064","url":null,"abstract":"The October 2021 edition of Journal of Psychopharmacology focussed on the contemporary topic of translational psychopharmacology. Translational research is critical for the development of early interventions and improved therapeutics for mental health conditions. In this respect, the continual updating of information gained from reciprocal forward (preclinical) and reverse (clinical) translational approaches is necessary. Despite the enthusiasm for translational psychopharmacology in the preclinical research community, there are many challenges if we are to achieve the crucial goal of developing therapies with superior efficacy and tolerability over current drugs for neuropsychiatric conditions. At a recent meeting of a preclinical subpanel of the Journal of Psychopharmacology editorial board, members debated opportunities to improve the validity and translation of preclinical research models. A particular focus being the importance of understanding the clinical relevance of a model and its readouts and how well the mechanisms associated with those readouts and arising novel drug targets translate to the clinic. Importantly, consideration was given to moving away from pharmacological models towards the development of approaches which recapitulate more clinically relevant readouts. Some key points are summarised below.","PeriodicalId":156490,"journal":{"name":"Journal of Psychopharmacology (Oxford, England)","volume":"1 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2022-06-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"122849042","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":"Adverse experiences resulting in emergency medical treatment seeking following the use of lysergic acid diethylamide (LSD)","authors":"Emma I Kopra, J. Ferris, J. Rucker, Benjamin McClure, A. Young, C. Copeland, A. Winstock","doi":"10.1177/02698811221099650","DOIUrl":"https://doi.org/10.1177/02698811221099650","url":null,"abstract":"Background: Recreational lysergic acid diethylamide (LSD) use is growing in popularity amid increasing research interest on psychedelics and their possible therapeutic potential yet; the potent psychotropic effects of LSD may result in adverse reactions and behaviour. Aims: This study aimed to investigate the 12-month incidence and nature of LSD-related adverse experiences resulting in emergency medical treatment (EMT) seeking in an international sample of people reporting LSD use. Methods: We use data from the 2017 Global Drug Survey – a large anonymous online survey on patterns of drug use conducted between November 2016 and January 2017. Results: Out of 10,293 past-year LSD users, 102 (1.0%) reported seeking EMT, with a per-event risk estimate of 0.2%. Younger age, comorbid mental health conditions and higher frequency of use were associated with increased risk of EMT seeking. The most common symptoms were psychological, including anxiety, panic and confusion, with the most common explanatory factors cited by respondents being poor ‘setting’ and ‘mindset’. Most responders reported feeling back to normal within 24 h, but 11 participants experienced persistent issues after 4 weeks. Conclusion: The results suggest that LSD is a relatively safe drug in recreational settings. Adverse reactions are typically short-lived, self-limiting and psychological in nature. Sub-optimal set and setting were commonly reported as suspected contributory factors. Within clinical settings, patient screening, preparatory sessions and supervision should reduce these acute risks considerably.","PeriodicalId":156490,"journal":{"name":"Journal of Psychopharmacology (Oxford, England)","volume":"8 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2022-06-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"127923523","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":"Over the counter low-dose cannabidiol: A viewpoint from the ACRE Capacity Building Group.","authors":"Christine Mary Hallinan,&nbsp;Edward Eden,&nbsp;Myfanwy Graham,&nbsp;Lisa-Marie Greenwood,&nbsp;Jessica Mills,&nbsp;Amirali Popat,&nbsp;Linda Truong,&nbsp;Yvonne Bonomo","doi":"10.1177/02698811211035394","DOIUrl":"https://doi.org/10.1177/02698811211035394","url":null,"abstract":"<p><p>Amidst growing global acceptance of medicinal cannabinoids as a potential therapeutic interest in cannabidiol (CBD) is increasing. In Australia in 2020, a government inquiry examined the barriers that the public are experiencing in accessing medicinal cannabis. A number of recommendations to improve access were made. In response to these recommendations, the Australian therapeutics regulatory authority down-scheduled CBD from Prescription Only (Schedule 4) to Pharmacist Only (Schedule 3). As a group of early to mid-career researchers of the Australian Centre for Cannabinoid Clinical and Research Excellence (ACRE), we propose some considerations in relation to over-the-counter availability of CBD and opportunities to improve knowledge about its potential therapeutic benefits alongside its increased uptake.</p>","PeriodicalId":156490,"journal":{"name":"Journal of Psychopharmacology (Oxford, England)","volume":" ","pages":"661-665"},"PeriodicalIF":4.1,"publicationDate":"2022-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39273635","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":"Prospects for new drugs to treat binge-eating disorder: Insights from psychopathology and neuropharmacology.","authors":"David J Heal,&nbsp;Sharon L Smith","doi":"10.1177/02698811211032475","DOIUrl":"https://doi.org/10.1177/02698811211032475","url":null,"abstract":"<p><strong>Background: </strong>Binge-eating disorder (BED) is a common psychiatric condition with adverse psychological and metabolic consequences. Lisdexamfetamine (LDX) is the only approved BED drug treatment. New drugs to treat BED are urgently needed.</p><p><strong>Methods: </strong>A comprehensive review of published psychopathological, pharmacological and clinical findings.</p><p><strong>Results: </strong>The evidence supports the hypothesis that BED is an impulse control disorder with similarities to ADHD, including responsiveness to catecholaminergic drugs, for example LDX and dasotraline. The target product profile (TPP) of the ideal BED drug combines treating the psychopathological drivers of the disorder with an independent weight-loss effect. Drugs with proven efficacy in BED have a common pharmacology; they potentiate central noradrenergic and dopaminergic neurotransmission. Because of the overlap between pharmacotherapy in attention deficit hyperactivity disorder (ADHD) and BED, drug-candidates from diverse pharmacological classes, which have already failed in ADHD would also be predicted to fail if tested in BED. The failure in BED trials of drugs with diverse pharmacological mechanisms indicates many possible avenues for drug discovery can probably be discounted.</p><p><strong>Conclusions: </strong>(1) The efficacy of drugs for BED is dependent on reducing its core psychopathologies of impulsivity, compulsivity and perseveration and by increasing cognitive control of eating. (2) The analysis revealed a large number of pharmacological mechanisms are unlikely to be productive in the search for effective new BED drugs. (3) The most promising areas for new treatments for BED are drugs, which augment noradrenergic and dopaminergic neurotransmission and/or those which are effective in ADHD.</p>","PeriodicalId":156490,"journal":{"name":"Journal of Psychopharmacology (Oxford, England)","volume":" ","pages":"680-703"},"PeriodicalIF":4.1,"publicationDate":"2022-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1177/02698811211032475","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39229428","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":"A phase 1 study to assess potential interaction between ASP8062 and alcohol in healthy adult subjects.","authors":"Mototsugu Ito,&nbsp;Anna Spence,&nbsp;Mary Beth Blauwet,&nbsp;Nakyo Heo,&nbsp;Ronald Goldwater,&nbsp;Paul Maruff,&nbsp;Gerard J Marek","doi":"10.1177/02698811211058967","DOIUrl":"https://doi.org/10.1177/02698811211058967","url":null,"abstract":"Background: ASP8062 is a novel orally active GABAB receptor positive allosteric modulator in clinical development for the treatment of alcohol use disorder (AUD) and opioid use disorder (OUD). Aims: This study assessed the potential pharmacokinetic/pharmacodynamic interaction between ASP8062 and alcohol under single-dose conditions in healthy adults. Methods: A double-blind, placebo-controlled, crossover phase 1 study was conducted in which 20 subjects were randomly assigned to four treatment sequences (ASP8062 + alcohol; ASP8062 + placebo alcohol; placebo + alcohol; placebo + placebo alcohol) each consisting of four treatment periods, separated by washout periods of at least 14 days. An analysis of variance was used to assess pharmacokinetic interaction and a mixed-effects analysis of covariance was used to assess pharmacodynamic interaction. Results/outcomes: After administration of alcohol, a mild to minimal increase in plasma exposure (AUCinf and Cmax) of ASP8062 was observed, but tmax and t½ for ASP8062 remained unchanged after administration of alcohol. In contrast, ASP8062 did not affect the AUClast and Cmax of ethanol. No clinically relevant differences in cognition measurements were observed with ASP8062 compared with placebo, but there were expected impairments in psychomotor and executive function with alcohol alone. ASP8062 in combination with alcohol resulted in worse scores in cognition measurements than alcohol alone, but this potentiation was not consistent. ASP8062 administered alone was safe and well-tolerated and safety findings in subjects administered alcohol alone were not augmented when ASP8062 was administered in combination with alcohol. Conclusion/interpretation: The data support further clinical studies investigating ASP8062 in patients with AUD.","PeriodicalId":156490,"journal":{"name":"Journal of Psychopharmacology (Oxford, England)","volume":" ","pages":"756-767"},"PeriodicalIF":4.1,"publicationDate":"2022-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39906281","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":"Role of the norepinephrine transporter polymorphisms in atomoxetine treatment: From response to side effects in children with ADHD.","authors":"Melike Kevser Gul,&nbsp;Elif Funda Sener,&nbsp;Muge Gulcihan Onal,&nbsp;Esra Demirci","doi":"10.1177/02698811211015245","DOIUrl":"https://doi.org/10.1177/02698811211015245","url":null,"abstract":"<p><strong>Objective: </strong>Atomoxetine (ATX), one of the most commonly used drugs after stimulants in attention deficit hyperactivity disorder (ADHD) treatment, is an inhibitor of the norepinephrine transporter (<i>NET/SLC6A2</i>), which is also associated with the etiology of ADHD. In this study, we aimed to investigate the effect of <i>NET</i> gene polymorphisms on response to ATX treatment and to find the answers to the questions about whether there is a relationship between the severity of the disorder and the observed side effects in children with ADHD.</p><p><strong>Method: </strong>About 100 children with ADHD and 80 healthy controls (HCs) were included in this study. The dose of ATX was started at 0.5 mg/kg/day and titrated at 1.2 mg/kg/day. Response to treatment of 78 patients was evaluated 2 months after the beginning of the treatment. After whole blood samples were obtained, DNAs were isolated, and samples were stored at -80°C. Two single-nucleotide polymorphisms (SNPs) (rs12708954 and rs3785143) were analyzed by real-time quantitative PCR (qRT-PCR).</p><p><strong>Results: </strong>The patients with both rs12708954 and rs3785143 heterozygous genotype had better treatment response and more side effects than patients with wild type. There was not found any association between any of the investigated <i>NET</i> polymorphisms and ADHD severity.</p><p><strong>Conclusion: </strong>It was, however, found that the <i>NET</i> rs12708954 and rs3785143 genotypes affect the treatment response to ATX in our study; thus, further studies with a large population are needed to understand the effects of <i>NET</i> polymorphisms on treatment, side effects, and also the severity of ADHD.</p>","PeriodicalId":156490,"journal":{"name":"Journal of Psychopharmacology (Oxford, England)","volume":" ","pages":"715-722"},"PeriodicalIF":4.1,"publicationDate":"2022-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1177/02698811211015245","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38946545","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":"Neural mechanisms underlying psilocybin’s therapeutic potential – the need for preclinical in vivo electrophysiology","authors":"Rebecca Smausz, Joanna Neill, J. Gigg","doi":"10.1177/02698811221092508","DOIUrl":"https://doi.org/10.1177/02698811221092508","url":null,"abstract":"Psilocybin is a naturally occurring psychedelic compound with profound perception-, emotion- and cognition-altering properties and great potential for treating brain disorders. However, the neural mechanisms mediating its effects require in-depth investigation as there is still much to learn about how psychedelic drugs produce their profound and long-lasting effects. In this review, we outline the current understanding of the neurophysiology of psilocybin’s psychoactive properties, highlighting the need for additional preclinical studies to determine its effect on neural network dynamics. We first describe how psilocybin’s effect on brain regions associated with the default-mode network (DMN), particularly the prefrontal cortex and hippocampus, likely plays a key role in mediating its consciousness-altering properties. We then outline the specific receptor and cell types involved and discuss contradictory evidence from neuroimaging studies regarding psilocybin’s net effect on activity within these regions. We go on to argue that in vivo electrophysiology is ideally suited to provide a more holistic, neural network analysis approach to understand psilocybin’s mode of action. Thus, we integrate information about the neural bases for oscillatory activity generation with the accumulating evidence about psychedelic drug effects on neural synchrony within DMN-associated areas. This approach will help to generate important questions for future preclinical and clinical studies. Answers to these questions are vital for determining the neural mechanisms mediating psilocybin’s psychotherapeutic potential, which promises to improve outcomes for patients with severe depression and other difficulty to treat conditions.","PeriodicalId":156490,"journal":{"name":"Journal of Psychopharmacology (Oxford, England)","volume":"73 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2022-05-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"114395453","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":"Postpartum depression: A role for psychedelics?","authors":"C. Jairaj, J. Rucker","doi":"10.1177/02698811221093793","DOIUrl":"https://doi.org/10.1177/02698811221093793","url":null,"abstract":"Background: Postpartum depression (PPD) is a major public health concern and has, at its core, a sense of maternal ‘disconnection’ – from the self, the infant, and the support system. While PPD bears similarities with MDD, there is increasing evidence for its distinct nature, especially with the unique aspect of the mother-infant relationship. Current treatment modalities for PPD, largely based on those used in major depressive disorder (MDD), have low remission rates with emerging evidence for treatment resistance. It is, therefore, necessary to explore alternative avenues of treatment for PPD. Objective: In this narrative review, we outline the potential therapeutic rationale for serotonergic psychedelics in the treatment of PPD, and highlight safety and pragmatic considerations for the use of psychedelics in the postpartum period. Methods: We examined the available evidence for the treatment of PPD and the evidence for psychedelics in the treatment of MDD. We explored safety considerations in the use of psychedelics in the postpartum period. Results: There is increasing evidence for safety, and encouraging signals for efficacy, of psilocybin in the treatment of MDD. Psilocybin has been shown to catalyse a sense of ‘reconnection’ in participants with MDD. This effect in PPD, by fostering a sense of ‘reconnection’ for the mother, may allow for improved mood and maternal sensitivity towards the infant, which can positively impact maternal role gratification and the mother-infant relationship. Conclusion: Psychedelic assisted therapy in PPD may have a positive effect on the mother-infant dyad and warrants further examination.","PeriodicalId":156490,"journal":{"name":"Journal of Psychopharmacology (Oxford, England)","volume":"52 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2022-05-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"129560909","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":"Effect of alcohol coadministration on the pharmacodynamics, pharmacokinetics, and safety of lemborexant: A randomized, placebo-controlled crossover study","authors":"I. Landry, N. Hall, J. Aluri, G. Filippov, B. Setnik, Satish Dayal, L. Reyderman, M. Moline","doi":"10.1177/02698811221080459","DOIUrl":"https://doi.org/10.1177/02698811221080459","url":null,"abstract":"Background: Lemborexant is a dual orexin receptor antagonist approved to treat insomnia in adults in several countries including the USA, Canada, and Japan. Aims: This study was conducted to investigate effects of lemborexant and alcohol coadministration on postural stability, cognitive performance, and the pharmacokinetics, safety, and tolerability of lemborexant. Methods: This was a Phase 1, double-blind, placebo-controlled, four-period crossover study in 32 healthy adults. Individuals were randomized into one of four treatment sequences to receive single doses of placebo, lemborexant 10 mg (LEM10), alcohol (males, 0.7 g/kg; females, 0.6 g/kg), and LEM10 plus alcohol, each separated by a 14-day washout. Postural stability (body sway) was measured by ataxiameter and a cognitive performance assessment battery evaluated four domains of attention and memory. Results: Pharmacodynamic outcomes were analyzed for the 18 participants who completed all four treatments. Change from baseline in body sway showed no significant differences between lemborexant plus alcohol versus alcohol alone. Compared with alcohol alone, coadministration of lemborexant with alcohol showed additive negative effects on cognitive performance domains, corresponding approximately with peak plasma lemborexant concentrations (median = 1.5 h). Cognitive performance was also impaired with lemborexant alone at 0.5 and 2 h in this experimental paradigm with morning dosing. Alcohol increased plasma lemborexant exposure by 70% based on area under the curve to 72 h, and increased peak plasma lemborexant concentrations by 35%. The most commonly reported treatment–emergent adverse event was somnolence. Conclusion: Coadministration of lemborexant with alcohol showed additive negative effects on cognitive measures, but not on postural stability, compared with alcohol alone. Lemborexant exposure was increased with alcohol. Lemborexant alone or with alcohol was well tolerated. Patients are advised not to consume alcohol with lemborexant.","PeriodicalId":156490,"journal":{"name":"Journal of Psychopharmacology (Oxford, England)","volume":"487 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2022-05-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"133759762","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}